ABSTRACTIntroduction:Human Immunodeficiency Virus (HIV) is a global health problem that is almost recorded in every country. The long-term and long-term negative impacts of HIV cases are stigma and discrimination in people with HIV (PLHIV). The purpose of this study is to find out the stigma and discrimination felt by PLHIV.Method:This study design of systematic review from 4 electronic databases namely Scopus ScienceDirect, Sage and ProQuest by using keywords tailored to Medical Subject Headings (MeSH) including "Stress", "covid", "nursing", "hospital". This study uses PICOS framework to prevent research bias and analysed using descriptive analysis.Results:The results of the analysis of the article showed from 761 articles have been identified title, abstract and full-text so that recorded 15 articles that can be reviewed. The article consists of various designs, namely RCT, cross sectional and qualitative studies. Analysis shows that stigma and discrimination are social phenomena that manifest in several social areas.Conclusion:Stigma and discrimination in people with HIV (PLHIV) is still common, stigma is carried out by the wider community to their own families. The family approach is necessary to improve well-being as well as improve the social community of the family.

Schizophrenia comprises various symptom domains, including positive and negative symptoms. Machine learning showed that a) negative symptoms are significantly interrelated with PHEM (psychosis, hostility, excitation, and mannerism) symptoms, formal thought disorders (FTD) and psychomotor retardation (PMR); and b) stable phase schizophrenia comprises two distinct classes, namely Major Neuro-Cognitive Psychosis (MNP, largely overlapping with deficit schizophrenia) and Simple NP (SNP). In this study, we recruited 120 MNP patients and 54 healthy subjects and measured the above-mentioned symptom domains. In MNP, there were significant associations between negative and PHEM symptoms, FTD and PMR. A single latent trait, which is essentially unidimensional, underlies these key domains of schizophrenia and MNP and additionally shows excellent internal consistency reliability, convergent validity, and predictive relevance. Confirmatory Tedrad Analysis indicates that this latent vector fits a reflective model. The lack of discriminant validity shows that PHEM and negative symptoms greatly overlap and probably measure the same construct. Soft Independent Modeling of Class Analogy (SIMCA) shows that MNP (diagnosis based on negative symptoms) is better modeled using PHEM symptoms, FTD, and PMR than negative symptoms. In conclusion, in stable phase MNP, a restricted sample of the schizophrenia population, negative and PHEM symptoms, FTD and PMR belong to one underlying latent vector reflecting overall severity of schizophrenia (OSOS). The bi-dimensional concept of “positive” and “negative” symptoms cannot be validated and, therefore, future research in stable phase schizophrenia should consider that the latent phenomenon OSOS as well as its 8 reflective manifestations are the key factors of schizophrenia phenomenology.

Amnestic mild cognitive impairment (aMCI) is a condition characterized by mild deficits in episodic and semantic memory and learning. The conversion rate of aMCI to Alzheimer disease (AD) is significantly higher in aMCI than in the general population. The aim of this study is to examine whether aMCI is a valid diagnostic category or whether aMCI comprises different subgroups based on cognitive functions. We recruited 60 aMCI patients, 60 with AD and 61 healthy controls who completed neuropsychological tests of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD-NP) and biomarkers including serum anion gap (AGAP). Principal component analysis, support vector machine and Soft Independent Modeling of Class Analogy (SIMCA) showed that AD patients and controls were highly significantly discrimanted from each other, while patients with aMCI overlap considerably with normal controls. SIMCA showed that 68.3% of the aMCI patients were assigned to the control class (named: aMCI-HC), 15% to AD (aMCI-AD), while 16.6% did not belong to either class (aMCI-strangers). aMCI-HC subjects showed sings of very mild cognitive decline and impaired recall. aMCI-strangers showed signs of mild cognitive impairment with impaired fluency and naming. aMCI-AD cases showed a cognitive profile reminiscent of AD an increased AGAP levels. In conclusion, our SIMCA model may classify subjects afforded a clinical diagnosis of aMCI according to Petersen’s criteria into three clinically relevant subgroups and help in the early detection of AD by identifying aMCI patients at risk to develop AD and those that have an AD prodrome.

Background: In recent years, the abusive use of the smartphone has reached a situation that could be considered pathological, although there is no such classification in the DSM-IV. In this sense, different instruments to assess this problematic use or addiction to the smartphone are used. Among them, we found the SPAI, which has been validated in the Spanish language. The main difficulty of these scales is to establish a cut-off point that determines such mobile addiction. On the other hand, self-perception has been used in different addictions as a predictor of the problem. Aim: The objective of this study is to establish the cutting point in the scores of the SPAI scale validated in Spanish, using as a referent the self-perception of addiction values. Methods: A receiver operating characteristics (ROC) analysis was carried out, establishing as the cut-off point the one that presented a higher value of Youden J, indicative of its sensitivity and specificity. Results: 2598 participants from the university community completed the SPAI-Spain questionnaire. When using the self-perception of smartphone addiction as the benchmark value, a score of 44 has been established as the cutting point of the SPAI questionnaire, with a Youden J corresponding to 0.416. Conclusions: The implementation of a cut-off point of the SPAI questionnaire makes it an instrument that allows early identification of those individuals at risk of addiction as well as the establishment of preventive and/or intervention measures.

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.

Opioids are highly addictive substances with a relapse rate of over 90%. While preclinical models of chronic opioid exposure exist for studying opioid dependence, none recapitulate the relapses observed in human opioid addiction. The mechanisms associated with opioid dependence, the accompanying withdrawal symptoms and the relapses that are often observed months or years after opioid dependence are poorly understood. Therefore, we developed a novel model of chronic opioid exposure whereby the level of administration is self-directed with periods of behavior acquisition, maintenance and then extinction alternating with reinstatement. This profile arguably mirrors that seen in humans, with initial opioid use followed by alternating periods of abstinence and relapse. Recent evidence suggests that dietary interventions that reduce inflammation, including omega-3 fatty acids such as docosahexaenoic acid (DHA), may reduce substance misuse liability. Using the self-directed intake model, we characterize the observed profile of opioid use and demonstrate that a diet enriched in polyunsaturated fat acids (PUFAs) ameliorates oxycodone-seeking behaviors in the absence of drug availability and reduces anxiety. Guided by the major role gut microbiota have on brain function, neuropathology, and anxiety, we profile the microbiome composition and the effects of chronic opioid exposure and DHA supplementation. We demonstrate that withdrawal of opioids led to a significant depletion in specific microbiota genera whereas DHA supplementation increased microbial richness, phylogenetic diversity, and evenness. Lastly, we examined the activation state of microglia in the striatum and found that DHA supplementation reduced the basal activation state of microglia. These preclinical data suggest that a diet enriched in PUFAs could be used as a treatment to alleviate anxiety induced opioid-seeking behavior and relapse in human opioid addiction.

The interactions between work and personal life are important for ensuring well-being especially during COVID-19 where the lines between work and home are blurred. Work-life interference/imbalance can result in work-related burnout, which has been shown to have negative effects on faculty members’ physical and psychological health. Although our understanding of burnout has advanced considerably in recent years, little is known about the effects of burnout on nursing faculty turnover intentions and career satisfaction. Thus, this study aimed to test a hypothesized model examining the effects of work-life inference on nursing faculty burnout (emotional exhaustion and cynicism), turnover intentions and ultimately, career satisfaction. A predictive cross-sectional design was used. An online national survey of nursing faculty members was administered throughout Canada in Summer 2021. Nursing faculty who held full-time or part-time positions in Canadian academic settings were invited via email to participate in the study. Data was collected from an anonymous survey housed on Qualtrics. Descriptive statistics and reliability estimates were computed. The hypothesized model was tested using structural equation modeling. Data suggest that work-life interference significantly increase burnout which contribute to both higher turnover intentions and lower career satisfaction. Turnover intentions in turn was negatively associated with career satisfaction. The findings add to the growing body of literature linking burnout to turnover and dissatisfaction, highlighting key antecedents and/or drivers of burnout among nurse academics. These results provide suggestions for suitable areas for the development of interventions and policies within the organizational structure to reduce the risk of burnout during and post-COVID-19 and improve faculty retention.

The variations in socioeconomic status (SES) between different social classes of a population correspond to differences in accessibility to all resources available and able to improve global health. While SES is now known as one of the main determinants for a good health and a good aging, its influence on sleep disorders (SD) is not well understood. SES is a concept, not directly observable but estimated using indicators like income, education, occupational status and area of living. This theoretical review explores some theories linking environment of people with occurrence of SD, with different patterns associated to SES. A model of interaction is proposed to summarize and conceptualizes these interactions and to promote more research on the topic.

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).

Rationale: Major depressive disorder (MDD) is characterized by signaling aberrations in interleukin (IL)-6, IL-10, beta-endorphins as well as mu (MOR) and kappa (KOR) opioid receptors. Here we examined whether these biomarkers may aid in the classification of unknown subjects into the target class MDD.Methods: The aforementioned biomarkers were assayed in 60 first-episode, drug-naïve depressed patients and 30 controls. We analyzed the data using joint principal component analysis (PCA) performed on all subjects to check whether subjects cluster by classes; support vector machine (SVM) with 10-fold validation; and linear discriminant analysis (LDA) and SIMCA performed on calibration and validation sets and we computed the figures of merit and learnt from the data. Results: PCA shows that both groups were well separated using the first three PCs, while correlation loadings show that all 5 biomarkers have discriminatory value. SVM and LDA yielded an accuracy of 100% in validation samples. Using SIMCA there was a highly significant discrimination of both groups (model-to-model distance=87.5); all biomarkers showed a significant discrimination and modeling power, while 10% of the patients were identified as outsiders and no aliens could be identified.Discussion: We have delineated that MDD is a distinct class with respect to neuro-immune and opioid biomarkers and that future unknown subjects can be authenticated as having MDD using this SIMCA fingerprint. Precision psychiatry should employ SIMCA a) to authenticate patients as belonging to the claimed target class and identify other subjects as outsiders, members of another class or aliens; and b) to acquire knowledge through learning from the data by constructing a biomarker fingerprint of the target class.

Background: Schizophrenia and treatment-resistant schizophrenia (TRS) are associated with aberrations in immune-inflammatory pathways. Increased High Mobility Group Protein 1 (HMGB1), an inflammatory mediator, and Dickkopf-Related Protein (DKK1), a Wnt/β-catenin signaling antagonist, affect the blood-brain-barrier and induce neurotoxic effects and neurocognitive deficits.Aim of the study: The present study aims to examine HMGB1 and DDK1 in non-responders to treatments with antipsychotics (NRTT, n=60), partial RTT (PRTT, n=55) and healthy controls (n=43) in relation to established markers of schizophrenia including IL-6, IL-10 and CLL11 (eotaxin); and to delineate whether these proteins are associated with the schizophrenia symptom subdomains and neurocognitive impairments.Results: HMGB1, DKK1, IL-6 and CCL11 were significantly higher in schizophrenia patients than in controls. DKK1 and IL-6 were significantly higher in NRTT than in PRTT and controls while IL-10 was higher in NRTT than in controls. Binary logistic regression analysis showed that schizophrenia was best predicted by increased DDK1 and HMGB1 while NRTT (versus PRTT) was best predicted by increased IL-6 and CCL11 levels. A large part of the variance in psychosis, hostility, excitation, mannerism and negative (PHEMN) symptoms, and formal thought disorders was explained by HMGB1, IL-6, and CCL11 while most neurocognitive functions were predicted by HMGB1, DDK1 and CCL11. Conclusion: The neurotoxic effects of HMGB1, DKK1, IL-6 and CCL11 including effects on the blood-brain-barrier and the Wnt/β-catenin signaling pathway may cause impairments in executive functions, and working, episodic and semantic memory and explain, in part, PHEMN symptoms and a non-response to treatment with antipsychotic drugs.

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.

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.

Background: Temporal lobe epilepsy (TLE) is the most common focal epilepsy subtype in adults and is frequently accompanied by depression, anxiety and psychosis. Aberrations in total paraoxonase (PON)1 status may occur in TLE and those psychiatric conditions. Methods: We examined paraoxonase (PON)1 status, namely Q192R PON1 genotypes and PON1 enzymatic activities, in 40 normal controls and 104 TLE patients, 27 without comorbidities, and 77 with comorbidities including mood disorders (n=25), anxiety disorders (n=27) and psychosis (n=25). Outcomes: CMPAase and arylesterase activities were significantly lower in TLE and mesial temporal sclerosis (MTS) with and without psychiatric comorbidities than in normal controls. The areas under the ROC curve of CMPAase were 0.893 (0.037) for TLE and 0.895 (±0.037) for MTS. Partial Least Squares (PLS) path analysis showed that there were specific indirect effects of PON1 genotype on TLE severity (p<0.0001) and psychopathology (p<0.0001), which were both mediated by lowered CMPAase activity, while arylesterase activity was not significant. The severity of TLE was significantly associated with psychopathology scores. Furthermore, PON1 CMPAase activity was inversely associated with Mini Mental State Examination scores. Interpretation: The severity of TLE and comorbidities are to a large extent explained by lowered PON1 enzyme activities and by effects of the Q192R genotype which are mediated by lowered CMPAase activity. Total PON1 status plays a key role in the pathophysiology of TLE, MTS and psychiatric comorbidities by increasing the risk of oxidative toxicity. PON1 enzyme activities are new drug targets in TLE to treat seizure frequency and psychiatric comorbidities.

There is now evidence that, based on cytokine profiles, bipolar disorder (BD) is accompanied by simultaneous activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS), and that both components may be associated with the staging of illness. Nevertheless, no BD studies have evaluated the IRS/CIRS ratio using CD (cluster of differentiation) molecules expressed by peripheral blood activated T effector (Teff) and T regulatory (Treg) subpopulations. This study examined T cell subsets both before and after ex vivo anti CD3/CD28 stimulation using flow cytometric immunophenotyping in 25 euthymic BD patients and 21 healthy controls as well as human cytomegalovirus (HCMV)-specific IgG antibodies. BD is associated with a significantly lowered frequency of baseline (unstimulated) CD3+CD8+CD71+ and CD4+CD25+FOXP3 and increased CD4+CD25+FOXP3+CD152+ frequencies and with lowered stimulated frequencies of CD3+CD8+CD71+, CD4+CD25+FOXP3+CD152+ and CD4+CD25+FOXP3+GARP cells and, consequently, by an increased stimulated Teff/Treg ratio. Moreover, the number of manic, but not hypomanic or depressive episodes, is significantly and negatively associated with the stimulated proportions of CD3+CD4+CD154+, and CD69+ and CD71+ expression on CD4+ and CD8+ cells, while duration of illness (≥ 10 years) is accompanied by a depleted frequency of stimulated CD152+ Treg, and CD154+ and CD71+ CD4+ T cells. BD and anti-human cytomegalovirus (HCMV) IgG levels significantly interact to decrease the expression of CD4+CD25+FOXP+GARP T phenotypes. In conclusion, BD is characterized by deficits in immune-regulatory functions while the staging of illness is characterized by additional impairments is Teff and Treg activation. HCMV seropositivity may contribute to an immune-risk phenotype associated with BD.

Objective: Major depression (MDD) and a lifetime history of MDD are characterized by increased nitrosylation, while bipolar disorder type 1 (BP1), but not BP2, is accompanied by highly increased levels of oxidative stress and nitric oxide (NO) production. Nevertheless, it is unknown whether nitrosylation is involved in BP and whether there are differences in nitrosylation between BP1 and BP2.Methods: Serum IgM antibodies directed against nitroso (NO)-adducts were examined in MDD, BP1, BP2 and healthy controls, namely IgM responses to NO-cysteine, NO-tryptophan (NOW), NO-arginine and NO-albumin (SBA) in association with IgA/IgM responses to Gram-negative bacteria, IgG responses to oxidized low-density lipoprotein (oxLDL) and serum peroxides.Results: Serum IgM levels against NO adducts were significantly higher in BP1 and MDD as compared with healthy controls, whereas BP2 patients occupied an intermediate position. IgM responses to NO-albumin were significantly higher in BP1 and MDD than in BP2 patients. There were highly significant associations between the IgM responses to NO-adducts and IgG responses to oxLDL and IgA/IgM responses to Gram-negative bacteria.Conclusions: BP1 and MDD are characterized by an upregulation of the nitrosylome (the proteome of nitrosylated proteins), and increased IgM responses to nitrosylated conjugates. Increased nitrosylation may be driven by increased bacterial translocation and is associated with lipid peroxidation processes. Innate like (B1 and marginal zone) B cells and increased nitrosylation may play a key role in the major affective disorders through activation of immune-inflammatory and oxidative pathways, cardiovascular comorbidity and impairments in antioxidant defenses, neuro-glial interactions, synaptic plasticity, neuroprotection, neurogenesis, etc.

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.

Attention Deficit Hyperactivity Disorder is a neurodevelopmental disorder characterised by core symptoms of impulsivity, locomotor hyperactivity, and inattention affecting around 5% of children and adolescents worldwide. Although this brain illness is wrongly considered a childhood disorder, increasing evidences suggest that it can persist into adulthood in about 65% of cases leading to significant clinical, socio-relational, and occupational disabilities. Pharmacological and non-pharmacological treatments currently available permit to achieve numerous benefits, in particular, if started early in childhood, however, quality of life of patients affected by ADHD could be compromised in any case in terms of self-esteem, ability to finalize projects, and personal satisfaction. In this study we evaluated the impact of micronutrient formulations on ADHD symptoms in both children and adults analyzing results of randomized, placebo-controlled trials.

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.

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.

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.

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.

In Schizophrenia, pathway-genotypes may be constructed by combining interrelated immune biomarkers with changes in specific neurocognitive functions that represent aberrations in brain neuronal circuits. These constructs provide insight on the phenome of schizophrenia and show how pathway-phenotypes mediate the effects of genome X environmentome interactions on the symptomatology/phenomenology of schizophrenia. Nevertheless, there is a lack of knowledge how to construct pathway-phenotypes using Partial Least Squares (PLS) path modeling and Soft Independent Modeling of Class Analogy (SIMCA). This paper aims to provide a step-by-step utilization guide for the construction of pathway-phenotypes that reflect aberrations in the neuroimmune - brain circuit axis (NIBCA) in deficit schizophrenia. This NIBCA index is constructed using immune biomarkers (CCL-2, CCL-11, IL-1β, sIL-1RA, TNF-α, sTNFR1, sTNFR2) and neurocognitive tests (Brief Assessment of Cognition in Schizophrenia) predicting overall severity of schizophrenia (OSOS) in 120 deficit SCZ and 54 healthy participants. Using SmartPLS path analysis, a latent vector is extracted from those biomarkers and cognitive tests, which shows a good construct reliability (Cronbach alpha and composite reliability) and replicability and which is reflectively measured through its NIBCA manifestations. This NIBCA pathway-phenotype explains 75.0% of the variance in PHEMN (psychotic, hostility, excitation, mannerism and negative) symptoms. Using SIMCA, we constructed a NIBCA pathway-class that defines deficit schizophrenia as a qualitatively distinct nosological entity and which allows patients with deficit schizophrenia to be authenticated as belonging to the deficit schizophrenia class. In conclusion, our nomothetic approach to develop a nomological network combining neuro-immune and neurocognitive phenome markers to predict OSOS and cross-validate a diagnostic class generated replicable models reflecting the key phenome of the illness, which may mediate the effects of genome X environmentome interactions on the final outcome phenome features, namely symptomatology and phenomenology.

In schizophrenia, a single latent trait underlies psychosis, hostility, excitation, mannerism, negative (PHEMN) symptoms, formal thought disorders (FTD) and psychomotor retardation (PMR). Schizophrenia is accompanied by a breakdown of gut and blood-brain-barrier (BBB) pathways, increased tryptophan catabolite (TRYCAT) levels, bacterial translocation, and lowered natural IgM and paraoxonase (PON)1 activity. The aim of this study was to examine the factor structure of schizophrenia symptom domains and the biomarker correlates of these factors. We recruited 80 patients with schizophrenia and 40 healthy subjects and assessed the IgA/IgM responses to paracellular/transcellular (PARA/TRANS) ratios, IgA responses to TRYCATs, natural IgM to malondialdehyde and Gram-negative bacteria, and PON1 enzymatic activity.Direct Hierarchical Exploratory Factor Analysis showed a bifactorial oblique model with a) a general factor which loaded highly on all symptom domains, named overall severity of schizophrenia (“OSOS”); and b) a single-group factor (SGF) loading on negative symptoms and PMR. We found that 40% of the variance in the OSOS score was explained by IgA/IgM to PARA/TRANS ratio, male sex and education while 36.9% of the variance in SGF score was explained by IgA to PARA/TRANS, IgM to Gram-negative bacteria, female sex (positively associated) and IgM to MDA, and PON1 activity (negatively associated). Schizophrenia phenomenology comprises two biologically-validated dimensions, namely a general OSOS dimension and a single-group negative symptom dimension, which are associated with a breakdown of gut/BBB barriers, increased bacterial translocation and lowered protection against oxidation, inflammation and bacterial infections through lowered PON1 and natural IgM.

Adolescence is a critical developmental period associated with an increase in stress, the appearance of anxiety and depressive symptoms, and changes in sleep patterns. Even though the disruption of sleep patterns in stress and anxiety and depressive disorders is well known, the independent effects of childhood trauma and stressful life events on sleep patterns are less understood. We tested the independent effects of stress (childhood trauma and stressful life events) while controlling for anxiety and depression on adolescent sleep patterns. Seven hundred fifty-two adolescents completed self-report questionnaires about childhood trauma, stressful life events, anxiety, and depression. Four sleep factors identifying movement during sleep, sleep regularity, sleep disturbances and sleep pressure were extracted in the principal component analysis of sleep questions. Both childhood trauma and recent stressful life events were significantly associated with sleep disturbances before and after controlling for anxiety and depression.

No studies have examined the immune fingerprint of major neuro-cognitive psychosis (MNP) or deficit schizophrenia using M1 macrophage cytokines in combination with chemokines such as CCL-2 and CCL-11. The present study delineated the neuro-immune fingerprint of MNP/deficit schizophrenia by analyzing plasma levels of IL-1β, sIL-1RA, TNF-α, sTNFR1, sTNFR2, CCL-2 and CCL-11 in MNP (n=120) versus healthy controls (n=54) in association with neurocognitive deficits (as assessed with the Brief Assessment of Cognition in Schizophrenia) and PHEMN (psychotic, hostility, excitation, mannerism and negative) symptoms. All immune biomarkers were significantly higher in MNP than in normal controls. MNP was best predicted by a combination of CCL-11, TNF-α, IL-1β and sIL-1RA which yielded a bootstrapped (n=2000) area under the Receiver Operating Curve of 0.985. Composite scores reflecting M1 macrophage activity and neurotoxic potential including combined effects of CCL-11 plus CCL-2 were significantly increased in MNP. Nevertheless, the effects of increased IL-1β and TNF-α in MNP were attenuated (statistically) by increased sIL-1RA and sTNFR2, two negative immune-regulatory markers. A large part of the variance in PHEM (38.4%-52.6%) and negative (65.8-7439%) symptoms was explained by combinations of immune markers whereby CCL-11 was consistently the most important. The immune markers also explained a large part of the variance in the Mini Mental State examination, list learning, digit sequencing task, category instances, controlled word association, symbol coding and Tower of London. Soft Independent Modeling of Class Analogy performed on the biomarkers showed that the inter-class distance between the models constructed around MNP and controls was 19.3 indicating a good separation. Partial Least Squares analysis showed that 72.7% of the variance in overall phenomenology was explained by the regression on IL-1β, sIL-1RA, CCL-11, TNF-α (all positively) and education (inversely). It is concluded that the combination of the above-mentioned markers defines MNP as a distinct neuro-immune disorder and that those markers in combination explain a large part of the variance in memory and executivive impairments and PHEMN symptoms.

The present study explored the effects of a Second-generation mindfulness-based intervention known as Flow Meditation (Meditación-Fluir) in the improvement of life habits. A sample of university students (n = 51) in Spain were randomly assigned to a seven-week mindfulness treatment or a waiting list control group. Results showed that compared to the control group, individuals in the mindfulness group demonstrated significant improvements across all outcome measures, including healthy eating habits (balanced diet, intake rate, snacking between meals, decrease in consumption by emotional states negative, increased consumption by negative emotional states, amount of consumption, meal times, consumption of low-fat products), tobacco, alcohol and cannabis consumption, and resting habits. There were differences between males and females in some of these variables and a better effect of the treatment was evident in the females of the experimental group as compared to males. The Flow Meditation program shows promise for fostering healthy life habits, thus decreasing behaviors related to maladaptive eating, tobacco, alcohol and drug consumption, as well as negative resting habits, in university students. This mindfulness program can significantly contribute in the treatment of eating disorders and addictions, wherein negative emotional states and impulsivity are central features of the condition.

ackground: This study aimed to examine the effects of a woodworking program on psychosocial health in older adults who had mild cognitive impairment (MCI) or mild dementia (MD) in Korea. Setting: The study was carried out in a dementia center in Seoul in Korea. Population: A total of 61 participants who had MCI or MD were allocated into two groups: the experimental group (EG, n = 35) and the control group (CG, n = 26). Methods: This study was carried out using a nonequivalent control group pre-test–post-test design. The EG participated in the woodworking program a total of 10 times for 120 min per session twice a week for 5 weeks, and the CG did not participate in the woodworking program. Both groups completed the same survey before and after the intervention. In the survey, demographic characteristics, psychological health (life satisfaction, depression, self-efficacy, and resilience), and social health (social isolation and social support) were measured. Results: In the within-group comparison, there was no significant difference between any factors of the CG before and after the intervention. In contrast, the EG had a significant improvement before and after the woodworking program. Participants in the EG with MCI and MD significantly improved their social support (p < 0.05). Psychological factors (life satisfaction, depression, and self-efficacy) were positively changed, although not significantly. Conclusions: The woodworking program promoted psychosocial health, such as life satisfaction, resilience, and social support, among older adults with mild cognitive impairment and mild dementia.

Background: There is now evidence that schizophrenia and deficit schizophrenia are neuro-immune conditions and that oxidative stress toxicity (OSTOX) may play a pathophysiological role. Aims of the study: To compare OSTOX biomarkers and antioxidant (ANTIOX) defenses in deficit versus non-deficit schizophrenia. Methods: We examined lipid hydroperoxides (LOOH), malondialdehyde (MDA), advanced oxidation protein products (AOPP), sulfhydryl (-SH) groups, paraoxonase 1 (PON1) activity and PON1 Q192R genotypes, total radical-trapping antioxidant parameter (TRAP) as well as immune biomarkers in patients with deficit (n=40) and non-deficit (n=40) schizophrenia and healthy controls (n=40). Results: Deficit schizophrenia is characterized by significantly increased levels of AOPP and lowered -SH, and PON1 activity, while no changes in the OSTOX/ANTIOX biomarkers were found in non-deficit schizophrenia. An increased OSTOX/ANTIOX ratio was significantly associated with deficit versus non-deficit schizophrenia (Odds ratio=3.15, p<0.001). Partial least squares analysis showed that 47.6% of the variance in a latent vector extracted from psychosis, excitation, hostility, mannerism, negative symptoms, psychomotor retardation, formal thought disorders, and neurocognitive test scores was explained by LOOH+AOPP, PON1 genotype + activity, CCL11, tumor necrosis factor (TNF)-α, IgA responses to neurotoxic tryptophan catabolites (TRYCATs), whereas -SH groups and IgM responses to MDA showed indirect effects mediated by OSTOX and neuro-immune biomarkers. Discussion: Our findings indicate that with increasing overall severity of schizophrenia, neuro-immune and neuro-oxidative (especially protein oxidation indicating chlorinative stress) toxicities become more prominent and together with lowered antioxidant defenses and impairments in innate immunity-associated resilience against neurotoxic processes shape a distinct nosological entity, namely deficit schizophrenia.

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.

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.

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.

Objective: A previous study showed that schizophrenia is accompanied by lowered levels of trace/metal elements including cesium. There are no data whether changes in cesium, rubidium and rhenium are associated with activated immune-inflammatory pathways, cognitive impairments, and the symptomatology of schizophrenia. Methods: This study measured cesium, rubidium, and rhenium, cognitive impairments (using the Brief Assessment of Cognition in Schizophrenia) and the cytokines/chemokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and CCL11 (eotaxin) in 120 schizophrenia patients and 54 healthy controls. Severity of illness was assessed using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the Fibromyalgia and Chronic Fatigue Syndrome Rating (FF) Scale and the Hamilton Depression Rating Scale (HAM-D). Results: Serum cesium was significantly lower in schizophrenia patients as compared with controls. Serum cesium was significantly and inversely associated with CCL11 and TNF-α, but not IL-1β. Moreover, there were significant inverse associations between serum cesium levels and the BPRS, FF, HAM-D and SANS scores and positive correlations between cesium and neurocognitive probe results including the Tower of London, Symbol Coding, Controlled Word Association, Category Instances, Digit Sequencing Task, and List Learning tests. Conclusion: The results suggest that lowered serum cesium levels may play a role in the pathophysiology of SCZ, specific symptom domains including negative, depressive and fatigue symptoms, neurocognitive impairments (spatial working, episodic and semantic memory and executive functions) and neuro-immune pathways as well.

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.

Mental stress state recognition using electroencephalogram (EEG) signals for real-life applications needs a conventional wearable device. This requires an efficient number of EEG channels and an optimal feature set. The main objective of the study is to identify an optimal feature subset that can best discriminate mental stress states while enhancing the overall performance. Thus, multi-domain feature extraction methods were employed, namely, time domain, frequency domain, time-frequency domain, and network connectivity features, to form a large feature vector space. To avoid the computational complexity of high dimensional space, a hybrid feature selection (FS) method of minimum Redundancy Maximum Relevance with Particle Swarm Optimization and Support Vector Machine (mRMR-PSO-SVM) is proposed to remove noise, redundant, and irrelevant features and keep the optimal feature subset. The performance of the proposed method is evaluated and verified using four datasets, namely EDMSS, DEAP, SEED, and EDPMSC. To further consolidate, the effectiveness of the proposed method is compared with that of the state-of-the-art heuristic methods. The proposed model has significantly reduced the features vector space by an average of 70% in comparison to the state-of-the-art methods while significantly increasing overall detection performance.

Parkinson's Disease (PD) is a neurodegenerative disorder that affects the motor system of the human body. Currently, the available treatments are limited and often have undesirable side effects. In this context, the aim of this study was to develop a novel combinational formulation of Apomorphine and Quetiapine and evaluate its efficacy in a rat model of PD. The formulation was prepared using the solvent evaporation technique and characterized for its physicochemical properties. The in-vitro drug release was evaluated using the Franz diffusion cell method, and the pharmacokinetics of the combination was studied in rats. The behavioural and biochemical parameters were evaluated in the rats using the Rotarod, pole test, and biochemical assays. The results showed that the developed formulation had satisfactory physicochemical properties and exhibited sustained drug release. The pharmacokinetic studies showed that the combination exhibited a longer residence time than the individual drugs. The behavioural and biochemical parameters showed that the combination was effective in improving motor function and reducing oxidative stress. In conclusion, the developed Apomorphine and Quetiapine combination formulation showed promising results in improving motor function and reducing oxidative stress in rat model of PD. Further studies are required to evaluate the safety and efficacy of the developed formulation in humans.

Background and objectives: The inadequate knowledge of complementary and alternative medicine (CAM) among health professionals may put their clients in risky situation because they then would find information about CAM from unreliable sources. Clinical psychologists (CPs), as health professionals, have also the opportunity to provide psychoeducation on the latest CAM scientific research to their clients. The current study aimed to explore knowledge and educational needs of CAM among CPs in Indonesia because previous studies on exploring CAM knowledge and educational needs of CAM were primarily conducted in Western countries. Materials and Methods: Data were collected through semi-structured face-to-face interviews with 43 CPs in public health centers (PHCs) in Indonesia. Most interviews were held at the PHCs where participants worked and interviews lasted for 55 minutes, on average. The interview recordings were transcribed and were analyzed using deductive thematic analysis. Results: Five main themes emerged within participants’ responses regarding CAM knowledge and educational needs. First (CAM understanding), participants’ responses ranged from those with little or no prior knowledge of CAM treatments and uses, to those with much greater familiarity. Second (source of knowledge), participants’ access ranged widely in terms of references, from popular to scientific literature. Third (why is it important?), participants identified CAM essentially as part of Indonesian culture and it was therefore crucial to have this cultural knowledge. Fourth (the challenges and what is needed?), the challenges for improving participants’ knowledge came from personal and institutional levels. Fifth (what and how to learn?), participants advised that only CAM treatments that fit in brief psychotherapy sessions should be introduced in professional training. Conclusions: This qualitative study discovered that CAM was neither well-known nor understood widely. Participants advised that professional associations and health institutions should work together in enhancing knowledge of CAM and incorporating CAM education into psychology education.

Accumulating evidence suggests that TNF-α-mediated immune-neurotoxicity contributes to cognitive impairments and the overall severity of schizophrenia (OSOS). There are no data whether peripheral IL-6 and IL-4 may affect the phenome of schizophrenia above and beyond the effects of TNF-α and whether those cytokines are regulated by lowered natural IgM to malondialdehyde (MDA) and paraoxonase 1 enzyme activity. We assessed the aforementioned biomarkers in schizophrenia patients with (n=40) and without (n=40) deficit schizophrenia and 40 healthy controls. Deficit schizophrenia was best predicted by a combination of increased IL-6 and PON1 status (QQ genotype and lowered CMPAase activity) and lowered IgM to MDA. Partial Least Squares bootstrapping shows that 41.0% of the variance in negative symptoms, psychosis, hostility, excitation, mannerism, psychomotor retardation, and formal thought disorders was explained by increased TNF-α and PON1 status (QQ genotype and lowered CMPAase activity), lowered IL-4 and IgM to MDA as well as male sex and lowered education. We found that 47.9% of the variance in verbal fluency, word list memory, true recall, Mini-Mental State Examination, and executive functions was predicted by increased TNF-α and lowered IL-4, IgM to MDA and education. In addition, both TNF-α and IL-4 levels were significantly associated with lowered IgM to MDA, while TNF-α was correlated with PON1 status. These data provide evidence that the symptomatic (both the deficit subtype and OSOS) and cognitive impairments in schizophrenia are to a large extent mediated by the effects of immune-mediated neurotoxicity as well as lowered regulation by the innate immune system.

Objective: About a third of schizophrenia patients are treatment-resistant to antipsychotic therapy. No studies established the fingerprints or pathway-phenotypes of treatment-resistant schizophrenia. The present study aimed to delineate the pathway-phenotypes of non-responders (NRTT) and partial responders (PRTT) to treatment using machine learning. Methods: We recruited 115 schizophrenia patients and 43 healthy controls and measured schizophrenia symptom dimensions, neurocognitive tests, plasma CCL11, interleukin-(IL)-6, IL-10, Dickkopf protein 1 (DKK1), high mobility group box-1 protein (HMGB1), κ- and µ-opioid receptors (KOR and MOR, respectively), endomorphin-2 (EM-2), and β-endorphin. Results: Machine learning showed that the NRTT group is a qualitatively distinct class and is significantly discriminated from PRTT with an accuracy of 100% using a neuro-immune-opioid-cognitive (NIOC) pathway-phenotype with as main determinants list learning, controlled word association, and Tower of London test scores, CCL11, IL-6, and EM2. The top-5 symptom domains separating NRTT from PRTT were in descending order: psychomotor retardation, negative symptoms, psychosis, depression, and mannerism. Moreover, a NIOC pathway also discriminated PRTT from healthy controls with an accuracy of 100% while all PRTT and controls were authenticated as belonging to their respective classes. Conclusion: A non-response to treatment with antipsychotics is determined by increased severity of specific symptom profiles coupled with deficits in executive functions, and episodic and semantic memory, and aberrations in neuro-immune and opioid pathways. No patients showed complete remission after treatment indicating that non-remitting in PRTT is attributable to increased HMGB1 and residual deficits in attention, executive functions, and semantic memory.

Regular exercise can reduce depression. However, the uptake of exercise is limited in patients with end-stage renal disease undergoing hemodialysis. To address the gap, we designed a gamified non-weight-bearing exercise program (Exergame), which can be executed during hemodialysis treatment. The Exergame is virtually supervised based on its interactive feedback via wearable sensors attached on lower extremities. We examined the effectiveness of this program to reduce depression symptom compared to supervised exercise in 73 hemodialysis patients (age=64.5±8.7years, BMI=31.6±7.6kg/m2). Participants were randomized into an Exergame group (EG) or a Supervised-exercise group (SG). Both groups received similar exercise tasks for 4-week, 3-session per week, 30-min per session, during hemodialysis treatment. Depression symptom was assessed at baseline and 4-week using Center for Epidemiologic Studies Depression (CES-D). Both groups showed significant reduction in depression score (37%, p<0.001, Cohen’s effect size d=0.69 in EG vs. 41%, p<0.001, d=0.65 in SG) with no between-group difference for the observed effect (p>0.050). The EG expressed a positive exercise experience including fun, safety, and helpfulness of sensor-feedback. Together, results suggested that the virtually-supervised low-intensity Exergame is feasible during routine hemodialysis treatment. It is as effective as supervised-exercise to reduce depression symptom, while reducing burden of administrating exercise in dialysis clinics.

A 47-year-old physician suddenly noticed a persistent difficulty maintaining attention. He was awake, alert, and oriented. After two hours he developed fever, ageusia, and anosmia. He denied any previous history of psychiatric illness and was hydrated at the time of the subjective attention impairment. On admission, the patient remained oriented. He reported the persistence of attention problems, anosmia, and mild fatigue. The oxygen saturation 99% while he was breathing ambient air. Laboratory tests were unremarkable. A high-resolution computed tomography of the chest was normal. Nasopharyngeal and throat swabs specimens on reverse transcription-polymerase chain reaction analysis tested positive for SARS-CoV2. On illness day 3, the examination was unchanged, but he continued to complain of difficulties to stay focused. Then, he performed an objective attention test. The test demonstrated a moderate attentional impairment. On day 6, the patient reported a subjective worse in his concentration and performed a second test. Although his physical examination remained normal, the attention performance was worse as compared to day 3. Eight hours after worsening of attention impairment, the patient’s oxygen saturation dropped to 94%. From illness days 9 to 14, the patient evolved with clinical improvement. On day 10, a third objective attention test indicated a mild deficit. On day 16, he did not report any other symptom and the attention test was completely normal. Then, the patient returned to work. Neurological symptoms had been previously described in COVID- 19 patients. However, no previous research had investigated early cognitive deficits preceding the traditional symptoms.

OBJETIVE: This study analyses the views of four groups of healthcare professionals who may play a role in the management of suicidal behaviour. The goal was to identify key factors for suicide prevention in different areas of the healthcare system. METHODOLOGY: Qualitative research was conducted using focus groups made up of different healthcare professionals who participated in the identification, management and prevention of suicidal behaviour. Professionals included were primary care physicians, psychologists, psychiatrists and emergency physicians. RESULTS: ‘Suicide’ was amongst the most relevant terms that came up in discussions most of the times it appeared associated with words such as ‘risk’, ‘danger’ or ‘harm’. In the analysis by categories, the four groups of professionals agreed that interventions in at-risk behaviours are first in importance. Prevention was the second main concern with greater significance among psychiatrists. DISCUSSION: Primary care professionals claim for more time to address patients at risk for suicide and an easier access to and communication with the mental health network. Emergency care professionals have a lack of awareness of their role in the detection of risk for suicide in patients who seek attention at emergency care facilities for reasons of general somatic issues. Mental health care professionals are in high demand in case of self-harm but they would like to receive specific training in dealing with g suicidal behaviour.

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.

Psychiatric disorders are mental, behavioral or emotional disorders. These conditions are prevalent, one in four adults suffer from any type of psychiatric disorders world-wide. It has always been observed that psychiatric disorders have a genetic component, however new methods to sequence full genomes of large cohorts have identified with high precision genetic risk loci for these conditions. Psychiatric disorders include, but are not limited to, bipolar disorder, schizophrenia, autism spectrum disorder, anxiety disorders, major depressive disorder, and attention-deficit and hyperactivity disorder. Several risk loci for psychiatric disorders fall within genes that encode for voltage-gated calcium channels (Ca_Vs). Calcium entering through Ca_Vs is key for multiple neuronal processes. In this review, we will summarize recent findings that link Ca_Vs and their auxiliary subunits to psychiatric disorders. First, we will provide a general overview of Ca_Vs structure, classification, function, expression and pharmacology. Next, we will summarize tools and databases to study risk loci associated with psychiatric disorders. We will examine functional studies of risk variations in Ca_V genes when available. We will review pharmacological evidence of the use of Ca_V modulators to treat psychiatric disorders. Our review will be of interest for those studying pathophysiological aspects of Ca_Vs.

According to the recent data, nitric oxide (NO) is a chemical messenger that mediates functions such as vasodilation and neurotransmission, it also possesses antimicrobial and antitumoral activities. Nitric oxide has been implicated in neurotoxicity associated with stroke and neurodegenerative diseases, neural regulation of smooth muscle, including peristalsis, and penile erection. We searched for full-text English publications in Pubmed and SNPedia databases using keywords and combined word searches (nitric oxide, single nucleotide variants, single nucleotide polymorphisms, genes) over the past 15 years. In addition, earlier publications of historical interest were included in the review. In our review, we have sum up all NOS1, NOS2, NOS3, and NOS1AP single nucleotide variants (SNVs) involved in the development of mental disorders and neurological diseases/conditions. The results of studies we have discussed in this review are contradictory, that might be due to different designs of the studies, small sample sizes in some of them, as well as different social and geographical characteristics. However, the contribution of genetic and environmental factors has been understudied, that makes this issue increasing for researchers as the understanding of these mechanisms can support a search for new approaches to pathogenetic and disease-modifying treatment.

Background: In this secondary analysis of the Supporting the Modification of Lifestyle In Lowered Emotional States (SMILES) randomised controlled trial, we investigated if the beneficial effects of a dietary intervention on clinical depression were driven, in part, by reducing the consumption of foods classified as ultra-processed.Methods: The SMILES trial enrolled 67 adults with major depressive disorder, randomly assigning them to either a 12-week modified Mediterranean dietary intervention or a social support control. Our analysis included 44 participants with non-missing dietary data and at least one valid Montgomery–Åsberg Depression Rating Scale (MADRS) assessment at 12 weeks of follow-up. The Nova food classification system was used to estimate the proportion of ultra-processed foods in the overall diet (percentage of grams) based on data from seven-day food diaries. We fitted linear regression models under blinded conditions to determine whether ultra-processed food intake-change from baseline to 12 weeks moderated the dietary intervention effects on depressive symptoms. We estimated mean differences in depressive symptoms along with ninety-five per cent confidence intervals (95%CIs).Results: For participants in the dietary intervention, there was an additional 2.5-point improvement in MADRS scores for each 10% reduction in the dietary share of ultra-processed foods compared to participants in the control group (between-group mean differences in depressive symptoms: −2.46, 95%CIs −4.71 to −0.20, p=0.039, η _p ² of 0.10).Conclusions: These preliminary findings suggest that the therapeutic benefit of a dietary intervention for depression may stem, at least in part, from reductions in the dietary share of ultra-processed foods.

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.

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.

The etiology of autism spectrum disorder (ASD) has not yet been completely elucidated. Through time, multiple attempts have been made to uncover the causes of ASD. Different theories have been proposed, such as that it is caused by “Gods Wrath,” alternations in the gut–brain axis with an emphasis on gut dysbiosis, post vaccine complications, and genetic or even autoimmune causes. In this review we present data covering over 170 000 participants at age ranging from 2 to 14 years focusing on human cell changes rather than using animal models found in previous studies. The male/female ratio was 4:1. Data collection occurred in many countries covering ethnically diversified subjects. Moreover, we aim to show how the progress in genetic techniques influence the explanation found in medical White Papers based on the human genetic samples we have observed from our studies

Abstract: Objective: Internet gaming disorder (IGD) is an emerging psychiatric disorder that has received attention over the past decade. Few studies have attempted to describe this disorder in the Saudi population. This study aimed to examine the prevalence of IGD and associated factors. A cross-sectional study was conducted using translated Arabic and a validated questionnaire targeting both genders in Saudi Arabia. Methodology: A cross-sectional study using a validated questionnaire (IGD-20) and targeting Arabic-speaking children, youth, and transitional age including both genders. A snowball approach was used to sample our population using an electronic survey. Logistic regression was used to examine factors associated with IGD diagnosis. The study was guided by the STROBE statement. Results: Among 419 individuals who participated in the study, 171 were classified as non-IGD, 167 were at risk for IGD (RIGD), and 72 were IGD. There is no significant association between IGD diagnosis and gender, nationality, residence, and family income. Time playing per week was significantly associated with IGD diagnosis (X2=49.256, p<0.01). There is a significant association between IGD-20 groups and categorical age groups (X2=10.096, p<0.01). Among our sample, the percentages of males (54.2%) and females (45.8%) who met the criteria for IGD were comparable. Conclusion: IGD and RIGD prevalence was significantly high in both age groups. Both males and females were affected similarly.

Study nature of epidemiological risk factors and patterns of distribution of mortality from Alzheimer's (D_A) in 160 countries. An exponential Malthus model was used to construct adequate approximations of statistical data. Proportionality of average lifetime after 55 years (Δt) to education index (Ψ) was established. Ranking of countries by increasing value of ΨΔt showed that D_A depends exponentially on ΨΔt and all countries can be divided into three groups in accordance with level of their economic development. In series of countries of low, medium and highly developed, their average values of D_A increase exponentially. Growth of D_A in developed countries in post-industrial epoch was explained by emergence of a new risk factor Alzheimer's of a mental nature. A mismatch of complexity or, on contrary, primitiveness of profession with level of mental development of worker, provokes development of chronic stress in him, fraught with pathologies of cognitive function metabolism in elderly. The geography of Alzheimer's disease was explained by the dependence of the human mentality on latitudinal climate change and on the chiral factor of a solar nature acting at night on a sleeping person.

: BACKGROUND: The prevalence of smoking among students is a growing concern, particular-ly among medical students. Being associated with stress, competitiveness, and various social in-fluences, smoking can have detrimental effects on self-esteem and self-efficacy and may create a vicious cycle that may contribute to students’ well-being and academic performance out-comes.METHODS: A cross-sectional study on 456 medical students was conducted via an online survey using structured questionnaires on socio-demographic characteristics, smoking habits, nicotine dependence, self-esteem, and self-efficacy. RESULTS: The prevalence of smoking was 31.1% The scores of self-esteem and self-efficacy were positively correlated with smoking habits (W1=0.957, W2=0.975, P<0.05). Students presented rather low smoking addiction with male stu-dents having slightly higher scores than female students on self-esteem and self-efficacy, mili-tary students had higher self-esteem scores than civilians with physical activity having a posi-tive correlation with non-smoking behavior. CONCLUSION: According to our results, self-esteem and self-efficacy were slightly positively correlated with smoking habits. Furthermore, there was no statistically significant association between other social factors and smoking. Our results may develop a theoretical basis for medical students’ psychological variables studying for further implementation of university educational programs and preventive interventions em-powering students towards an overall better quality of life, addressing, among others, smoking behaviors.

Postpartum depression (PPD) can predispose to physical and mental health problems in women. However, PPD is associated with health and perceived social support but their causal relationship is unclear. Therefore, this study intended to evaluate the association of PPD with insomnia, mental health, and physical health. Convenience sampling technique was used to collect data from 320 (52.8 %) young and middle aged postpartum women, in the outpatient departments of obstetrics and gynecology in Government Maula Bakhsh Hospital, District Head Quarter in Sargodha, Pakistan. The Edinburgh Postnatal depression scale, Pittsburg sleep quality index, Warwick-Edinburgh mental wellbeing scale, Patient health questionnaire, and Multidimensional scale of perceived social support were used to measure study variables. Results revealed a significant positive relationship of PPD with physical health (r= .45, p=.001), while a negative relationship with insomnia (r= -.24, p<.001), and perceived social support (r= -.38, p=.001). Results further confirmed that perceived social support played a moderating role (β = .97, p=.01) in the relationship between PPD and mental health among females. This study concluded that perceived social support has an important role in PPD and women’s health. The study also concluded that poor health is a risk indicator for identifying aid in the early stages of postpartum among women.

ADHD, a neurodevelopmental condition, is distinguished by a triad of symptoms including inattention, hyperactivity, and impulsivity. It is frequently accompanied by comorbidities such as anxiety, depression, and learning disabilities. As a result, clinicians often face challenges in accurately diagnosing ADHD and differentiating it from other conditions. As a prospective remedy for ADHD, scientists have investigated Transcranial Direct Current Stimulation (tDCS), a non-invasive technique of stimulating the brain. It involves applying low-intensity electrical currents to specific regions of the brain to modulate neural activity. This review paper aims to provide an overview of the comorbidities associated with ADHD and the differential diagnosis of the condition. It also explores the potential of tDCS as a treatment option for ADHD, including its mechanisms of action and efficacy in improving ADHD symptoms. The comorbidities discussed in this review include anxiety disorders, mood disorders, and substance use disorders. These comorbidities are frequently seen in individuals with ADHD and can complicate the diagnosis and treatment of the condition. The paper also highlights the importance of considering comorbidities when assessing ADHD, as well as the potential impact of these conditions on treatment outcomes. The differential diagnosis section of the paper explores conditions that can present with symptoms similar to ADHD, such as anxiety disorders, mood disorders, and learning disabilities. It emphasizes the need for a thorough assessment and differential diagnosis to identify ADHD and differentiate it from other conditions accurately. The final section of the paper discusses the potential of tDCS as a treatment option for ADHD. It examines the mechanisms of action of tDCS and its efficacy in improving ADHD symptoms, including attention, hyperactivity, and impulsivity. It also explores the potential for tDCS to improve comorbid conditions associated with ADHD. Overall, this review provides a comprehensive overview of comorbidities and differential diagnoses in ADHD and the potential of tDCS as a treatment option. The paper highlights the importance of a thorough assessment and personalized treatment plan for individuals with ADHD, particularly those with comorbidities.

Through the use of a simplified model of consciousness this paper illustrates the symptoms of schizophrenia linked to neocortical structures and functions. It makes the case that the bewildering and varied presentation of symptoms in schizophrenia can be analyzed and explained using such models. The model is used to illustrate the central thesis of the paper, that schizophrenia is a disorder of neurogenesis which leads to progressive neurochemical, functional and neurophysiological changes that create the characteristic behaviors of the disease.

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.

Anxiety disorders are among the most common mental disorders worldwide, and often respond incompletely to existing treatments. Selenium, a micronutrient that is a component of several biologically active selenoproteins, is also involved in several aspects of brain functioning, and may exert antidepressant and anxiolytic effects through multiple pathways. The current paper is a scoping review of translational, observational and interventional evidence on the potential role of selenium and its compounds in the management of anxiety and related disorders. Evidence from animal models suggests that this approach may be promising. Though evidence from observational studies in humans is inconsistent and affected by several confounding factors, the available evidence from randomized controlled trials suggests that selenium supplementation may be beneficial in the management of certain anxiety-related conditions, such as anxiety in medically ill patients, prevention of anxiety following exposure to traumatic stress, and obsessive-compulsive disorder. This paper provides a critical evaluation of the existing evidence base, including unanswered questions that could serve as the focus of further research, and outlines the potential benefits and risks associated with the use of selenium in anxiety disorders.

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.

Contemporary research has found that people with autism spectrum disorder (ASD) exhibit aberrant immunological function, with a shift toward increased cytokine production and unusual cell function. Microglia and astroglia were found to be significantly activated in immuno-cytochemical studies, and cytokine analysis revealed that the macrophage chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and transforming growth factor β-1 (TGFB-1), all generated in the neuroglia, constituted the most predominant cytokines in the brain. Taurine (2-aminoethanesulfonic acid) is a promising therapeutic molecule able to increase the activity of antioxidant enzymes and ATPase, which may be protective against aluminum-induced neurotoxicity. It can also stimulate neurogenesis, synaptogenesis, and reprogramming of proinflammatory M1 macrophage polarization by decreasing mitophagy (mitochondrial autophagy) and raising the expression of the markers of the anti-inflammatory and pro-healing M2 macrophages, such as macrophage mannose receptor (MMR, CD206) and IL-10, while lowering the expression of the M1 inflammatory factor genes. Taurine also induces autophagy, which is a mechanism that is impaired in microglia cells and is critically associated with the pathophysiology of the ASD. We hypothesize here that taurine could reprogram the metabolism of M1 macrophages that are overstimulated in the nervous system of people suffering from ASD, thereby decreasing the neuroinflammatory process, neuronal death, and improving cognitive functions. Therefore, we think that taurine can serve as an important lead for the development of novel drugs for the ASD treatment.

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.

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.

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.

Disgust evolved as a way to protect one’s self from illness. DS-R measures disgust propensity of three kinds of disgust (Core, Animal Reminder and Contamination). Although the DS-R scale was refined mainly with young and largely female student population its impact on educational orientation has not been assessed. In the present study we examined the DS-R scoring and the choice of postgraduate studies in medical (n= 94) and psychology (n= 97) students. They responded to an anonymous web-based survey and completed the DS-R and a questionnaire on their demographics and plans for postgraduate studies. Female students outnumbered males (3:1) and scored higher in Total DS-R score (median: 59 vs. 50, p<0.05). Psychology students scored higher in all three kinds of disgust (p<0.05), indicating a higher level of disease avoidance. Medical students willing to follow Internal Medicine scored higher in Core Disgust (p<0.05) while psychology students willing to study Experimental Psychology scored lower in Animal Reminder subscale (p<0.001). Also, the higher the psychology students scored in Core Disgust scale the higher was the probability to choose Experimental Psychology. In conclusion, disgust propensity as rated by DS-R differentiates medical from psychology students and is also related to orientation preferences in postgraduate studies.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Given the growing evidence of gut microbiota being involved in psychiatric (including neurodevelopmental) disorders, we aimed to identify differences in gut microbiota composition between participants with ADHD and controls and to investigate the role of the microbiota in inattention and hyperactivity/impulsivity. Fecal samples were collected from 107 participants (NADHD=42; Ncontrols=50; NsubthreholdADHD=15; range age: 13-29 years). The relative quantification of bacterial taxa was done using 16S ribosomal RNA gene amplicon sequencing. Beta-diversity revealed significant differences in bacterial composition between participants with ADHD and healthy controls, which was also significant for inattention, but showing a trend in case of hyperactivity/impulsivity only. Ten genera showed nominal differences (P < 0.05) between both groups, of which seven genera were tested for their association with ADHD symptom scores (adjusting for age, sex, body mass index, time delay between feces collection and symptoms assessment, medication use and family relatedness). Our results show that variation of a genus from the Ruminococcaceae family (Ruminococcaceae_UCG_004) is associated (after multiple testing correction) with inattention symptoms, and suggest a role of gut microbiota in ADHD pathophysiology.

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.

The COVID-19 pandemic is one of the past century's deadliest and most widespread viral outbreaks, with higher mortality rates in men than women. Disruptions in funeral rituals and customs, no social recognition of the loss, and limited social support intricate the grieving process and are linked with disenfranchised (not openly acknowledged, socially recognized, or publicly mourned) grief. Depression is also highly comorbid with complicated grief. Losing a spouse can be devastating, but more severe for women with limited or no resources, vulnerable to the patriarchal society. In the current COVID-19 era, increased uncertainty and disenfranchised grief can worsen the clinical scenario and intervention, as highlighted by the present case report of disenfranchised grief with depressive symptoms in a 30 years old woman from rural India who, after a year of her marriage, lost her husband due to COVID-19. This case study emphasizes the impact of multiple axes of disadvantages due to sociodemographic and cultural determinants that can complicate the grieving process in the current context. The bioecological model of grief recovery considered the individual features and the societal/environmental factors to postulate the appropriate intervention. Finding meaning and purpose in life, and restoration-oriented coping were successful for clinical management.

Estimation of the reality can easily be flawed, hence, in order to result in accurate and useful estimates the process has to be protected from bias and confounding and should follow other methodological milestones inherent to different types of empirical observations. Candidate-gene association studies are a specific form of observations that have been rather extensively applied in psychiatry yielding valuable information on various aspects – when methodologically adequate and used in appropriate settings. However, certain flaws that may occur in such studies might not be bluntly obvious, at least not at first glance, and may pass unnoticed by researchers and reviewers. This case study uses two recent published candidate-gene association reports suggesting involvement of cannabinoid receptor type 1 and of heat shock protein single nucleotide polymorphisms in development of neurocognitive performance and psychopathology in a cohort of adult first episode psychosis patients to point-out the types of flaws inevitably resulting in inaccurate and useless estimates.

The article presents the potential of liposomal cannabidiol in the treatment of Panic Disorder, when used in integration with Complex Cognitive Psychotherapy. The advantages of the integrated treatment, developed by the Author, and based on the use of liposomal cannabidiol combined with cognitive psychotherapy, are discussed. A new and original tool is presented and described, developed, and tested for the first time by the Author and called NegEnt Panic Blocker.

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.

Neuropsin is a brain-expressed extracellular matrix serine protease that governs synaptic plasticity through activity-induced proteolytic cleavage of synaptic proteins. Its substrates comprise several molecules central to structural synaptic plasticity, and studies in rodents have documented its role in cognition and the behavioral and neurobiological response to stress. Intriguingly, differential usage of KLK8 (neuropsin gene) splice forms in the fetal and adult brain has only been reported in humans, suggesting that neuropsin may serve a specialized role in human neurodevelopment. Through systematic interrogation of large-scale genetic data, we review KLK8 regulation in the context of mental health and provide a summary of clinical and preclinical evidence supporting a role for neuropsin in the pathogenesis of mental illness.

Introduction: Around a million people are reported to die by suicide every year, and due to the stigma associated with the nature of the death, this figure is usually assumed to be an underestimate. Suicide may be prevented if prompt intervention is taken to mitigate risk. Machine learning and artificial intelligence-based modelling, such as natural language processing (NLP) and other text analytics approaches, has the potential to become a major technique for the detection, diagnosis, and treatment of people who are suffering from mental health issues. The primary aims of this research are to determine whether NLP techniques have been utilised in the field of suicide prevention, and if so, were they effective? What were their limitations? Methods: PubMed, EMBASE, MEDLINE, PsycInfo, and Global Health databases were searched for studies that reported use of NLP for suicide ideation or self-harm. Thematic analysis was used to synthesise and analyse the included studies. Findings were reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement, and the Mixed Methods Appraisal Tool (MMAT) was used in assessing paper quality. Result: The preliminary search of five databases generated 387 results. Removal of duplicates resulted in 158 potentially suitable studies. Twenty papers were finally included in this review. Discussion: Studies show that combining structured and unstructured data in NLP data modelling yielded more accurate results than utilizing either alone. Also, to reduce suicides, people with mental problems must be continuously and passively monitored. Further, NLP and other machine learning/artificial intelligence technologies can be used to address health inequities and electronic health records provide valuable data for creating suicide risk tools. Finally, Online, social media, and smartphone applications can be leverage in detecting people with suicide ideation. Conclusion: The use of artificial intelligence and machine learning opens new avenues for considerably guiding risk prediction and advancing suicide prevention frameworks. The review's analysis of the included research revealed that the use of NLP may result in low-cost and effective alternatives to existing resource-intensive methods of suicide prevention. To summarise, there is substantial evidence that NLP is useful in identifying people who have suicide ideation.

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.

Intensive care nurses are highly prone to occupational stress and burnout, affecting their physical and mental health. The occurrence of the pandemic and related events increased nurses’ workload and exacerbated stress and burnout. We conducted a prospective longitudinal mixed-methods study with a cohort of nurses working in a medical ICU (COVID unit; n = 14) and cardiovascular ICU (non-COVID unit; n = 5). Each participant was followed for six 12-hour shifts. Validated questionnaires measured occupational stress and burnout prevalence. Wrist-worn wearable technologies recorded physiological indices of stress. Participants elaborated on the contributors to stress via post-study questionnaire. Data were analyzed using statistical and qualitative methods. Participants who cared for COVID patients at the COVID unit were 3.71 times more likely to experience stress (p &lt; .001) in comparison to non-COVID unit participants. No differences in stress levels were found when the same participants worked with COVID and non-COVID patients at different shifts at the COVID unit. The cohorts expressed similar contributors to stress including communication tasks, patient acuity, clinical procedures, admission processes, proning, labs, and assisting coworkers. Nurses in COVID units, irrespective of whether they care for a COVID patient, may experience high occupational stress and burnout.

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.

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.

Subjective Cognitive Decline (SCD) is a possible earliest detectable sign of dementia, but we do not know what mental processes lead to elevated concern. We summarize the previous literature on the biomarkers and functional neuroanatomy of SCD. To extend the current most-popular theory of SCD, compensatory hyperactivition, we introduce a new model: breakdown of homeostasis in the prediction error minimization system. A cognitive prediction error is a discrepancy between an implicit cognitive predictions and the corresponding outcome. Experiencing frequent prediction errors may be a primary source of elevated subjective concern. Our homeostasis breakdown model explains the progression both from normal cognition to SCD and from SCD to advanced dementia stages.

Previous research suggests that the economic crisis can affect mental health. The purpose of this study was to analyse the association of risk of poor mental health with various socioeconomic, demographic, health, quality of life and social support variables; and to evaluate the contribution of socioeconomic variables most affected by the beginning of the economic crisis (employment situation and income) on the changes in the prevalence of the risk of poor mental health between 2005 and 2010. A study of prevalence evolution in adult population residents of the Valencian Community in the Spanish Mediterranean was conducted. We studied 5781 subjects in 2005 and 3479 in 2010. Logistic regression models have been adjusted to analyse the association between variables. A standardization procedure was carried out to evaluate which part of the changes in overall prevalence could be attributed to variations in the population structure by age, sex, employment status and income between the years under study. The prevalence of GHQ + increased from 2005 to 2010, in both men and women. Several variables were closely associated with the risk of poor mental health (sex, age, country of birth, number of non-mental chronic diseases, social support, disability, cohabitation in couple, employment status, and income). The changes produced as a result of the onset of the economic crisis in income and unemployment (increase in low income and in unemployment rates) contributed to the increase of poor mental health risk. This could confirm the sensitivity of mental health to the economic deterioration caused by the crisis.

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.

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.

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.

Post-traumatic stress disorder (PTSD) is a debilitating mental health disorder that causes significant dysfunction in individuals. Currently, there are many approved Pharmacotherapy and Psychotherapy treatment options for PTSD, but unfortunately, half of the patients do not respond to traditional therapies. In this article, we reviewed clinical trials and research on 3,4-methylenedioxymethamphetamine (MDMA) assisted Psychotherapy in PTSD patients, its pharmacokinetics and current treatment guidelines for PTSD. Based on the results of the efficacy of MDMA assisted Psychotherapy from six phases II Randomized controlled trials. MDMA-assisted Psychotherapy for PTSD has received the “Breakthrough Therapy” designation from the FDA. MDMA can potentially reduce PTSD symptoms even in treatment-resistant cases by increasing certain neurohormones, i.e. dopamine, serotonin, norepinephrine and oxytocin. It also modulates activities in the brain regions involved in fear and anxiety. Future research is needed to show whether the advantages outweigh the disadvantages and whether its use can be integrated into available treatment options for PTSD.

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

Suicide is a major public health concern in South Korea, and self-poisoning by pesticides is one of the common methods of suicide. Pesticide ban policies have been successful for suicide prevention; however, no studies have shown their effect according to occupational groups. The present study analyzed suicide and suicide by pesticide rates among South Korean workers age 15-64 in 2003-2017, their associations with occupational groups, and the impact of three major economic indices on these factors. Workers in the agriculture, forestry, and fishery industries have relative risks of 5.62 (95% CI: 5.54-5.69) for suicide overall and 25.49 (95% CI: 24.46-26.57) for suicide by pesticide. The real gross domestic product (RGDP) has a positive association with suicide overall only in the last five-year period investigated in this study, and the unemployment rate consistently has a positive association. The economic status and policy for suicide prevention affect suicide and suicide by pesticide rates differently among occupational groups and different time periods. Policy addressing suicidal risk for different occupational groups should be of concern in South Korea.

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.

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.

Background and objectives: Only a few studies analyzed the physical activity level of elderly people living alone in local communities and evaluated the relationship between it and mental health. The purpose of this study was to investigate the relationship between physical activity and depression in the elderly living alone and to provide basic data for the prevention of depression in the elderly. Materials and Methods: We analyzed 256 elderly people living alone aged 65 years or older who completed the 2014 Korea National Health and Nutrition Examination Survey. Depression was defined as a score of 10 or higher using Patient Health Questionnaire-10(PHQ-9). This study investigated walking per week, days of muscular strength exercise performance in the past one week, days of flexibility exercise in the past one week, mean hours in a sitting position per day, the numbers of days and hours conducting a high intensity physical activity in the past one week, and numbers of days and hours conducting a medium intensity physical activity in the past one week to define physical activity. Our study presented prevalence odds ratios (pOR) and 95% confidence interval (CI) by using complex sample logistic regression analysis in order to identify the relationship between physical activity and depression. Results: The results of complex sample logistic regression analysis showed that flexibility exercise was significantly related to depression (p <0.05). On the other hand, the mean hours in a sitting position per day, aerobic physical activity, walking, and muscular strength exercise were not significantly related to geriatric depression. Conclusions: The results of our study implied that persistent flexibility exercise might be more effective to maintain a healthy mental status than muscular strength exercise. A longitudinal study is required to prove the causal relationship between physical activity and depression in the old age.

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.

Huntington's disease (HD) is a rare genetic neurodegenerative disorder that causes motor disorders, neuropsychiatric symptoms and a progressing deterioration of cognitive functions. Complex issues resulting from the hereditary nature of HD, the complexity of symptoms and the concealed onset of the disease have a great impact on the quality of life of family carers. The caregivers are called as “forgotten people” in HD family, also in genetic counseling. This study aims to explore the reliability and validity of the Huntington’s Disease Quality of Life Battery for carers (HDQoL-C) within a Polish population. 90 carers recruited from the Enroll-HD study in Polish research centres of the European Huntington`s Disease Network completed a polish translation of the HDQoL-C. Data was subjected to Principle Components Analysis and reliability measures. The Polish version of the shortened versions of the HDQoL–C is similarly valid compared to the original English version and suitable for use within this population. The HDQoL-C has previously demonstrated a wide range of benefits for practitioners in capturing and understanding carer experience and these benefits can now be extended to Polish speaking populations.

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.

Background: Studies exploring the possible protective effect of coffee and tea consumption on dementia showed inconsistent results so far. We aimed to investigate whether consumption of tea and different types of coffee at midlife are associated with dementia later in life and, whether sex or ApoE4 influence such association. Methods: We included 7381 participants from the Norwegian HUNT Study. Self-reported questionnaires assessed daily consumption of coffee and tea at baseline. After 22 years, individuals 70 years or older were screened on cognitive impairment. Results: General coffee consumption and tea consumption was not associated with dementia risk. Compared to daily consumption of 0-1 cups of coffee, daily consumption of ≥8 cups of boiled coffee was associated with increased dementia risk in women (OR:1.83, 95% CI: 1.10-3.04, p-value for trend=0.03) and daily consumption of 4-5 cups of other types of coffee was associated with a decrease in dementia risk in only men (OR 0.48, 95% CI: 0.32-0.72, p-value for trend =0.05). Furthermore, the association between boiled coffee and increased dementia risk was only found in ApoE4 non-carriers. Differences by sex or ApoE4 carrier status were not supported by strong statistical evidence for interaction. Conclusion: Type of coffee may play a role in the direction of the association between coffee-drinking habits and dementia later in life.

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.

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.

Schizophrenia is a chronic neuropsychiatric syndrome with a significant impact on daily function and quality of life. All available guidelines suggest a combined treatment approach with pharmacologic agents and psychological interventions. However, one in three patients is a non-responder, the effect on negative and cognitive symptoms is limited, and many drug-related adverse effects complicate clinical management. As a result, discovering novel drugs for schizophrenia presents a significant challenge for psychopharmacology. This narrative review of the literature aims to present recently approved and newly discovered pharmacological substances for the treatment of schizophrenia as well as their suggested mechanism of action. We discuss seven novel drugs, three of which have been approved by the FDA (Olanzapine/Samidorphan, Lumateperone, and Pimavanserin). The rest are under clinical trial investigation (Ulotaront, CVL-231, Xanomeline/Trospium, Brilaroxazine). Additional basic and clinical research is, however, required not only to improve our understanding of the neurobiology and potential novel targets in schizophrenia treatment but also to establish modern and more effective therapeutical interventions with friendlier side-effect profiles.

Background: Young adults, particularly university students might be at greater risk of developing psychological distress, and exhibiting symptoms of anxiety and depression during the COVID-19 pandemic. Objective: The primary objective of this study was to explore and compare the determinants and predictors of mental health (anxiety and depression) during and after COVID-19 lockdown among university students. Methods: This was an observational, cross-sectional study with a sample size of 417 students. An online survey utilizing International Physical Activity Questionnaire–Short Form (IPAQ-SF), General Anxiety Disorder–7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) was distributed to Universiti Tunku Abdul Rahman students via Google forms. Results: During lockdown, family income [χ² (1, n=124) = 5.155, p=0.023], and physical activity [χ² (1, n=134) = 6.366, p=0.012] were associated with anxiety, while depression was associated with gender [χ² (1, n=75) = 4.655, p=0.031]. After lockdown, family income was found to be associated with both anxiety [χ2 (1, n=111) = 8.089, p=0.004], and depression [χ2 (1, n=115) =9.305, p=0.002]. During lockdown, family income (OR=1.60, p=0.018), and physical activity (OR=0.59, p=0.011) were predictors for anxiety, and gender (OR=0.65, p=0.046) being the only predictor for depression. After lockdown, family income was a predictor for both anxiety (OR=1.67, p=0.011), and depression (OR=1.70, p=0.009). Conclusion: Significant negative effects attributed to the COVID-19 lockdown, and certain factors predisposed to the worsening of mental health status in university students. Family income, physical activity level, and gender were some of the major determinants that influenced the anxiety and depression.

Mood and anxiety disorders affect pregnant people and their families at increased rates throughout the perinatal period. Geographic, financial, and social barriers persist in identification and access to care that preclude adequate diagnosis and treatment of anxiety and mood disorders. These challenges have been exacerbated by the COVID-19 pandemic, particularly for Black and Indigenous People and People of Color (BIPOC) who already experience increased risk for adverse mental health outcomes and faced structural barriers to accessing perinatal mental health care at baseline. The literature shows that integrated care can improve mental health outcomes and save billions of dollars in annual healthcare costs. This study evaluated a novel statewide integrated care effort designed to facilitate access to perinatal mental health care for OB/GYN patients. In addition to enrollment data, variables studied were maternal program satisfaction, retention rates, and preliminary maternal mental health outcomes. 285 patients were ever referred for care. Of this, we contacted 259 patients (91%) and enrolled 209 (72%). Of the 209, 48 were lost to follow up, while 107 remained enrolled at the time of data analysis. 54 patients met their treatment goals. 97% of individuals asserted they were satisfied with the services they received. Black race and public insurance predicted faster attrition from treatment; risk for interpersonal violence exposure and substance use were not related to attrition. Preliminary mental health outcomes showed significant decreases in anxiety and depression, with the most dramatic decreases in the first month of treatment. The MC3 Perinatal care program is a viable, patient-endorsed collaborative care model that increases access to perinatal mental health and facilitate access to outside resources.

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.

The serious impact of Adolescent’s Free Sex Behavior will affect their developmental task. Having proper education and having optimal sex counseling are related to sexual behavior in adolescents. The alternative for this phenomenon recently has involved adolescents participating as peer counselors because they are more susceptible to peer influence. Online peer counselor programs may promote progression into depth understanding of sexual behavior among adolescents. This paper provides an overview of the effect of peer counselors on reproductive health among adolescents. It describes many conceptual frameworks about free sex behaviors, risk factors among adolescents, and the role of peer counselors in improving health reproductive behavior among adolescents.

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.

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.

Background: Our study aimed to examine how modulating variables such as social support, health anxiety, coping, gender, being separated from home, and lockdown can modify or amplify the effect of perceived stress as a starting variable in the point of view of the output variable, dissociation. Methods: A cross-sectional survey was conducted in online form at two points in time: the beginning and the later stage of the COVID-19 pandemic. Results: We received a total of 1711 responses. Perceived stress moderately correlated with dissociation in both International and Hungarian samples. Health anxiety showed a strong direct and indirect correlation with dissociation. Regarding social support, the support of family significantly decreased the dissociative experiences in the Hungarian sample through mediating the stress and directly as well. In the international sample, the goal-oriented coping strategy had a strong decreasing effect on all dissociation scales in the first measurement, through mediation of perceived stress. As to the Hungarian sample, positive thinking was found to decrease dissociation through decreasing perceived stress. Conclusion: The cause and effect relationship between stress and dissociation may be tinctured by health anxiety, coping and social support, influencing dissociacion directly and indirectly. Social support, mainly support of the family and problem-focused coping strategies seem to alleviate dissociation-provoking effect of stress.