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Schizophrenia and other psychotic disorders are highly debilitating psychiatric conditions that lack a clear etiology and exhibit polygenic inheritance underlain by pleiotropic genes. The prevailing explanation points to the interplay between predisposing genes and environmental exposure. Accumulated evidence suggests that epigenetic regulation of the genome may mediate dynamic gene–environment interactions at the molecular level by modulating the expression of psychiatric phenotypes through transcription factors. This systematic review summarizes the current knowledge linking schizophrenia and other psychotic disorders to epigenetics, based on PubMed and Web of Science database searches conducted according to the PRISMA guidelines. Three groups of mechanisms in case–control studies of human tissue (i.e., postmortem brain and bio-fluids) were considered: DNA methylation, histone modifications, and non-coding miRNAs. From the initial pool of 3,204 records, 152 studies met our inclusion criteria (11,815/11,528, 233/219, and 2,091/1,827 cases/controls for each group, respectively). Many of the findings revealed associations with epigenetic modulations of genes regulating neurotransmission, neurodevelopment, and immune function, as well as differential miRNA expression (e.g., upregulated miR-34a, miR-7, and miR-181b). Overall, actual evidence moderately supports an association between epigenetics and schizophrenia and other psychotic disorders. However, heterogeneous results and cross-tissue extrapolations call for future work. Integrating epigenetics into systems biology may critically enhance research on psychosis and thus our understanding of the disorder. This may have implications for psychiatry in risk stratification, early recognition, diagnostics, precision medicine, and other interventional approaches targeting epigenetic fingerprints.

Background Although subacute and chronic gastrointestinal symptoms are very common in primary care, epidemiological date are sparse. The aim of the study was to examine and quantify the prevalence of subacute and chronic gastrointestinal symptoms and their associations with somatic and mental disorders in the general population. Methods Data were collected prospectively between 1981 (age m = 22, f = 23) and 2008 (age 49/50) from the Zurich Cohort Study ( n  = 292 men, 299 women), a representative general population survey. The participants were assessed using a semi-structured interview, the “Structured Psychopathological Interview and Rating of the Social Consequences of Psychological Disturbances for Epidemiology” (SPIKE). Prevalence rates were computed to be representative of the general population aged 22–50. Associations were quantified by odds ratios (ORs) and their 99% confidence intervals (CI). Results The prevalences of intestinal and of gastric symptoms were significantly higher among women in all categories examined. For example, any gastric symptoms: f. 26.4% vs m.15.2%; any intestinal symptoms: 27.6% vs 14.6%; nausea/vomitus: 19.1% vs 4.5%; constipation: 15.8% vs 6.5% (all p  < 0.001). Strong associations (all p  < 0.0001) were found between fatigue (1 month) and chronic stomach (OR = 9.96, 99%-CI: 5.53–17.94) and chronic intestinal symptoms (OR = 9.02, 99%-CI: 4.92–16.54). Panic attacks were associated with subacute intestinal symptoms (OR = 4.00, 99%-CI: 2.43–6.59). Anxiety was more strongly associated with subacute intestinal symptoms (OR = 3.37, 99%-CI: 2.23–5.08) than with subacute stomach symptoms (OR = 1.85, 1.20–2.86). Bipolar disorders were associated with subacute stomach symptoms (OR = 1.83, 1.18–2.17) and unipolar depression with subacute intestinal symptoms (OR = 2.05, 1.34–3.15). Conclusions Remarkably high prevalence rates of gastric and intestinal complaints were observed in women (over 1/4; men 1/7). Fatigue/neurasthenia was the strongest co-factor in both conditions. Various syndromes related to anxiety, phobia, and panic disorders showed further significant associations. The integration of psychiatric and/or psychological treatment could help address the functional part of gastric and intestinal syndromes.

Resonance is the phenomenon of one person unconsciously mirroring the motor actions as basis of emotional expressions of another person. This shared representation serves as a basis for sharing physiological and emotional states of others and is an important component of empathy. Contagious laughing and contagious yawning are examples of resonance. In the interpersonal contact with individuals with schizophrenia we can often experience impaired empathic resonance. The aim of this study is to determine differences in empathic resonance—in terms of contagion by yawning and laughing—in individuals with schizophrenia and healthy controls in the context of psychopathology and social functioning. We presented video sequences of yawning, laughing or neutral faces to 43 schizophrenia outpatients and 45 sex- and age-matched healthy controls. Participants were video-taped during the stimulation and rated regarding contagion by yawning and laughing. In addition, we assessed self-rated empathic abilities (Interpersonal Reactivity Index), psychopathology (Positive and Negative Syndrome Scale in the schizophrenia group resp. Schizotypal Personality Questionnaire in the control group), social dysfunction (Social Dysfunction Index) and executive functions (Stroop, Fluency). Individuals with schizophrenia showed lower contagion rates for yawning and laughing. Self-rated empathic concern showed no group difference and did not correlate with contagion. Low rate of contagion by laughing correlated with the schizophrenia negative syndrome and with social dysfunction. We conclude that impaired resonance is a handicap for individuals with schizophrenia in social life. Blunted observable resonance does not necessarily reflect reduced subjective empathic concern.

Abstract In subjects at risk for psychosis, the studies on gray matter volume (GMV) predominantly reported volume loss compared with healthy controls (CON). However, other important morphological measurements such as cortical surface area (CSA) and cortical thickness (CT) were not systematically compared. So far, samples mostly comprised subjects at genetic risk or at clinical risk fulfilling an ultra-high risk (UHR) criterion. No studies comparing UHR subjects with at-risk subjects showing only basic symptoms (BS) investigated the differences in CSA or CT. Therefore, we aimed to unravel the contribution of the 2 morphometrical measures constituting the cortical volume (CV) and to test whether these groups inhere different morphometric features. We conducted a surface-based morphometric analysis in 34 CON, 46 BS, and 39 UHR to examine between-group differences in CV, CSA, and CT vertex-wise across the whole cortex. Compared with BS and CON, UHR individuals presented increased CV in frontal and parietal regions, which was driven by larger CSA. These groups did not differ in CT. Yet, at-risk subjects who later developed schizophrenia showed thinning in the occipital cortex. Furthermore, BS presented increased CSA compared with CON. Our results suggest that volumetric differences in UHR subjects are driven by CSA while CV loss in converters seems to be based on cortical thinning. We attribute the larger CSA in UHR to aberrant pruning representing a vulnerability to develop psychotic symptoms reflected in different levels of vulnerability for BS and UHR, and cortical thinning to a presumably stress-related cortical decomposition.

Accurate information about preferred suicide methods is important for devising strategies and programmes for suicide prevention. Our knowledge of the methods used and their variation across countries and world regions is still limited. The aim of this study was to provide the first comprehensive overview of international patterns of suicide methods. Data encoded according to the International Classification of Diseases (10th revision) were derived from the WHO mortality database. The classification was used to differentiate suicide methods. Correspondence analysis was used to identify typical patterns of suicide methods in different countries by providing a summary of cross-tabulated data. Poisoning by pesticide was common in many Asian countries and in Latin America; poisoning by drugs was common in both Nordic countries and the United Kingdom. Hanging was the preferred method of suicide in eastern Europe, as was firearm suicide in the United States and jumping from a high place in cities and urban societies such as Hong Kong Special Administrative Region, China. Correspondence analysis demonstrated a polarization between pesticide suicide and firearm suicide at the expense of traditional methods, such as hanging and jumping from a high place, which lay in between. This analysis showed that pesticide suicide and firearm suicide replaced traditional methods in many countries. The observed suicide pattern depended upon the availability of the methods used, in particular the availability of technical means. The present evidence indicates that restricting access to the means of suicide is more urgent and more technically feasible than ever.

Dopamine is involved in the pathophysiology of schizophrenia. Disrupted salience processing by the salience network (SN) may be a central link between dysregulated dopamine function and psychotic symptoms. However, dopaminergic influence on the SN and its presumed influence on psychotic and subpsychotic symptoms or psychotic-like experiences in healthy individuals remain unclear. Therefore, we investigated dopamine-induced changes in functional connectivity of the right anterior insula (rAI), a central SN hub, and their association with psychotic-like experiences. We enrolled 54 healthy, right-handed male subjects in a randomized, double-blind, cross-sectional placebo-controlled experiment. Psychotic-like experiences were assessed using the revised Exceptional Experiences Questionnaire (PAGE-R). They then received either placebo (n = 32) or 200 mg L-DOPA (n = 33), a dopamine precursor, orally and underwent resting-state functional magnetic resonance imaging. In a seed-to-voxel approach, we analyzed dopamine-induced changes in functional connectivity of the rAI and assessed the relationship between functional connectivity changes and PAGE-R score. L-DOPA reduced functional connectivity between the rAI and the left auditory cortex planum polare. In the placebo group, we found a strong negative correlation between PAGE-R score and rAI to planum polare functional connectivity; in the L-DOPA group, there was a strong positive correlation between PAGE-R score and functional connectivity between rAI and planum polare. The PAGE-R score explained about 30% of the functional connectivity variation between rAI and planum polare in the two groups. Our findings suggest that psychotic-like experiences are associated with dopamine-induced disruption of auditory input to the SN, which may lead to aberrant attribution of salience.

BackgroundThe Clinical descriptions and diagnostic guidelines for the ICD-11 Classification of mental and behavioural disorders should soon be finalized. To measure their potential impact, the new proposed definitions of bipolar disorders in ICD-11 were applied to data from the Zurich cohort study and compared with the definitions of ICD-10 and DSM-5.ResultsWe found little difference between ICD-11 and ICD-10 in the identification of subjects with bipolar disorders, but compared to DSM-5 a considerable increase in the diagnosis of hypomanic episodes and therefore of bipolar-II disorders.ConclusionsCompared to ICD-10 and DSM-5 the definition of hypomanic episodes according to ICD-11 represents important progress. A higher prevalence of BP-II disorder makes sense from a clinical point of view. Further transcultural research is needed into whether out-patient treatment should be included as a criterion for hypomania. Pure mania is unfortunately missing as an independent and codable disorder in the international diagnostic manuals, whether ICD-11 or DSM-5.

An international six-centre randomised controlled trial comparing individual placement and support (IPS) with usual vocational rehabilitation for people with serious mental illness found IPS to be more effective for all vocational outcomes. To determine which patients with severe mental illness do well in vocational services and which process and service factors are associated with better outcomes. Patient characteristics and early process variables were tested as predictors of employment outcomes. Service characteristics were explored as predictors of the effectiveness of IPS. Patients with previous work history, fewer met social needs and better relationships with their vocational workers were more likely to obtain employment and work for longer. Remission and swifter service uptake were associated with working more. Having an IPS service closer to the original IPS model was the only service characteristic associated with greater effectiveness. The IPS service was found to be more effective for all vocational outcomes. In addition, maintaining high IPS fidelity and targeting relational skills would be a valuable focus for all vocational interventions, leading to improved employment outcomes. Motivation to find work may be decreased by satisfaction with current life circumstances.

Depression is highly prevalent in the working population and is associated with significant loss of workdays; however, access to evidence-based treatment is limited. This study evaluated the effectiveness of a Web-based intervention in reducing mild to moderate depression and sickness absence. In an open-label randomized controlled trial, participants were recruited from a large-scale statutory health insurance and were assigned to two groups. The intervention group had access to a 12 week Web-based program consisting of structured interactive sessions and therapist support upon request. The wait-list control group had access to unguided Web-based psycho-education. Depressive symptoms were self-assessed at baseline, post-treatment, and follow-up (12 weeks after treatment) using the Patient Health Questionnaire (PHQ-9) and Beck Depression Inventory (BDI-II) as primary outcome measures. Data on sickness absence was retrieved from health insurance records. Intention-to-treat (ITT) analysis and per-protocol (PP) analysis were performed. Of the 180 participants who were randomized, 88 completed the post-assessment (retention rate: 48.8%, 88/180). ITT analysis showed a significant between-group difference in depressive symptoms during post-treatment in favor of the intervention group, corresponding to a moderate effect size (PHQ-9: d=0.55, 95% CI 0.25-0.85, P<.001, and BDI-II: d=0.41, CI 0.11-0.70, P=.004). PP analysis partially supported this result, but showed a non-significant effect on one primary outcome (PHQ-9: d=0.61, 95% CI 0.15-1.07, P=.04, and BDI-II: d=0.25 95% CI -0.18 to 0.65, P=.37). Analysis of clinical significance using reliable change index revealed that significantly more participants who used the Web-based intervention (63%, 63/100) responded to the treatment versus the control group (33%, 27/80; P<.001). The number needed to treat (NNT) was 4.08. Within both groups, there was a reduction in work absence frequency (IG: -67.23%, P<.001, CG: -82.61%, P<.001), but no statistical difference in sickness absence between groups was found (P=.07). The Web-based intervention was effective in reducing depressive symptoms among adults with sickness absence. As this trial achieved a lower power than calculated, its results should be replicated in a larger sample. Further validation of health insurance records as an outcome measure for eHealth trials is needed. International Standard Randomized Controlled Trial Number (ISRCTN): 02446836; http://www.isrctn.com/ISRCTN02446836 (Archived by WebCite at http://www.webcitation.org/6jx4SObnw).

Abstract Background Between unaffected mental health and diagnosable psychiatric disorders, there is a vast continuum of functioning. The hypothesized link between striatal dopamine signaling and psychosis has guided a prolific body of research. However, it has been understudied in the context of multiple interacting factors, subclinical phenotypes, and pre-postsynaptic dynamics. Method This work investigated psychotic-like experiences and D2/3 dopamine postsynaptic receptor availability in the dorsal striatum, quantified by in vivo [11C]-raclopride positron emission tomography, in a sample of 24 healthy male individuals. Additional mediation and moderation effects with childhood trauma and key dopamine-regulating genes were examined. Results An inverse relationship between nondisplaceable binding potential and subclinical symptoms was identified. D2/3 receptor availability in the left putamen fully mediated the association between traumatic childhood experiences and odd beliefs, that is, inclinations to see meaning in randomness and unfounded interpretations. Moreover, the effect of early adversity was moderated by a DRD2 functional variant (rs1076560). The results link environmental and neurobiological influences in the striatum to the origination of psychosis spectrum symptomology, consistent with the social defeat and diathesis–stress models. Conclusions Adversity exposure may affect the dopamine system as in association with biases in probabilistic reasoning, attributional style, and salience processing. The inverse relationship between D2/3 availability and symptomology may be explained by endogenous dopamine occupying the receptor, postsynaptic compensatory mechanisms, and/or altered receptor sensitivity. This may also reflect a cognitively stabilizing mechanism in non-help-seeking individuals. Future research should comprehensively characterize molecular parameters of dopamine neurotransmission along the psychosis spectrum and according to subtype profiling.