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.

Neuropsin is an extracellular matrix serine protease that governs the proteolytic cleavage of synaptic proteins and consequently synaptic structural plasticity. In the brain, its substrates include the cell adhesion molecules Neuregulin-1 and L1CAM, that have been linked to neurodevelopmental processes and disorders, such as schizophrenia and bipolar disorder. Neuropsin mRNA is abundant in the cerebellum and several peripheral tissues from mid-gestation but is mainly expressed in cortical and limbic tissues postnatally. Differential usage of neuropsin 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. Accordingly, both the expression and proteolytic activity of neuropsin are subject to regulation by neural activity as well as by environmental risk factors associated with mental illness, such as psychophysiological stress. Intriguingly, dysregulation of neuropsin has been reported in depression and Alzheimer’s disease and its implication in mental disorder is supported by genetic and epigenome wide studies. Here we review neuropsin regulation in mental health and provide a summary of clinical and preclinical evidence supporting a role for neuropsin in the pathogenesis of mental disorders.

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.

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.

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.

Background: There is now evidence that immune and opioid systems show functional reciprocal relationships and that both systems may participate in the pathophysiology of major depression (MDD). Objective: The present study was carried out to delineate differences between MDD patients and healthy controls in dynorphin and kappa opioid receptor (KORs) in association with levels of β-endorphins and mu opioid receptors (MORs), interleukin-6 (IL-6) and IL-10. Method: The present study recruited 60 drug-free male participants with MDD aged 24-70 year and 30 age-matched healthy males as control group and measured serum levels of dynorphin, KOR, β-endorphin, MOR, IL-6 and IL-10. Results: Serum dynorphin, KOR, β-endorphin and MOR are significantly increased in MDD as compared with controls. The increases in the dynorphin/KOR system and β-endorhin/MOR system are significantly intercorrelated and are both strongly associated with increased IL-6 and IL-10 levels. Dynorphin, β-endorphin, KOR and both cytokines showed a good diagnostic performance for MDD versus controls, whereby both opioid peptides and cytokines show a bootstrapped (n=2000) area under the receiver operating curve of 0.972. KOR and the dynorphin/KOR system are both significantly decreased in depressed subjects with comorbid nicotine dependence. Conclusion: Our findings suggest that in MDD, immune activation is associated with a simultaneous activation of dynorphin/KOR and β-endorhin/MOR signaling and that these opioid systems may participate in the pathophysiology of depression by a) exerting immune regulatory activities attenuating the primary immune response; and b) modulating reward responses and mood as well as emotional and behavioral responses to stress.

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.

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. 

Objective: To examine associations between IgA responses to Gram-negative gut-commensal bacteria and peri-menstrual symptoms and sex hormone levels during the menstrual cycle in women with and without premenstrual symptoms. Methods: Forty women aged 18-45 years completed the Daily Record of Severity of Problems (DRSP) during all 28 consecutive days of the menstrual cycle. We assayed, in plasma,, IgA responses to 6 Gram-negative bacteria, i.e. Hafnei alvei, Pseudomonas aeruginosa, Morganella morganii, Klebsiella pneumoniae, Pseudomonas putida and Citrobacter pylori, progesterone and oestradiol at days 7, 14, 21 and 28 of the menstrual cycle. Results: Significant changes in Δ (actual minus one week earlier) IgA to LPS of the 6 Gram-negative bacteria during the menstrual cycle were observed with peak IgA levels at T4 (day 28) and lows at T1 or T2 (day 7 or 14). The Δ IgA changes in H. alvei, M. Morganii, P. putida during the menstrual cycle were significantly and positively associated with changes in the total DRSP score, and severity of physio-somatic, anxiety and breast-craving, but not depressive, symptoms. The changes in IgA responses to LPS were largely predicted by changes in progesterone and steady-state levels of progesterone averaged over the luteal phase. Discussion: Menstrual cycle-associated changes in IgA directed against LPS and by inference bacterial translocation may be driven by effects of progesterone on transcellular, paracellular and vascular pathways thereby contributing to the severity of physio-somatic and anxiety symptoms as well as fatigue, breast swelling and food cravings.  

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.

Major depressive disorder (MDD) is associated with changes in the levels of the cations calcium (Ca) and magnesium (Mg) as well as circulating pro- and anti-inflammatory cytokines. The immune-inflammatory nature of MDD has encouraged researchers to use anti-inflammatory drugs as an adjuvant treatment for MDD. However, the effect of this treatment on cation levels has not been studied. The present study examined a) differences in both cations between drug-naïve MDD patients and controls, and b) the effects of a combination of sertraline and ketoprofen, an anti-inflammatory drug, on Ca and Mg (both total and ionized). In the same patients we also examined the associations between both cations and IL-1β, IL-4, IL-6, IL-18, IFN-γ, TGF-β1, zinc and indoleamine 2,3-dioxygenase (IDO). Clinical improvement was estimated using the Beck Depression Inventory-II (BDI-II) at baseline and after follow up for two months. Serum Ca and Mg (total and ionized) were significantly lower in MDD patients as compared with controls, while treatment significantly increased calcium but decreased magnesium levels. There were significant and inverse correlations between the BDI-II scores from baseline to endpoint and Ca (both total and ionized), but not Mg, levels. The effects of calcium on the BDI-II score remained significant after considering the effects of zinc, IDO and an immune activation z unit weighted composite score based on the sum of all cytokines. There was a significant and inverse association between this immune activation index and calcium levels from baseline to endpoint. In conclusion, reduced levels of both cations play a role in the pathophysiology of major depression. Increased calcium levels are coupled to the clinical efficacy of antidepressants and attenuation of immune activation. The suppressant effect of antidepressants on Mg levels may be a side effect of those drugs. New antidepressant treatments should be developed that increase the levels both Ca and Mg.

Deficit schizophrenia is characterized by leaky tight and adherens junctions and bacterial translocation. Here we examine whether (deficit) schizophrenia is accompanied by leaky paracellular, transcellular and vascular barriers in the gut and blood brain barriers. We measured IgA responses to occludin, claudin-5, E-cadherin and β-catenin (paracellular pathway, PARA), talin, actin, vinculin and epithelial intermediate filament (transcellular pathway, TRANS) and plasmalemma vesicle-associated protein (PLVAP, vascular pathway) in 78 schizophrenia patients and 40 controls. IgA responses to claudin-5, E-cadherin and β-catenin, the sum of the four PARA proteins and the ratio PARA/TRANS were significantly higher in deficit schizophrenia than in non-deficit schizophrenia and controls. A large part of the variance in PHEMN (psychosis, hostility, excitation, mannerism and negative) symptoms, psychomotor retardation, formal thought disorders, verbal fluency, word list memory, word list recall and executive functions was explained by the PARA/TRANS ratio coupled with plasma IgA responses to Gram-negative bacteria, IgM to malondialdehyde, CCL-11 (eotaxin), IgA levels of the ratio of noxious to more protective tryptophan catabolites (NOX/PRO TRYCATs) and a plasma immune activation index. Moreover, IgA levels to Gram-negative bacteria were significantly associated with IgA to E-cadherin, β-catenin and PLVAP, while IgA levels to claudin-5 were significantly predicted by IgA to E-cadherin, NOX/PRO TRYCAT ratio, Gram-negative bacteria and CCL11. The phenomenology of the deficit syndrome is to a large extent explained by the cumulative effects of lowered natural IgM, breakdown of the paracellular and vascular pathways, increased bacterial translocation, peripheral immune-inflammatory responses and indices of BBB breakdown.

We aimed to evaluate the feasibility and preliminary efficacy of trauma-focused group psychotherapy in adolescents who experienced traumatic events in Korea. Participants were assigned and recruited from two sites in Korea. Children in Disaster: Evaluation and Recovery (CIDER) V1.0 is a trauma-focused group psychotherapy approach consisting of psychoeducation, normalization, stabilization, and techniques of managing the traumatic memory. The CIDER intervention consists of eight 50-minute-long sessions. The effectiveness of the intervention was evaluated using the Korean version of the Children’s Response to Traumatic Events Scale-Revised (K-CRTES-R), the Beck Depression Inventory (BDI), the State Anxiety Inventory for Children (SAIC), and the Pediatric Quality of Life Inventory (PedQL). Data were analyzed by Wilcoxon signed-rank test. We recruited 22 traumatized adolescents (mean age 16 years; SD 1.43; range 13–18 years old; 71.4% boys) in this pilot study. The K-CRTES-R scores were significantly improved (Z = −2.85, p < 0.01). The BDI demonstrated the effectiveness of the therapy (Z = −2.35, p < 0.05). The assessment of the PedQL supported the effect of CIDER (Z = −3.08, p < 0.01). However, there was no statistically significant differences in the SAIC scores (Z = −1.90, p > 0.05). The results show that there is preliminary evidence that CIDER intervention reduces post-traumatic stress and depressive symptoms and improves quality of life. Our findings indicate that CIDER is feasible for treating adolescents exposed to traumatic events. Larger controlled trials are needed to establish the efficacy of this trauma-focused group psychotherapy and examine its impact on post-traumatic stress disorder.

Objective: The aim of the current study was to examine whether and to what extent mood disorders, comprising major depression and bipolar disorder, are accompanied by structural changes in the brain as measured using voxel-based morphometry (VBM). Methods: We have performed a VBM study using a 3Т MRI system (GE Discovery 750w) in patients with mood disorders (n=50), namely 39 with major depression and 11 with bipolar disorder, compared to 42 age, sex and education matched healthy controls. Results: Our results show that depression was associated with significant decreases in grey matter (GM) volume restricted to regions located in medial frontal and anterior cingulate cortex on the left side and middle frontal gyrus, medial orbital gyrus, inferior frontal gyrus (triangular and orbital parts), and middle temporal gyrus (extending to the superior temporal gyrus) on the right side. When the patient group was separated into bipolar disorder and major depression the reductions remained significant only for the patients with major depressive disorder. Conclusions: Using VBM the present study was able to replicate decreases in GM volume restricted to frontal and temporal regions in patients with mood disorders mainly major depression, as compared with healthy controls. 

In 2011, it was reviewed that there is a strong co-occurrence between major depression and chronic fatigue syndrome (CFS), with fatigue and physio-somatic symptoms being key symptoms of depression, and depressive symptoms appearing during the course of CFS. Moreover, the comorbidity between both conditions may in part be explained by activated immune-inflammatory pathways, including increased translocation of Gram-negative bacteria and increased levels of pro-inflammatory cytokines, such as interleukin (IL)-1. Nevertheless, the possible involvement of activated microglia in this comorbidity has remained unclear. This paper aims to review microglial disturbances in major depression, CFS and their comorbidity. A comprehensive literature search was conducted using the PubMed / MEDLINE database to identify studies that are relevant to this current review. Depressed patients present neuroinflammatory alterations, probably related to microglial activation, while animal models show that a microglial response to immune challenges including lipopolysaccharides is accompanied by depressive-like behaviors. Recent evidence from preclinical studies indicate that activated microglia have a key role in the onset of fatigue. In chronic inflammatory conditions, such as infections and senescence, microglia orchestrate an inflammatory microenvironment thereby causing fatigue. In conclusion, based on our review we may posit that shared immune-inflammatory pathways and activated microglia underpin comorbid depression and CFS and that activated microglia are the main orchestrators of this comorbidity. As such, microglial activation and neuro-inflammation may be promising targets to treat the overlapping manifestations of both depression and CFS.

Background: India has one-fifth of the world's population and the number of people suffering from mental illness is assumed to be huge considering the contribution of mental disorders to the overall burden of the disease being 13.9 %. Objectives of Study: To estimate prevalence and patterns of mental illnesses to assess the current mental health services and systems in the Madhya Pradesh. Material and Methods: Multi-stage, stratified, random cluster sampling technique, with random selection based on probability proportionate to size at each stage. A total of 3240 individuals aged 18 years and above were interviewed. Both quantitative and qualitative methods were employed. A set of 10 instruments including Mini International Neuro-psychiatric Interview were utilized. Results: The overall weighted prevalence for any mental illness was 16.7% lifetime and 13.9% current. Treatment-gap for all mental health problems is as high as 91% in the state along with huge socioeconomic impact of mental illness. Conclusions: This huge burden of mental, behavioural and substance use disorders, in Madhya Pradesh, calls for immediate attention of political leaders, policy makers, health professionals, opinion-makers and society at large. It is hoped that the data from the study will inform mental health policy and legislation and help shape mental health care delivery systems in the country.

The current crisis in psychopharmacology has a long history and needs to be addressed with innovative and effective strategies. Here we discuss some of the roots of this crisis and suggest that the therapeutic use of psychedelic drugs represents a promising and integrative treatment with enduring effects for mental health problems.

In 2001, the first author of this paper reported that schizophrenia is associated with an increased frequency of the haptoglobin (Hp)-2 gene. The precursor of Hp-2 is zonulin, a molecule that affects intercellular tight junction integrity. Recently, we reported increased plasma IgA/IgM responses to Gram-negative bacteria in deficit schizophrenia indicating leaky gut and gut dysbiosis. The current study was performed to examine the integrity of the paracellular (tight and adherens junctions) and transcellular (cytoskeletal proteins) pathways in deficit versus non-deficit schizophrenia. We measured IgM responses to zonulin, occludin, E-cadherin, talin, actin and vinculin in association with IgA responses to Gram-negative bacteria, CCL-11, IgA responses to tryptophan catabolites (TRYCATs), immune activation and IgM to malondialdehyde (MDA) and NO-cysteinyl in 78 schizophrenia patients and 40 controls. We found that the ratio of IgM to zonulin + occudin / talin + actin + viculin (PARA/TRANS) was significantly greater in deficit than in non-deficit schizophrenia and higher in schizophrenia than controls and was significantly associated with increased IgA responses to Gram-negative bacteria. IgM responses to zonulin were positively associated with schizophrenia (versus controls), while IgM to occludin was significantly associated with deficit schizophrenia (versus non-deficit schizophrenia and controls). A large part of the variance (90.8%) in negative and PHEM (psychosis, hostility, excitation and mannerism) symptoms was explained by PARA/TRANS ratio, IgA to Gram-negative bacteria, IgM to E-cadherin and malondialdehyde (MDA) and memory dysfunctions, while 53.3% of the variance in the latter was explained by PARA/TRANS ratio, IgA to Gram-negative bacteria, CCL-11, TRYCATs and immune activation. The results show an upregulated paracellular pathway with breakdown of the tight and ahherens junctions and increased bacterial translocation in deficit schizophrenia. These dysfunctions in the intestinal paracellular route together with lowered natural IgM, immune activation and production of CCL-11 and TRYCATs contribute to the phenomenology of deficit schizophrenia.

There is now evidence that major depression is accompanied by lowered serum zinc, an immune-inflammatory biomarker. However, the effect of anti-inflammatory drugs as adjuvant to antidepressants on serum zinc and copper in relation to pro- and anti-inflammatory cytokines are not studied. The aim of the present work is to examine the effects of treatment with sertraline with and without ketoprofen on serum levels of zinc and copper in association with immune-inflammatory biomarkers in drug-naïve major depressed patients. We measured serum zinc and copper, interleukin (IL)-1β, IL-4, IL-6, IL-18, interferon (IFN)-γ, and transforming growth factor (TGF)-β1 in 40 controls and 133 depressed patients. The clinical efficacy of the treatment was measured using the Beck Depression Inventory-II (BDI-II) at baseline and 8 weeks later. In drug-naïve major depressed patients we found significantly reduced baseline levels of serum zinc and copper in association with upregulation of all cytokines, indicating activation of the immune-inflammatory responses system (IRS) as well as the compensatory immune regulatory system (CIRS). Treatment with sertraline significantly increased zinc and decreased copper levels, while ketoprofen did not have a significant add-on effect on zinc but attenuated the suppressant effects of sertraline on copper levels. During treatment, there was a significant inverse association between serum zinc and activation of the IRS/CIRS. The improvement in the BDI-II during treatment was significantly associated with increments in serum zinc coupled with attenuation of the IRS/CIRS. In conclusion, lower serum zinc is a hallmark of depression, while increments in serum zinc and attenuation of the immune-inflammatory response during treatment appear to play a role in the clinical efficacy of sertraline. Intertwined changes in zinc levels and the immune response play a role in the pathophysiology of major depression and participate in the mechanisms underpinning the clinical efficacy of antidepressants.

BACKGROUND: Stable-phase schizophrenia may comprise two distinct nosological entities namely Major Neuro-Cognitive Psychosis (MNP, largely overlapping with the deficit syndrome) and simple NP (SNP), which are defined by neuroimmune and neurocognitive abnormalities. Furthermore, cognitive impairments and PHEM (psychotic, hostility, excitation, mannerism) and negative symptoms load on the same dimension.METHODS: The current study aimed to investigate associations of psychomotor retardation (PMR) and clinical as well as biomarker characteristics of schizophrenia. We recruited 40 healthy controls and 79 schizophrenia patients and measured IgA responses to tryptophan catabolites (TRYCATs), IgM to malondialdehyde and nitroso (NO)-cysteinyl, macrophage inflammatory protein-1 (MIP-1), soluble interleukin (IL)-1 receptor antagonist (sIL-1RA), IL-10, CCL-11 as well as PMR items of different rating scales and motor screening task (MOT). RESULTS: PMR differentiated schizophrenia from controls and MNP from SNP. In addition, PMR was strongly associated with executive functions, deficits in episodic and semantic memory, PHEM and negative (PHEMN) symptoms. Around 50% of the variance in PMR was predicted by the cumulative effects of immune activation, CCL-11, TRYCATs and NO-Cysteinyl levels, and lowered natural IgM. PRM may be reliably combined with PHEMN symptoms and memory and executive impairments into one latent vector reflecting overall psychopathology.CONCLUSIONS: Current findings indicate that PMR may be a key psychopathological feature of schizophrenia and mainly MNP. In addition, PMR and associated impairments in memory and executive functions, and PHEMN symptoms may be driven by deficits in the compensatory immune regulatory system (natural IgM) combined with increased production of neurotoxic immune products, namely TRYCATs and IgM to NO-cysteinyl, and an endogenous cognition deteriorating chemokine, namely CCL-11.

Background: It is unknown whether lowered steady state levels of sex hormones coupled with changes in those hormones during the menstrual cycle could be associated with the presence and severity of premenstrual syndrome (PMS).Objective: To examine associations between levels of progesterone and oestradiol during the menstrual cycle and PMS severity considering different diagnostic criteria for PMS.Methods: Forty women aged 18-45 years with a regular menstrual cycle completed the Daily Record of Severity of Problems (DRSP) for all 28 consecutive days of the menstrual cycle. Blood was sampled at days 7, 14, 21 and 28 to assay oestradiol and progesterone. Results: We developed a new diagnosis of peri-menstrual syndrome, which is characterized by increased DRSP severity in pre and post-menstrual periods and increased scores on the major DRSP dimensions, i.e. depression, physio-somatic symptoms, breast tenderness and appetite, and anxiety. This new diagnosis performed better than classical diagnoses of PMS, including the one presented by the American College of Obstetricians and Gynecologists. Lowered steady state levels of progesterone, when averaged over the menstrual cycle, together with declining progesterone levels during the luteal phase predict severity of peri-menstrual symptoms. Steady state levels of oestradiol and declining oestradiol levels during the cycle are also related to DRSP severity although most of these effects appeared to be mediated by progesterone. Conclusion: A significant increase in menstrual-cycle related symptoms can best be conceptualized as “peri-menstrual syndrome” and may result from “corpus luteum insufficiency”, which may result from suboptimal pre-ovulatory follicular development. Future research should trial Clomiphene citrate (given the first 5 days of the cycle) and a mid-cycle injection of human Chorionic Gonadotrophin in subjects with peri-menstrual syndrome.

We aimed at developing and validating a scale on the beliefs and attitudes of mental health professionals towards services users’ rights in order to provide a valid evaluation instrument for training activities with heterogeneous professional groups. Items were extracted from a review of previous instruments, as well as from several focus groups which have been conducted with different mental health stakeholders. The preliminary scale consisted of 44 items and was administered to 480 mental health professionals. After eliminating non-discriminant and low weighting items, a final scale of 25 items was obtained. Exploratory and confirmatory factor analyses produced a four-factor solution consisting of four dimensions; system criticism/justifying beliefs, freedom/coercion, empowerment/paternalism and tolerance/discrimination. The scale shows high concordance with our theoretical model as well as adequate parameters of explained variance, model fit and internal reliability.

Major Depression Disorder (MDD) is accompanied by an immune response characterized by increased levels of pro-inflammatory and immune-regulatory cytokines and cytokine-induced stimulation of indoleamine-2,3-dioxygenase (IDO). There is also some evidence that anti-inflammatory drugs may have a clinical efficacy in MDD.The aim of this study is to examine the clinical effects of an eight-week combinatorial treatment of ketoprofen (a nonsteroidal anti-inflammatory drug) combined or not with sertraline, on serum levels of IDO, interferon (IFN)-γ, interleukin (IL)-4 and transforming growth factor (TGF)-β1 in association with changes in the Beck-Depression Inventory-II (BDI-II). The study included 140 MDD patients and 40 normal controls. The pre-treatment serum levels of IDO, IFN-γ, TGF-β1 and IL-4 were significantly higher in MDD patients compared with the control group. Treatment with sertraline with or without ketoprofen significantly reduced the increased baseline production of all 4 biomarkers to levels which were similar as those of normal controls. Ketoprofen add-on had a significantly greater effect on IDO and BDI-II as compared with placebo. The reductions in IDO, IL-4 and TGF-β1 during treatment were significantly associated with those in the BDI-II.In conclusion, the clinical efficacy of both sertraline + ketoprofen may be ascribed at least in part to attenuated IDO levels and immune-inflammatory responses in MDD. Moreover, add-on treatment with ketoprofen may augment the efficacy of sertraline by attenuating IDO. However, these treatments may also significantly reduce the more beneficial properties of T helper-2 and T regulatory (Treg) immune subsets. Future research should develop immune treatments that target the immune-inflammatory response in MDD, while enhancing the compensatory immune-regulatory system (CIRS).

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.

Although, staging models gained momentum to stage define affective disorders, no attempts were made to construct mathematical staging models using clinical and biomarker data in patients with major depression and bipolar disorder.The aims of this study were to use clinical and biomarker data to construct statistically-derived staging models, which are associated with early lifetime traumata (ELTs), affective phenomenology and biomarkers.In the current study, 172 subjects participated, 105 with affective disorders (both bipolar and unipolar) and 67 controls. Staging scores were computed by extracting latent vectors (LVs) from clinical data including ELTs, recurring flare ups and suicidal behaviors, outcome data such as disabilities and health-related quality of life (HR-QoL), and paraoxonase (PON)1 actvities and nitro-oxidative stress biomarkers.Recurrence of episodes and suicidal behaviors could reliably be combined into a LV with adequate composite reliability (the “recurrence LV”), which was associated with female sex, the combined effects of multiple ELTs, disabilities, HR-QoL and impairments in cognitive tests. All those factors could be combined into a reliable “ELT-staging LV” which was significantly associated with nitro-oxidative stress biomarkers. A reliable LV could be extracted from serum PON1 activities, recurrent flare ups, disabilities and HR-QoL.Our ELT-staging index scores the severity of a relevant affective dimension, shared by both major depression and bipolar disorder, namely the trajectory from ELTs, a relapsing course and suicidal behaviors to progressive disabilities. Patients were classified into three stages, namely an early stage; a relapse-regression stage; and a suicidal-regression stage. Lowered lipid-associated antioxidant defenses may be a drug target to prevent the transition from the early to the later regression stages.

Psychiatric disorders share the same pattern of longitudinal evolution and have courses that tend to be chronic and recurrent. These aspects of chronicity and longitudinal evolution of psychiatric disorders are currently studied under the neuroprogression framework. Interestingly, considering the plasticity of the brain, it is necessary to emphasize the bidirectional nature of neuroprogression. We review evidence highlighting alterations of the brain associated with the longitudinal evolution of psychiatric disorders from the framework of neuroplastic adaptation to pathology. This new framework highlights that substantial plasticity and remodelling may occur beyond the classic neuroprogressive framework, which is characterized only by loss of grey matter volume, decreased brain connectivity, and chronic inflammation. We also integrate the brain economy concept in the neuroplastic adaptation to pathology framework, emphasizing that to preserve its economy, i.e., function, the brain learns how to cope with the disease by adapting its architecture. This approach can disentangle both the specific pathophysiology of psychiatric symptoms and the adaptation to pathology, thus offering a new framework for both diagnosis and treatment.

The variations in the socioeconomic status between different social class of a population correspond to differences in accessibility to all resources available and able to improve global health. While socioeconomic status is now known as one of the main determinants for a good health and a good aging, its influence on sleep disorders is not well understood. The socioeconomic status 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 sleep disturbances, with different patterns associated to socioeconomic status. A model of interaction is proposed to summarize and conceptualizes these interactions and to promote more research on the topic.

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.

Sleep disorders (SD) have a complex aetiology, and socioeconomic status (SES) as determined by social class, household income, ethnicity and education plays an important role in their development. As SD are associated with cognitive impairment and mood disorders, they in turn impact SES. Socioeconomic status also influences allostatic load caused by chronic accumulation of stress throughout life. Environmental and psychological stressors have a direct effect on SD, and they are modulated by SES, in combination with comorbidities like obesity and cardiovascular disease. This review explores the recent theories about the influence of SES on the development of SD in the general population, whether or not occurring with comorbidities, and also focusses on the interplay between socioeconomic status, circadian rhythms, aging and clinical outcomes like metabolic diseases and cancer.

Background: First episode psychosis (FEP), schizophrenia and affective disorders are accompanied by activation of the immune inflammatory response system (IRS). The compensatory immune-regulatory reflex system (CIRS) is a regulatory immune response that is induced by the IRS but exerts negative feedback through, for example, increased levels of anti-inflammatory cytokines such as IL-4, IL-13 and IL-10. Different phenotypes of schizophrenia may exhibit distinct IRS and CIRS immune profiles.Aims: This study aims to examine the IRS and CIRS components, including macrophagic M1, T-helper (Th)-1, Th-2, Th-17 and T-regulatory (Treg) phenotypes, in antipsychotic-naïve FEP patients before and after risperidone treatment.Methods: We included 31 antipsychotic-naïve FEP patients who had measurements of IRS and CIRS biomarkers before and after treatment with risperidone for 10 weeks, and 22 healthy controls.Results: Antipsychotic-naive FEP patients showed interrelated increments in M1, Th-1, Th-2, Th-17 and Treg phenotypes and a relatively greater IRS response (especially granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6 and IL-12) as compared with the CIRS response (IL-4, IL-13, IL-5 and IL-10). Inflammatory markers, especially IL-6 and IL-8, were significantly correlated with negative, psychotic, affective and excitation symptom dimensions. Treatment with risperidone significantly suppressed the IRS and CIRS. Baseline levels of CIRS biomarkers, especially higher soluble tumor necrosis factor receptor-1 and IL-10 predicted clinical improvement during treatment.Discussion: Our findings indicate that FEP is characterized by robust IRS (M1 + Th-1 + Th-17) and CIRS responses, suggesting that monocytes, macrophages, Th-1, Th-2, Th-17 and Treg cells are activated. The findings indicate that a) FEP patients are prone to the detrimental effects of M1, Th-1, Th-17 and Th-2 cells, which may contribute to long-lasting abnormalities in brain circuitry; and b) in FEP, the CIRS may contribute to recovery from the acute phase of illness. Enhancing the CIRS is a new drug target to treat FEP.

In this paper we propose a novel theoretical framework, which was previously developed for major depression and bipolar disorder, namely the compensatory immune-regulatory reflex system (CIRS), as applied to the neuro-immune pathophysiology of schizophrenia and its phenotypes, including first episode psychosis (FEP), acute relapses, chronic and treatment resistant schizophrenia (TRS), comorbid depression, and deficit schizophrenia. These schizophrenia phenotypes and manifestations are accompanied by increased production of positive acute phase proteins, including haptoglobin and α2-macroglobulin, complement factors, and macrophagic M1 (IL-1β, IL-6 and TNF-α), T helper (Th)-1 (interferon-γ and IL-2R), Th-2 (IL-4, IL-5), Th-17 (IL-17) and T regulatory (Treg; IL-10 and transforming growth factor (TGF)-β1) cytokines, cytokine-induced activation of the tryptophan catabolite (TRYCAT) pathway as well as chemokines, including CCL-11 (eotaxin), CCL-2, CCL-3 and CXCL-8. While the immune profiles in the different schizophrenia phenotypes indicate activation of the immune-inflammatory response system (IRS), there are simultaneous signs of CIRS activation, including increased levels of the IL-1 receptor antagonist (sIL-1RA), sIL-2R and tumor necrosis factor-a receptors, Th-2 and Treg phenotypes with increased IL-4 and IL-10 production, and increased levels of TRYCATs and haptoglobin, α2-macroglobulin and other acute phase reactants, which have immune-regulatory and anti-inflammatory effects. Signs of activated IRS and CIRS pathways are also detected in TRS, chronic and deficit schizophrenia indicating that these conditions are accompanied by a new homeostatic setpoint between upregulated IRS and CIRS components. In FEP, increased baseline CIRS activity is a protective factor which may predict favorable clinical outcomes. Moreover, impairments in the CIRS are associated with deficit schizophrenia and greater impairments in semantic and episodic memory. It is concluded that CIRS plays a key role in the pathophysiology of schizophrenia by negatively regulating the primary IRS and contributing to recovery from the acute phase of illness. Components of the CIRS may offer promising therapeutic targets for schizophrenia.

In order to summarized the polygenic background of psychiatric diseases, polygenic risk scores (PRS) have been developed. Recently, PRS have been use to predict patients with higher comorbidities in psychiatric diseases, like dual diagnosis. PRS are principally derived in analysis of Caucasian and Asian populations, we are not aware of how this PRS could be applied in populations with high admixture. In order to explored this, the present work has the aim to analyzed if previous calculated PRS for psychiatric diseases could predict dual diagnosis in Mexican population, and also, if PRS calculation could be influenced by Mexican Amerindian (MA) global ancestry. We performed PRS calculation, using PRSice, with summary genome-wide association statistics previously published for psychiatric diseases, and also, performed Nagelkerke correlation test in order to established if PRS are correlated with dual diagnosis. We found that dual diagnosis could be predicted by major depressive disorder polygenic risk score. Nevertheless, schizophrenia polygenic risk score is highly correlated with global MA ancestry, independently of the schizophrenia diagnosis. Our results reinforced the notion that PRS calculation could be deviated by the MA global ancestry, nevertheless analysis on larger sample sizes are required in order to clarified this issue.

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.

Postpartum depression (PPD) has serious effects on maternal and infant morbidity and mortality. This study aimed to determine the prevalence of postpartum depression in mothers of under-twos in military barracks in Lagos. The Edinburgh Postnatal Depression Scale (EPDS) and a modified version of the General Help-Seeking questionnaire (GHSQ) were administered to 316 mothers of under-twos in 3 of 12 military barracks in Lagos, Nigeria to determine PPD and major depressive events (MDE). Risk of PPD was established at EPDS scores of >12. Good help-seeking practices were ascribed to scores of 20 or more on the GHSQ. Risk of PPD was found in 15.5% of respondents, and good help-seeking in 3.8% and 11.4% for personal/emotional and harming self/baby respectively. Bivariate analysis using Chi square showed statistically significant positive associations between lower scores for EPDS and higher educational levels of respondents, perception of partner support and being in lower wealth quintiles (p<0.05). Use of the EPDS was accepted among mothers of children aged under two years. Opportunities to educate pregnant women and new mothers about PPD using existing social networks, perinatal and infant screening programmes in the barracks can be leveraged upon to improve mental health delivery as part of maternity care.

The microbiome gut brain (MGB) axis involves bidirectional routes of communication and has emerged as a potential therapeutic target for multiple medical specialities including psychiatry. Significant numbers of preclinical trials have taken place with some transitioning to clinical studies in more recent years. Some positive results have been reported secondary to probiotic administration in both healthy populations and specific patient groups. This review aims to summarise the current understanding of the MGB axis and the preclinical and clinical findings relevant to psychiatry. The link between the gut microbiome and irritable bowel syndrome (IBS) is well established. Significant differences have been identified between the microbiome of patients with a diagnosis of depressive disorder and healthy controls. Similar findings have occurred in patients diagnosed with bipolar affective disorder. A probiotic containing Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium bifidum produced clinically measurable symptom improvement in patients with depressive disorder. To date some promising results have suggested that probiotics could play a role in the treatment of stress-related psychiatric disease. However, more well-controlled clinical trials are required to determine which clinical conditions are likely to benefit most significantly from this novel approach.

Using analytic approach we study the effect of HPA axis secretions to the emotional variation of bipolar II disorder patient. Modified Duffing – Van der Pol oscillator was used to model the emotional variation, that was solved analytically using multiple scale perturbation to obtain an asymptotic solution. The solution was graphed to understand the effect of the variation of the cortisol to the oscillator. It was observed that the increase or decrease of the HPA hormone from the basal level in the body system, affects the mood variation of bipolar II disorder patients.

Major depressive disorder (MDD) is a common mental disorder, which results in seriously impaired condition in the patients and great global disability burden. In light of its quite diverse etiologies, comorbidity with many other diseases, and complex underlying pathology, it has been a great challenge to understand the physiological basis of MDD, which may be a complex of related diseases, rather than a single one. In addition to the partial understanding of MDD, the individual heterogeneities among patients may render the development of a universal treatment an elusive goal. But studying how each of currently available treatments affects the disease can generate useful information to stratify patients into different subtypes for individualized treatments. In this case report, we present the first report of repeated success of using meditation as the only treatment of MDD, compared to initial success but no remission with other conventional antidepressants on the same patient. We hypothesized that the short but continuous natural pain during one-hour meditation sittings has the therapeutic effect to treat depression in the case of this patient and potentially others with MDD. This special opportunity of eliminating tremendous heterogeneity among different individuals has enabled us to probe deeply into the potential mechanism of depression treatments and the complex physiology of depression itself, both of which have likely profound implications in the treatment of other MDD patients as well. More importantly, this case report helps us dissect one specific component of meditation for its long-known and well-established benefit against depression.

The correlation and comorbidity between depression and chronic pain have been observed for a long time. Generally, it is considered that the two conditions reinforce each other, whereas the causal relationship between them is not clear. However, some evidence suggested that chronic pain may reverse the progression of depression in some cases. This article presents a selective review of clinical and pharmacological relationship between depression and pain, and their interactions at neurochemical and neurobiological levels. In addition, we open a discussion on a recent case report of repeated success of using short but continuous pain (SCP) during meditation as the only treatment for depression, compared to initial success but no remission with other conventional antidepressants on the same patient. Together this review proposes an updated model for depression and its various treatments that is based on synaptic and system homeostasis. More importantly, it suggests that SCP may benefit depression recovery through its properties that are different from either acute or chronic pain and represents a novel research area that has been largely neglected to date.

Major depressive disorder (MDD) is a common mental disorder, which results in seriously impaired condition in the patients and great global disability burden. In light of its quite diverse etiologies, comorbidity with many other diseases, and complex underlying pathology, it has been a great challenge to understand the physiological basis of MDD, which may be a complex of related diseases, rather than a single one. In addition to the partial understanding of MDD, the individual heterogeneities among patients may render the development of a universal treatment an elusive goal. But studying how each of currently available treatments affects the disease can generate useful information to stratify patients into different subtypes for individualized treatments. In this case report, we present the first report of repeated success of using meditation as the only treatment of MDD, compared to initial success but no remission with other conventional antidepressants on the same patient. We hypothesized that the short but continuous natural pain during one-hour meditation sittings has the therapeutic effect to treat depression in the case of this patient and potentially others with MDD. This special opportunity of eliminating tremendous heterogeneity among different individuals has enabled us to probe deeply into the potential mechanism of depression treatments and the complex physiology of depression itself, both of which have likely profound implications in the treatment of other MDD patients as well. More importantly, this case report helps us to dissect one specific component of meditation for its long-known and well-established benefit against depression.

The correlation and comorbidity between depression and chronic pain have been observed for a long time. Generally, it is considered that the two conditions reinforce each other, whereas the causal relationship between them is not clear. However, some evidence suggested that chronic pain may reverse the progression of depression in some cases. This article presents a selective review of clinical and pharmacological observations between depression and pain, and their interactions at neurochemical and neurobiological levels. In addition, we open a discussion on a recent case report of repeated success of using short but continuous pain during meditation as the only treatment of depression, compared to initial success but no remission with other conventional antidepressants on the same patient. Together this review proposes an updated model for depression and its various treatments that is based on synaptic and system homeostasis. More importantly, it suggests that short but continuous pain may benefit depression recovery through its properties that are different from either acute or chronic pain and represents a novel research area that has been largely neglected to date.

Introduction. Few studies have compared the dependence to different tobacco and nicotine products. Besides how dependence may vary between tobacco products there is even less known how it relates to other common drugs, e.g. caffeine. In this study degree of dependence was compared between snus, cigarettes, nicotine replacement (NR), electronic cigarettes and coffee. Methods. An internet panel was used to obtain a representative sample of 3001 Swedes. The responders were asked among other related things about their use of snus, NR, traditional cigarette or e-cigarette use and coffee consumption. The indicators of dependence used were: A. the Heavy Smoking Index, B. The proportions that used within 30 min after raising in the morning, C. rating the first use in the morning as the most important and D. Stating that it would be very hard to give up entirely. Results. Significantly fewer among coffee drinkers started use within 30 minutes of awakening compared with all other products. The first use of the day was found to be more important for snus users compared with other products. On HSI there was no difference between snus and cigarettes. Snus and cigarettes were rated as being more difficult to give up than NR and coffee. Conclusion. Dependence to traditional cigarettes and snus seem to be relatively similar while NR was rated lower and coffee lowest. Since the prevalence of caffeine use in all forms is so much more prevalent than nicotine use there might be more persons in the society heavily dependent on caffeine. Implication. Tobacco products are likely more dependence forming that NR products and coffee. The addiction to coffee or caffeine is seldom discussed in the society. But if there are more individuals heavily dependent on coffee than nicotine and some nicotine containing products like snus and even more so NR are not that much more harmful than coffee how problematic is the addiction?

Background and objectives: due to the neurotoxic effect caused by high levels of cortisol, studies suggest that stress and certain psychiatric disorders, such as mood disorders, have influences under the hippocampus, causing a decrease in volume and consequent memory changes. This study aims to evaluate the relationship between hippocampal volume in patients with mood disorders under therapy. Materials and Methods: the PRISMA protocol for systematic reviews was followed. Pubmed, Cochraine and Scielo databases were searched by terms “Hippocampus”, “Mood Disorders” and “MRI”, and variants in other languages, in human, from January 2011 to September 2016. The individual quality of the articles was analyzed using the Cochraine modified scale for clinical trials and the Agency for Healthcare Research and Quality scale for observational studies. Results: all studies showed reduction of hippocampal volume in depressive patients. Change in hippocampal volume is not related to the use of antidepressant. Particularly the sub-region of the subculum is more reduced, without lateralizations. Significant relationship between stress and right hippocampal reduction. The findings seem to point out: a common pathway of hippocampus reduction, mediated by stress, explaining memory deficits due to depression, where the cortisol pathway seems to act; alteration in the prefrontal cortex; reduction in the subiculum related to inhibition of the hypothalamic-pituitary-adrenal axis, corroborating the hypothesis of cortisol. Conclusions: the papers suggest: association between global hippocampal atrophy with mood disorders; reduction of hippocampal subiculum; refractoriness to clinical treatment among patients with lower hippocampal volume.

Alzheimer’s Disease (AD) is a neurodegenerative condition that currently has no known cure. The principles of the expanding field of network medicine (NM) have recently been applied to AD research. The main principle of NM proposes that diseases are much more complicated than one mutation in one gene, and incorporate different genes, connections between genes, and pathways that may include multiple diseases to create full scale disease networks. AD research findings as a result of the application of NM principles have suggested that functional network connectivity, myelination, myeloid cells, and genes and pathways may play an integral role in AD progression, and may be integral to the search for a cure. Different aspects of the AD pathology could be potential targets for drug therapy to slow down or stop the disease from advancing, but more research is needed to reach definitive conclusions. Additionally, the holistic approaches of network pharmacology in traditional Chinese medicine (TCM) research may be viable options for the AD treatment, and may lead to an effective cure for AD in the future.

Context: A clinical video telehealth (CVT) program was implemented improve access and quality of dementia care to patients and their caregivers in rural areas. The program was offered as part of an established dementia clinic/geriatric primary care clinic in collaboration with five community-based outpatient clinics (CBOC’s) affiliated with the Tennessee Valley Healthcare System (TVHS) in middle Tennessee. Telehealth support was provided by a physician – social worker team visit. Methods: Telehealth training and equipment were provided to clinic personnel, functioning part-time with other collateral clinical duties. Patients and caregivers were referred by primary care providers and had an average of 1 to 2 CVT encounters originating at their local CBOC lasting 20 to 30 minutes. Clinical characteristics and outcomes of patients and caregivers receiving CVT support were collected by retrospective electronic medical record (EMR) review. Results: Over a 3-year period 45 CVT encounters were performed on patient-caregiver pairs, followed for a mean of 15 (1-36) months. Some 80% patients had dementia confirmed and 89% of these had serious medical comorbidities, took an average of 8 medications, and resided at a distance of 103 (76-148) miles from the medical center. Dementia patients included 33% with late stage dementia, 25% received additional care from a mental health provider, 23% took antipsychotic medications, 19% transitioned to a higher level of care, and 19% expired an average of 10.2 months following consultation. Caregiver distress was present in 47% of family members. Consult recommendations included 64% community-based long-term care services and supports (LTSS), 36% medications, and 22% further diagnostic testing. Acceptance of the CVT encounter was 98%, with 8770 travel miles saved. Conclusion: CVT is well received and may be helpful in providing dementia care and supporting dementia caregivers to obtain LTSS for high-need older adults in rural areas.

Background: Schizophrenia is a severe psychiatric disorder that has a large impact on patients’ lives. In addition to Western medicine, the use of additional treatments, such as acupuncture, in treating the positive, negative, and cognitive symptoms is increasing. Methods: We conducted a systematic review on the use of acupuncture as an add-on treatment for patients with schizophrenia that are in regular care, with a special focus on the treatment of the often accompanying co-morbid sleep disorders. In this study, we searched the Medline, ScienceDirect, Cochrane Library, Scopus, and ERIC databases with a cut-off date of December 31, 2017, thereby following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol. Results: Our search resulted in 26 eligible studies. Most studies showed limited evidence for the use of acupuncture as add-on therapy in the treatment of clinical symptoms, but beneficial effects have been reported in the treatment of co-morbid sleep disorders. Conclusions: Limited evidence was found for the use of acupuncture as add-on therapy in the treatment of patients with schizophrenia; however, positive results were found in the treatment of sleep disorders, but this result needs to be confirmed in large, randomized, controlled trials.

Although the number of unwed mothers have mental health problems and intellectual disability, little research have focused on their mental and cognitive status. Since there has been public stigma of unwed mother in South Korea, they tend to conceal their status and less likely to seek psychiatric and psychological help. In this context, this study aims to assess current status of their mental health and intellectual characteristics. A total 48 unwed mothers from two shelter homes in South Korea were agreed to participate in the study. To compare mental health and intellectual abilities of unwed mothers with the general women population, reference data from national studies was used. Unwed mothers were more likely to have mood disorder, post traumatic stress disorder(PTSD), alcohol and nicotine use disorder, attention-deficit hyperactivity disorder (ADHD) than the general women population. Among 48 participants, 20 (41.7%) were lower than 70 Intelligence Quotient (IQ) and the mean of IQ (78.31) was significantly lower than normalized IQ mean of general women population. In logistic regression analysis, psychiatric disorders were associated intellectual disability. This study confirmed that unwed mothers dwelling in Korean shelter homes have more experience of mental disorders and lower intellectual ability than general women population.

The Samenta study was conducted in 2009 in the Greater Paris area to estimate the prevalence of psychiatric disorders among the homeless. A cross-sectional survey was performed with a three-stage random sample of homeless people (n = 859), including users of day services, emergency shelters, hot meal distribution, long-term rehabilitation centres and social hotels. Information was collected by a lay interviewer, using the Mini International Neuropsychiatric Interview, and completed by a psychologist through an open clinical interview. In the end, a psychiatrist assessed the psychiatric diagnosis according to the ICD10. One third of the homeless in the Paris area had at least one severe psychiatric disorder: psychotic disorders (13%), anxiety disorders (12%) or severe mood disorders (7%). One in five was alcohol dependent and 18% were drug users. Homeless women had significantly higher prevalence of anxiety disorders and depression and men were more likely to suffer from psychotic disorders. Homeless people of French origin were at higher risk of SPD, as well as people who experienced various adverse life events before the age of 18 (running away, sexual violence, parental disputes, and/or addictions) and those who experienced homelessness for the first time before the age of 26. The prevalence rates of main psychiatric disorders within the homeless population of our study are consistent with those reported in other Western cities. Our results advocate for an improvement in detection, housing and care of psychiatric homeless.

The Samenta study was conducted in 2009 in the Greater Paris area to estimate the prevalence of psychiatric disorders among the homeless. A cross-sectional survey was performed with a three-stage random sample of homeless people (n = 859), including users of day services, emergency shelters, hot meal distribution, long-term rehabilitation centres and social hotels. Information was collected by a lay interviewer, using the Mini International Neuropsychiatric Interview, and completed by a psychologist through an open clinical interview. In the end, a psychiatrist assessed the psychiatric diagnosis according to the ICD10. One third of the homeless in the Paris area had at least one severe psychiatric disorder: psychotic disorders (13%), anxiety disorders (12%) or severe mood disorders (7%). One in five was alcohol dependent and 18% were drug users. Homeless women had significantly higher prevalence of anxiety disorders and depression and men were more likely to suffer from psychotic disorders. Homeless people of French origin were at higher risk of SPD, as well as people who experienced various adverse life events before the age of 18 (running away, sexual violence, parental disputes, and/or addictions) and those who experienced homelessness for the first time before the age of 26. The prevalence rates of main psychiatric disorders within the homeless population of our study are consistent with those reported in other Western cities. Our results advocate for an improvement in detection, housing and care of psychiatric homeless.

Apart from their established role in embryonic development Nerve Growth Factors (NGFs) have diverse functions in the nervous system. Their role in integration of physiological functioning of the nervous system is now attracting attention. In the present analysis, we propose a novel paradigm about a novel role of NGFs: NGFs play imperative role in maintaining psychological integrity of an individual as a biological system. This function may be mediated through HPA-axis- operated homeostatic mechanisms; stress induced disruption of which may lead to psychiatric disorders. Current literature suggests existence of constitutive homeostatic regulatory mechanisms for NGFs disruption which may lead to pertinent and imperative behavioural effects. NGFs are known to play crucial role in endocrine regulation. This is especially true with the prototype ‘NGF’ and Brain Derived Neurotrophic Factor (BDNF). These moieties have been observed to play important function in maintaining neuro-endocrine homeostasis thereby having a profound impact on the psychological health of an individual. Role of NGFs and HPA-axis activation (in separate studies) in developing psychiatric disorders - especially those born of stress - have been reported. Literature suggests their unique interplay for producing a common effect which might be implicated in stress induced genesis of psychiatric disorders. This aspect, therefore, needs to be elucidated further as a disease etiogenesis model. This model may yield important insights into the biology of psychiatric disorders and may open ways for new therapeutic approaches.

Music therapy has served as complementary and alternative medicine for various neurological disorders. Five Phases Music Therapy (FPMT) employs the theory of five phases and five music scales or tones (宫Gong (do), 商Shang (ri), 角Jue (mi), 徵Zhi (so) and 羽Yu (la)) to analyze and treat mind-body illness. In Chinese Medicine (CM), the five music scales are used to connect the human body and the universe, interpret personalities and constitution and analyze the influences of climatic changes on health. FPMT has a self-contained theory and routine of practice application. Large amounts of clinical and fundamental reports have been available and clinical benefits have been obtained. However more systemic clinic research esp. evidence-based and random controlled trials must be performed to validate and optimize its routines and biological and neurological mechanism must be further explored. It’s reasonable to believe that the effective music therapy will attract more attention from the world outside China with the introduction of FPMT.

Many emotionally disturbed children who have been maltreated and are legally separated from their parents or primary caregivers live in group homes and receive compulsory education. Such institutions provide various special intervention programs. Taiko, a Japanese style of group drumming, is one such program because playing drums in a group may improve children’s emotional well-being. However, evidence for its efficacy has not been well established at the biological level. In this study, we measured salivary levels of oxytocin (OT), a neuropeptide associated with social memory and communication, in three conditions (recital, practice, and free sessions) in four classes of school-aged children. Following the sessions, OT concentrations showed changes in various degrees and directions (no change, increases, or decreases). However, the mean OT concentration changes after each session increased, ranging from 112% to 165%. Plasma OT concentrations were equally sensitive to drum playing in school-aged boys and girls. However, the difference between practice and free play sessions was only significant among elementary school boys aged 8-12 years. The results suggest that younger boys are most responsive to this type of educational music intervention.

In current diagnostic systems, schizophrenia and bipolar disorder are still conceptualized as distinct categorical entities. Recently, both clinical and genetic evidence have challenged this Kraepelinian dichotomy. There are only few longitudinal studies addressing the potential overlaps between these conditions. Here, we present design and first results of the PsyCourse study, an ongoing transdiagnostic study of the affective-to-psychotic continuum that combines longitudinal deep phenotyping and dimensional assessment of psychopathology with an extensive collection of biomaterial. Within the DSM-IV framework, we compare two broad diagnostic groups: one consisting of predominantly affective and one of predominantly psychotic disorders. Depressive, manic, and psychotic symptoms as well as global functioning over time were analyzed. Furthermore, we explore the effects of polygenic risk scores for schizophrenia on diagnostic group membership and address their effects on non-participation in follow-up visits. While phenotypic results show differences in both current psychotic and manic symptoms, depressive symptoms did not vary between both groups. Polygenic risk scores for schizophrenia significantly explained part of the variability of the diagnostic group. Furthermore, there was a trend that a higher polygenic loading for schizophrenia was associated with attrition. Because of its unique properties, the PsyCourse study presents a prime resource for the interrogation of complex genotype-phenotype relationships.

Apart from their established role in embryonic development Nerve Growth Factors (NGFs) have diverse functions in the nervous system. Their role in integration of physiological functioning of the nervous system is now attracting attention. In the present analysis, we propose a new paradigm about a novel role of NGFs. We hypothesize that NGFs play imperative role in maintaining psychological integrity of an individual as a biological system. This function may be mediated through HPA-axis- operated homeostatic mechanisms; stress induced disruption of which may lead to psychiatric disorders. Current literature suggests existence of constitutive homeostatic regulatory mechanisms for NGFs disruption which may lead to important behavioural effects. NGFs have been shown to play crucial parts in endocrine regulation. This is especially true with the prototype ‘NGF’ and Brain Derived Neurotrophic Factor (BDNF). These moieties have been observed to play important role in maintaining neuro-endocrine homeostasis thereby having a profound impact on the psychological health of an individual. Role of NGFs and HPA-axis activation (in separate studies) in developing psychiatric disorders - especially those born of stress - have been established. Literature suggests their unique interplay for producing a common effect which might be implicated in stress induced genesis of psychiatric disorders. This aspect, therefore, needs to be elucidated further as a disease etiogenesis model. This model may yield important insights into the evolution of psychiatric disorders and may open ways for new therapeutic approaches.

Music therapy has served as complementary and alternative medicine for various neurological disorders. Five Phases Music Therapy (FPMT) employs the theory of five phases and five music scales or tones (Gong (do), Shang (ri), Jue (mi), Zhi (so) and Yu (la)) to analyze and treat mind-body illness. In Chinese Medicine (CM) the five music scales are used to connect the human body and the universe, summarize personalities and constitution and analyze the influences of climatic changes on health. FPMT has a self-contained theory and routine of practice application. Large amount of clinical and fundamental reports has been available and clinical benefits have been obtained. However more systemic clinic research esp. Evidence-based and random controlled trials must be performed to validate and optimize it’s routines and biological and neurological mechanism must be further explored. It’s reasonable to believe that the introduction of FPMT to the world outside China may attract more attentions to use this effective music therapy.

Although suicide is a major public health issue worldwide, we understand little of the onset and development of suicidal behavior. Suicidal behavior is argued to be the end result of the complex interaction between psychological, social and biological factors. Epidemiological studies resulted in a range of risk factors for suicidal behavior, but we do not yet understand how their interaction increases the risk for suicidal behavior.  A new approach called network analysis can help us better understand this process as it allows to visualize and quantify complex association between many different symptoms or risk factors. A network analysis of data contain information on suicidal patients can help us understand how risk factors interact and how their interaction is related to suicidal thoughts and behaviour. A network perspective has been successfully applied to the field of depression and psychosis, but not yet to the field of suicidology. In this theoretical article, I will introduce the concept of network analysis to the field of suicide prevention, and offer directions for future applications and studies.

Although suicide is a major public health issue worldwide, we understand little of the onset and development of suicidal behavior. Suicidal behavior is argued to be the end result of the complex interaction between psychological, social and biological factors. A new approach called network analysis can help us better understand suicidal behavior as it allows to visualize and quantify complex association between many different symptoms or risk factors. Risk factors for suicidal behaviour such as intensity of suicidal thoughts and impulsivity are thought to cause each other. A network perspective can help us understand how these risk factors interact and how their interaction is related to future suicidal behaviour. A network perspective has been successfully applied to the field of depression and psychosis, but not yet to the field of suicidology. In this theoretical article, I will introduce the concept of network analysis to the field of suicide prevention, and offer directions for future applications and studies.

Although suicide is a major public health issue worldwide, we understand little of the onset and development of suicidal behavior. Suicidal behavior is argued to be the end result of the complex interaction between social, biological and environmental factors. Traditional epidemiological analytics techniques are not equipped to deal with this complexity. A new technique called network analysis can help us better understand suicidal behavior as it allows to visualize and quantify complex association between many symptoms. It moves away from the idea that symptoms are caused by an underlying common cause such as depression or suicidality. Instead, symptoms are thought to cause each other. A network perspective has been successfully applied to the field of depression, psychosis and PTSD, but not yet to the field of suicidology. In this perspective article, I will argue that a network perspective on suicidal behavior can help us to 1) better understand suicidal behavior, 2) develop more sensitive diagnostic tools for subgroups of patients, and 3) help the personalized treatment of suicidal behavior. I will provide examples based on real data, and offer directions for future studies.

The purposes of this study were to identify clinician’s characteristics associated with higher prescription rates of long-acting injectable (LAI) antipsychotics, as well as the information sources influencing medical decision-making about treatment of schizophrenia. We surveyed 202 psychiatrists during 6 regional French conferences (Bordeaux, Lyon, Marseille, Nice, Paris, Strasbourg). Data on the characteristics of practice, prescription rates of antipsychotic and information sources about their clinical decisions were collected. Most of psychiatrists used second-generation antipsychotic (SGA), and preferentially an oral formulation, in the treatment of schizophrenia. SGA LAI was prescribed to 30.4% of schizophrenic patients. The duration and the type of practice did not influence the class or formulation of antipsychotics used. The clinicians following the higher percentage of schizophrenic patients were associated with the higher use of LAI antipsychotics and the lower use of oral SGA. Personal experience, government regulatory approval and guidelines for the treatment of schizophrenia were the 3 main contributing factors guiding the clinical decision-making of clinicians about treatment of schizophrenia. The more clinicians follow schizophrenic patients, the more they use LAI antipsychotic. The development of specialised programmes with top specialists should lead to better use of LAI in the treatment of schizophrenia.

Music has the innate potential to reach all parts of the brain, stimulates certain brain areas which are not achievable through other modalities. Music Therapy (MT) is being used for more than a century to treat individuals who needs personalized care. MT optimizes motor, speech and language responsibilities of the brain and improves cognitive performance. Pervasive developmentdisorder (PDD) is a multifaceted, neuro developmental disorder and autism spectrum disorder (ASD) comes under PDD, which is defined by deficiencies in three principal spheres: social connection with others, communicative and normal movement skills. The conventional imaging studies illustrate reduced brain area connectivity in people with ASD, involving selected parts of the brain cortex. People with ASD express much interest in musical activities which engages the brain network areas and improves communication and social skills.The main objective of this review is to analyze the potential role of MT in treating the neurological conditions, particularly ASD. Evidence based studies have reported the extensive therapeutic application of music on various part of the brain in a nonverbal child with autism through hearing or making music.Hence we hypothesized that MT intervention can improve the communication capacity in people with ASD, than customary neurorestoration therapy alone.

Objective: The main purpose of this study was to investigate the mental health of Cypriot citizens, living in the current difficult period of economic recession. Specific objective was to investigate the different factors (gender, age, socio-economic factors, etc.) that may affect the levels of emotional distress, anxiety and depression in visitors of the Rural Health Centre of Kofinou. Materials and Methods: The sample consisted of total 300 Cypriots who visited Kofinou Health Centre in the period between August and September 2015. For the middle-aged citizens the Greek version of the HADS scale (Hospital Anxiety Depression Scale) was administered to 150 persons (Michopoulos I., 2007), while for the visiting senior citizens (aged over 65 years) the Greek version of the GDS scale (Geriatric Depression Scale) was used (Fountoulakis K., et al., 1999). All analyses were performed with the social science analysis package SPSS (version 21). Results: HADS: A total of 150 people of average age 47±11,5 years (23-64), were 56% women, while the 77.3% stated they had drastic reduction of income as well as 46.7% suffered from chronic disease. The 36.6% and 28.7% of the visitors showed moderate and severe forms of anxiety and depression, accordingly. Higher emotional distress is associated with lower educational level (p<0,001). Moreover, patients with low income have higher levels of anxiety (p=0,003), depression (p=0,036) and total emotional distress (p=0,007), while those with chronic disease have a higher stress (p<0,001), depression (p<0,001) and total emotional distress symptoms (p<0,001) compared to non - patients. GDS: 150 patients out of which 77 were women (51.3%). The average age of participants was 72±5,5 years. 93(62%) participants declared a drastic reduction of income due to the financial crisis while 139 (92.7%) stated they had chronic disease. 53 participants (35.3%) think they have symptoms of depression after the economic crisis. The women showed higher level of geriatric depression symptoms than men (p<0.001). Higher levels of depression is associated with lower income (p=0.001). Conclusions: The study shows that stress levels, depression and emotional distress are increased in specific population groups. The main factors affecting the mental health of the participants are the presence of chronic disease, income and level of education.