Childhood Trauma in Schizophrenia: Current Findings and Research Perspectives

Schizophrenia is a severe neuropsychiatric disorder with persistence of symptoms throughout adult life in most of the affected patients. This unfavorable course is associated with multiple episodes and residual symptoms, mainly negative symptoms and cognitive deficits. The neural diathesis-stress model proposes that psychosocial stress acts on a pre-existing vulnerability and thus triggers the symptoms of schizophrenia. Childhood trauma is a severe form of stress that renders individuals more vulnerable to developing schizophrenia;neurobiological effects of such trauma on the endocrine system and epigenetic mechanisms are discussed. Childhood trauma is associated with impaired working memory, executive function, verbal learning, and attention in schizophrenia patients, including those at ultra-high risk to develop psychosis. In these patients, higher levels of childhood trauma were correlated with higher levels of attenuated positive symptoms, general symptoms, and depressive symptoms;lower levels of global functioning;and poorer cognitive performance in visual episodic memory end executive functions. In this review, we discuss effects of specific gene variants that interact with childhood trauma in patients with schizophrenia and describe new findings on the brain structural and functional level. Additive effects between childhood trauma and brain-derived neurotrophic factor methionine carriers on volume loss of the hippocampal subregions cornu ammonis (CA)4/dentate gyrus and CA2/3 have been reported in schizophrenia patients. A functional magnetic resonance imaging study showed that childhood trauma exposure resulted in aberrant function of parietal areas involved in working memory and of visual cortical areas involved in attention. In a theory of mind task reflecting social cognition, childhood trauma was associated with activation of the posterior cingulate gyrus, precuneus, and dorsomedial prefrontal cortex in patients with schizophrenia. In addition, decreased connectivity was shown between the posterior cingulate/precuneus region and the amygdala in patients with high levels of physical neglect and sexual abuse during childhood, suggesting that disturbances in specific brain networks underlie cognitive abilities. Finally, we discuss some of the questionnaires that are commonly used to assess childhood trauma and outline possibilities to use recent biostatistical methods, such as machine learning, to analyze the resulting datasets

Role of psychiatric hospitals during a pandemic: introducing the Munich Psychiatric COVID-19 Pandemic Contingency Plan

BACKGROUND Psychiatry is facing major challenges during the current coronavirus disease 2019 (COVID)-19 pandemic. These challenges involve its actual and perceived role within the medical system, in particular how psychiatric hospitals can maintain their core mission of attending to people with mental illness while at the same time providing relief to overstretched general medicine services. Although psychiatric disorders comprise the leading cause of the global burden of disease, mental healthcare has been deemphasised in the wake of the onslaught of the pandemic: to make room for emergency care, psychiatric wards have been downsized, clinics closed, psychiatric support systems discontinued and so on. To deal with this pressing issue, we developed a pandemic contingency plan with the aim to contain, decelerate and, preferably, avoid transmission of COVID-19 and to enable and maintain medical healthcare for patients with mental disorders. AIMS To describe our plan as an example of how a psychiatric hospital can share in providing acute care in a healthcare system facing an acute and highly infectious pandemic like COVID-19 and at the same time provide support for people with mental illness, with or without a COVID-19 infection. METHOD This was a descriptive study. RESULTS The plan was based on the German national pandemic strategy and several legal recommendations and was implemented step by step on the basis of the local COVID-19 situation. In addition, mid- and long-term plans were developed for coping with the aftermath of the pandemic. CONCLUSIONS The plan enabled the University Hospital to maintain medical healthcare for patients with mental disorders. It has offered the necessary flexibility to adapt its implementation to the first and second waves of the COVID-19 pandemic in Germany. The plan is designed to serve as an easily adaptable blueprint for psychiatric hospitals around the world

DAOA/G72 predicts the progression of prodromal syndromes to first episode psychosis

The genetic factors determining the progression of prodromal syndromes to first episode schizophrenia have remained enigmatic to date. In a unique prospective multicentre trial, we assessed whether variants at the d-amino acid oxidase activator (DAOA)/G72 locus influence progression to psychosis. Young subjects with a prodromal syndrome were observed prospectively for up to 2 years to assess the incidence of progression to schizophrenia or first episode psychosis. Of the 82 probands with a prodromal syndrome, 21 probands experienced progression to psychosis within the observation period. Assessment of nine common variants in the DAOA/G72 locus yielded two variants with the predictive value for symptom progression: all four probands with the rs1341402 CC genotype developed psychosis compared with 17 out of 78 probands with the TT or CT genotypes (χ2 = 12.348; df = 2; p = 0.002). The relative risk for progression to psychosis was significantly increased in the CC genotype: RR = 4.588 (95% CI = 2.175–4.588). Similarly, for rs778294, 50% of probands with the AA genotype, but only 22% of probands with a GG or GA genotype progressed to psychosis (χ2 = 7.027; df = 2; p = 0.030). Moreover, haplotype analysis revealed a susceptibility haplotype for progression to psychosis. This is one of the first studies to identify a specific genetic factor for the progression of prodromal syndromes to schizophrenia, and further underscores the importance of the DAOA/G72 gene for schizophrenia

Predictors of competitive employment in individuals with severe mental illness: results from an observational, cross-sectional study in Germany

BACKGROUND: Employment is of great importance as it is associated with various positive effects. Individuals with severe mental illness (SMI) are often excluded from competitive employment. Current data on employment of individuals with mental illness are rare, and influencing factors are under-researched. The present study examines possible predictors of competitive employment among individuals with SMI. METHODS: This was a cross-sectional and multicentered study of 300 individuals with SMI aged 18 to 65 years. The following inclusion criteria were used: (I) diagnosis of schizophrenia, schizotypal and delusional disorders (ICD-10 F2x), or affective disorders (ICD-10 F3x), (II) duration of psychiatric illness ≥ 2 years, and (III) substantial impact of illness on social functioning. Participants were interviewed by trained staff using standardised instruments. The relationship between potential predictors (age, sex, education, marital status, living situation, migration background, psychosocial functioning, age at first mental problem, physical illness, work ability) and employment was analysed using a hierarchic binary logistic regression model. RESULTS: Only one-third (34%) of participants were competitively employed. Almost one-third were unemployed (30%), and 28% reported early retirement due to mental illness. Psychosocial functioning was positively associated with competitive employment (OR = 1.09, 95% CI: 1.05 – 1.13, p < 0.001); concurrent chronic physical illness was negatively associated with competitive employment (OR = 0.38, 95% CI: 0.21 – 0.71, p = 0.002). CONCLUSIONS: Findings confirm a high risk of exclusion from competitive employment among individuals with SMI. Nonetheless, a substantial proportion of individuals are employed. Findings call for efforts to maintain or enhance workforce participation among individuals with SMI. A special focus should be placed on improving physical health and strengthening psychosocial functioning. TRIAL REGISTRATION: The study was registered in the German Clinical Trials Register (DRKS) under the registration number DRKS00015801 before the start of recruitment (Registration date: 21.02.2019)

Employment status and desire for work in severe mental illness: results from an observational, cross-sectional study

PURPOSE: People with a severe mental illness (SMI) are at particular risk of occupational exclusion. Among the approaches to occupational rehabilitation, supported employment (SE) has been proven to be the most effective. A requirement to enter SE-programs is that individuals must want to seek competitive employment. The aim of this work is to investigate the relationship between serious mental illness and the desire to work including potential predictors. METHODS: This is a cross-sectional observational study of patients with SMI aged 18–65 years (n = 397). Patients were interviewed by trained staff using standardised instruments. The relationship between potential predictors and a strong preference for employment were analysed using a hierarchic binary logistic regression model. RESULTS: Only about one-quarter (27.9%) of SMI patients is in competitive employment. Another quarter is unemployed (25.9%). Results show that the desire for competitive employment is strong among more than half of the SMI patients. Among the unemployed, two-thirds express a strong desire for work. These individuals are an ideal target group for SE interventions. Comorbid chronic physical illness, diagnosis, and the subjectively judged ability to work are associated with the desire for work. CONCLUSION: Our data confirm a substantial exclusion of individuals with SMI from the workforce. In general, care needs for workplace interventions are not being met and leave much room for improvement. In addition to employment status, the desire for work should be routinely assessed. STUDY REGISTRATION: The study was registered in the German Clinical Trials Register (DRKS) (https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00015801) and under the WHO-Platform “International Clinical Trials Registry Platform” (ICTRP) (https://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00015801) under the registration number DRKS00015801 before the start of recruitment (Registration date: 21.02.2019)

The role of migration in mental healthcare: treatment satisfaction and utilization

Migration rates increase globally and require an adaption of national mental health services to the needs of persons with migration background. Therefore, we aimed to identify differences between persons with and without migratory background regarding (1) treatment satisfaction, (2) needed and received mental healthcare and (3) utilization of mental healthcare. In the context of a cross-sectional multicenter study, inpatients and day hospital patients of psychiatric settings in Southern Germany with severe affective and non-affective psychoses were included. Patients’ satisfaction with and their use of mental healthcare services were assessed by VSSS-54 and CSSRI-EU; patients’ needs were measured via CAN-EU. In total, 387 participants (migratory background: n = 72; 19%) provided sufficient responses for analyses. Migrant patients were more satisfied with the overall treatment in the past year compared to non-migrant patients. No differences between both groups were identified in met and unmet treatment needs and use of supply services (psychiatric, psychotherapeutic, and psychosocial treatment). Despite a comparable degree of met and unmet treatment needs and mental health service use among migrants and non-migrants, patients with migration background showed higher overall treatment satisfaction compared to non-migrants. The role of sociocultural and migrant-related factors may explain our findings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12888-022-03722-8

Characterisation of age and polarity at onset in bipolar disorder

BACKGROUND Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools. AIMS To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics. METHOD Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts. RESULTS Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = -0.34 years, s.e. = 0.08), major depression (β = -0.34 years, s.e. = 0.08), schizophrenia (β = -0.39 years, s.e. = 0.08), and educational attainment (β = -0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO. CONCLUSIONS AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses

Prefrontal cortex gyrification index in twins: an MRI study

Cortical development and folding seems to be under environmental as well as genetic control. The aim of our study was to estimate the genetic influence on gyrification and cortical volumes, comparing prefrontal gyrification index (GI) in monozygotic (MZ) and dizygotic (DZ) twin pairs, and unrelated pairs. Twenty-four subjects (6 pairs of MZ and 6 pairs of DZ twins) were included in this study. Prefrontal cortical folding (gyrification) was measured by an automated and manual version of the gyrification index (A-GI, M-GI) according to previously published protocols. MR-imaging was performed and 3 representative slices were selected from coronar MR-imaging scans. The volumes of the total brain, temporal lobes, prefrontal lobes, and cerebellum were analyzed, too. To evaluate similarity in GI, absolute differences in GI, and brain volumes as well as intraclass correlations of twin pairs were compared with regard to twin status. Finally, a control group of unrelated pairs was assembled from the first two study groups and analyzed. Compared to unrelated pairs, twin pairs exhibited more similarity concerning different brain volumes and a trend to more similarity concerning A-GI. MZ twins did not present more similarity concerning GI (automatically and manually measured) and volume measurements compared to DZ twins. Different factors, like intrauterine factors, postnatal development conditions, and especially environmental factors might account for the differences between related and unrelated pairs. The nonexistence of a pronounced similarity in MZ twins compared to DZ twins concerning prefrontal GI raises questions about the extent of genetic influence on GI