An epigenetic association analysis of childhood trauma in psychosis reveals possible overlap with methylation changes associated with PTSD

Patients with a severe mental disorder report significantly higher levels of childhood trauma (CT) than healthy individuals. Studies have suggested that CT may affect brain plasticity through epigenetic mechanisms and contribute to developing various psychiatric disorders. We performed a blood-based epigenome-wide association study using the Childhood Trauma Questionnaire-short form in 602 patients with a current severe mental illness, investigating DNA methylation association separately for five trauma subtypes and the total trauma score. The median trauma score was set as the predefined cutoff for determining whether the trauma was present or not. Additionally, we compared our genome-wide results with methylation probes annotated to candidate genes previously associated with CT. Of the patients, 83.2% reported CT above the cutoff in one or more trauma subtypes, and emotional neglect was the trauma subtype most frequently reported. We identified one significant differently methylated position associated with the gene TANGO6 for physical neglect. Seventeen differentially methylated regions (DMRs) were associated with different trauma categories. Several of these DMRs were annotated to genes previously associated with neuropsychiatric disorders such as post-traumatic stress disorder and cognitive impairments. Our results support a biomolecular association between CT and severe mental disorders. Genes that were previously identified as differentially methylated in CT-exposed subjects with and without psychosis did not show methylation differences in our analysis. We discuss this inconsistency, the relevance of our findings, and the limitations of our study.publishedVersio

Polygenic risk for schizophrenia and bipolar disorder in relation to cardiovascular biomarkers

Individuals with schizophrenia and bipolar disorder are at an increased risk of cardiovascular disease (CVD), and a range of biomarkers related to CVD risk have been found to be abnormal in these patients. Common genetic factors are a putative underlying mechanism, alongside lifestyle factors and antipsychotic medication. However, the extent to which the altered CVD biomarkers are related to genetic factors involved in schizophrenia and bipolar disorder is unknown. In a sample including 699 patients with schizophrenia, 391 with bipolar disorder, and 822 healthy controls, we evaluated 8 CVD risk biomarkers, including BMI, and fasting plasma levels of CVD biomarkers from a subsample. Polygenic risk scores (PGRS) were obtained from genome-wide associations studies (GWAS) of schizophrenia and bipolar disorder from the Psychiatric Genomics Consortium. The CVD biomarkers were used as outcome variables in linear regression models including schizophrenia and bipolar disorder PGRS as predictors, age, sex, diagnostic category, batch and 10 principal components as covariates, controlling for multiple testing by Bonferroni correction for the number of independent tests. Bipolar disorder PGRS was significantly (p = 0.03) negatively associated with BMI after multiple testing correction, and schizophrenia PGRS was nominally negatively associated with BMI. There were no other significant associations between bipolar or schizophrenia PGRS, and other investigated CVD biomarkers. Despite a range of abnormal CVD risk biomarkers in psychotic disorders, we only found a significant negative association between bipolar disorder PGRS and BMI. This has previously been shown for schizophrenia PGRS and BMI, and warrants further exploration

Patterns of childhood adverse events are associated with clinical characteristics of bipolar disorder

Background Previous studies in bipolar disorder investigating childhood trauma and clinical presentations of the illness have mainly focused on physical and sexual abuse. Our aim was to explore further the relationship between childhood trauma and disease characteristics in bipolar disorder to determine which clinical characteristics were most strongly associated with childhood trauma total score, as well as subtypes of adverse childhood events, including physical, sexual, emotional abuse and neglect. Methods 141 Patients with bipolar disorder were consecutively recruited, and disease history and clinical characteristics were assessed. History of childhood abuse was obtained using the Childhood Trauma Questionnaire (CTQ). Statistical methods used were factor analysis, Poisson and linear regression, and generalized additive modeling (GAM). Results The factor analysis of CTQ identified three factors: emotional abuse/neglect, sexual abuse and physical abuse. There were significant associations between CTQ total score and earlier onset of illness, reduced level of psychosocial functioning (GAF; Global Assessment of Functioning) and decreased number of hospitalization, which mainly were due to the factor emotional abuse/neglect. Physical abuse was significantly associated with lower GAF scores, and increased number of mood episodes, as well as self-harm. Sexual abuse was significantly associated with increased number of mood episodes. For mood episodes and self-harm the associations were characterized by great variance and fluctuations. Conclusions Our results suggest that childhood trauma is associated with a more severe course of bipolar illness. Further, childhood abuse (physical and sexual), as well as emotional abuse and neglect were significantly associated with accelerating staging process of bipolar disorder. By using specific trauma factors (physical abuse, sexual abuse and emotional abuse/neglect) the associations become both more precise, and diverse

Summaries of plenary, symposia, and oral sessions at the XXII World Congress of Psychiatric Genetics, Copenhagen, Denmark, 12-16 October 2014

The XXII World Congress of Psychiatric Genetics, sponsored by the International Society of Psychiatric Genetics, took place in Copenhagen, Denmark, on 12-16 October 2014. A total of 883 participants gathered to discuss the latest findings in the field. The following report was written by student and postdoctoral attendees. Each was assigned one or more sessions as a rapporteur. This manuscript represents topics covered in most, but not all of the oral presentations during the conference, and contains some of the major notable new findings reported

The relationship between genetic liability, childhood maltreatment, and IQ: findings from the EU-GEI multicentric case-control study

This study investigated if the association between childhood maltreatment and cognition among psychosis patients and community controls was partially accounted for by genetic liability for psychosis. Patients with first-episode psychosis (N = 755) and unaffected controls (N = 1219) from the EU-GEI study were assessed for childhood maltreatment, intelligence quotient (IQ), family history of psychosis (FH), and polygenic risk score for schizophrenia (SZ-PRS). Controlling for FH and SZ-PRS did not attenuate the association between childhood maltreatment and IQ in cases or controls. Findings suggest that these expressions of genetic liability cannot account for the lower levels of cognition found among adults maltreated in childhood

The relationship between genetic liability, childhood maltreatment, and IQ: findings from the EU-GEI multicentric case-control study

This study investigated if the association between childhood maltreatment and cognition among psychosis patients and community controls was partially accounted for by genetic liability for psychosis. Patients with first-episode psychosis (N = 755) and unaffected controls (N = 1219) from the EU-GEI study were assessed for childhood maltreatment, intelligence quotient (IQ), family history of psychosis (FH), and polygenic risk score for schizophrenia (SZ-PRS). Controlling for FH and SZ-PRS did not attenuate the association between childhood maltreatment and IQ in cases or controls. Findings suggest that these expressions of genetic liability cannot account for the lower levels of cognition found among adults maltreated in childhood

Cannabis use as a potential mediator between childhood adversity and first-episode psychosis: results from the EU-GEI case-control study

Background Childhood adversity and cannabis use are considered independent risk factors for psychosis, but whether different patterns of cannabis use may be acting as mediator between adversity and psychotic disorders has not yet been explored. The aim of this study is to examine whether cannabis use mediates the relationship between childhood adversity and psychosis. Methods Data were utilised on 881 first-episode psychosis patients and 1231 controls from the European network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Detailed history of cannabis use was collected with the Cannabis Experience Questionnaire. The Childhood Experience of Care and Abuse Questionnaire was used to assess exposure to household discord, sexual, physical or emotional abuse and bullying in two periods: early (0–11 years), and late (12–17 years). A path decomposition method was used to analyse whether the association between childhood adversity and psychosis was mediated by (1) lifetime cannabis use, (2) cannabis potency and (3) frequency of use. Results The association between household discord and psychosis was partially mediated by lifetime use of cannabis (indirect effect coef. 0.078, s.e. 0.022, 17%), its potency (indirect effect coef. 0.059, s.e. 0.018, 14%) and by frequency (indirect effect coef. 0.117, s.e. 0.038, 29%). Similar findings were obtained when analyses were restricted to early exposure to household discord. Conclusions Harmful patterns of cannabis use mediated the association between specific childhood adversities, like household discord, with later psychosis. Children exposed to particularly challenging environments in their household could benefit from psychosocial interventions aimed at preventing cannabis misuse

Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis: the EU-GEI study

Background A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone. Methods We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case–control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS − ORexposure − ORPRS + 1] with adjustment for potential confounders. Results There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) −1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI −6.25 to 20.88). Conclusions Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates