Childhood trauma and cardiometabolic risk in severe mental disorders: The mediating role of cognitive control.

BACKGROUND: Cardiometabolic risk is increased in severe mental disorders (SMDs), and there appears to be a relationship between childhood trauma and cardiometabolic risk, possibly related to adverse health behavior. The current study examined the association between childhood trauma and serum lipids and adiposity in SMDs and the potential mediating role of cognitive and personality characteristics. METHODS: Participants with schizophrenia and bipolar spectrum disorders (N = 819) were included, cardiometabolic risk factors (serum lipids, body mass index, and waist circumference) were measured, and history of childhood trauma was assessed by the Childhood Trauma Questionnaire. Cognitive and personality characteristics were available in subsamples, with assessments of cognitive control, impulsiveness, self-esteem, and affective lability. Linear regressions and mediation analyses with Hayes' PROCESS were performed, adjusting for age, sex, antipsychotic agent propensity of metabolic side-effect, and diagnostic group. RESULTS: Experience of three or more subtypes of childhood trauma was positively associated with waist circumference in patients with SMDs (p = 0.014). There were no other significant associations between trauma variables and lipid or adiposity measures in the total sample. Cognitive control was a significant mediator between experience of one or two subtypes of childhood trauma and waist circumference. CONCLUSIONS: The results indicate childhood trauma as a predisposing factor for increased waist circumference in individuals with SMDs. Poorer cognitive control, suggestive of adverse health behavior, might be a mediating factor of the association, and the findings indicate the potential importance of increased focus on these factors in prevention and treatment regimens targeting cardiometabolic health.

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.

Affective lability across psychosis spectrum disorders.

BACKGROUND: Despite apparent clinical remission, individuals with psychotic disorders often experience significant impairments across functional domains. Thus, there is a need to search beyond management of core symptoms to optimize treatment outcomes. Affective dysregulation is considered a risk factor for poor clinical and functional outcomes in many mental disorders, but research investigating such features in psychosis, particularly in schizophrenia, is limited. We aimed to investigate the level of affective lability (AL) in participants with schizophrenia- and bipolar spectrum disorders (n = 222) compared to healthy controls (n = 140), as well as clinical correlates of AL in the diagnostic groups. METHODS: The Affective Lability Scale (ALS-SF) was used to measure total score of AL and subscores covering the domains of anxiety/depression, depression/elation, and anger. An analysis of covariance was performed to compare the ALS-SF total score between groups, correcting for potential confounders, as well as standard multiple regression analyses for diagnosis-specific investigations of the relationship between AL and demographic and clinical features. RESULTS: Both the schizophrenia- and bipolar spectrum group had significantly higher ALS-SF total score compared to controls (p < 0.001), and no significant differences between the patient groups were found. In the schizophrenia group, current psychotic and depressive symptoms were significantly and independently associated with AL (p = 0.012 and p = 0.024, respectively). CONCLUSIONS: The findings indicate that AL is elevated in psychotic disorders and that it transcends diagnostic boundaries. Further research into the causal relationship between psychotic and affective symptoms and AL, as well as its role as a potential therapeutic target in psychosis spectrum disorders, is warranted.

Do sleep disturbances contribute to cognitive impairments in schizophrenia spectrum and bipolar disorders?

Sleep disturbances and cognitive impairments are both frequent across psychotic disorders, with debilitating effects on functioning and quality of life. This study aims to investigate if sleep disturbances are related to cognitive impairments in schizophrenia spectrum (SCZ) and bipolar disorders (BD), if this relationship varies between different sleep disturbances (insomnia, hypersomnia or delayed sleep phase (DSP)) and lastly, if this relationship differs between clinical groups and healthy controls (HC). We included 797 patients (SCZ = 457, BD = 340) from the Norwegian Centre for Mental Disorders Research (NORMENT) study in Norway. Sleep disturbances were based on items from the Inventory of Depressive Symptoms-Clinician rated scale (IDS-C). Their relationship with several cognitive domains was tested using separate ANCOVAs. A three-way between-groups ANOVA was conducted to test if the relationship with cognitive impairments varies between different sleep disturbances. These analyses revealed significantly poorer processing speed and inhibition in those with any sleep disturbance versus those without, also after adjusting for several covariates. The relationship between sleep disturbances and cognition was similar across SCZ and BD, and there were significant effects of insomnia and hypersomnia on both processing speed and inhibition. No association between sleep disturbances and cognition was found in HC. Sleep disturbances contribute to cognitive impairments in psychotic disorders. Processing speed and inhibition is poorer in patients with sleep disturbances. Impairments in these domains are related to insomnia and hypersomnia. These findings suggest that treating sleep disturbances is important to protect cognitive functioning, alongside cognitive remediation in psychotic disorders.

Sleep disturbances in schizophrenia spectrum and bipolar disorders - a transdiagnostic perspective.

BACKGROUND: Sleep disturbances are prevalent in severe mental disorders but their type and frequency across diagnostic categories has not been investigated in large scale studies. METHODS: Participants with Schizophrenia spectrum disorders (SCZ, (N = 617)), Bipolar disorders (BD, (N = 440)), and Healthy Controls (HC, (N = 173)) were included in the study. Sleep disturbances (insomnia, hypersomnia and delayed sleep phase) were identified based on items from the Inventory of Depressive Symptoms - Clinician rated scale. Clinical symptoms were assessed with the Positive and Negative Syndrome scale and level of functioning with the Global assessment of Functioning scale. RESULTS: The rate of any sleep disturbance was 78% in SZ, 69% in BD and 39% in HC. Insomnia was the most frequently reported sleep disturbance across all groups. Both diagnostic groups reported significantly more of any sleep disturbances than HC (P < 0.001). Having a sleep disturbance was associated with more severe negative and depressive symptoms and with lower functioning across diagnostic groups (P < 0.001, η2 = 0.0071). Hypersomnia was the only sleep disturbance associated with previous treatment history. CONCLUSION: Sleep disturbances, including insomnia, hypersomnia and delayed sleep phase, are frequent in SCZ and BD, and associated with more severe clinical symptomatology across diagnostic groups. This suggests that sleep disturbance is a clinically relevant transdiagnostic phenomenon.

Validity of the Birchwood insight scale in patients with schizophrenia spectrum- and bipolar disorders.

The aim of this study is to investigate the validity of the Norwegian version of the Insight Scale (IS) in large and representative samples of patients with schizophrenia spectrum disorders, bipolar I disorder and bipolar II disorder. A total of 997 participants were included (schizophrenia spectrum disorders: 557; bipolar I disorder: 282; bipolar II disorder: 138). Confirmatory factor analysis was conducted to investigate the construct validity and bivariate correlational analysis was applied to investigate convergent validity. Confirmatory factor analyses indicated a reasonable model fit to the original three-factor subscale structure of the IS in all three diagnostic groups. The IS total score and its subscales correlated significantly with both the insight items in the Young Mania Rating Scale and the Positive and Negative Syndrome Scale in both schizophrenia spectrum disorders and bipolar I disorder. In the bipolar II disorder group, however, the IS subscales correlated poorly with both the observer-rated measures. Our study supports the construct validity of the IS in both schizophrenia spectrum disorder- and bipolar disorder populations. The study also demonstrates that patients' self-reports of insight correspond to observer-based single item ratings of insight in bipolar I disorder and schizophrenia spectrum disorders.

Elevated hair cortisol is associated with childhood maltreatment and cognitive impairment in schizophrenia and in bipolar disorders.

BACKGROUND: The neural diathesis-stress model is useful to understand schizophrenia (SZ) and bipolar (BD) disorders. Childhood maltreatment could affect the Hypothalamic-Pituitary-Adrenal (HPA)-axis and lead to chronic changes in stress-sensitivity, which can be measured with hair cortisol concentrations (HCC), representing long-term, cumulative cortisol levels. Here we investigated if childhood trauma experiences are associated with chronic changes in the HPA axis in severe mental disorders. METHODS: Participants with SZ or BD (N = 63) and healthy controls (N = 94) were included, and HCC was measured by ELISA. History of childhood maltreatment was assessed using the Childhood Trauma Questionnaire (CTQ). Global function and symptom levels were obtained using the Global Assessment of Functioning (GAF) Scale and the Positive and Negative Syndrome Scale (PANSS). A neuropsychological test battery (MATRICS) was performed to assess cognitive functions. RESULTS: Our study shows for the first time that patients with a history of childhood maltreatment have higher HCC relative to both healthy controls and patients without a history of childhood maltreatment (P = 0.01, ƞp2 = 0.046). In addition, patients experiencing a mood episode had higher HCC than patients in remission (P = 0.03). Lastly, we are the first to show that patients with higher HCC had poorer cognitive performance, specifically working memory (P = 0.01). All associations were irrespective of diagnostic group. A factor analysis confirmed a subgroup within the patients characterized by childhood maltreatment and elevated HCC. CONCLUSIONS: Findings support the neural diathesis-stress model in SZ and BD pointing to long-term changes in HPA-axis following childhood maltreatment experiences.

Childhood maltreatment severity is associated with elevated C-reactive protein and body mass index in adults with schizophrenia and bipolar diagnoses.

BACKGROUND: Several studies have described an association between childhood maltreatment and inflammatory markers in the psychotic disorders (schizophrenia [SZ] and bipolar disorder [BD]). Previous studies have been relatively small (<50 participants), and the severity of abuse and the putative influence of body mass index (BMI) have not been properly investigated. METHODS: The combined effects of childhood abuse severity and clinical diagnosis on inflammatory markers were investigated in a large sample (n=483) of patients with a disorder on the psychosis spectrum and in healthy controls (HCs). Plasma levels of inflammatory markers (high-sensitivity C-reactive protein [hs-CRP], soluble tumor necrosis factor receptor type 1 [TNFR-R1], glycoprotein 130 [gp130]) were analyzed, and BMI and data on childhood trauma events, on the basis of the Childhood Trauma Questionnaire (CTQ), were obtained from all participants. RESULTS: Patients had increased levels of hs-CRP (P<0.001, Cohens d=0.4), lower levels of gp130 (P<0.001, Cohens d=0.5), higher BMI (P<0.001, Cohens d=0.5) and reported more childhood maltreatment experiences (P<0.001, Cohens d=1.2) than the HC group. The severity of childhood abuse (up to three types of abuse: sexual abuse, physical abuse, and emotional abuse) was associated with elevated BMI (f=8.46, P<0.001, Cohen's d=0.5) and hs-CRP (f=5.47, P=0.001, Cohen's d=0.3). Combined effects of patient status and severity of childhood abuse were found for elevated hs-CRP (f=4.76, P<0.001, Cohen's d=0.4). Differences among the groups disappeared when BMI was added to the model. DISCUSSION: Trauma-altered immune activation via elevated hs-CRP in patients with SZ and BD may be mediated by higher BMI; however, the direction of this association needs further clarification.