ARTICLE | doi:10.20944/preprints202209.0426.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: angiotensin-converting enzyme (ACE); antipsychotic medication; polymorphism, insertion/deletion; treatment response
Online: 28 September 2022 (03:12:20 CEST)
We investigated whether a functional insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) influenced antipsychotic treatment. At baseline, and after 8 weeks of treatment with various antipsychotic medications, we assessed patients’ Positive and Negative Syndrome Scale (PANSS) scores, PANSS factors, and metabolic syndrome-related parameters (fasting plasma lipid and glucose levels, and body mass index). A total of 186 antipsychotic-naïve first-episode psychosis patients or nonadherent chronic psychosis individuals (99 males and 87 females) were genotyped by polymerase chain reaction analysis. The ACE-I/D polymorphism was significantly associated with changes in PANSS psychopathology only (p < 0.05). Compared to ACE-II homozygous males, ACE-DD homozygous and ACE-ID heterozygous males manifested significantly greater decreases in PANSS positive score, PANSS excitement factor, and PANSS cognitive factor. ACE-DD homozygous females manifested higher decreases in PANSS depression factor compared to ACE-II homozygous and ACE-ID heterozygous females. The polymorphism’s effect size was estimated as moderate to strong, while its contribution to the PANSS psychopathology ranged from ~5.4–8.7%, with the lowest contribution observed for PANSS positive score changes and the highest for PANSS depressive factor changes. Our results indicated that ACE-I/D polymorphism had a statistically significant but weak gender-specific impact on psychopathology data and showed no association between ACE-I/D polymorphism and metabolic syndrome-related parameters.
ARTICLE | doi:10.20944/preprints202209.0307.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: emotional intelligence; brain injury; cognitive impairment
Online: 20 September 2022 (13:14:54 CEST)
Background: Cognitive-behavioral alterations can occur after an acquired brain injury. It is a stressful situa-tion for patient and relatives. Objectives: To develop and evaluate a synchronous online training program on emotional intelligence (EI) for caregivers of adult patients with cognitive-behavioral impairment due to acquired brain injury. Methods: A quasi-experimental study was designed, a target population of ten caregivers attended to a one-month virtual synchronous course about EI. The emotional status of caregivers was registered one-month-previous and one-month-post program using comparative measures: The Trait Meta-Mood Scale (TMMS-24) and the Positive and Negative Affect Schedule (PANAS). Results: Median age of the ten caregivers was 48 years, 80% of women with a median care-time of 6 years. 50% of them were spouses of the patients. 60% of the patients were affected by stroke (hemorrhagic or ischemic cause). The main cognitive impairment of the patients reported by relatives was memory deficit. After re-ceiving training, favorable changes were found regarding emotional affect measured with the PANAS, both positive (increase) and negative (decrease), as well as with the TMMS-24-mood-repair area (p < 0.05). Conclusions: Training in EI helps caregivers to make their mood more positive and improve aspects of their emotional intelligence such as emotional regulation.
REVIEW | doi:10.20944/preprints202209.0278.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Suicide attempt; behaviour; prevention; Facebook
Online: 19 September 2022 (10:33:36 CEST)
Background: Facebook represents a new dimension for global information sharing. Suicidal behaviours and attempts are growingly reported on Facebook. This scoping review explores the various aspects of suicidal behaviours associated with Facebook, discussing the challenges and preventive measures. Methods: PubMed, Google Scholar, and Scopus were searched for related articles published in English up to October 2021, using different combinations of "Facebook" and "suicide". A group of consultant psychiatrists screened the records and read the full-text articles to extract relevant data. Results: Facebook impacts suicidal behaviours in different aspects. Announcing suicides through sharing notes or personal information, which can be helpful in prediction of suicide, and harmful since negatively affects audience. Live-streaming videos of suicide is another aspect, which questions the ability of Facebook to monitor shared contents that can negatively affect the audience. Helping bereaved families to share feelings and seek support online, commemorating the lost person by sharing their photos is another positive impact. Moreover, it can provide real-world details of everyday user behaviours, which are helpful to predict suicide risk, primarily through novel machine-learning techniques, and provide early warning and valuable help to prevent it. It can also provide a timeline of the user's activities and state of mind before suicide. Conclusions: Social media can detect suicidal tendencies, provide support for those seeking help, comfort family and friends with their grief, and provide insights via timelining the users' activities leading to their suicide. The lack of quantitative studies on evaluating preventative efforts on Facebook was one of the limitations. The creators' commitment and the users' social responsibility will be required to create a mentally healthy Facebook environment.
ARTICLE | doi:10.20944/preprints202209.0268.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: COVID-19 outbreak; lockdown protocols; individual and social activities; mental health challenges; older people; Indonesia
Online: 19 September 2022 (07:51:50 CEST)
The COVID-19 pandemic has caused detrimental impacts on different population groups throughout the world. This study aimed to explore the impacts of the COVID-19 pandemic’s mandatory lockdown protocols on activities and mental health conditions of community-dwelling older people in Jakarta, Indonesia. A qualitative design using one-on-one in-depth interviews was employed to collect data from the participants (n=24) who were recruited using the snowball sampling technique. Data analysis was guided by a qualitative data analysis framework. The findings showed that before the COVID-19 outbreak participants engaged in different kinds of regular individual and social activities. However, the COVID-19 outbreak and its mandatory lockdown protocols significantly influenced both their activities and social life, which led to social disconnection and financial difficulties for them. COVID-19 outbreak, mandatory lockdown protocols, and disruption of individual and social activities of the participants also caused mental health challenges to them, including feelings of loneliness, loss, sadness, stress, and anger. The findings suggest that there is a need for intervention programs addressing the socio-economic and mental health impacts of the COVID-19 pandemic on older populations to help them cope with these challenges. Future studies involving large-scale older populations to comprehensively understand COVID-19 impacts on them are recommended.
ARTICLE | doi:10.20944/preprints202209.0265.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: mental health; migrant health; undocumented migrants; COVID-19; coping strategy; Myanmar; Thailand; mixed method
Online: 19 September 2022 (05:40:23 CEST)
Migrant population have always been vulnerable for high burden of social exclusion, mental disorders, physical illness and economic crisis. The current COVID-19 pandemic has further created the frantic plight among them, particularly for the undocumented migrant workers in global south. We have conducted a mixed method study among the undocumented Myanmar migrant workers (UMMWs) in Thailand to explore how the COVID-19 disruption has impacted on their mental health and what are the coping strategies adopted by them. Following the onset of COVID-19 and the recent coup d'etat in Myanmar, our current study is the first attempt to understand the mental health status and predicament of this neglected migrant group. A total of 398 UMMWs were included in the online survey among whom 23 participated in qualitative interviews. The major mental health issues reported by the study participants were depression, generalised anxiety disorder, frustration, stress and panic disorder while loss of employment, worries about the pandemic, social stigma, refused access to healthcare, lockdown and fear of detention were the predominant contributing factors. In response, we identified two key coping mechanisms- coping at personal layer (listening to music, playing online game, praying, self-motivation) and social layer (chatting with family and friends, visiting religious institutions). These findings point to the importance of policy and intervention programs aimed to uphold mental health at such humanitarian conditions. Sustainable institutional mental health care support and social integration for the migrant workers irrespective of their legal status should be ensured.
ARTICLE | doi:10.20944/preprints202209.0228.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: functional connectivity; functional magnetic-resonance imaging; resting state; mood disorders; classification
Online: 15 September 2022 (09:20:26 CEST)
Aim. In the current study, we aimed at identifying resting-state brain networks, which are different in patients with depression compared to healthy individuals. Moreover, we analyzed the potential for clinical use of different network measures that could discriminate the two groups and thus help the diagnostic process. Method and subjects. We recruited 90 subjects: 49 healthy controls (HC) and 41 patients with a major depressive episode (MDE). All subjects underwent clinical evaluation and functional resting-state MRI. The data were processed to investigate functional connectivity network measures across the two groups using Brain Connectivity Toolbox. The statistical inferences were made at the functional networks level, using false discovery rate method. Independent samples t-test was performed on the network measures mean values to reveal differences between HC and MDE groups. Permutation-based statistical testing was used to test the significance of the difference between the distributions of the network measures by nodes for HC and MDE groups. Linear discriminant analysis was used to differentiate between the groups. Results and discussion. Significant differences in FC between depressed patients and healthy controls were found with the most prominent changes encompassing within-region as well as between-region connectivity of occipital lobe areas such as precuneus (PreCu), cuneus (Cu), superior occipital gyrus (SOG), lingual gyrus (LG), fusiform gyrus (FG), cerebellum, along with limbic structures including the hippocampus (Hipp) and cingulate gyrus. Linear discriminant analysis demonstrated that the full connectivity matrices, as well as those with only the significant connections identified in advance, were the most precise in differentiating between depression and health. These measures reached precision levels of 97% and 94%, respectively. Conclusion. Our study delivered further evidence about impairment of functional connectivity networks in MDE that may contribute to differentiate patients with depression from healthy subjects.
ARTICLE | doi:10.20944/preprints202209.0213.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: community care; integrated care; mental health; service users and relatives’ interventions; service users and relatives’ interaction
Online: 14 September 2022 (16:27:56 CEST)
Relatives play an important role in mental health service users’ care. Interventions directed either at service users or their relatives may influence the other person as well. The project Activa’t per la salut mental (Get active for mental health) consisted of a series of four interventions addressed at people diagnosed with mental disorders and their relatives to help them in their recovery process, increasing their agency and quality of life. The objective of the present study is to evaluate the interaction of the participation of service users on their relatives’ outcomes and vice versa. The impact of the project was evaluated within an RCT. The treatment group had access to all the circuit interventions while the control group received treatment as usual and could only access one of the interventions. All participants were evaluated at baseline, six months, and twelve months after the end of the first intervention. Service users were evaluated with the Stages of recovery questionnaire, and relatives with the Family Burden Interview Schedule II and the Duke-UNC-11 questionnaires. The interaction between service users and their relatives was analysed by means of correlational analyses within the intervention group. Service users baseline characteristics influenced in the level of participation of relatives and vice versa. The results also indicated an interaction between service users’ recovery score changes on the change of care burden of relatives. Service users’ participation levels interacted with the decrease of relatives’ burden. These results can be extremely helpful in fostering interactive benefits in future projects addressing the wellbeing of mental health service users and their relatives. Future studies could use specific designs to explore the directionality of the causality of these effects.
ARTICLE | doi:10.20944/preprints202209.0121.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Cathinones; Designer drugs; Bath salts; Neuronal injury; astroglial injury; Calpain; Caspase
Online: 8 September 2022 (09:14:34 CEST)
This study aims to examine the cytotoxicity mechanisms of synthetic cathinone (bath salts) on rat primary cultured neurons and primary astroglial cells, and to assess their neurobehavioral effects on mice. We administered methylenedioxypyrovalerone (MDPV) to both rat primary cultured neurons and primary astroglial cells to assess cell injury. We also analyzed the effects of MDPV on these cell cultures using immunocytochemistry. We utilized western blotting to assess the breakdown of αII-spectrin and glial fibrillary acidic protein (GFAP) induced by MDPV. The western blotting experiment also included calpain and caspase inhibitors (SNJ1945 and Z-D-DCB, respectively) and pro-apoptotic and pro-necrotic agents (Staurosporine and calcium ionophore A23187, respectively). Lastly, we assessed MDPV’s effects on behavioral effects using rotarod, locomotor activity, elevated plus maze, Morris water maze, forced swimming, and open field tests. MDPV caused a dose-dependent release of LDH in both cerebrocortical neuron-astroglia mixed cultures and primary astroglial cultures. MDPV also caused neurite breakages and astroglial process retraction on immunocytochemistry. Lastly, MDPV induced αII-spectrin breakdown in western blotting experiments. Co-administration of calpain and caspase inhibitors reduced the degradation of αII-spectrin and GFAP. MDPV administration also increased anxiety-like behavior and locomotor activity in the mice. Synthetic cathinones, which share structural similarities with methamphetamine, also induce significant neurotoxic effects and neurobehavioral effects on rodent models. These neurotoxic effects are likely mediated by calpain and caspase-induced apoptosis and necrosis, while astroglial death is likely only due to calpain activation. Therefore, further research may focus on pharmacological interventions targeting these pathways to mitigate the cytotoxic impact of cathinones in humans.
ARTICLE | doi:10.20944/preprints202209.0110.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: ADHD; Antisocial Behavior; Sense of Coherence; Protective Factors
Online: 7 September 2022 (11:03:25 CEST)
Numerous studies have established the link between ADHD and antisocial behavior, one of the most serious functional impairments caused by the disorder. However, research on protective factors that mitigate this link is still lacking. The Salutogenic Model of Health offers the “Sense of Coherence” (SOC), establishing that individuals who see their lives as logical, meaningful, and manageable are more resistant to various risk factors and diseases. The present study examines for the first time whether SOC is also a protective factor against ADHD-related different types of antisocial behaviors (severe/mild violent behavior, verbal violence, property crimes, public disorder, and drug abuse). 2260 participants aged 15-50 completed online questionnaires assessing the level of ADHD symptoms, antisocial behaviors, and SOC. An interaction between ADHD and SOC was found in predicting each type of antisocial behavior. The link between ADHD and antisocial behavior was significantly weaker for high than low SOC participants, regardless of age group. The current study found that people with high SOC are protected against the effect of ADHD on one of the most serious functional impairments, antisocial behavior. These findings suggest that SOC is a protective factor from the adverse effects of ADHD, justifying further prospective and intervention studies.
REVIEW | doi:10.20944/preprints202209.0069.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: acetylated E2F4; synapsis; tissue homeostasis; Alzheimer’s disease; 5xFAD mice; neuroinflammation; microgliosis; reactive astrocytes.
Online: 5 September 2022 (13:52:27 CEST)
E2F4 was initially described as a transcription factor with a key function in the regulation of cell quiescence. Nevertheless, a number of recent studies have established that E2F4 can also play a relevant role in cell and tissue homeostasis as well as tissue regeneration. For these non-canonical functions, E2F4 can also act in the cytoplasm, where it is able to interact with many homeostatic and synaptic regulators. Since E2F4 is expressed in the nervous system, it may fulfill a crucial role in brain function and homeostasis, being a promising multifactorial target for neurodegenerative diseases and brain aging. The regulation of E2F4 is complex as it can be chemically modified through acetylation, from which we present evidence in the brain, as well as methylation, and phosphorylation. The phosphorylation of E2F4 within a conserved threonine motif induces cell cycle re-entry in neurons, while a dominant negative form of E2F4 (E2F4DN), in which the conserved threonines have been substituted by alanines, has been shown to act as a multifactorial therapeutic agent for Alzheimer’s disease (AD). We have generated transgenic mice neuronally expressing E2F4DN. We have recently shown using this mouse strain that expression of E2F4DN in 5xFAD mice, a known murine model of AD, improved cognitive function, reduced neuronal tetraploidization, and induced a transcriptional program consistent with modulation of amyloid-beta (Abeta) peptide proteostasis and brain homeostasis recovery. 5xFAD/E2F4DN mice also showed reduced microgliosis and astrogliosis in both cerebral cortex and hippocampus at 3-6 months of age. Here we have analyzed the immune response in 1 year-old 5xFAD/E2F4DN mice, concluding that reduced microgliosis and astrogliosis is maintained at this late stage. In addition, the expression of E2F4DN also reduced age-associated microgliosis in wild-type mice, thus stressing its role as a brain homeostatic agent. We conclude that E2F4DN transgenic mice represent a promising tool for the evaluation of E2F4 as a therapeutic target in neuropathology and brain aging.
ARTICLE | doi:10.20944/preprints202208.0458.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: mental illness; homicide; violence; psychiatry; Penrose hypothesis; deinstitutionalization
Online: 26 August 2022 (10:00:36 CEST)
The association between mental illness and violent crimes such as homicide is complex. In 1939, Lionel Penrose hypothesized that the availability of psychiatric hospital beds was inversely related to the prison population, presumably due to the hospitalization of potential offenders with a mental illness. Subsequent studies have found evidence for this association, but questions remain about the contributions of confounding factors. Moreover, there has been a move towards deinstitutionalization and community care of the mentally ill over the past six decades. In this study, the association between national homicide rates and three measures of the availability of psychiatric care – the numbers of psychiatrists, general hospital psychiatric beds, and psychiatric hospital beds per 100,000 population – was examined using a time-lagged correlation analysis. Associations between homicide rates and socioeconomic factors associated with crime were also examined. It was found that the availability of psychiatrists and of general hospital psychiatric beds were both negatively correlated with homicide rates, and that the association with general hospital psychiatric beds remained significant even after correction for confounding factors. These results suggest the need for a more nuanced interpretation of Penrose’s original formulation, involving the interplay of social, economic factors and psychological factors rather than linear causality.
ARTICLE | doi:10.20944/preprints202208.0391.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: scale design; reliability; validity; first responders; mental health; workplace; occupational stress; humiliation; betrayal
Online: 23 August 2022 (03:50:00 CEST)
First responders, such as police officers, paramedics, and fire-fighters are at an increased risk of experiencing negative mental health outcomes compared to the general population. This predisposition can partially be attributed to common occupational stressors, such as poor workplace culture and mistreatment from leadership, which may provoke strong feelings of betrayal and humiliation. The Workplace Assessment Scale (WAS) was developed as there is currently no appropriate measure to assess such feelings in the first responder population. The scale consists of the Betrayal Subscale and the Humiliation Subscale, each comprised of 5 Likert scale questions which ask participants to report the frequency at which they experience specific feelings associated with their workplace. This pilot validation study was conducted to assess preliminary reliability and validity of the WAS, using data which was originally collected as part of a larger first responder-based observational study. Based on 21/22 (95%) participant responses, the internal consistency appeared to be strong for both sub-scales as well as the overall questionnaire. However, item 9 will likely require modification or deletion from the scale. The validity analysis found no significant correlations between WAS and other psychiatric scales. Additional research is needed for further analysis and validation of the WAS.
ARTICLE | doi:10.20944/preprints202208.0355.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: developmental delay; de novo mutation; protein-protein interaction; PPI interface; protein in-teractome; PsymuKB
Online: 19 August 2022 (04:50:42 CEST)
Mutations, especially those at the protein-protein interaction (PPI) interface, have been associated with various diseases. Meanwhile, though de novo mutations (DNMs) have been proven important in neuropsychiatric disorders, such as developmental delay (DD), the relationship between PPI interface DMNs and DD has not been well studied. Here we curated developmental delay DNM datasets from the PsyMuKB database and showed that DD patients showed a higher rate and deleteriousness in DNM missense on the PPI interface than sibling control. Next, we identified 302 DD-related PsychiPPIs, defined as PPI harboring a statistically significant number of DNM missenses at their interface, and 42 DD candidate genes from PsychiPPI. We then observed that PsychiPPIs preferentially affected hub proteins in the human protein interactome network. When analyzing DD candidate genes using gene ontology and gene spatio-expression, we found that PsychiPPI genes carrying PPI interface mutations, such as FGFR3 and ALOX5, were enriched in development-related pathways and the development of the neocortex, and cerebellar cortex, suggesting their potential involvement in the etiology of DD. Our results demonstrated that DD patients carried an excess burden of PPI-truncating DNM, which could be used to efficiently search for disease-related genes and mutations in large-scale sequencing studies. In conclusion, our comprehensive study indicated the significant role of PPI interface DNMs in developmental delay pathogenicity.
ARTICLE | doi:10.20944/preprints202208.0344.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: ethnic identity; mental health; migrant; transcultural psychiatry; youth
Online: 18 August 2022 (10:58:41 CEST)
Background: The number of young Japanese Brazilians, who are return migrants with Japanese ancestral roots, is increasing rapidly in Japan. However, the characteristics of their mental health and the relation between mental health and a complex ethnic identity remains unclear. Methods: This cross-sectional study compared 25 Japanese-Brazilian high school students with 62 Japanese high school students living in the same area. Research using self-report questionnaires on mental health, help-seeking behavior tendencies, and ethnic identity was conducted. The Japanese-Brazilian group was also divided into high and low ethnic identity groups, and their mental health conditions were compared. Results: The Japanese-Brazilian group had significantly poorer mental health conditions and lower ethnic identities than the Japanese group and were less likely to seek help from family members and close relatives. Among the Japanese Brazilians, those with low ethnic identity had significantly poorer mental health than those with high ethnic identity. Conclusions: Young Japanese Brazilians may face conflicts of ethnic identity that can disturb their mental health. To build an inclusive society, the establishment of community services to support mental health and to help return migrants develop their ethnic identity is essential.
ARTICLE | doi:10.20944/preprints202208.0341.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Schizophrenia; cell types proportions; differential expression genes; functional pathways; CIBERSORTx
Online: 18 August 2022 (10:54:05 CEST)
Schizophrenia (SCZ) is a severe mental disorder that may result in hallucinations, delusions, and extremely disordered thinking. How each cell type in the brain contributes to SCZ occurrence is still unclear. Here, we leveraged the human dorsolateral prefrontal cortex bulk RNA-seq data, then used the RNA-seq deconvolution algorithm CIBERSORTx to generate SCZ brain single-cell RNA-seq data for a comprehensive analysis to understand SCZ-associated brain cell types and gene expression changes. Firstly, we observed that the proportions of brain cell types in SCZ differed from normal samples. Among these cell types, astrocyte, pericyte, and PAX6 cells were found to have a higher proportion in SCZ patients (astrocyte: SCZ = 0.163, Control = 0.145, P.adj = 4.9×10-4; pericyte: SCZ = 0.057, Control = 0.066, P.adj = 1.1×10-4; PAX6 : SCZ = 0.014, Control = 0.011, P.adj = 0.014), while the L5/6_IT_CAR3 cells and LAMP5 cells are the exact opposite (L5/6_IT_Car3 : SCZ = 0.102, Control = 0.108, P.adj = 0.016; LAMP5 : SCZ = 0.057, Control = 0.066, P.adj = 2.2×10-6). Next, we investigated gene expression in cell types and functional pathways in SCZ. We observed chemical synaptic transmission dysregulation in two types of GABAergic neurons (PVALB and LAMP5), and immune reaction involvement in GABAergic neurons (SST) and non-neuronal cell types (endothelial and oligodendrocyte). Furthermore, we observed that some differential expression genes from bulk RNA-seq displayed cell-type-specific abnormal in the expression of molecules in SCZ. Finally, the cell types with the SCZ-related transcriptomic changes could be considered to belong to the same module since we observed two major similar coordinated transcriptomic changes across these cell types. Together, our results offer novel insights into cellular heterogeneity and the molecular mechanisms underlying SCZ.
ARTICLE | doi:10.20944/preprints202208.0297.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: foehn wind; psychopathology; BSCL; mental health; weather; meteorological factors; climate change
Online: 17 August 2022 (04:04:41 CEST)
Psychiatric patients are particularly vulnerable to strong weather stimuli, such as foehn, a hot wind that occurs in the alps. However, there is a dearth of research regarding its impact on mental health. This study investigated the impact of foehn wind among patients of a psychiatric hospital located in a foehn area in the Swiss Alps. Analysis was based on anonymized datasets obtained from routine records on admission and discharge, including the Brief Symptom Checklist (BSCL) questionnaire, as well as sociodemographic parameters (age, sex, and diagnosis). Between 2013 and 2020 a total of 10,456 admission days and 10,575 discharge days were recorded. All meteorological data were extracted from the database of the Federal Office of Meteorology and Climatology of Switzerland. We estimated the effect of foehn on the BSCL items using a distributed lag model. Significant differences were found between foehn and non-foehn admissions in obsession-compulsion, Interpersonal Sensitivity, depression, Anxiety, Phobic Anxiety, Paranoid Ideation, and General Severity Index (GSI) (p <.05). Our findings suggest that foehn wind events may negatively affect specific mental health parameters in patients. More research is needed to fully understand the impact of foehn’s events on mental health.
ARTICLE | doi:10.20944/preprints202208.0227.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: COVID-19; depression; anxiety; post-acute COVID-19 syndrome; post-COVID
Online: 12 August 2022 (04:56:33 CEST)
Background: This study aimed to examine the course of Depression and anxiety in COVID-19 survivors with a psychiatric history compared with those without a psychiatric history. Methods: A web-based cross-sectional survey for COVID-19 survivors was conducted from July to September 2021. 6016 COVID-19 survivors, the accuracy of whose responses was determined to be assured, were included in analyses. Exposures included psychiatric history and time since COVID-19 infection, and the main outcomes and measures included severity of depression and anxiety, as assessed using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. Results: Mean severity of PHQ-9 and GAD-7 were significantly higher in participants with a psychiatric history than in those without a psychiatric history. Two-way analysis of covariance for PHQ-9 showed a significant main effect of the presence of psychiatric history and a significant interaction effect of psychiatric history × time since infection. Two-way analysis of covariance for the GAD-7 score revealed a significant main effect of the presence of psychiatric history and time since COVID-19 infection and the interaction effect of these factors. Conclusions: The course of depression and anxiety was more severe in COVID-19 survivors with a psychiatric history than in those without a psychiatric history.
REVIEW | doi:10.20944/preprints202208.0180.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Nitrous Oxid; N₂O; nangs; systematic review; harm reduction; drug use
Online: 9 August 2022 (11:29:40 CEST)
Background Nitrous Oxide (N₂O) is a dissociative anaesthetic that is sometimes used recreationally. The prevalence of N₂O use is difficult to quantify but appears to be increasing. Research on N₂O harms and application of harm reduction strategies are limited. The aim of this mixed method systematic review was to collate and synthesise the disparate body of research on recreational nitrous oxide use to inform harm reduction approaches tailored for young people. Methods To identify publications reporting recreational use of N₂O, a search of public health, psychology and social science databases was conducted. Databases included PubMed, CIHNAL, PsycINFO, Scopus and Web of Science. Gray literature and Google advanced search were also used. Due to limited published literature on the recreational use of N₂O, no limit was placed on publication date or study type. A thematic synthesis extracted descriptive and analytical themes from the selected studies. Quality appraisal was conducted using the CASP Tool for Qualitative studies and the Joanna Briggs Institute case report assessment tool Results The search retrieved 407 reports. Thirty-four were included in the final analysis including sixteen case reports. The included studies were primarily concerned with raising awareness of the apparently increasing use and subsequently increasing harms of recreational N₂O use. There was limited reference to policy or legislative responses in any published studies, no suggestions for harm reduction strategies or application of service level responses. In general, individuals lack awareness of N2O related harms. Conclusion The review found three key areas that deserve further consideration including: 1) policy, 2) service delivery, and 3) harm associated with N₂O use. We recommend a top-down (policy) and bottom-up (services delivery/services users) approach to harm reduction for N₂O use which also includes further consultation and research with both groups. Future research could explore young people’s experience of N₂O use including benefits and problems to inform contextually relevant harm reduction strategies.
ARTICLE | doi:10.20944/preprints202208.0178.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: alcohol dependence; comorbidity; gene network; genome-wide association study; sex differences
Online: 9 August 2022 (10:35:29 CEST)
At least 50% of factors predisposing to alcohol dependence (AD) are genetic and women affected with this disorder present with more psychiatric comorbidities, probably indicating different genetic factors involved. We aimed to run a genome-wide association study (GWAS) followed by a bioinformatic functional annotation of associated genomic regions in male and female patients with AD and eight related clinical measures. A genome-wide significant association of rs220677 with AD (p-value = 1.33×10^-8 calculated with the Yates-corrected Chi-square test under the assumption of dominant inheritance) was discovered in female patients. Associations of AD and related clinical measures with seven other single nucleotide polymorphisms listed in previous GWAS of psychiatric and addiction traits were differently replicated in male and female patients. The bioinformatic analysis showed that regulatory elements in the eight associated linkage disequilibrium blocks define the expression of 80 protein-coding genes. Nearly 68% of these and of 120 previously published coding genes associated with alcohol phenotypes directly interact in a single network. This study indicates that a number of genes behind the pathogenesis of AD are different in male and female patients, but implicated molecular mechanisms are functionally connected. The results also suggest the genetic basis of sex-specific psychiatric comorbidities of AD.
REVIEW | doi:10.20944/preprints202207.0219.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: personalized psychiatry; psychiatric disorders; induced pluripotent stem cells; brain organoids
Online: 14 July 2022 (11:46:51 CEST)
The polygenic and multifactorial nature of many psychiatric disorders has hampered the personalized medicine approach implementation in clinical practice. However, induced pluripotent stem cell (iPSC) technology has emerged as an innovative tool for patient-specific disease modeling to expand the pathophysiology knowledge and treatment perspectives in the last decade. Current technologies enable adult human somatic cell reprogramming into induced pluripotent stem cells (iPSCs) to generate neural cells and direct neural cell conversion to model organisms that exhibit phenotypes close to human diseases, thereby effectively representing relevant aspects of neuropsychiatric disorders. iPSCs reflect patient pathophysiology and pharmacological responsiveness, particularly when cultured under conditions that recapitulate spatial tissue organization in brain organoids. Recently, the application of iPSCs has been frequently associated with gene editing that targets the disease-causing gene to deepen the illness pathophysiology and conduct drug screening. Moreover, gene editing has provided a unique opportunity to repair the putative causative genetic lesions in patient-derived cells. Here, we review the use of iPSC technology to model and potentially treat neuropsychiatric disorders by illustrating the key studies on a series of mental disorders, including schizophrenia, major depression disorder, bipolar disorder, and autism spectrum disorder. The future perspective will involve the development of organ-on-a-chip platforms that control the microenvironmental conditions to reflect individual pathophysiological by adjusting physiochemical parameters according to personal health data. This strategy could open new ways to build a disease model that considers individual variability and tailors personalized treatments.
REVIEW | doi:10.20944/preprints202207.0130.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Keywords: mitochondria; stress resilience; plasticity; stress; kynurenine; Alzheimer’s disease; neurodegenerative; depression; anxiety; psychiatric
Online: 8 July 2022 (03:56:36 CEST)
Nearly half a century has passed since the discovery of cytoplasmic inheritance of human chloramphenicol resistance. The inheritance was then revealed to take place maternally by mitochondrial DNA (mtDNA). Later, a number of mutations in mtDNA were identified as a cause of severe inheritable metabolic diseases with neurological manifestation, and the impairment of mitochondrial functions has been probed in the pathogenesis of a wide range of illnesses including neurodegenerative diseases. Recently growing number of preclinical studies has revealed that animal behaviors are influenced by the impairment of mitochondrial functions and possibly by the loss of mitochondrial stress resilience. Indeed, as high as 54% of patients with one of the most common primary mitochondrial diseases, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, present psychiatric symptoms including cognitive impairment, mood disorder, anxiety, and psychosis. Mitochondria are multifunctional organelles which produce cellular energy and play a major role in other cellular functions including homeostasis, cellular signaling, and gene expression, among other. Mitochondrial functions are observed to be compromised and to become less resilient under continuous stress. Meanwhile, stress and inflammation have been linked to the activation of the tryptophan (Trp)-kynurenine (KYN) metabolic system, which observably contributes to development of pathological conditions including neurological and psychiatric disorders. This narrative review discusses the functions of mitochondria and the Trp-KYN system, the interaction of the Trp-KYN system with mitochondria, and the current understanding of the involvement of mitochondria and the Trp-KYN system in preclinical and clinical studies of major neurological and psychiatric diseases.
ARTICLE | doi:10.20944/preprints202207.0079.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Virtual reality; health professionals; anxiety; immersive therapy
Online: 5 July 2022 (16:01:27 CEST)
Background: Immersive therapy through virtual reality represents a novel strategy used in psychological interventions, but there is still a need to strengthen the evidence on its effects on health professionals’ mental health. Objective: To analyze the results of immersive therapy through virtual reality in the levels of anxiety and secondly, well-being of the health professionals working in a regional hospital in Olot (Spain). Methods: Pilot quasi-experimental study including a group of 35 women (mean age=45.7, SD=8.43) health professionals who undertook immersive therapy for 8 weeks. The intervention was implemented through virtual reality, and its effect on anxiety levels and well-being was evaluated through the Hamilton and Eudemon scales, respectively. Data on age, gender, active pharmacological or psychological treatment, mental health disorders and number of sessions were also collected. Results: Statistically significant (p<0.001) improvement in anxiety and well-being was found, with large and moderate effect sizes (0.90 and 0.63 respectively). In addition, these changes were clinically significant. No significant associations were found between the improvements and the different variables, but a greater trend was identified among the group of professionals with untreated or unidentified levels of anxiety. Conclusion: This group of health professionals showed statistically and clinically significant improvement in anxiety and well-being after the application of immersive therapy using virtual reality. Further studies with a control group are necessary to further analyze this novel intervention.
REVIEW | doi:10.20944/preprints202207.0064.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: suicide; social pain; psychache; endogenous opioid system; oxytocin; serotonin; endocannabinoids; buprenorphine; psilocybin; ketamine
Online: 5 July 2022 (07:43:48 CEST)
Suicidal behaviour is a public health problem whose magnitude is both substantial and increasing. Since many individuals seek medical treatment following a suicide attempt, strategies aimed at reducing further attempts in this population are a valid and feasible secondary prevention approach. An evaluation of the available evidence suggests that existing treatment approaches have limited efficacy in this setting, highlighting the need for innovative approaches to suicide prevention. Existing research on the neurobiology of social pain has highlighted the importance of this phenomenon as a risk factor for suicide, and has also yielded several attractive targets for pharmacological preventive strategies. In this paper, the available evidence related to these targets is synthesized and critically evaluated. The way in which social pain is related to the “anti-suicidal” properties of recently approved treatments, such as ketamine and psilocybin, is also examined. Such strategies may be effective for the short-term reduction of suicidal ideation and behaviour in individuals who have made a suicide attempt suicide prevention, particularly in cases where social pain is identified as a contributory factor. These pharmacological approaches may be effective regardless of the presence or absence of a specific psychiatric diagnosis.
ARTICLE | doi:10.20944/preprints202206.0395.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Mental Health; Primary Health Care; Collaborative Care; Health Assessment
Online: 29 June 2022 (05:05:41 CEST)
The supply of mental health processes in primary care has gaps. This study aims to analyze the association of agreement criteria and flows between primary care teams and the Family Health Support Center (NASF) for mental health collaborative care, considering the difference between capital and non-capital cities in Brazil. This cross-sectional study was conducted based on secondary data from the Primary Care Access and Quality Improvement Program. Agreement criteria and flows were obtained from 3883 NASF teams of the matrix support or collaborative care. The Chi-square test and multiple Poisson regression were used; p < 0.05 was considered statistically significant. Prevalence ratios of negative associations demonstrated protective factors for support actions: follow-up at Psychosocial Care Center, management of psychopharmacotherapy, offer of other therapeutic actions, care process for users of psychoactive substances, and offer of activities to prevent the use of psychoactive substances. Collaborative care in primary care was effective, and capital cities were a protective factor compared with non-capital cities.
REVIEW | doi:10.20944/preprints202206.0296.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: new materialism; assemblage; storyboarding; HIV; adherence; antiretroviral therapy; young people; perinatal infection; qualitative evidence synthesis; biopsychosocial
Online: 21 June 2022 (10:54:56 CEST)
Young people living with perinatal infections of Human Immunodeficiency Virus (YLPHIV) face a chronic disease, with treatment including adherence to life-long antiretroviral treatment (ART). The aim of this QES was to explore adherence to ART for YLPHIV as an assemblage within the framework of the BPS model with a new materialist perspective. We searched up to November 2021 and followed the ENTREQ and Cochrane guidelines for QES. All screening, data extraction and critical appraisal was done in duplicate. We analysed and interpreted the findings innovatively, by creating images of meaning, a storyboard, and storylines. We then reported the findings in a narrative first person story. We included 47 studies and identified 9 storylines. We found that treatment adherence has less to do with humans’ preferences, motivations, needs and dispositions, and more to do with how bodies, viruses, things, ideas, institutions, environments, social processes, and social structures assemble. This QES highlights that adherence to ART for YLPHIV is a multisensorial experience in a multi agentic world. Future research into rethinking the linear and casual inferences we are accustomed too in evidence-based health care is needed if we are to adopt multidisciplinary approaches to address pressing issues such as adherence to ART.
REVIEW | doi:10.20944/preprints202206.0004.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Long-COVID; cognitive disorders; rehabilitation
Online: 1 June 2022 (05:50:58 CEST)
There is mounting evidence that patients with severe COVID-19 disease may have symptoms that continue beyond the acute phase, extending into the early chronic phase. Often referred to as 'Long COVID'. Simultaneously, case investigations have shown that COVID-19 individuals might have a variety of neurological problems. The accurate and accessible assessment of cognitive function in patients post COVID-19 infection is thus of increasingly high importance for both public and individual health. Little is known about the influence of COVID-19 on the general cognitive levels but more importantly, at sub functions level. Therefore, we first aim to summarize current level of evidence supporting a negative impact of COVID-19 infection on cognitive functions. 27 studies have been included in the systematic review representing a total of 94,103 participants (90,317 COVID-19 patients and 3,786 healthy controls). We then performed a meta-analysis summarizing the results of 5 studies (959 participants, 513 patients) to quantify the impact of COVID-19 on cognitive functions. The overall effect, expressed in Standardized Mean Differences, is -0.56 [95%CI -0.79 ; -0.34]. To prevent disability, we finally discuss the different approaches available in rehabilitation to help these patients and to avoid long-term complication.
REVIEW | doi:10.20944/preprints202205.0413.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: financial capacity instruments; Semi-Structured Clinical Interview for Financial Capacity; deci-sional capacity; mild cognitive impairment; gamification
Online: 31 May 2022 (07:37:21 CEST)
Financial capacity instruments are psychometric tools designed to evaluate individual decisional capacity based on financial decisions. As tests are complex and need special conditions for administration and evaluation, it is difficult to use them in daily geriatric clinics. Our scoping review objective was to evaluate existing financial capacity instruments from the perspective of simplicity and portability. We evaluated one English speaking knowledge database (Medline) using a dedicated MeSH terminology. The review yielded one independent instrument, The Semi-Structured Clinical Interview for Financial Capacity, that can be easy adapted for every-day clinical use. It is simple to understand and perform and do not need trained personnel for administration. It can be finalized in 15 minutes. Initially validated on 261 subjects (with different forms of cognitive impairment), it showed good accuracy and precision mainly in subjects with cognitive impairment. The test is less apt to detect early or fluctuating cognitive impairment. Simplicity, the main advantage of the test, allows gamification fact that increases portability. Familiar images (coins, money) that are used for performing simple tasks does not need complex translation and adaptation. In form of a game, the test is suitable for serial administration, increasing the chance for early capacity reduction detection. Results reflect a physician judgement related to the subjects’ capacity to understand and execute simple financial instructions and not financial proficiency scores. The main limitation of our review is that we investigated only one, English speaking, knowledge database. The scoping strategy generated a financial capacity instrument that can be used in geriatric clinics for early diagnostic of decisional capacity reduction. Further studies are needed to evaluate the reliability and validity of the test in conditions of serial administration and in populations having various financial experience.
ARTICLE | doi:10.20944/preprints202205.0409.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: childhood trauma; major depressive disorder; bipolar disorder; sex difference; age
Online: 31 May 2022 (03:39:57 CEST)
Background. We investigated, for the first time, whether there are any sex differences in retrospective self-reported childhood maltreatment (CM) in Italian adult patients with major depressive disorder (MDD) or bipolar disorder (BD). Furthermore, the potential impacts of patients’ age on the CM self-report was investigated. Methods. This retrospective, cross-sectional study used the data documented in the electronic medical records of patients who were hospitalized for a 4-week psychiatric rehabilitation program. The CM was assessed using the 28-item Childhood Trauma Questionnaire (CTQ), which evaluates emotional, physical, and sexual abuse, as well as emotional and physical neglect. The linear and logistic regression models were used (α = 0.01). Results. Three hundred thirty five patients with MDD (255 women and 80 men) and 168 with BD (97 women and 71 men) were included. In both samples, considerable CM rates were identified, but no statistically significant sex differences were detected in the variety of CTQ-based CM aspects. There was a significant association, with no sex differences, between the increasing patients’ age and a decreasing burden of CM. Conclusion. Both women and men with MDD or BD experienced a similar and considerable CM burden. Our findings support the routine CM assessment in psychiatric clinical practice.
ARTICLE | doi:10.20944/preprints202205.0291.v2
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Yoga of Immortals (YOI); depression; healthcare workers; insomnia; anxiety; PHQ-8 (Pa-tient Health Questionnaire-8); ISI (Insomnia Severity Index); digital health
Online: 24 May 2022 (04:49:45 CEST)
The COVID-19 pandemic has caused significant medical and psychological challenges worldwide, and not only exceeded the capacity of hospitals and intensive care units but also an individuals’ ability to cope with life. Health-care workers have continued to provide care for patients despite exhaustion, fear of transmission to themselves and their family, illness or death of friends and colleagues, and losing many patients. They have also faced additional stress and anxiety due to long shifts combined with unprecedented population restrictions, including personal isolation. In this study, we study the effect of an app-based Yoga of Immortals (YOI) intervention on mental health of healthcare workers. In this study, the health care workers were digitally recruited, and their psychological parameters were measured using validated questionaries. The participants were randomly grouped into control and test groups. The validated psychological measures were the Patient Health Questionnaire-8 (PHQ-8), Insomnia Severity Index (ISI) and generalized anxiety disorder (GAD-7) scales. The digital YOI intervention significantly reduced the anxiety, depression symptoms, and insomnia in healthcare workers of all age groups. In contrast, there was no improvement in the control group. This study details the effectiveness of an app-based YOI intervention in healthcare workers.
ARTICLE | doi:10.20944/preprints202205.0160.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Bibliometric; Parkinson’s Disease; Phenolic compound
Online: 12 May 2022 (07:58:20 CEST)
Objective: The aim of this study was to identify and characterize the 100 most cited articles on Parkinson's disease (PD) and phenolic compounds (PCs). Methods: Articles were selected in the Web of Science Core Collection up to January 2022 based on predetermined inclusion criteria, and the following bibliometric parameters were extracted: the number of citations, title, keywords, authors, year, study design, tested PC and therapeutic target. MapChart was used to create worldwide networks, and VOSviewer software was used to create bibliometric networks. Descriptive statistical analysis was used to identify the most researched PCs and therapeutic targets in PD. Results: The most cited article was also the oldest. The most recent article was published in 2020. Asia and China were the continent and the country with the most articles in the list (55% and 29%, respectively). In vitro studies were the most common experimental designs among the 100 most cited articles (46%). The most evaluated PC was epigallocatechin. Oxidative stress was the most studied therapeutic target. Conclusion: Despite the demonstrations in laboratorial studies, the results obtained point to the need for clinical studies to better elucidate this association.
ARTICLE | doi:10.20944/preprints202205.0144.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Perinatal depression; prognosis; prognostic modeling; nomogram; Pakistan
Online: 10 May 2022 (15:40:48 CEST)
Task sharing approaches are challenged by the barriers fundamental to the use of non-specialists who lack specialist mental health training required to triage the candidates who could benefit from task-shared treatments. However, these challenges could be offset by using standardized and easy-to-implement algorithmic devices (e.g., nomograms) to help with the targeted dissemination of interventions. Therefore, the present investigation posits a prognostic model and a nomogram to predict the prognosis of perinatal depression among women in rural Pakistan. This secondary analysis utilizes data based on 903 pregnant women with depression who participated in a cluster randomized controlled trial that tested the effectiveness of the Thinking Healthy Program in rural Rawalpindi, Pakistan. The participants were recruited from 40 union councils in two sub-districts of Rawalpindi and randomly assigned to intervention and enhanced usual care. Sixteen sessions of the THP intervention were delivered by trained community health workers to women with depression over pregnancy and the postnatal period. A trained assessment team used the Structured Clinical Interview for the DSM-4 current major depressive episode module to diagnose depression at the baseline and post-intervention. The intervention received by the participants emerged as the most significant predictor in the model. Among clinical factors, baseline severity of core-emotional symptoms emerged as an essential predictor, followed by atypical symptoms and insomnia. Higher severity of these symptoms was associated with a poorer prognosis. Other important predictors of a favorable prognosis included living with paternal and maternal grandmothers, financial empowerment, higher socioeconomic class, and living in a joint family system. This prognostic model yielded acceptable discrimination (c-statistic =0.75) and calibration to aid in personalized delivery of psychological treatment.
ARTICLE | doi:10.20944/preprints202204.0121.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: cancer; insomnia; sleep; circadian; the DBST index
Online: 13 April 2022 (08:36:14 CEST)
Patients with cancer experience insomnia or sleep disturbances. This study aimed to explore whether the discrepancy between a patient's desired time in bed and total sleep time (DBST) index is a measurement tool for insomnia severity or sleep onset latency [SOL] in patients with cancer. This retrospective medical records review study gathered clinical information and rating scale scores including Insomnia Severity Scale (ISI), Cancer-related Dysfunctional Beliefs about Sleep scale (C-DBS), Patient Health Questionnaire-9 items (PHQ-9), State subcategory of State and Trait Anxiety Inventory, and Short form of Fear of Progression Questionnaire. Sleep indices of time variables (bedtime, sleep onset time, and wake-up time), duration variables [SOL, time in bed (TIB), time in bed for 24 hours (TIB/d), and duration from wake-up time to bedtime (WTB)], and the DBST index were calculated. The ISI score was predicted by PHQ-9 (β=0.34, P<0.001), C-DBS (β=0.17, P=0.034), and DBST index (β=0.22, P=0.004) with a significant correlation with the DBST index (r=0.19, p=0.020). The DBST index was significantly correlated with long SOL (r=0.23, P=0.005). Long SOL was predicted by early bedtime (β=0.18, P=0.045), short WTB (β=-0.26, P=0.004), and high DBST index (β=0.19, P=0.013). The DBST index was significantly correlated with a predicting variable each for insomnia severity and SOL in patients with cancer.
ARTICLE | doi:10.20944/preprints202203.0327.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: tryptophan; kynurenine; kynurenic acid; passive avoidance; cognitive domain; memory; cognitive enhancer; neurotransmission; receptor blockers; translational
Online: 24 March 2022 (08:57:45 CET)
Kynurenic acid (KYNA) is an endogenous tryptophan (Trp) metabolite known to possess neuroprotective property. KYNA plays critical roles in nociception, neurodegeneration, and neuroinflammation. A lower level of KYNA is observed in patients with neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases or psychiatric disorders such as depression and autism spectrum disorders, whereas a higher level of KYNA is associated with the pathogenesis of schizophrenia. Little is known about the optimal concentration for neuroprotection and the threshold for neurotoxicity. In this study the effects of KYNA on memory functions were investigated by passive avoidance test in mice. Six different doses of KYNA were administered intracerebroventricularly to previously trained CFLP mice and they were observed following 24 hours. High doses of KYNA (i.e., 20-40 μg/2 μl) significantly decreased the avoidance latency, whereas a low dose of KYNA (0.5 μg/2 μl) significantly elevated it compared with controls, suggesting that the low dose of KYNA enhanced memory function. Furthermore, six different receptor blockers were applied to reveal the mechanisms underlying the memory enhancement induced by KYNA. The series of tests revealed the possible involvement of the serotonergic, dopaminergic, α and β adrenergic, and opiate systems in the nootropic effect. The study confirmed that a low dose of KYNA improved a memory component of cognitive domain, which was mediated by, at least in part, four systems of neurotransmission in an animal model of learning and memory.
ARTICLE | doi:10.20944/preprints202203.0279.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: recovery; mental illness; mental health; psychiatry; social inclusion; occupational therapy; occupations; time use; activities of daily living; work.
Online: 21 March 2022 (08:56:09 CET)
Research has consistently found that people with mental illness (known as consumers) experience lower levels of participation in meaningful activities, which can limit their opportunities for recovery support. The aim of this study was to describe the outcomes of participation in a group program designed to address all stages of activity participation, known as Pathways to Participation (P2P). A descriptive longitudinal design was utilized, collecting data at three time points. Outcomes were measured by the Camberwell Assessment of Need Short Appraisal (CANSAS), Recovery Assessment Scale – Domains and Stages (RAS-DS), Behaviour and Symptom Identification Scale (BASIS-24), Living in the Community Questionnaire (LCQ) and time use diaries. All data was analysed using descriptive statistics, and Chi square analyses. Seventeen consumers completed baseline data, eleven contributed post program data and eight provided follow up data. Most were female (63.64%) and had been living with mental illness for 11.50 (± 7.74) years on average. Reductions in unmet needs and improvements in self-rated recovery scores were re-ported, but no changes were identified in either time use or psychosocial health. The findings indicate the P2P program may enable consumers to achieve positive activity and participation out-comes as part of their personal recovery.
ARTICLE | doi:10.20944/preprints202203.0257.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: biomarkers; electroencephalography; event related potentials; heart rate variability; diagnosis; sensitivity; specificity
Online: 17 March 2022 (15:19:38 CET)
The combination of statistical learning technologies with large databases of psychophysiological data has appropriately generated enthusiastic interest in future clinical applicability. It is argued here that this enthusiasm should be tempered with the understanding that significant obstacles must be overcome before the systematic introduction of psychophysiological measures into neuropsychiatric practice becomes possible. The nonspecificity of psychophysiological measures complicates their use in diagnosis. Low test-retest reliability complicates use in longitudinal assessment, and quantitative psychophysiological measures can normalize in response to placebo intervention. Ten cautionary observations are introduced and, in some instances, possible directions for remediation are suggested.
ARTICLE | doi:10.20944/preprints202203.0191.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: COVID-19; pandemic; GAD-7; mental health; quality of life; Asia
Online: 14 March 2022 (16:20:20 CET)
This study aims to identify factors associated with anxiety levels of adults living in Singapore before the pandemic and during the COVID-19 outbreak. Data were collected using a cross-sectional web-based survey conducted from July to November 2020 accruing 264 eligible participants. Ordered logistic regression was used to assess Generalized Anxiety Disorder-7 (GAD-7), ranked as minimal (0-4), mild (5-9), moderate (10-14), and severe (15-21) before the pandemic and during the pandemic. About 74% of participants were female, 50% were aged 25-34, and 50% were married. The GAD-7 level went up from pre-pandemic for both moderate (from 12.5% to 16%) and severe GAD (from 2% to 11%). Alcohol consumption (AOR 1.79, 95% CI 1.04-3.06), loneliness (AOR 1.28, 95% CI 1.05-1.54), and difficulty in switching off social media (AOR 2.21, 95% CI 1.29-3.79) predicted increased GAD-7 levels. The quality of life (AOR 0.84, 95% CI 0.79-0.90) was significantly associated with decreased GAD-7 levels. The results heighten the awareness that early initiation of mental health support is crucial for the population in addition to the various financial support measures provided by the government as they are adapting to live with the COVID-19 pandemic.
ARTICLE | doi:10.20944/preprints202203.0099.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: long-acting injectable; antipsychotic; depot; schizophrenia spectrum disorder; schizophrenia; schizoaffective; inpatient; prescribing pattern
Online: 7 March 2022 (12:33:39 CET)
Long-acting injectable antipsychotics (LAIs) offer many benefits to patients with schizophrenia spectrum disorder (SSD). They are used with very different frequencies due to questions of eligibility or patients’ and prescribers’ attitudes towards LAI use. We assessed the prescribing rates of LAIs in a large academic psychiatric hospital with public service mandate in Switzerland and compared them with other countries and health care systems. To our knowledge this study is the first to investigate the inpatient LAI-use in Europe. Medical records of all patients diagnosed with SSD discharged from the Clinic of Adult Psychiatry of the University Hospital of Psychiatry Zurich over a 12-month period from January to December 2019 were evaluated regarding the prescribed antipsychotics at the time of discharge. The rates of use of LAIs among all patients and among patients receiving LAI eligible antipsychotic substances were assessed retrospectively. We assessed records of 885 patients with SSD. Among all cases 13.9% received an LAI. Among patients who received antipsychotic medication that was eligible for LAI use 28.3% (n=434) received an agent as LAI. These included paliperidone palmitate (69.9%), aripiprazole monohydrate (14.6%), risperidone (4.9%) and first-generation LAIs (9.8%). Compared to international frequencies of LAI administration, the prescription rate of LAIs in SSD patients was low. Further studies will evaluate patient- and prescriber-related reasons for this low rate.
REVIEW | doi:10.20944/preprints202202.0156.v2
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: esketamine; ketamine; ketamine assisted psychotherapy; eating disorder; anorexia nervosa; bulimia nervosa; binge eating disorder; pharmacology; psychedelics; treatment
Online: 7 March 2022 (08:34:11 CET)
Eating disorders (EDs) are serious, life-threatening psychiatric conditions associated with physical and psychosocial impairments, as well as high morbidity and mortality. Given the chronic refractory nature of EDs and the paucity of evidence-based treatments, there is a pressing need to identify novel approaches for this population. The noncompetitive N-methyl-D-aspartate receptor (NMDAr) antagonist, ketamine, has recently been approved for treatment-resistant depression, exerting rapid and robust antidepressant effects. It is now being investigated for several new indications, including obsessive-compulsive, post-traumatic, and substance use disorder; and shows transdiagnostic potential for EDs, particularly among clinical non-responders. As such, the aim of this review is to examine contemporary findings on the treatment of EDs with ketamine, whether used as a primary, adjunctive, or combination psychopharmacotherapy. Avenues for future research are also discussed. Overall, results are encouraging and point to therapeutic value, yet are limited to case series and reports on anorexia nervosa. Further empirical work is thus needed to explore ketamine efficacy across ED subgroups; establish safety profiles and optimize dosing; and develop theory-driven, targeted treatment strategies at the individual patient level.
REVIEW | doi:10.20944/preprints202203.0062.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Major depression; inflammation; sickness behaviour; mechanism; model; microglia; zcitokynes; CRP; blood brain barrier; choroid plexus
Online: 3 March 2022 (10:28:08 CET)
Current lines of research into mood disorders indicate that immune mediators participating in the pathophysiology of chronic somatic disorders have potent influences on brain functions, even when these mediators are produced in peripheral tissues. Elevated levels of circulating immune molecules have been consistently associated with depressive symptoms in a number of clinical populations and experimental models, to the extent that major depressive disorder (MDD) is now seen, at least in part, as a disorder of immunity. This paradigm has brought to the fore the use of anti-inflammatory therapies as adjunctive to standard antidepressant therapy with the hope to improve treatment efficacy, particularly in those cohorts that do not respond well to standard medication. Such new practice requires the availability of biomarkers to tailor these new therapies to those most likely to benefit but also clear mechanisms of action describing the interaction between peripheral immunity and brain function. These mechanisms are generally studied in preclinical models that try to recapitulate the human disease through peripherally induced sickness behaviour as the model for immune-induced MDD. After an appraisal of the data in rodent models and their adherence to the data in clinical cohorts, we propose a modified model of periphery-brain interaction that goes beyond the currently established view of interaction between peripheral cytokines and microglia cells as the driver of depression. Instead, we suggest that brain barriers are primary actors in the communication between body and brain and, as a consequence, in the pathophysiology of the disease. This model suggests novel biomarkers, novel targets for therapies as well as a novel mechanism for resistance to standard treatments.
ARTICLE | doi:10.20944/preprints202202.0285.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Bullying; Oral health; Indigenous; Children; Australia
Online: 23 February 2022 (05:26:35 CET)
Making life better for Indigenous peoples is a global priority. Although bullying and oral health have always been a topic of concern, there is limited information regarding the impact of this problem in the general population, with no evidence in this regard among the Australian Indigenous population. Thus, we aimed to quantify the relationship between bullying victimization and oral health problems by remoteness among 766 Australian Indigenous children aged between 10–15-year-olds using data from the LSIC study. Bivariate and multilevel mixed-effect logistic regression analyses were employed. Findings indicated children self-reported bullying more than parents reported their children were being bullied (44% vs 33.6%), with a higher percentage from rural/remote areas than urban areas. Parents reported oral health problem increases the probability (OR 2.20, p<0.05) of being bullied in Indigenous children living in urban areas. Racial discrimination, lower level of parental education and poor child oral hygiene increase the risk of bullying victimization. Parental happiness with life and a safe community was associated with a lower risk of bullying. Dental problems are linked with Australian Indigenous children experiencing bullying victimization. Cultural resilience and eliminating discrimination maybe two modifiable paths to ameliorating health issues associated with bullying in the Australian Indigenous community.
ARTICLE | doi:10.20944/preprints202202.0167.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: mental health; mental health literacy; psychological vulnerability; health promotion; adult
Online: 11 February 2022 (21:40:28 CET)
Resumo: Este estudo teve como objetivo avaliar a Saúde Mental Positiva (SPM) e a sua relação com características sociodemográficas, literacia em saúde mental e escala de vulnerabilidade psicológica (PVS) em estudantes universitários portugueses com idades compreendidas entre os 17 e os 62 anos. Foi realizado um estudo descritivo-correlacional. Uma pesquisa online foi realizada para avaliar variáveis demográficas, e vários questionários foram aplicados para avaliar saúde mental positiva, vulnerabilidade psicológica e alfabetização em saúde mental. Os dados foram coletados de 1º de novembro de 2019 a 1º de setembro de 2020. No geral, 3.405 alunos participaram do estudo. Os resultados mostram que 67,8% dos alunos revelaram um alto nível de PMH, 31,6% apresentaram um nível médio de PMH e 0,6% apresentaram um nível baixo de PMH. Os estudantes do sexo masculino relataram maior satisfação pessoal (t (3170) = -2,39, p=0,017) e autonomia (t (3170) = -3,33, p=0,001), no PMH em relação ao sexo feminino. Alunos sem bolsa pontuaram mais alto (t (3.127) = -2,04, p=0,42) no PMH do que alunos com bolsa. Estudantes que não foram deslocados de casa relataram maior (t (3170) = -1,99, p=0,047) Autocontrole em PMH do que aqueles deslocados de sua casa. Estudantes universitários com resultados de PMH mais altos têm resultados de PVS mais baixos e resultados de Alfabetização mais altos. Os achados deste estudo contribuirão para identificar as necessidades de intervenção dos alunos na PMH. Estudantes universitários com resultados de PMH mais altos têm resultados de PVS mais baixos e resultados de Alfabetização mais altos. Os achados deste estudo contribuirão para identificar as necessidades de intervenção dos alunos na PMH. Estudantes universitários com resultados de PMH mais altos têm resultados de PVS mais baixos e resultados de Alfabetização mais altos. Os achados deste estudo contribuirão para identificar as necessidades de intervenção dos alunos na PMH.
ARTICLE | doi:10.20944/preprints202202.0124.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: primary health care; family health strategy; health personnel; adaptation; psychological
Online: 8 February 2022 (16:23:26 CET)
The aim was to analyze the coping strategies used by primary health care (PHC) professionals. A cross-sectional, descriptive-analytical study was conducted with professionals working in primary health care units in São José do Rio Preto, a large city in the interior of São Paulo, Brazil. For data collection we used an instrument developed by the researchers, containing sociodemographic and professional variables, as well as the Problem Coping Modes Scale (EMEP). We evaluated 333 PHC professionals. A difference was observed between the scores of the four coping strategies (p<0.001), with the highest score for the problem-focused strategy (3.8) and the lowest score for the emotion-focused strategy (2.4). Physicians had the lowest scores in coping strategies focused on religious practices/fantastical thinking (p<0.001) and pursuit of social support (p=0.045), while community health agents had the highest scores in these coping strategies). Professionals working in PHC have different coping strategies for the problems and stressful situations experienced in the work environment. These strategies can involve more positive attitudes focused on confrontation and problem solving, to emotional responses that involve attitudes of avoidance and denial that involve attitudes of avoidance and denial of the problem.
ARTICLE | doi:10.20944/preprints202201.0447.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: mass multivariate analysis; neuroimaging, depression, schizophrenia
Online: 31 January 2022 (11:07:48 CET)
We have used Mass Multivariate Method on structural, resting state and task related fMRI data from two groups of patients with schizophrenia and depression, respectively, in order to define several regions of significant relevance to the differential diagnosis between those conditions. The regions included the left Planum polare, Left opercular part of the inferior frontal gyrus (OpIFG), Medial orbital gyrus (MOrG), Posterior Insula (PIns), and Parahippocampal gyrus (PHG). This study delivers evidence that multimodal neuroimaging approach can potentially enhance the validity of psychiatric diagnosis. Either structural, or resting state or task related functional MRI modality cannot provide independent biomarkers. Further studies need to consider and implement a model of incremental validity to combine clinical measures with different neuroimaging modalities to discriminate depressive disorders from schizophrenia. Biological signatures of disease on the level of neuroimaging are more likely to underpin broader nosological entities in psychiatry.
REVIEW | doi:10.20944/preprints202201.0134.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: TRYCATs; MDD; MDE; Suicidal behavior; Kynurenine pathway
Online: 11 January 2022 (10:39:25 CET)
Kynurenine or tryptophan catabolite (TRYCAT) pathway contributes to the pathophysiology of major depression disorder (MDD) and major depressive episodes (MDE) in bipolar disorder and suicidal behaviors. The consequences of the overactivation of this pathway large reduced tryptophan (TRP) levels in peripheral blood and the CNS and increased levels of neurotoxic TRYCATs including kynurenine (KYN), 3-hydroxy kynurenine (3HK), quinolinic acid (QA), xanthurenic acid (XA), and picolinic acid (PA). However, other TRYCATs are protective, such as kynurenic acid (KA) and anthranilic acid (AA). Inflammation and cell-mediated immune activation along with oxidative and nitrosative stress (O&NS) may stimulate the first and rate-limiting enzyme of this pathway, namely indoleamine-2,3-dioxygenase (IDO). Therefore, during depression, balancing neuroprotective versus neurotoxic TRYCATs and balancing activation of the immune response system (IRS) versus the compensatory immune response system is crucial for achieving better treatment outcomes. Furthermore, targeting the causes of TRYCAT pathway activation (immune activation and O&NS) is probably the most effective strategy to treat depression. In the present review, we aim to provide a comprehensive explanation of the impact of TRYCATs in terms of pathophysiology and treatment of MDD and MDE.
ARTICLE | doi:10.20944/preprints202112.0080.v2
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: DTI; resting state; schizophrenia; FATCAT; tractography
Online: 5 January 2022 (10:35:07 CET)
Schizophrenia is widely seen as a disorder of dysconnectivity. Neuroimaging studies have examined both structural and functional connectivity in the disorder, but these modalities have rarely been integrated directly. We scanned 29 patients with schizophrenia and 25 healthy control subjects and acquired resting state fMRI and diffusion tensor imaging. The Functional and Tractographic Connectivity Analysis Toolbox (FATCAT) was used to estimate functional and structural connectivity of the default mode network. Correlations between modalities were investigated, and multimodal connectivity scores (MCS) were created using principal components analysis. Nine of 28 possible region pairs showed consistent (>80%) tracts across participants. Correlations between modalities were found among those with schizophrenia for the prefrontal cortex, posterior cingulate, and lateral temporal lobes with frontal and parietal regions, consistent with frontotemporoparietal network involvement in the disorder. In patients, MCS values correlated with several aspects of the Positive and Negative Syndrome Scale, positively with those involving inwardly directed psychopathology, and negatively with those involving external psychopathology. In this preliminary sample, we found FATCAT to be a useful toolbox to directly integrate and examine connectivity between imaging modalities. A consideration of conjoint structural and functional connectivity can provide important information about the network mechanisms of schizophrenia.
ARTICLE | doi:10.20944/preprints202112.0374.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: COVID-19 pandemic; children and adolescents; machine learning; post-hoc explainability; model calibration
Online: 22 December 2021 (16:21:19 CET)
The global spread of COVID-19 led the World Health Organization to declare a pandemic on 11 March 2020. To decelerate this spread, countries have taken strict measures that affected the lifestyle and economy. Various studies have been focused on the identification of COVID-19 impact to mental health of children and adolescents via traditional statistical approaches. However, a machine learning methodology must be developed to explain the main factors that contribute to the change of mood state of children and adolescents during the first lockdown. Therefore, to this study an explainable machine learning pipeline is presented focusing on children and adolescents in Greece, where a strict lockdown was imposed. The target group consists of children and adolescents, recruited from children and adolescent mental health services, who present mental health problems diagnosed before the pandemic. The proposed methodology imposes: (i) data collection via questionnaires; (ii) a clustering process to identify the groups of subjects with amelioration, deterioration and stability to their mood state; (iii) a feature selection process to identify the most informative features that contribute to mood state prediction; (iv) a decision-making process based on an experimental evaluation among classifiers; (v) calibration of the best performing model and (v) a post-hoc interpretation of the features’ impact on the best performing model. The results showed that a blend of heterogeneous features from almost all feature categories is necessary to increase our understanding regarding the effect of COVID-19 pandemic on the mood state of children and adolescents.
ARTICLE | doi:10.20944/preprints202112.0301.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Schizophrenia; indoleamine-dioxygenase; inflammation; neuro-immune; oxidative and nitrosative stress; biomarkers
Online: 20 December 2021 (09:56:45 CET)
The tryptophan catabolite (TRYCAT) pathway is implicated in the pathophysiology of schizophrenia (SCZ) since the rate-limiting enzyme indoleamine-dioxygenase (IDO) may be induced by inflammatory and oxidative stress mediators. This systematic review searched PubMed, Web of Science, and Google Scholar for papers published from inception until August 2021 and meta-analyzed the association between SCZ and TRYCATs in the central nervous system (CNS) and peripheral blood. We included 61 studies comprising 2813 patients and 2948 healthy controls. In the CNS we found a significant (p<0.001) increase in the kynurenine/tryptophan (KYN/TRP) (standardized mean difference, SMD=0.769, 95% confidence interval, CI: 0.456; 1.082) and kynurenic acid (KA)/KYN+TRP (SMD=0.697, CI:0.478-0.917) ratios, KA (SMD=0.646, CI: 0.422; 0.909) and KYN (SMD=1.238; CI: 0.590; 1.886), while the 3OH-kynurenine (3HK) + KYN-3-monooxygenase (KMO)/KYN ratio was significantly reduced (SMD=-1.089, CI: -1.682; -0.496). There were significant differences between KYN/TRP, (KYN+KA)/TRP, (3HK+KMO)/KYN, KA, and KYN levels among the CNS and peripheral blood, and among serum and plasma KYN. The only useful peripheral marker of CNS TRYCATs findings was the increased KYN/TRP ratio in serum (SMD=0.211, CI: 0.056; 0.366, p=0.007), but not in plasma. There was no significant increase in a neurotoxic composite score based on KYN, 3HK, and picolinic, xanthurenic, and quinolinic acid. SCZ is accompanied by increased IDO activity in the CNS and serum, and reduced KMO activity and a shift towards KA production in the CNS. This CNS TRYCATs profile indicates neuroprotective, negative immunoregulatory and anti-inflammatory effects. Peripheral blood levels of TRYCATs are dissociated from CNS findings except for a modest increase in serum IDO activity.
ARTICLE | doi:10.20944/preprints202112.0256.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: COVID-19; lockdown; primary care; lifestyle; health resources.; alcohol abuse desorder
Online: 15 December 2021 (14:47:13 CET)
The disruption in healthcare attention to people with alcohol dependence, along with psychological decompensation consequence of lockdown derived from COVID-19 pandemic, could have a negative impact on people who suffers from alcohol abuse disorder. Retrospective observational study of 9,966 men aged ˃16 years registered as having diagnosis of alcohol abuse disorder in the electronic medical records (EMR) of the Aragon Regional Health Service (Spain). Of those who were not infected during the study period (9,576), clinical (Glutamate-oxaloacetate -GOT-, Glutamate pyruvate -GPT-, creatinine, glomerular filtration, systolic blood pressure -SBP-, diastolic blood pressure -DBP-, total cholesterol, LDL, HDL, triglycerides, and body mass index -BMI-), pharmacological (dose per inhabitant per day -DHD- of drugs used in addictive disorders, benzodiazepines and antidepressants) and health resource use variables (primary and specialized care) were considered. Student´s T-test for matched samples was performed. After carrying out the Levene´s test, the Student´s T-test was used to analyze the changes in clinical variables between alcohol abuse disorder patients with and without COVID-19. Only creatinine and LDL show a significant but clinically irrelevant changes just after and 6 months after the end of strict lockdown. The total number of DHDs for all drugs included in the study (except for Benzodiazepines), decreased. In the same way, the use of health services by these patients also decreased. The impact of COVID-19 among this group of patients has been moderate. The reorganization of health and social services after the declaration of the state of alarm in our country, made possible the maintenance of care for this vulnerable patients.
ARTICLE | doi:10.20944/preprints202112.0083.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Psychological distress; Fear; Coping; COVID-19; Bangladesh; Dental; Mental health
Online: 6 December 2021 (15:22:59 CET)
Background: Psychological sufferings are observed among dental students during their academic years, which had been intensified during the COVID-19 pandemic. Objectives: This study assessed the levels and identified factors associated with psychological distress, fear and coping experienced by dental undergraduate students in Bangladesh. Methods: A cross sectional online survey was conducted during October-November, 2021. The Kessler Psychological Distress Scale (K-10), Fear of COVID-19 Scale (FCV-19S) and Brief Resilient Coping Scale (BRCS) were used in order to assess psychological distress, fear and coping strategies respectively. Results: A total of 327 students participated; the majority (72%) were 19-23 years old and females (75%). One in five participants were infected with COVID-19 and 15% reported contact with COVID-19 cases. Negative financial impact (AOR 3.72, 95%CIs 1.28-10.8), recent or past COVID-19 infection, contact with COVID-19 cases were associated with higher levels of psychological distress; but being a 3rd year student (0.14, 0.04-0.55) and being satisfied about current social life (0.11, 0.03-0.33) were associated with lower levels of psychological distress. Being a 3rd year (0.17, 0.08-0.39) and a 4th year student (0.29, 0.12-0.71) were associated with lower levels of fear. Health care service use and feeling positive about life were associated with medium to high resilience coping. Conclusions: This study iden-tified dental students in Bangladesh who were at higher risk of psychological distress, fear and coping during the ongoing pandemic. Development of mental health support system within dental institution should be considered in addition to the academic and clinical teaching.
ARTICLE | doi:10.20944/preprints202111.0554.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Metabolic syndrome; Mental disorders; Obesity; Multimorbidity
Online: 30 November 2021 (10:38:08 CET)
Background: Metabolic syndrome (MS) is associated with a greater risk of morbimortality. Ob-jective: To estimate the prevalence of Metabolic Syndrome (MS) and associated factors in patients of a Psychosocial Care Center (CAPS) in the city of Salvador, state of Bahia, Brazil. Method: Cross-sectional study set at CAPS in the city of Salvador-Bahia, between August 2019 and February 2020. MS was evaluated according to the National Cholesterol Education Program's Adult Treatment Panel III. In addition to descriptive statistics, gross and adjusted prevalence ratios were described. Results: MS was found in 100 (35.2%) individuals, 116 (40.9%) were obese and 165 (58.1%) had increased waist circumference. Polypharmacy was identified in 63 (22.3%) patients and 243 (85.9%) used antipsychotics. In the gross evaluation, the female (PR = 1.88; 95% CI: 1.35-2.63) and the use of antidepressants (PR = 1.41; 95%CI: 1.05-1.88) were associated with MS. After logistic re-gression, depression (PR = 1.86; 95%CI: 1.38-2.51), acanthosis (PR = 1.50; 95%CI: 1.18 - 1.90), use of antipsychotics (PR = 1.88; 95%CI: 1.13 - 2.75) and the hypertriglyceremic waist (PR = 3.33; 95%CI: 2.48- 4.46) were associated with MS. Conclusion: The prevalence of MS alerts to multimorbidity among individuals with mental disorders and the need for clinical screening.
REVIEW | doi:10.20944/preprints202107.0507.v2
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: depression; chronic autoimmune thyroiditis; BDNF
Online: 29 November 2021 (12:03:01 CET)
Various autoimmune diseases, including autoimmune hypothyroidism (AHT), are associated with a higher risk of developing mood disorders throughout life. Depression is accompanied by the changes in the levels of inflammatory and trophic factors, including interleukines (IL-1beta, IL-2, IL-6), interferon alpha (IFN-alpha), tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP) and brain derived neurotrophic factor (BDNF). Similar disturbances in the cytokine profile are seen in AHT patients and their relatives. Disclosure of the relationship between the co-existence of depression and autoimmune subclinical thyroiditis indicates that the pathomecha-nism of depression may be related to the changes in the immune system, it is possible that both conditions may be caused by the same immune processes. The above hypothesis is indirectly sup-ported by the observations that the treatment with both antidepressants and levothyroxine leads to a decrease in the levels of proinflammatory cytokines with an increase in BDNF concentrations, simultaneously correlating with an improvement in the clinical parameters. However, so far there are no long-term studies determining the causal relationship between depression, thyroid auto-antibodies, and cytokine profile, which could bring us closer to understanding the interrelation-ships between them and facilitate the use of an adequate pharmacotherapy, not necessarily psy-chiatric. We consider the above issues insufficiently investigated but of great importance. This ar-ticle is an overview of the available literature as well as an introduction to our research project.
ARTICLE | doi:10.20944/preprints202111.0442.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Men's Health; COVID-19; Mental Disorders; Stress, Psychological; Social Support
Online: 24 November 2021 (08:13:48 CET)
Objective: to analyze the relationships between sociodemographic variables, intolerance to uncertainty (INT), social support and psychological distress (i.e., indicators of Common Mental Disorders [CMDs] and perceived stress [PS]) in Brazilian men during the COVID-19 pandemic. Methods: a cross-sectional study with national coverage, of the web survey type, and conducted with 1,006 Brazilian men during the period of social circulation restriction imposed by the health authorities in Brazil, for suppression of the coronavirus and control of the pandemic. Structural equation modeling analysis was performed. Results: Statistically significant direct effects of race/skin color (λ=0.268; p-value<0.001), socioeconomic status (SES) (λ=0.306; p-value<0.001), household composition (λ=0.281; p-value<0.001), PS (λ=0.513; p-value<0.001) and INT (λ=0.421; p-value<0.001) were evidenced in the occurrence of CMDs. Black-skinned men, with higher SES, living alone and with higher PS and INT levels presented higher prevalence values of CMDs. Conclusions: high levels of PS and INT were the factors that presented the strongest associations with the occurrence of CMDs among the men. It is necessary to implement actions to reduce the stress-generating sources, as well as to promote an increase in resilience and the development of intrinsic reinforcements to deal with uncertain threats.
ARTICLE | doi:10.20944/preprints202111.0323.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Suicide; questionnaire; validity; reliability
Online: 18 November 2021 (11:17:37 CET)
Objective: Our goal is to develop an online questionnaire to survey the prevalence of suicidal behavior. Methods: We developed a questionnaire with 51 variables and proceeded with validations. Validations were performed using face validity, content validity, and construct validity. Reliability was performed by test-rest. Results: The face validity was 1.0 and the content validity was 0.91. The exploratory factor analysis got KMO = 0.86 and extracted one principal factor. The confirmatory factor analysis demonstrates RMSEA= 0.000 and CFI=1.000. The test-retest had an intraclass correlated coefficient of 0.98. Conclusion: The adequate development questionnaire was validated, and we have an instrument to survey suicide behaviors in the pandemic time.
ARTICLE | doi:10.20944/preprints202111.0219.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Diabetic Ketoacidosis; Mental health; Type 1 diabetes; Transition; Glycemia
Online: 12 November 2021 (12:04:43 CET)
The transition of people from paediatric to adult diabetes services is associated with worsening glycaemia and increased diabetes-related hospitalisation. This study compared the clinical characteristics of those with and without mental health conditions among attenders at a diabetes young adult clinic diabetes before and after changes in service delivery. Retrospective review of 200 people with diabetes attending a Sydney public hospital over eight years corresponding to the period before (2012-2016) and after (2017-2018) restructuring of a clinic for young adults aged 16-25 years. Characteristics of those with and without mental health conditions (depression, anxiety, diabetes related distress, eating disorders), were compared. Among clinic attenders (type 1 diabetes n=184, 83.2%), 40.5% (n=89) had a mental health condition particularly, depression (n=57, 64%), which was higher among Indigenous than non-Indigenous people (5.6% vs 0.8% p=0.031) but similar between diabetes type. Over eight years, those with, compared with those without a mental health condition had higher HbA1c at the last visit (9.4%[79 mmol/mol] vs 8.7% [71 mmol/mol], p=0.027), the proportion with diabetic ketoacidosis (DKA 60.7% vs 42.7%,p=0.009), smoking (38.4 vs 13.6%,p=0.009), retinopathy (9.0 vs 2.3%,p=0.025), multiple DKAs (28.4 vs 16.0%,p=0.031) were significantly higher. Having a mental health condition was associated with 2.02 (95% Confidence intervals 1.1-3.7) fold increased risk of HbA1c ≥ 9.0%[75mmol/mol]. Changes to the clinic were not associated with improvements in mental health condition (39.0% vs 32.4%, p=0.096). In conclusion, we found that mental health conditions, particularly depression, are common in this population and are associated with diabetes complications. Diabetes type and clinic changes did not affect the reported mental health conditions. Additional strategies are required to reduce complication risks among those with mental health conditions. .
ARTICLE | doi:10.20944/preprints202111.0121.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: schizophrenia; MTHFD1 1958 G> A; folate metabolism; methylation; tetrahydrobiopterin
Online: 5 November 2021 (12:51:14 CET)
Despite a large amount of data on the association of folate metabolism disturbances with different aspects of schizophrenia, the role of the MTHFD1 1958 G>A polymorphism in this disorder is barely studied. The aim of this study was to assess the distribution of alleles and genotypes frequencies of MTHFD1 1958 G>A in patients with schizophrenia and healthy controls and to study the association of allele/genotype carriage of this SNP with biochemical markers of one-carbon metabolism and with the severity of schizophrenia symptoms. Methods: In 57 patients with schizophrenia and 37 healthy volunteers the carriage of alleles/genotypes of the MTHFD1 1958 G>A and biochemical markers of folate metabolism disturbances were evaluated. Clinical symptoms of schizophrenia and the severity of extrapyramidal side effects of therapy were assessed in patients. Results: an association of the wild GG genotype with schizophrenia was shown (GG versus AG / AA: χ2 = 7.31; p = 0.007). The serum folate level in carriers of the wild genotype GG is lower (in all participants p = 0.024, in patients p = 0.10), and the level of cobalamin in this subgroup is higher (in all participants p = 0.047, in patients p = 0.091) than in carriers of other genotypes. Patients carrying the G allele had less severe negative symptoms (p = 0.0041) and extrapyramidal side effects of antipsychotics (p = 0.054), than patients with AA genotype. The age of psychosis manifestation is the later, the more wild alleles G are present in the genotype (p = 0.00195).
ARTICLE | doi:10.20944/preprints202110.0384.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: thiadizines; serotonin transporter (SERT); serotonin-1A receptor; serotonin-3 receptor; docking; docking energy; binding affinity; binding mechanism; c-Fos; immunohistochemistry; electrophysiology
Online: 26 October 2021 (12:32:43 CEST)
L-17 is a thiadiazine derivative with putative anti-inflammatory, neuroprotective, and antidepressant-like properties. In this study, we applied combined in silico, ex vivo, and in vivo electrophysiology techniques to reveal the potential mechanism of action of L-17. PASS 10.4 Professional Extended software suggested that L-17 might have pro-cognitive, antidepressant, and antipsychotic effects. Docking energy assessment with AutoDockVina predicted that the binding affinities of L-17 to the serotonin transporter (SERT) and serotonin receptors 3 and 1A (5-HT3 and 5-HT1A) receptors are compatible to the selective serotonin reuptake inhibitor (SSRI) fluoxetine and selective antagonists of 5-HT3 and 5-HT1A receptors, granisetron and WAY100135, respectively. Acute pre-treatment with L-17 robustly increased c-Fos immunoreactivity in the amygdala (central nucleus), suggesting increased neuronal excitability in this brain area after L-17 administration. Acute L-17 also dose-dependently inhibited of 5-HT neurons of the dorsal raphe nucleus (DRN). This inhibition was partially reversed by subsequent administration of WAY100135, suggesting the involvement of extracellular 5-HT. Based on in silico predictions, c-Fos immunohistochemistry, and in vivo electrophysiology, we suggest that L-17 is a potent 5-HT reuptake inhibitor and/or partial 5-HT1A receptor antagonist. Thus, L-17 might be a representative of a new class of antidepressant drugs. Since L-17 also possesses neuro- and cardio-protective properties, it can be useful in post-stroke and post-myocardial infarction (MI) depression. In general, combined in silico predictions and ex vivo neurochemical and in vivo electrophysiological assessment might be a useful strategy for early preclinical assessment of the affectivity and neural mechanism in action of the novel CNS drugs.
ARTICLE | doi:10.20944/preprints202110.0372.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: 3MDR; treatment-resistant PTSD; military; veterans; mental health; emotional regulation
Online: 26 October 2021 (09:51:46 CEST)
Multi-modal Motion-assisted Memory Desensitization and Reprocessing Therapy (3MDR), an interactive, virtual-reality assisted, exposure-based intervention for PTSD, has shown promising results for treatment-resistant Posttraumatic Stress Disorder (TR-PTSD) among military members (MMs) and Veterans in Randomized Controlled Trials. Previous research has suggested that emotional regulation (ER) and emotional dysregulation (ED) may be factors which are correlated with symptom severity and maintenance of TR-PTSD. This embedded mixed-methods pilot study (n=9) sought to explore the impact of 3MDR on ER and ED of MMs and Veterans. Difficulties in Emotional Regulation Scale (DERS-18) data was collected at baseline, prior to each session, and at 1 week, 1 month and 3 months post-intervention and analyzed using a Wilcoxon signed-ranks test. Qualitative data collected from sessions, debriefs, and follow-up interviews were transcribed and descriptively analyzed. Results demonstrated statistically significant decreases in DERS-18 scores from pre-intervention to post-intervention at each timepoint. Qualitatively, participants perceived improvements in ER within specified DERS-18 domains. We describe how 3MDR’s unique and novel approach may address ED through cognitive-motor stimulation, narration, divergent thinking, reappraisal of aversive stimuli, dual-task processing, and reconsolidation of traumatic memories. Further investigation is underway to better understand the underlying neurobiological mechanisms by which 3MDR addresses ER and PTSD.
REVIEW | doi:10.20944/preprints202110.0232.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: twice exceptionality; autism spectrum disorder; neuroimaging; MRI
Online: 15 October 2021 (16:17:13 CEST)
There is a long-standing association between exceptional cognitive abilities, of various sorts, and neuropsychiatric illness, but it has historically largely been investigated in an exploratory and non-systematic way. One group in which this association has been investigated with more rigor is in subjects who have been identified as twice exceptional; an educational term describing subjects who are both gifted and diagnosed with a neuropsychiatric disability. This term covers multiple conditions, but is of specific interest in particular in the study of autism spectrum disorder. Recent findings have led to the development of a hypothesis that a certain degree of the neurobiology associated with autism might even be advantageous for individuals and could lead to high giftedness, while becoming disadvantageous, once a certain threshold is surpassed. In this model, the same neurobiological mechanisms confer an increasing advantage up to a certain threshold, but become pathological past that point. Twice-exceptional individuals would be exactly at the inflection point, being highly gifted, but also symptomatic at the same time. Here, we review how existing neuroimaging literature on autism spectrum disorder can inform research on twice exceptionality specifically. We propose to study key neural networks with a robust implication in ASD to identify the neurobiology underlying twice-exceptionality. A better understanding of the neural mechanisms of twice exceptionality should help to better understand resilience and vulnerability to neurodevelopmental disorders and tofurther support affected individuals.
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: feeding and eating disorder; genome-wide association study; methylation quantitative trait loci
Online: 8 October 2021 (14:23:39 CEST)
Eating disorders (ED) are characterized by alterations in eating behavior. The genetic factors shared between ED diagnoses have been underexplored. The present study aimed to perform a genome-wide association study on individuals with disordered eating behaviors in the Mexican population, blood methylation quantitative trait loci (blood-meQTL) analysis, and in silico function prediction by different algorithms. The analysis included a total of 1803 individuals. Genome-wide association study and blood-meQTL analysis were performed by logistic and linear regression. In silico functional variant prediction, phenome-wide, and transcriptome-wide association studies by different algorithms were analyzed. In the genome-wide association study, we identified 44 single-nucleotide polymorphisms (SNP) associated at a nominal value and 7 blood-meQTL at a genome-wide umbral. The SNPs were enriched in genome-wide associations of the metabolic and immunologic domains. In the in silico analysis, the SNP rs10419198 located on an enhancer mark could change the expression of PRR12 on blood, adipocytes, and brain areas that regulate food intake. The present study supports the previous associations of genetic variation in the metabolic domain with ED.
ARTICLE | doi:10.20944/preprints202109.0500.v2
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: burnout; healthcare workers; mediation analysis; covid-19 pandemic; mental health
Online: 1 October 2021 (14:50:44 CEST)
The COVID19 pandemic tested the performance of hospitals and intensive care units around the world. Health care workers (HCWs) have been used to develop mental symptoms, but this was especially true during the COVID19 pandemic when HCWs must deal with many other sources of stress and anxiety that can usually be avoided, and long-term shifts and unprecedented population restrictions have weakened people's ability to cope with stress. The research aims to observe the dynamic interplay between burnout, depression, distress, and anxiety in HCWs working in various settings, with specific a focus on Emotional exhaustion, depersonalization, and a diminished sense of personal achievement in mediating a worst mental health status during the first wave of the COVID19 pandemic in Italy. To analyze that we performed a mediation analysis, from which resulted a strong correlation among depression, psychological distress, health perception and anxiety, and the impact of job burnout on anxiety, depression, and distress. Gender seemed to have a strong correlation with burnout, anxiety, and distress; the impact of COVID19 pandemic on Quality of Life seemed to affect anxiety and depression; the changing of mansion influenced depression and job burnout. Encouraging supportive and educational strategies would certainly be recommended to policy makers.
REVIEW | doi:10.20944/preprints202109.0449.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: glutathione; glutamate; psychosis; schizophrenia; redox; antioxidant; oxidative stress; myelin; spectroscopy
Online: 27 September 2021 (12:47:39 CEST)
Schizophrenia continues to be an illness with poor outcome. Most mechanistic changes occur many years before the first episode of schizophrenia; these are not reversible after the illness onset. A developmental mechanism that is still modifiable in adult life may center on intracortical glutathione (GSH). A large body of pre-clinical data has suggested the possibility of notable GSH-deficit in a subgroup of patients with schizophrenia. Nevertheless, studies of intracortical GSH are not conclusive in this regard. In this review, we highlight the recent ultra-high field magnetic resonance spectroscopic studies linking GSH to critical outcome measures across various stages of schizophrenia. We discuss the methodological steps required to conclusively establish or refute the persistence of GSH-deficit subtype and clarify the role of the central antioxidant system in disrupting the brain structure and connectivity in the early stages of schizophrenia. We propose in-vivo GSH quantification for patient selection in forthcoming antioxidant trials in psychosis. This review offers directions for a promising non-dopaminergic early intervention approach in schizophrenia.
ARTICLE | doi:10.20944/preprints202109.0397.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Hypertension management; Complications of cardiovascular; Quality of Life
Online: 23 September 2021 (09:03:57 CEST)
The aim of this study as to determine the relationship between the factors of demography, comor-bidity, medication, lifestyle, and access to health services related to the QoL of people with hy-pertension and its complications in Sleman Regency, Yogyakarta. The study was conducted in a cross-sectional manner using data from Sleman HDSS (Health and Demographic Surveillance System) from 2015 to 2018 in cycles 3 and 2 with the inclusion criteria of hypertensive patients and their complications aged 25 years or older obtained by using a total sampling of 532 people. Measurement of QoL using Short Form 12v2 2a and 2b questionnaires presented in the Physical Component Summary (PCS) and Mental Component Summary (MCS). Data analysis using Mann-Whitney test and Kruskal Wallis test. The results showed factors related to the QoL in PCS were variables of gender, age, diagnosis of hypertension and its complications, the presence of comorbidities, fatty foods, drug consumption in the last two weeks, while factors related to the mental component (MCS) were education and occupation seen from the p-value <0.05. QoL with hypertension and its complications influence and decrease the physical than the patient's mental condition.
REVIEW | doi:10.20944/preprints202109.0201.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: chronic fatigue syndrome; Myalgic Encephalomyelitis; inflammation; neuro-immune; oxidative and nitrosative stress; antioxidants
Online: 13 September 2021 (10:57:26 CEST)
There is evidence that chronic fatigue spectrum disorders (CFAS-D) including Myalgic Encephalomyelitis (ME), chronic fatigue syndrome (CFS) and chronic fatigue with physiosomatic symptoms including when due to comorbid medical disease are characterized by neuroimmune and neuro-oxidative biomarkers. The present study was performed to delineate the protein-protein interaction (PPI) network of CFAS-D and to discover the pathways, molecular patterns and domains enriched in their PPI network. We performed network, enrichment and annotation analysis using differentially expressed proteins and metabolics, which we established in CFAS-D patients. PPI network analysis revealed that the backbone of the highly connective CFAS-D network comprises NFKB1, CTNNB1, ALB, peroxides, NOS2, TNF, and IL6, and that the network comprises interconnected immune-oxidative-nitrosative and Wnt/catenin subnetworks. MultiOmics enrichment analysis shows that the CFAS-D network is highly significantly associated with cellular (antioxidant) detoxification, hydrogen peroxide metabolic process, peroxidase and oxidoreductase activity, IL10 anti-inflammatory signaling, and neurodegenerative, canonical Wnt, the catenin complex, cadherin domains, cell-cell junctions and TLR2/4 pathways; and the transcription factors NF-κB and RELA. The top-10 DOID annotations of the CFAS-D network include four intestinal, three immune system disorders, cancer and infectious disease. Custom GO term annotation analysis revealed that the CFAS-D network is associated with a response to a toxic substance, lipopolysaccharides, bacterium or virus. In conclusion, CFAS-D may be triggered by a variety of stimuli and their effects are mediated by aberrations in the cross-talks between redox, NF-κB, and Wnt/catenin signaling pathways leading to dysfunctions in multicellular organismal homeostatic processes.
REVIEW | doi:10.20944/preprints202109.0159.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: suicide; neuro-immune; inflammation; oxidative and nitrosative stress; depression; mood disorders; schizophrenia; psychiatry
Online: 8 September 2021 (20:03:03 CEST)
A meta-analysis showed a significant association between activated immune-inflammatory and nitro-oxidative (IO&NS) pathways and suicide attempts (SA). There are no data whether suicidal ideation (SI) is accompanied by activated IO&NS pathways and whether there are differences between SA and SI. The current study searched PubMed, Google Scholar, and Web of Science, for articles published from inception until May 10, 2021, and systematically reviewed and meta-analyzed the association between recent SA/SI (< 3 months) and IO&NS biomarkers. We included studies which compared psychiatric patients with and without SA and SI and controls (either healthy controls or patients without SA or SI) and used meta-analysis (random-effect model with restricted maximum-likelihood) to delineate effect sizes with 95% confidence intervals (CI). Our search included 59 studies comprising 4.034 SA/SI cases and 12.377 controls. Patients with SA/SI showed activated IO&NS pathways (SMD: 0.299; CI: 0.200; 0.397) when compared to controls. The immune profiles were more strongly associated with SA than with SI, particularly when compared to healthy controls, as evidenced by activated IO&NS pathways (SMD: 0.796; CI: 0.503; 1.089), an immune-inflammatory response (SMD: 1.409; CI: 0.637; 1.462), inflammation (SMD: 1.200; CI: 0.584; 1.816), and neurotoxicity (SMD: 0.904; CI: 0.431; 1.378). The effects sizes of the IO&NS, immune-inflammatory response and inflammatory profile were significantly greater in SA than in SI. In conclusion: increased neurotoxicity due to inflammation and nitro-oxidative stress and lowered neuroprotection may explain at least in part why psychiatric patients show increased SA and SI. The IO&NS pathways are more pronounced in recent SA than in SI.
REVIEW | doi:10.20944/preprints202109.0070.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: stroke; inflammation; neuro-immune; cytokines; hemostasis; coagulation; protein-protein interactions
Online: 3 September 2021 (15:11:00 CEST)
This study used established biomarkers of death due to ischemic stroke (IS) and performed network, enrichment, and annotation analysis. Protein-protein interaction (PPI) network analysis revealed that the backbone of the highly connective network of IS death consisted of IL6, ALB, TNF, SERPINE1, VWF, VCAM1, TGFB1, and SELE. Cluster analysis revealed immune and hemostasis subnetworks, which were strongly interconnected through the major switches ALB and VWF. Enrichment analysis revealed that the PPI immune subnetwork of death due to IS was highly associated with TLR2/4, TNF, JAK-STAT, NOD, IL10, IL13, IL4, and TGF-β1/SMAD pathways. The top biological and molecular functions and pathways enriched in the hemostasis network of death due IS were platelet degranulation and activation, the intrinsic pathway of fibrin clot formation, the urokinase-type plasminogen activator pathway, post-translational protein phosphorylation, integrin cell surface interactions, and the proteoglycan-integrin-extra cellular matrix complex (ECM). Regulation Explorer analysis of transcriptional factors shows: a) that NFKB1, RELA and SP1 were the major regulating actors of the PPI network; and b) hsa-mir-26-5p and hsa-16-5p were the major regulating microRNA actors. In conclusion, prevention of death due to IS should consider that current IS treatments may be improved by targeting VWF, VEGFA, proteoglycan-integrin-ECM complex, NFKB/RELA and SP1.
ARTICLE | doi:10.20944/preprints202109.0037.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: COVID-19; disability; risk factors; communication; medical rehabilitation; psychosomatic patients; general public; infection; physical health; psychological health
Online: 2 September 2021 (12:08:42 CEST)
Background: During the COVID-19 pandemic, hygiene behaviors such as keeping distance, avoid-ing masses, wearing face masks and adhering to hand hygiene recommendations became impera-tive. The current study aims to determine factors interrelating with hygiene behaviors. Methods: 4,049 individuals (1,305 male, 2,709 female, aged 18-80 years) were recruited from rehabilitation clinics or freely on the internet and surveyed via online questionnaire between May 2020 and August 2021. Socio-demographics, hygiene behaviors, emotions (fear), life-satisfaction, risk factors and disability as well as communication were assessed. Results: Prevalence for hygiene behaviors was: keeping the distance 84.9%, avoiding mass gatherings 84.6%, wearing face masks 96.5% and hand hygiene 80.7%. Hygiene behaviors were significantly related to fear with linear and quad-ratic associations. Conclusion: Individuals with disabilities, risk factors and psychological symp-toms are more compliant. Especially hand hygiene should be targeted to achieve higher compli-ance rates. A medium level of fear is more functional than too elevated fear. Behavioral interven-tions and targeted communication aiming at improving different behaviors in orchestration can help individuals to remain healthy and maintain a high life-satisfaction. Thereby, communication in the healthcare setting is imperative and all involved individuals should become more aware of this to ensure high hygiene standards and patient safety.
ARTICLE | doi:10.20944/preprints202108.0456.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: psychiatry; effective connectivity; depression; salience network; schizophrenia; mood disorders
Online: 23 August 2021 (14:57:10 CEST)
This study was conducted to examine whether there are quantitative or qualitative differences in the connectome between psychiatric patients and healthy controls and to delineate the connectome features of major depressive disorder (MDD), schizophrenia (SCZ), bipolar disorder (BD) and the severity of these disorders. Toward this end, we have performed effective connectivity analysis of resting state functional MRI data in these three patient groups and healthy controls. We have used spectral Dynamic Causal Modeling (spDCM), and the derived connectome features were further subjected to machine learning. The results outlined a model of 5 connections, which discriminate patients from controls, comprising major nodes of the limbic system (amygdala (AMY), hippocampus (HPC) and anterior cingulate cortex (ACC)), the salience network (anterior insula (AI), fronto-parietal and dorsal attention network (middle frontal gyrus (MFG) corresponding to dorsolateral prefrontal cortex, frontal eye field (FEF)). Notably, the alterations in the self-inhibitory connection of the anterior insula emerged as a feature of both mood disorders and SCZ. Moreover, 4 out of the 5 connectome features that discriminate mental illness from controls are features of mood disorders (both MDD and BD), namely the MFG→FEF, HPC→FEF, AI→AMY, and MFG→AMY connections, whereas one connection is a feature of SCZ, namely the AMY→SPL connectivity. A large part of the variance in the severity of depression (31.6%) and SCZ (40.6%) was explained by connectivity features. In conclusion, dysfunctions in the self-regulation of the salience network may underpin major mental disorders, while other key connectome features shape differences between mood disorders and SCZ, and can be used as potential imaging biomarkers.
ARTICLE | doi:10.20944/preprints202108.0423.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: longitudinal study; emergency; infectious disease; organizational justice; stress; loneliness; compassion fatigue; meditation; prayer; insomnia; mental health; anaesthetists
Online: 23 August 2021 (10:22:05 CEST)
The COVID-19 pandemic has severely tested the physical and mental health of health care workers (HCWs). The various stages of the epidemic have posed different problems; consequently, only a prospective study can effectively describe the changes in the workers’ health. This repeated cross-sectional study is based on a one-year investigation (spring 2020 to spring 2021) of intensive care physicians in one of the two COVID-19 hub hospitals in Central Italy. Changes in their work activity due to the pandemic were studied anonymously together with their perception of organizational justice, occupational stress, sleep quality, anxiety, depression, burnout, job satisfaction, happiness, and intention to quit. In May-June 2021, one year after the baseline, doctors reported an increased workload, isolation at work and in social life, lack of time for physical activity and meditation and compassion fatigue. Stress was inversely associated with the perception of justice in safety procedures and directly correlated with work isolation. Occupational stress was significantly associated with anxiety, depression, burnout, dissatisfaction, and intention to quit. Procedural justice was significantly associated with happiness. Doctors believed vaccinations would help control the problem; however, this positive attitude had not yet resulted in improved mental health. Doctors reported high levels of distress (73%), sleep problems (28%), anxiety (25%), depression (64%). Interventions to correct the situation are urgently needed.
ARTICLE | doi:10.20944/preprints202108.0369.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: depression; gut-brain axis; motilin; serotonin; gamma-aminobutyric acid; gonadal hormones; hypothalamic-pituitary-thyroid axis; antidepressants; macrolide antibiotics
Online: 18 August 2021 (07:39:37 CEST)
Recent research has identified the gut-brain axis as a key mechanistic pathway and potential therapeutic target in depression. In this paper, the potential role of gut hormones as potential treatments or predictors of response in depression is examined, with specific reference to the peptide hormone motilin. This possibility is explored through two methods: (a) a conceptual review of the possible links between motilin and depression, including evidence from animal and human research as well as clinical trials, and (b) an analysis of the relationship between a functional polymorphism (rs2281820) of the motilin (MLN) gene and cross-national variations in the prevalence of depression. It was observed that (a) there are several plausible mechanisms, including interactions with diet, monoamine, and neuroendocrine pathways, to suggest that motilin may be relevant to the pathophysiology and treatment of depression, and (b) there was a significant correlation between rs2281820 allele frequencies and the prevalence of depression after correcting for multiple confounding factors. These results suggest that further evaluation of the utility of motilin and related gut peptides as markers of antidepressant response is required, and that these molecular pathways represent potential future mechanisms for antidepressant drug development.
ARTICLE | doi:10.20944/preprints202108.0320.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: bipolar disorders; metacognition; cognitive complaints; cognition; antipsychotic; impulsivity
Online: 16 August 2021 (11:03:23 CEST)
The determinants of metacognition are still poorly understood in bipolar disorders (BD). We aimed to examine the clinical determinants of metacognition, defined as the agreement between objective and subjective cognition in individuals with BD. The participants consisted of 281 patients with BD who underwent an extensive neuropsychological battery and clinical evaluation. To assess subjective cognition, participants provided a general rating of their estimated cognitive difficulties. Clinical characteristics of BD were also recorded, along with medication. We studied the potential moderation of the association between cognitive complaints and global objective cognitive performance by several clinical variables with ordinal logistic regressions. Depression and impulsivity were associated with greater cognitive complaints. The only variable that moderated the relationship between objective and subjective cognition in the global model was the prescription of antipsychotics. Patients taking antipsychotics had a poorer association between cognitive complaints and objective neuropsychological performance. This result suggests a role for dopamine in the modulation of metacognitive performance, and calls for the systematic control of antipsychotic medication in future studies documenting metacognitive deficits in severe and persistent mental disorders. Depression and impulsivity should be investigated as potential therapeutic targets for individuals with BD and cognitive complaints, before proposing an extensive neuropsychological evaluation.
ARTICLE | doi:10.20944/preprints202105.0665.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Sick leave; mental illness; predictors, prevention
Online: 27 May 2021 (11:36:39 CEST)
(1) Background: This study identifies and analyzes those variables that may influence sick leave due to mental illness, based on a retrospective descriptive study of a mutual insurance company in the industrialized region of southern Europe (Catalonia). (2) Methods: All workers who were on sick leave due to mental illness during the period 2009-2019 were included in the study. The relationships between sick leave due to mental illness and social/employment-related and economical and demographic factors were analyzed using multivariate logistic regression and Cox regression model. (3) Results: The period studied included 34,764 workers. Anxious-depressive disorders account for 83.3% of the diagnosed mental disorders. The age cohorts between 30 and 50 years represent 60% of the affected workers. Highest income and high population density regions are the most affected. The levels of mental illness are higher in spring and summer. Professions related to manufacturing industry, automobile mechanics companies, the hospitality industry, education and healthcare and social service companies was more heavily affected. (4) Conclusions: Population density and GDP per capita, the age cohort, the season of the year, the type of payment, the type of contract, and the worker’s business and profession can predict the appearance of sick leave due to mental illness. Mutual insurance companies should plan interventions to minimize these factors and avoid the socioeconomic consequences.
ARTICLE | doi:10.20944/preprints202104.0091.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: COVID-19; healthcare workers; United Kingdom; mental health; burnout; resilience; insomnia; depression; anxiety; lifestyle
Online: 5 April 2021 (10:24:40 CEST)
The burden of COVID-19 pandemic on health systems and the physical and mental health of healthcare workers (HCWs) has been substantial. This cross-sectional study aims to assess the effects of Covid-19 on the psychological wellbeing of mental health workers who provide care to a vulnerable patient population that have been particularly affected during this crisis. A total of 387 HCWs from across a large urban mental health service completed a self-administered questionnaire consisting of socio-demographic, lifestyle and work-based information and validated psychometric scales. Depression and anxiety were measured using the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder Scale (GAD-7) respectively, sleep problems with the Athens Insomnia Scale (AIS), burnout with the Maslach Burnout Inventory (MBI) and resilience with the Resilience Scale-14 (RS-14). Multivariable logistic regression analysis was performed to determine potential mediating factors. Prevalence of burnout was notable, with 52% recording moderate/severe in Emotional Exhaustion, 19.5% moderate/severe in Depersonalisation and 55.5% low/moderate Personal Accomplishment. Over half of all respondents (52%) experienced sleep problems; the presence of depressive symptoms was a significant predictor of insomnia. An increase in potentially harmful lifestyle changes, such as smoking, alcohol consumption and over-eating was also observed. However, high Resilience was reported by 70% of the sample and the importance of this is highlighted. Female gender was associated with increased levels of depression and emotional exhaustion while those with a history of mental health conditions were most at risk of affective symptoms, insomnia and burnout. Overall, our study revealed considerable levels of psychological distress and maladaptive coping strategies but also resilience and satisfaction with organizational support provided. Findings can inform tailored interventions in order to mitigate vulnerability and prevent long-term psychological sequelae.
REVIEW | doi:10.20944/preprints202012.0625.v3
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: depression; anxiety disorders; existential psychotherapy; logotherapy; meaning-centered psychotherapy; functional magnetic resonance imaging; biomarker; kynurenines; Martin Heidegger; Viktor Frankl
Online: 24 March 2021 (13:18:24 CET)
Psychotherapy is a comprehensive biological treatment modifying complex underlying cognitive, emotional, behavioral, and regulatory responses in the brain, leading patients with mental illness to a new interpretation of the sense of self and others. Psychotherapy is an art of science integrated with psychology and/or philosophy. Neurological science studies the neurological basis of cognition, memory, and behavior as well as the impact of neurological damage and disease on the functions, and their treatment. Both psychotherapy and neurological science deal with the brain; nevertheless, they continue to stay polarized far. Existential phenomenological psychotherapy (EPP) has been in the forefront of meaning-centered counseling for almost a century. The phenomenological approach in psychotherapy originated in the works of Martin Heidegger, Ludwig Binswanger, Medard Boss and Viktor Frankl, and it has been committed to account for the existential possibilities and limitations of one’s life. EPP provides philosophically rich interpretations and empowers counseling techniques to assist mentally suffering individuals by finding meaning and purpose of life. The approach has proven to be effective in treating mood and anxiety disorders. This narrative review article demonstrates the development of EPP, the therapeutic methodology, evidence-based accounts of its curative techniques, current understanding of mood and anxiety disorders in neurological science, and a possible converging path to translate and integrate meaning-centered psychotherapy and neuroscience, concluding that the existential phenomenological psychotherapy potently plays a synergistic role with the currently prevailing medication-based approaches for the treatment of mood and anxiety disorders.
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Nutritional Psychiatry; Mental Health Professionals; Psychiatrists; Psychologists; Psychotherapists; Education; Psychiatric Disorders; Diet; Supplements; Nutrition
Online: 16 February 2021 (13:36:58 CET)
Abstract: Nutritional interventions have beneficial effects on certain psychiatric disorder symptomatology and common physical health comorbidities. However, studies evaluating nutritional literacy in mental health professionals (MHP) are scarce. This study aimed to assess the degree of self-rated training and literacy relating to nutrition in MHPs. We conducted a cross-sectional survey across 52-countries. Surveys were distributed via colleagues and professional societies. Data were collected regarding self-reported general nutrition knowledge, nutrition education, learning opportunities, and the tendency to recommend food supplements or specific diets in clinical practice. In total, 1056 subjects participated in the study: 354 psychiatrists, 511 psychologists, 44 psychotherapists, and 147 MHPs in-training. All participants believed the diet quality of individuals with mental disorders was poorer compared to the general population (p<0.001). The majority of the psychiatrists (74.2%) and psychologists (66.3%) reported having no training in nutrition. Nevertheless, many of them used nutrition approaches, with 58.6% recommending supplements and 43.8% recommending specific diet strategies to their patients. Only 0.8% of participants rated their education regarding nutrition as ‘very good’. Almost all (92.9%) stated they would like to expand their knowledge regarding ‘Nutritional Psychiatry’. There is an urgent need to integrate nutrition education into MHP training, ideally in collaboration with nutrition experts to achieve best practice care.
ARTICLE | doi:10.20944/preprints202102.0194.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: COVID-19; health care workers; Greece; mental health; depression; anxiety; traumatic stress; burnout
Online: 8 February 2021 (11:41:59 CET)
COVID-19 pandemic has the potential to adversely affect the mental health of healthcare workers (HCWs). The public healthcare system in Greece was already facing serious challenges at the outset of the outbreak following years of austerity and an escalating refugee crisis. The multi-center, cross-sectional study aims to assess the levels and associated risk factors of anxiety, depression, traumatic stress and burnout of frontline staff in Greece. A total of 464 HCWs in six reference hospitals completed a self-administered questionnaire comprising of sociodemographic and work-related information and psychometric scales. The proportion of HCWs with symptoms of moderate/severe depression, anxiety and traumatic stress were 30%, 25% and 33% respectively. Burnout levels were particularly high with 65% of respondents scoring moderate/severe in Emotional Exhaustion, 92% severe in Depersonalization and 51% low/moderate in Personal Accomplishment. Predictive factors of adverse psychological outcomes included fear, perceived stress, risk of infection, lack of protective equipment and low social support. The psychological burden associated with Covid-19 in healthcare professionals in Greece is considerable with more than half experiencing at least mild mental health difficulties. Findings signal the need for immediate organizational and individually tailored interventions to enhance resilience and support wellbeing under pandemic conditions.
REVIEW | doi:10.20944/preprints202101.0087.v2
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: depression; metabolic syndrome; non-alcoholic fatty liver disease; hypothalamic-pituitary-adrenal axis; inflammation; oxidative stress; microbiota
Online: 8 January 2021 (10:16:21 CET)
Metabolic disorders, metabolic syndrome and non-alcoholic fatty liver disease, and depression are those of the most common and debilitating disorders worldwide that often coexist further increasing mortality risks. Although the exact mechanisms underlying this association are poorly known, several hypotheses have been proposed: antipsychotic medication and antidepressants use, diet and physical activity or any other lifestyle factors. However, the high co-occurrence rate of depression and metabolic disorders suggests a possible pathophysiological overlap. In this paper I review several raised mechanisms for this overlap which are the hypothalamic-pituitary-adrenal axis dysregulation, immune alterations with chronic inflammation, as well as oxidative stress. In my view, there is one common thread running through all the aforementioned areas of pathophysiology which is microbiota alteration. So far, several possible interventions in our microbiota have been introduced into clinical practice - dietary and other lifestyle changes, supplementation with prebiotics or probiotics, fecal microbiota transplantation – but with vague indications. A better characterization of the above associations may represent a critical step at phenotyping, and a more targeted approach to the treatment of both depressive and metabolic disorders. At the end of the paper, I give several practical applications for future studies.
ARTICLE | doi:10.20944/preprints202012.0754.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: attitudes; depression; developing countries; medical education; mental health; psychosis; service users; stigma
Online: 30 December 2020 (14:12:49 CET)
This study evaluated the impact of didactic videos and service user testimonial videos on mental illness stigma among medical students. Two randomized controlled trials were conducted in Nepal. Study 1 examined stigma reduction for depression. Study 2 examined depression and psychosis. Participants were Nepali medical students (Study 1:n=94, Study 2:¬n=213) randomized to three conditions: a didactic video based on the mental health Gap Action Programme (mhGAP), a service user video about living with mental illness, or a control condition with no videos. In Study 1, videos only addressed depression. In Study 2, videos addressed depression and psychosis. In Study 1, both didactic and service user videos reduced stigma compared to the control (F2,91=6.37, p=0.003). In Study 2 (depression and psychosis), there were no differences among the three arms (F2,210=2.07, p=0.13). When comparing Study 1 and 2, there was greater stigma reduction in the service user video arm with only depression versus service user videos with depression and psychosis (t(31)=-3.04, p=0.005). In summary, didactic and service user videos were associated with decreased stigma when content addressed only depression. However, no stigma reduction was seen when including depression and psychosis. This calls for different strategies based on types of mental illnesses. ClinicalTrials.gov identifier: NCT03231761
ARTICLE | doi:10.20944/preprints202012.0499.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: COVID-19; disaster preparedness; disaster response; natural disasters; community-based organizations
Online: 21 December 2020 (10:43:50 CET)
Background: This year has seen the emergence of two major crises, a significant increase in frequency and severity of hurricanes and the COVID-19 pandemic. However, little is known as to how each of these two events have impacted the other. A rapid qualitative assessment was conducted to determine the impact of the pandemic on preparedness and response to natural disasters and the impact of past experiences with natural disasters in responding to the pandemic. Methods: Semi-structured interviews were conducted with 26 representatives of 24 different community-based programs in southern Louisiana. Data were analyzed using procedures embedded in the Rapid Assessment Procedure – Informed Community Ethnography methodology, using techniques of immersion and crystallization and focused thematic analysis. Results: The pandemic has impacted the form and function of disaster preparedness, making it harder to plan for evacuations in event of a hurricane. Specific concerns included being able to see people in-person, providing food and other resources to residents who shelter in place, finding volunteers to assist in food distribution and other forms of disaster response, competing for funds to support disaster-related activities, developing new support infrastructures, and focusing on equity in disaster preparedness. However, several strengths based on disaster preparedness experience and capabilities were identified, including providing a framework for how to respond and adapt to COVID and integration of COVID response with their normal disaster preparedness activities. Conclusions: Although prior experience has enabled community-based organizations to respond to the pandemic, the pandemic is also creating new challenges to preparing for and responding to natural disasters.
REVIEW | doi:10.20944/preprints202009.0724.v2
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: clozapine; schizophrenia; early-onset; pregnancy; bipolar affective disorder; agranulocytosis; COVID-19; pharmacogenetic
Online: 9 November 2020 (11:48:29 CET)
Background: Clozapine (CLZ) use is precarious due to its neurological, cardiovascular, and hematological side effects; however, it is the gold standard in therapy-resistant schizophrenia (TRS) in adults and is underused. Objective: to examine the most recent CLZ data on (a) side effects concerning (b) recent pharmacological mechanisms, (c) therapy benefits, and (d) the particularities of the COVID-19 pandemic. Data sources: a search was performed in two databases (PubMed and Web of Science) using the specific keywords "clozapine" and "schizophrenia," "side effects," "agranulocytosis," "TRS," or "bipolar affective disorder (BAF)" for the last ten years. Study eligibility criteria: clinical trials on adults with acute symptoms of schizophrenia or related disorders. Results: We selected 37 studies, randomized controlled trials (RCTs), and clinical case series (CCS), centered on six main topics in the search area: (a) CLZ in schizophrenia, (b) CLZ in bipolar disorder, (c) side effects during the clozapine therapy, (d) CLZ in pregnancy, (e) CLZ in early-onset schizophrenia, and (f) CLZ therapy and COVID-19 infection. Limitations: We considered RCTs and CCS from two databases, limited to the search topics. Conclusions and implications of key findings: (a) Clozapine doses should be personalized for each patient based on pharmacogenetics testing when available; the genetic vulnerability postulates predictors of adverse reactions' severity; patients with a lower genetic risk could have less frequent hematological monitoring; (b) CLZ-associated risk of pulmonary embolism imposes prophylactic measures for venous thromboembolism; (c) convulsive episodes are not an indication for stopping treatment; the plasma concentration of clozapine is a better side effect predictor than the dosage; (d) COVID-19 infection may enhance clozapine toxicity, generating an increased risk of pneumonia. Therapy must be continued with proper monitoring of the white blood count, and the clozapine dose decreased by half until three days after the fever breaks; psychiatrists and healthcare providers must act together. Background: Clozapine (CLZ) use is precarious due to its neurological, cardiovascular, and hematological side effects; however, it is the gold standard in therapy-resistant schizophrenia (TRS) in adults and is underused. Objective: to examine the most recent CLZ data on (a) side effects concerning (b) recent pharmacological mechanisms, (c) therapy benefits, and (d) the particularities of the COVID-19 pandemic. Data sources: a search was performed in two databases (PubMed and Web of Science) using the specific keywords "clozapine" and "schizophrenia," "side effects," "agranulocytosis," "TRS," or "bipolar affective disorder (BAF)" for the last ten years. Study eligibility criteria: clinical trials on adults with acute symptoms of schizophrenia or related disorders. Results: We selected 37 studies, randomized controlled trials (RCTs), and clinical case series (CCS), centered on six main topics in the search area: (a) CLZ in schizophrenia, (b) CLZ in bipolar disorder, (c) side effects during the clozapine therapy, (d) CLZ in pregnancy, (e) CLZ in early-onset schizophrenia, and (f) CLZ therapy and COVID-19 infection. Limitations: We considered RCTs and CCS from two databases, limited to the search topics. Conclusions and implications of key findings: (a) Clozapine doses should be personalized for each patient based on pharmacogenetics testing when available; the genetic vulnerability postulates predictors of adverse reactions' severity; patients with a lower genetic risk could have less frequent hematological monitoring; (b) CLZ-associated risk of pulmonary embolism imposes prophylactic measures for venous thromboembolism; (c) convulsive episodes are not an indication for stopping treatment; the plasma concentration of clozapine is a better side effect predictor than the dosage; (d) COVID-19 infection may enhance clozapine toxicity, generating an increased risk of pneumonia. Therapy must be continued with proper monitoring of the white blood count, and the clozapine dose decreased by half until three days after the fever breaks; psychiatrists and healthcare providers must act together.
ARTICLE | doi:10.20944/preprints202010.0375.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: hope; mental health; reliability; validity; principal component analysis; schizophrenia
Online: 19 October 2020 (11:18:42 CEST)
Hope is important in the rehabilitation of persons with schizophrenia, through scales to measure hope are not appropriate for this population. The purpose of this cross-sectional study was to identify the psychometric properties of the Schizophrenia Hope Scale-9 (SHS-9) using data from 83 people with schizophrenia in four mental health centers and 762 healthy persons from two universities in South Korea. The mean (standard deviation) SHS-9 score of the participants with schizophrenia and healthy participants was 11.24 (4.90) and 14.83 (3.10), respectively. Lower scores indicate a lower level of hope. The internal consistency alpha coefficient was 0.92 with a 4-week test-retest reliability of 0.89. Criterion-related construct validity was established by examining the correlation between the SHS-9 and the State-Trait Hope Inventory scores. Divergent validity was identified through a negative relationship of SHS-9 with the Beck Hopelessness Scale. The construct validity of the SHS-9 was confirmed through principal component analysis with extraction methods, which resulted in a one-factor solution, accounting for 49–60% of the total item variance.. This study provided evidence for the validity and reliability of the SHS-9; therefore, it could be used to measure hope in people with schizophrenia.
ARTICLE | doi:10.20944/preprints202009.0619.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: COVID-19 Mexico; stress in healthcare professionals; COVID-19 stress scale
Online: 26 September 2020 (08:07:00 CEST)
The world is currently, subjected to the worst health crisis documented in modern history; an epidemic led by the novel coronavirus disease 2019 (COVID-19). At the epicenter of this crisis, healthcare professionals continue working to safeguard our well-being. To the regular high levels of stress, COVID new heights even more to healthcare professionals so depending on the area, specialty, and type of work. Here we investigated what are the tendencies, or areas most affected. Through an adaptation of the original COVID-stress scale, we developed a remote, fast test designed for healthcare professionals of the Northeastern part of Mexico, an important part of the country with economic and cultural ties to the US. Our results showed 4 key correlations as highly dependent: Work area – Xenophobia (p < 0.045), Work with COVID patients - Traumatic stress (p < 0.001) and Total number of COVID patients per day – Traumatic stress (p < 0.027), and Total number of COVID patients - Compulsive checking and reassurance. Overall concluding that normal levels of stress have increased (mild – moderate). Additionally, we further determine that the fear of being an asymptomatic patient (potential to spread without knowing) continues being a concern.
REVIEW | doi:10.20944/preprints202009.0417.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: schizophrenia; stress; drug policy; environment; contaminants; pesticides; fungi; prohibition
Online: 18 September 2020 (04:21:43 CEST)
Background: Most modern studies about human marijuana use have been made under a set of arbitrary cultural standards and policies not related to drug harm potential, loosely called Prohibition. Here we asked if potential health hazards generated by Prohibition are addressed in research design and analysis. Methods: For this, we have searched PubMed database (from inception to December 2017) for citations of prevalent contaminants of illegal street cannabis: fungi and pesticides. In addition, we performed full text evaluation of 23 studies selected from, and including, 2 meta-analysis reviews investigating potential health hazards from cannabis use. Results: Different combinations of the keywords cannabis, prohibition, pesticides, fungi, contaminants, cancer, schizophrenia, psychosis, show that these words coincide in less than 1% of the cannabis human studies within the database. In the scope of 141 abstracts in which the terms, cannabis and pesticides coincide, none is directed to distinguish cannabis and pesticide adverse effects on CNS. A similar picture emerges when fungi is the paired word. Full text evaluation shows that all but one of the studies analyzed, completely neglect or comment on the nature of cannabis source, legal status, or contamination as a confounding factor. Discussion: Our results show a potential bias on scientific investigation that may affect data reliability in informing about the health hazards of cannabis use. This finding suggests that other aspects of the Prohibition environment may also go unacknowledged. Conclusion: Prohibition related health risks usually go unacknowledged and unaccounted for in biomedical research on Cannabis.
ARTICLE | doi:10.20944/preprints202009.0347.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: mood disorders; depression; nitrosative and oxidative stress; IgM autoimmunity; neuro-immune; inflammation
Online: 16 September 2020 (04:17:25 CEST)
Major depression is accompanied by increased IgM-mediated autoimmune responses to oxidative specific epitopes (OSEs). Nevertheless, these responses have not been examined in bipolar disorder type 1 (BP1) and BP2. IgM responses to malondialdehyde (MDA), phosphatidinylinositol, oleic acid, and azelaic acid were determined in 35 healthy controls, and 101 mood disorder patients, namely 47 major depressed (MDD), 29 BP1, and 25 BP2 patients. We also measured serum total peroxides, IgG to oxidized LDL (oxLDL), IgM to nitroso-adducts, and IgM/IgA directed to lipopolysaccharides (LPS). IgM responses to OSEs were significantly higher in MDD and BP1 as compared with controls and higher in MDD than in BP2. Partial Least Squares (PLS) analysis showed that 57.7% of the variance in the clinical phenome of mood disorders was explained by number of episodes, IgM directed to OSEs and nitroso-adducts, IgG to oxLDL, and peroxides. There were significant specific indirect effects of IgA/IgM to LPS on the clinical phenome, which were mediated by peroxides, IgM OSEs, and IgG oxLDL. Using PLS we have constructed a data-driven nomothetic network which ensembled causome (increased plasma LPS load), adverse outcome pathways (namely neuro-affective toxicity), and clinical phenome features of mood disorders in a data-driven model. Based on those feature sets, cluster analysis discovered a new diagnostic class characterized by increased plasma LPS load, peroxides, autoimmune responses to OSEs and nitroso-adducts, and increased phenome scores. Using the new nomothetic network approach, we constructed a mechanistically transdiagnostic diagnostic class indicating neuro-affective toxicity in 74.3% of the mood disorder patients.
ARTICLE | doi:10.20944/preprints202009.0159.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Nicotine; Cotinine; Corticosterone; LCMS; Sex; C57BL/6J mouse; CYP2A5; Plasma Levels; Subcutaneous Injection
Online: 7 September 2020 (08:08:54 CEST)
We assessed if there were any sex-related differences in the ability of nicotine to increase plasma corticosterone secretion after single or repeated nicotine administration. For single-dose studies, male and female mice were habituated to the test room for 1 h and injected with saline or nicotine (0.25 or 1 mg/kg, s.c.). In repeated-dosing studies, mice were injected with saline or nicotine (1 mg/kg, s.c.) once daily for six days, and, on day 7, received nicotine (1 mg/kg, s.c.). The mice were euthanized 15 min later, and trunk blood was collected for the measurement of corticosterone, nicotine, and cotinine. Our results showed that saline or nicotine each significantly increased plasma corticosterone levels in both male and female mice, with a greater response in female mice. Plasma corticosterone levels were increased in male but not female mice after repeated compared to single nicotine administration. The level of cotinine, a biomarker of nicotine use, was significantly higher in female than in male mice. Taken together, these novel findings suggest that female mice responded to nicotine and stress of handling more than male mice and provide for the first-time quantitative data on the male-female differences in nicotine-induced elevations of corticosterone and of cotinine.
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Disabled Persons; Health Status; Iran; Psychometrics; Quality of Life; Reliability
Online: 7 September 2020 (03:24:54 CEST)
Aim: The aim of this study was to assess the performance of the SF-36 health survey (SF-36) in a sample of subjects with physical disabilities. Material and Methods: 305 patients recruited using the convenient sampling method from September 2019 to March 2020 in Kermanshah, Iran. Another similar 300 patients were selected to assess the confirmatory factor analysis (CFA). Results: The Cronbach’s α ranged from 0.70 to 0.93, and intra-class correlation coefficients from 0.71 to 0.88; and with the no ceiling and floor effect for two main subscales. Convergent validity was supported by moderate to good correlation between SF-36 subscales and Moorong self-efficacy subscales (r= 0.25- 0.53). The SF-36 divergently validated with HADS total score and subscales (r= -0.24- -0.65), concurrently validated with its subscales (r=0.49- 0.88), and physically discriminated between persons with different level of disability (t-test: p<0.001). Factorial analysis identified seven factors, confirmed with second-order in another 300 samples (chi-square (χ2/df) = 2.61(p < .001); RMSEA = 0.07 (90% CI = 0.07–0.08); AGFI=0.75; GFI = 0.78; CFI= 0.85; and NFI = 0.78). Conclusions: the SF-36 is a reliable and valid tool in physical disables. However, SF-36 shows insufficient eight-factor validity. Future studies should focus on evaluating other psychometric properties, such as sensitivity to change in subjects with physical disabilities.
ARTICLE | doi:10.20944/preprints202009.0149.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Smartphone Addiction; Middle School Students; Smartphone Usage Types; Depression; Parenting Attitude
Online: 6 September 2020 (16:27:01 CEST)
The purpose of this study was to examine the relationships between smartphone addiction of middle school students and smartphone usage types, depression, attention deficit hyperactivity disorder (ADHD), stress, interpersonal problems, and parenting attitude. This study was also performed with the aim of verifying the relationships among depression, ADHD, perceived stress, interpersonal problems, and parenting attitude, which are predictors of smartphone addiction. The subjects of this study were 487 local middle school students (234 males and 253 females). The measurement instruments used were the smartphone addiction scale, depression scale (PHQ-9), ADHD scale (K-ARS), perceived stress scale (PSS), interpersonal problem scale (KIIP-SC), and the parenting attitude scale. This study identified the relationships between the variables with correlation analysis and examined the predictors of smartphone addiction with hierarchical multiple regression analysis. According to the study results, the factors that influenced smartphone addiction were gender, stress, and interpersonal problems. In addition, when the confounding variables of smartphone addiction were controlled to examine the effects of smartphone usage types on smartphone addiction, social media use and music/videos were found to have a positively significant effect on smartphone addiction while study had a negatively significant effect. The order of the usage types with the highest influence on smartphone addiction was enjoying music/videos, social media use, and study. This suggests that selective intervention depending on the main smartphone usage type can be effective.
ARTICLE | doi:10.20944/preprints202009.0053.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: unstable angina, inflammation, neuro-immune, major depression, oxidative stress, antioxidants, atherogenicity
Online: 3 September 2020 (04:40:27 CEST)
Background. There is strong comorbidity between atherosclerosis (ATS) and depression which is attributed to increased atherogenicity, insulin resistance (IR), and immune and oxidative stress.Aim of the study. To examine the role of the above pathways and mu opioid receptor (MOR), β-endorphin, zinc, copper, vitamin D3, calcium, and magnesium in depression due to ATS / unstable angina (UA).Methods. Biomarkers were assayed in 58 controls and 120 ATS patients divided into those with moderate and severe depression according to the Beck Depression Inventory (BDI)-II score > 19 and > 29, respectively. Results. Neural network and logistic regression models showed that severe depression due to ATS/UA was best predicted by IL-6, UA, MOR, zinc, β-endorphin, calcium and magnesium and that moderate depression was associated with IL-6, zinc, MOR, β-endorphin, UA, atherogenicity, IR, and calcium. These neural networks yielded a significant discrimination of severe and moderate depression with an area under the ROC curve of 0.831 and 0.931, respectively. Using Partial Least Squares analysis, 66.2% of the variance in a latent vector extracted from the ATS/UA clinical features, BDI-II scores, atherogenicity, and IR could be explained by the regression on IL-6, IL-10, zinc, copper, calcium, MOR, and age. The BDI-II scores increased from controls to ATS to UA class III to UA class IV.Conclusions. Depression due to ATS/UA is a reflective manifestation of increased atherogenicity and IR, which are modulated by immune activation, aberrations in the endogenous opioid system, antioxidants, trace elements, and macrominerals.
ARTICLE | doi:10.20944/preprints202008.0709.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: COVID-19; lockdown; psychological impacts; self-harm; suicide; COVID-19 suicide; teenage suicide; adolescent suicide; youth suicide; press reporting suicide
Online: 31 August 2020 (05:43:25 CEST)
Background: The incidences of COVID-19 related suicide among adolescents and youths have been reported across the world. There is no cumulative study focusing on nature, patterns, and causative factors that lead to the present investigation. Methods: A purposive sampling of google news between 15 February to 6 July was performed. After excluding duplicate reports, the final list comprised a total of 37-suicide cases across 11 countries. Results: More male suicides were reported (21-cases, i.e., 56.76%), and the mean age of the total victims was 16.6±2.7 years (out of a total of 29-cases). About two-thirds of the suicides were from three countries named India (11-cases), United Kingdom (8-cases), and the USA (6-cases). Out of 23-student victims, 14 were school-going students. Hanging was the most common suicide method accounting in 51.4% of cases. The most common suicide causalities were related to mental sufferings such as depression, loneliness, psychological distress, etc., whereas either online schooling or overwhelming academic distress was placed as the second most risk factors followed by TikTok addiction-related psychological distress, and tested with COVID-19. Conclusion: The finding of the temporal distribution of suicides concerning lockdowns may help in exploring and evolving public measures to prevent/decrease pandemic-related suicides in young people.
ARTICLE | doi:10.20944/preprints202008.0606.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: life satisfaction; depression; self-esteem; stigma; out of school youth; structural equation modeling
Online: 27 August 2020 (09:02:07 CEST)
The purpose of this study was to assess the extent to which self-esteem and depression mediated the influence of internalized stigma on life satisfaction among Korean out-of-school youths. Cross-sectional data on 318 youths provided information on perceived stigma, self-esteem, depression, life satisfaction, and personal characteristics. A multinomial logistic regression analysis was followed by structured path analysis to investigate the mediation effects. Internalized stigma was negatively associated with life satisfaction. Self-esteem significantly mediated the influence of stigma on depression and the influence of depression on life satisfaction. Further, stigma directly and significantly influenced depression. This study demonstrated that self-esteem and depression were important to the relationship between internalized stigma and life satisfaction. Implications for possible policies and programs with the aim of helping out-of-school youths to integrate and lead successful satisfying lives are discussed.
ARTICLE | doi:10.20944/preprints202008.0431.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: depressive disorder; omega-3 fatty acids; lipid profile; fluidity of membrane; children and adolescents
Online: 20 August 2020 (05:48:48 CEST)
Depressive disorder (DD) is a psychiatric disorder whose molecular basis is not fully understood. It is assumed that reduced consumption of fish and omega-3 fatty acids (FA) is associated with DD. Other lipids like total cholesterol (TCH), LDL- and HDL-cholesterols (LDL-CH, HDL-CH) also play a role in depression. This study aimed to investigate the relationship between depressive disorder symptoms and lipid profile, LDL- and HDL-cholesterol subfractions, Paraoxonase 1 (PON1) activities and erythrocyte membrane fluidity in 58 depressive children and adolescents, as well as the effect of omega-3 FA on the monitored parameters. Depressive symptoms were assessed by the Children's Depression Inventory (CDI), lipid profile by standard biochemical procedures, LDL- and HDL-subfractions by the Lipoprint system. Basic biochemical parameters including lipid profile were compared with levels in 20 healthy children and were in the physiological range. We are the first to report that omega-3 FAs increase after 12 weeks of supplementation large HDL subfractions (anti-atherogenic) and decrease small HDL subfractions (pro-atherogenic) in depressed children. We found a negative correlation between CDI score and HDL-CH and large HDL subfraction, but not LDL-CH subfractions. CDI score was not associated with erythrocyte membrane fluidity. Our results suggest that HDL-CH and its subfractions, but not LDL-CH may play a role in the pathophysiology of depressive disorder.
ARTICLE | doi:10.20944/preprints202008.0421.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: deficit schizophrenia; cytokines; inflammation; neuro-immune; oxidative stress; leaky gut
Online: 20 August 2020 (03:24:47 CEST)
Current case definitions of schizophrenia (DSM-5, ICD), made through a consensus among experts, are not cross-validated and lack construct reliability validity. The aim of this paper is to explain how to use bottom-up pattern recognition approaches to construct a reliable and replicable nomothetic network reflecting the direct effects of risk resilience (RR) factors, and direct and mediated effects of both RR and adverse outcome pathways (AOPs) on the schizophrenia phenome. This study was conducted using data of 40 healthy controls and 80 patients with schizophrenia. Using partial least Squares (PLS) analysis, we found that 39.7% of the variance in the phenomenome (lowered self-reported quality of life) was explained by the unified effects of AOPs (IgA to tryptophan catabolites, LPS, and the paracellular pathway, cytokines, and oxidative stress biomarkers), the cognitome (memory and executive deficits), and symptomatome (negative symptoms, psychosis, hostility, excitation, mannerism, psychomotor retardation, formal thought disorders); 55.8% of the variance in the symptomatome was explained by a single trait extracted from AOPs and the cognitome; and 22.0% of the variance in the latter was explained by the RR (Q192R polymorphism and CMPAaase activity, natural IgM, and IgM levels to zonulin). There were significant total effects (direct + mediated) of RR and AOPs on the symptomatome and phenomenome. In the current study, we built a reliable nomothetic network that reflects the associations between RR, AOPs, and the phenome of schizophrenia and discovered new diagnostic subclasses of schizophrenia based on unified RR, AOPs, and phenome scores.
ARTICLE | doi:10.20944/preprints202008.0342.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: COVID-19 pandemic; virus’ transmission; fear of contagion; breathing difficulty; healthy adolescents; emotion awareness; anxiety-state
Online: 15 August 2020 (08:25:22 CEST)
The COVID-19 appears as a catastrophic health risk with psychological, emotional, social and relational implications. From the early stages of the virus spread, the elderly population was identified as the most vulnerable and the health authorities have rightly focused on such frailest population. Conversely, less attention was paid to emotional and psychological dimension of children and adolescents. Actually, they were less at risk quoad vitam or quoad valetudinem, nevertheless they had to face a reality of anxiety, fears and uncertainties. The current study investigated state anxiety and emotion awareness in a healthy sample of older adolescents, 84 females and 64 males, aged 17 to 19, during the pandemic lockdown, using Self-rating Anxiety Scale and the Italian Emotion Awareness Questionnaire. An unexpected anxious phenomenology, impacting the anxiety ideo-affective domain, was found, while the somatic symptomatology appeared to be less severe. The highest anxiety symptom were the breathing difficulties. These findings supported the hypothesis that the COVID-19 pandemic may be a risk condition for an increased state anxiety in older adolescents and suggest the need to provide 1. an effective, empathic communication system with the direct participation of older adolescents, 2. a psychological counseling service for stress management of adolescents.
ARTICLE | doi:10.20944/preprints202008.0207.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Social Anxiety Disorder; Social Phobia, Online Survey; Adult, Oman; Liebowitz Social Anxiety Scale
Online: 8 August 2020 (09:39:49 CEST)
Background: Social Anxiety Disorder (SAD) is among the most common anxiety disorders worldwide with data largely emerging from the Euro-American and Pacific Rim populations. In contrast, there is a dearth of studies among the populations of Arabian Gulf countries including Oman. This study has two interrelated aims: (i) to explore the prevalence of SAD among Omani adults, and (ii) to tease out the links between sociodemographic factors and SAD in Oman. Methods: A cross-sectional study via an online survey was conducted among 1019 adult Omani nationals residing in Oman. The presence of SAD was assessed using the Arabic version of the Liebowitz Social Anxiety Scale (LSAS). Result: Nearly half the participants (45.9%, n=468) endorsed themselves as having features of SAD as defined by LSAS. In the multivariate logistic analysis, participants below 40 years of age were 1.6 times (OR=1.568, p=0.026) more likely to have SAD than those who were 40 and older. Women were 1.3 times (OR=1.348, p=0.038) more likely to endorse SAD than men. Participants who had secondary or undergraduate education were respectively 1.5 times (OR=1.45, p=0.014) and 2.5 times (OR=2.509, p<.001) to have SAD than who were postgraduates. Conclusion: The present data suggest that 45.9% of the participants reached the cut-off for case-ness in LSAS, which is high compared to reports from other populations. As online survey respondents tend to belong to similar demographics, the current results need not be representative of the Omani adult population, which calls for studies that adopt more inclusive survey methods.
ARTICLE | doi:10.20944/preprints202008.0070.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: digital devices; digital media; toddler; children; language abilities
Online: 3 August 2020 (11:39:57 CEST)
Background: Over the past decade, the use of digital tools has grown and research evidence suggests that traditional media and new media offer both benefits and health risks for young children. The abilities to understand and use language represent two of the most important competencies developed during the first 3 years of life through the interaction of the child with people, objects, events, and other environmental factors. The main goal of our study is to evaluate the relationship between digital devices use and language abilities in children between 8-36 month, considering also the influence of several variables. Materials and Methods: We conducted a cross-sectional observational study on 260 healthy children (140 males = 54%) aged between 8-36 months (mean=23.5±7.18 months). All the parents completed a self-report questionnaire investigating the use of digital devices by their children, and a standardized questionnaire for the assessment of language skills (MacArthur). Multiple linear regression was used to evaluate the relationship between different variables. Subsequent moderation analysis were performed to verify the influence of other factors. Results: W found a statistically significant negative correlation between the total daily time of exposure to digital devices and the Actions and Gestures Quotient (ß=-0.397) in children between 8-17 months, and between the total daily time of exposure to digital devices and Language Quotient (ß=-0.224) in children between 18-36 months. Sex, level of education/job of parents, modality of use/content of digital device do not significantly affect these relationships. Conclusion: In our study we found that a longer time of exposure to digital devices was related to lower mimic-gestural skills in children from 8-17 months and to lower language skills in children between 18-36 months, regardless of age, sex, socio-economic status, content and modality of use. Further studies are needed to confirm and better understand this relationship, but parents and pediatricians are advised to limit the use of digital devices by children and encourage the social interaction to support the learning of language and communication skills in this age group.
REVIEW | doi:10.20944/preprints202007.0737.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: oxidative stress; redox; antioxidant; multiple sclerosis; biomarker; neurodegenerative disease; personalized medicine
Online: 31 July 2020 (08:40:46 CEST)
Worldwide, over 2.2 million people are suffered from multiple sclerosis (MS), a multifactorial demyelinating disease of the central nervous system, characterized by multifocal inflammatory or demyelinating attacks associated with neuroinflammation and neurodegeneration. The blood, cerebrospinal fluid, and postmortem brain samples of MS patients evidenced the presence of reduction-oxidation (redox) homeostasis disturbance such as the alternations of oxidative and antioxidative enzyme activities and the presence of degradation products. This review article discussed the components of redox homeostasis including reactive chemical species, oxidative enzymes, antioxidative enzymes, and degradation products. The reactive chemical species covered frequently discussed reactive oxygen/nitrogen species, rarely featured reactive chemicals such as sulfur, carbonyls, halogens, selenium, and nucleophilic species that potentially act as reductive as well as pro-oxidative stressors. The antioxidative enzyme systems covered the nuclear factor erythroid-2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) signaling pathway, a possible biomarker sensitive to the initial phase of oxidative stress. Altered components of the redox homeostasis in MS were discussed, some of which turned to be MS subtype- or treatment-specific and thus potentially become diagnostic, prognostic, predictive, and/or therapeutic biomarkers. Finally, monitoring a battery of redox components including oxidative, antioxidative and degradation products helps evaluate the redox status of MS patients, which expedites prolongation of remission, relapse prevention, and building personalized treatment plans.
BRIEF REPORT | doi:10.20944/preprints202007.0636.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Autism Spectrum Disorder; Attention-deficit/hyperactivity disorder; Behavioural Neuroscience; Mental Health; COVID-19; Pandemic; Paediatric Neurology
Online: 26 July 2020 (15:31:51 CEST)
Children and young people (CYP) with neurodevelopmental disorders (NDDs) may be particularly vulnerable to adverse mental health effects due to the COVID-19 pandemic. We conducted a cross-sectional U.K parent-reported study from 2nd April-2nd June 2020, using the Strengths & Difficulties Questionnaire. CYP with NDDs (n=371) compared to neurotypical controls, had a higher prevalence of emotional symptoms (42% vs 15%), conduct problems (28% vs 9%), and lower prosocial behaviours (54% vs 22%). Those with attention-deficit/hyperactivity disorder showed inflated conduct, and those with autism spectrum disorder exhibited decreased prosocial behaviours. Females with ASD had higher emotional symptoms compared to males.
REVIEW | doi:10.20944/preprints202005.0346.v2
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: mental health; COVID-19; school-going children; lockdown
Online: 22 July 2020 (07:43:01 CEST)
During this epidemic of COVID-19, children are in need of much concentration and profound love of the senior family members. Although the measures taken by the organizations are necessary to prevent the spread of the novel coronavirus, they may be causing widespread mental health issues, including depression and loneliness. Therefore, it is imperative that parents have to spend the lion-share of time with children while listening to them cordially. Parents can participate in sports with them to help them stay fit so that they can enjoy commemorating moments. However, in this additional time, the parents can also make them habituated to practice the rules of health, so does social distancing.
ARTICLE | doi:10.20944/preprints202007.0499.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: adolescents; cannabis; cognition; working memory; executive functions
Online: 22 July 2020 (05:42:03 CEST)
The developmental phase of adolescence is characterized by a multitude of neurocognitive and psychosocial changes and is therefore considered one of the most critical developmental periods of life. Experimentation on the use of substances often begins in adolescence and so does the addiction process. Most research in human subjects shows that chronic cannabis abuse is the cause of the impairment of some cognitive functions, affecting the performance on divided attention, verbal memory and working memory. In this study, we wanted to investigate how the abuse of cannabis (chronic, occasional and absence use) can influence global cognitive functioning, also through executive functions. From the statistical analyzes of our study, it emerges that the group of subjects who use chronic cannabis (group 1) has a significant drop in working memory tasks compared to the group that does not use it (group 3). In addition, the goal of future studies by our group is to verify the permanent alteration of cognitive processes affected through revaluations with calendar follow-up (controlled).
REVIEW | doi:10.20944/preprints202007.0425.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: autism spectrum disorder; neuroinflammation; kynurenine pathway; microglia; oxidative stress; mitochondrial disorder; immune deregulation; QUIN (quinolinic acid); KYNA (kynurenic acid); tryptophan catabolites
Online: 19 July 2020 (19:19:31 CEST)
Autism Spectrum Disorder etiopathogenesis is still unclear and no effective preventive and treatment measures have been identified. Research has focused on the potential role of neuroinflammation and kynurenine pathway. Here we review the nature of these interactions. Pre-natal or neonatal infections would induce microglial activation, with secondary consequences on behavior, cognition and neurotransmitter networks. Peripherally, higher levels of pro-inflammatory cytokines and anti-brain antibodies have been identified. Increased frequency of autoimmune diseases, allergies, and recurring infections have been demonstrated both in autistic patients and in their relatives. Genetic studies, also, have identified some important polymorphisms in chromosome loci related to human leukocyte antigen (HLA) system. The persistence of immune-inflammatory deregulation would lead to mitochondrial dysfunction and oxidative stress, creating a self-sustaining cytotoxic loop. Chronic inflammation activates kynurenine pathway with increase in neurotoxic metabolites and excitotoxicity, causing long-term changes in glutamatergic system, trophic support and synaptic function. Furthermore, overactivation of kynurenine’s branch induces depletion of melatonin and serotonin worsening ASD symptoms. In this scenario, kynurenine pathway appears as a pharmacological target to treat and prevent ASD. Thus, in genetically predisposed subjects aberrant neurodevelopment may derives from a complex interplay between inflammatory process, mitochondrial dysfunction, oxidative stress and kynurenine pathway overexpression. To validate previous hypothesis a new translational research approach is necessary.
REVIEW | doi:10.20944/preprints202007.0373.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: autism spectrum disorder; cannabinoids; cannabidiol; cannabidivarin; THC; problem behaviors; sleep; epilepsy; side effects.
Online: 17 July 2020 (09:19:13 CEST)
The etiopathogenesis of autism spectrum disorder (ASD) remains largely unclear. Among other biological hypotheses, researchers have evidenced an imbalance in the endocannabinoid (eCB) system, which regulates some functions typically impaired in ASD, such as emotional responses and social interaction. Also, cannabidiol (CBD), the non-intoxicating component of Cannabis sativa, has been recently approved for treatment-resistant epilepsy. Seizures represent frequent medical comorbidities of ASD and could be responsible for the onset or worsening of behavioral problems. Thus, it has been hypothesized that cannabinoids could be useful in improving some ASD symptoms. Our systematic review was conducted according to the PRISMA guidelines and aimed to summarize the literature regarding the use of cannabinoids in ASD. After searching in Web of KnowledgeTM, PsycINFO, and Embase, we included ten studies (eight papers and two abstracts). Four ongoing trials were retrieved in ClinicalTrials.gov. Findings are promising, as cannabinoids appeared to improve problem behaviors, sleep, hyperactivity, and communication deficits, with limited cardiac and metabolic side effects. Interestingly, they generally allowed to reduce the number of prescribed medications and decreased the frequency of seizures in epileptic patients. Mechanisms of action could be linked to the excitatory/inhibitory imbalance found in people with ASD. However, further trials need to be implemented with better characterization and homogenization of samples, and well-defined outcomes.