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

Early identification of treatment non-response in first-episode psychosis

Background Approximately one-third of patients with psychotic disorders does not respond to standard antipsychotic treatments. Consensus criteria for treatment resistance (TR) may aid the identification of non-response and subsequent tailoring of treatments. Since consensus criteria require stability of clinical status, they are challenging to apply in first-episode psychosis (FEP). This study aims to investigate (a) if an adaptation of consensus criteria can be used to identify FEP patients with early signs of TR (no early clinical recovery—no-ECR) after 1 year in treatment and (b) to what extent differences in antipsychotic treatments differentiate between outcome groups. Methods Participants with FEP DSM-IV schizophrenia spectrum disorders were recruited during their first treatment. A total of 207 participated in the 1-year follow-up. Remission and recovery definitions were based on adaptations of the “Remission in Schizophrenia Working Group” criteria and TR on adaptations of the “Treatment Response and Resistance in Psychosis” (TRRIP) working group criteria. Results 97 participants (47%) could be classified as no-ECR, 61 (30%) as ECR, and 49 (23%) as with partial ECR (P-ECR). Statistically significant baseline predictors of no-ECR matched previously identified predictors of long-term TR. Only 35 no-ECR participants had two adequate treatment trials and met the full TRRIP criteria. 21 no-ECR participants were using the same medication over the follow-up year despite the lack of significant effects. Conclusion The difference in the percentage of FEP participants classified as no-ECR versus TR indicates that we may underestimate the prevalence of early TR when using consensus criteria.publishedVersio

Sexual abuse and physical neglect in childhood are associated with affective theory of mind in adults with schizophrenia

Whereas childhood trauma is associated with reduced nonsocial cognition in schizophrenia, research on the relationship between childhood trauma and social cognition is limited and mixed. The aim of this study was to examine the association between childhood trauma and theory of mind (ToM) in persons with schizophrenia (n = 68) compared to healthy control participants (n = 70). Childhood trauma was assessed with the Childhood Trauma Questionnaire (CTQ), providing information on physical abuse, emotional abuse, sexual abuse, physical neglect and emotional neglect. ToM was indexed by the Movie for the Assessment of Social Cognition (MASC), which yields scores for total, cognitive and affective ToM, and for three error types (overmentalizing, undermentalizing, no mentalizing). Persons with schizophrenia had elevated rates of childhood trauma and lower ToM scores than healthy controls. In the schizophrenia group, associations between sexual abuse and affective ToM was statistically significant. In regression analyses, physical neglect was found to be the strongest predictor of affective ToM. In healthy controls, childhood trauma was not associated with ToM. Follow-up analyses comparing individuals with/without clinically significant childhood trauma, confirmed the findings for the schizophrenia group. No causal inferences can be made in this cross-sectional study, but the results suggest an illness-specific association between both sexual abuse and physical neglect in childhood, and adult affective ToM in individuals with schizophrenia

The impact of immigration and visible minority status on psychosis symptom profile

Purpose Immigrants have heightened risks of psychotic disorders, and it is proposed that migration influences symptom profiles. The purpose of this study was to investigate if either migration experience and/or visible minority status affected symptom profiles, using a cross-culturally validated five-factor model of the Positive and Negative Syndrome Scale (PANSS), in patients with broadly defined psychotic disorders. Methods PANSS was assessed in a large catchment area based sample of patients with psychotic disorders verified with the Structured Clinical Interview for DSM-IV (n = 1,081). Symptom profiles based on Wallwork et al. five-factor model were compared for Norwegians (73 %), white immigrants (10.5 %), and visible minority groups (16.5 %). Results Visible minorities were significantly younger, had less education, more often a schizophrenia diagnosis and higher PANSS positive, negative and disorganized/concrete factor scores than Norwegians and white immigrants. After controlling for confounders only the items “Delusions” and “Difficulty in abstract thinking” differed between groups. Multivariate analyses indicated that these items were not associated with immigration per se, but rather belonging to a visible minority. Conclusion We found mostly similarities in psychotic symptoms between immigrants and Norwegians when using a cross-culturally validated five-factor model of the PANSS. Immigration did not directly influence psychotic symptom profiles but visible minority groups had higher levels of “Delusions” and “Difficulty in abstract thinking”, both symptoms that are partially context dependent. The final publication is available at Springer

The Influence of Mental Health Literacy, Migration, and Education on the Duration of Untreated Psychosis

Background: Duration of untreated psychosis (DUP) is associated with outcome in psychotic disorders and influenced by contextual factors such as immigration. Here we aimed to investigate the effect of mental health literacy (MHL) on duration of untreated psychosis considering the influence of migration and education. Methods: A total of 269 participants who received their first adequate medical treatment for a psychotic disorder within the current or past year were included to the Thematically Organized Psychosis study in Oslo, Norway. Sociodemographic and clinical information was collected through systematic interviews. MHL was measured as “recognition of psychotic symptoms” and assessed by “The Attitudes and Beliefs about Mental Health Problems” schizophrenia version. Influence of education, migration and MHL on DUP was analyzed with hierarchical block-wise multiple regression analysis. Results: Recognition of psychotic symptoms explained a small but unique variance (2.3%) in DUP after the effects of other important predictors were controlled for. Longer DUP was also associated with less education, lower premorbid social, and academic functioning, a diagnosis within schizophrenia spectrum disorder, and earlier age of onset. The model explained 26% of variance in DUP. Migration after the age of six and length of education were associated with MHL but did not have a significant interaction with MHL in predicting DUP. Conclusions: MHL, measured as recognition of psychotic symptoms, has a small but significant independent effect on DUP. The effect of MHL was larger than years of education and migration history, and did not interact with either, in predicting DUP. This suggests that MHL is an independent factor in prevention strategies for early psychosis

Trauma-related altered states of consciousness in post-traumatic stress disorder patients with or without comorbid dissociative disorders

Background: The four-dimensional (‘4-D’) model has been proposed as a theoretical framework to understand and delineate trauma-related dissociative experiences, categorizing symptoms into trauma-related altered states of consciousness (TRASC) and normal waking consciousness (NWC), which occur along four dimensions: time, thought, body and emotion. Objective: The main aim of the present study was to evaluate the validity of this model in patients with post-traumatic stress disorder (PTSD), with and without comorbid dissociative disorders. Method: The predictions of the 4-D model were tested in 142 patients with PTSD, with (N = 46) and without (N = 96) comorbid dissociative disorders. Results: As predicted by the 4-D model, experiences of TRASC were less frequent and more specifically related to other measures of dissociation, dissociative disorder comorbidity and a history of childhood sexual abuse compared to experiences of NWC. The predicted lower intercorrelation of TRASC was not supported. Conclusion: The 4-D model represents a promising framework for understanding dissociation across trauma-related disorders

Childhood trauma mediates the association between ethnic minority status and more severe hallucinations in psychotic disorder

Background Ethnic minority status and childhood trauma are established risk factors for psychotic disorders. Both are found to be associated with increased level of positive symptoms, in particular auditory hallucinations. Our main aim was to investigate the experience and effect of childhood trauma in patients with psychosis from ethnic minorities, hypothesizing that they would report more childhood trauma than the majority and that this would be associated with more current and lifetime hallucinations. Method In this cross-sectional study we included 454 patients with a SCID-I DSM-IV diagnosis of non-affective or affective psychotic disorder. Current hallucinations were measured with the Positive and Negative Syndrome Scale (P3; Hallucinatory Behaviour). Lifetime hallucinations were assessed with the SCID-I items: auditory hallucinations, voices commenting and two or more voices conversing. Childhood trauma was assessed with the Childhood Trauma Questionnaire, self-report version. Results Patients from ethnic minority groups (n = 69) reported significantly more childhood trauma, specifically physical abuse/neglect, and sexual abuse. They had significantly more current hallucinatory behaviour and lifetime symptoms of hearing two or more voices conversing. Regression analyses revealed that the presence of childhood trauma mediated the association between ethnic minorities and hallucinations. Conclusions More childhood trauma in ethnic minorities with psychosis may partially explain findings of more positive symptoms, especially hallucinations, in this group. The association between childhood trauma and these first-rank symptoms may in part explain this group's higher risk of being diagnosed with a schizophrenia-spectrum diagnosis. The findings show the importance of childhood trauma in symptom development in psychosis. Copyright © Cambridge University Press 201

Clinical and socio-cultural insight in immigrants in their first episode of psychosis

Aim: Lack of insight into illness is frequent in psychotic disorders and seen as part of their primary pathology. The recognition of symptoms as psychotic, and beliefs about treatment alternatives, is also influenced by socio-cultural factors. Here we examined clinical insight into illness and beliefs about psychosis in immigrants in their first episode of psychosis compared to a reference group. Methods: 277 first episode psychosis participants were recruited to this cross-sectional study; 40 first- and 40 second-generation immigrants from Europe, Americas and Oceania (n=37), Asia including Turkey (n=28), or Africa (n=15). The Birchwood Insight Scale was used to measure clinical insight and “The Attitudes and Beliefs about Mental Health Problems”, schizophrenia version to assess socio-cultural beliefs. Results: Immigrants did not differ from the reference sample in clinical insight. After controlling for education level first generation immigrants were less likely to recognize psychotic symptoms (OR 2.9; Wald = 8.977, df 1, p =.003) and viewed hospitalization (OR 5.2; Wald = 20.388, df 1, p =.001) and treatment by a psychiatrist (OR 4.9; Wald = 6.609, df 1, p =.01)) as less beneficial than the reference group. Immigrants from Asia held more alternative explanations (OR 0.3; Wald = 6.567, df 1, p=.010). There were significantly stronger associations between clinical insight and socio-cultural beliefs in the reference group. Conclusions: Socio-cultural beliefs about psychosis in immigrants in first episode psychosis calls for more tailored information to this group, and emphasize the importance of treatment interventions involving both a cultural and personal perspective of insight

Sleep Disturbance Mediates the Link Between Childhood Trauma and Clinical Outcome in Severe Mental Disorders

Background The experience of childhood trauma is linked to more severe symptoms and poorer functioning in severe mental disorders; however, the mechanisms behind this are poorly understood. We investigate the relationship between childhood trauma and sleep disturbances in severe mental disorders including the role of sleep disturbances in mediating the relationship between childhood trauma and the severity of clinical symptoms and poorer functioning. Methods In total, 766 participants with schizophrenia-spectrum (n = 418) or bipolar disorders (n = 348) were assessed with the Childhood Trauma Questionnaire. Sleep disturbances were assessed through the sleep items in the self-reported Inventory of Depressive Symptoms. Clinical symptoms and functioning were assessed with The Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale. Mediation analyses using ordinary least squares regression were conducted to test if sleep disturbances mediated the relationship between childhood trauma and the severity of clinical symptoms and poorer functioning. Results Symptoms of insomnia, but not hypersomnia or delayed sleep phase, were significantly more frequent in participants with childhood trauma experiences compared to those without. Physical abuse, emotional abuse, and emotional neglect were significantly associated with insomnia symptoms. Insomnia symptoms partly mediate the relationship between childhood trauma and the severity of positive and depressive/anxiety symptoms, in addition to poorer functioning. Conclusion We found frequent co-occurrence of childhood trauma history and current insomnia in severe mental disorders. Insomnia partly mediated the relationship between childhood trauma and the severity of clinical symptoms and functional impairment

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