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Background: Schizophrenia is a disorder with considerable heterogeneity in course and outcomes, which is in part related to the patients' sex. Studies report a link between serum lipids, body mass index (BMI), and therapeutic response. However, the role of sex in these relationships is poorly understood. In a cross-sectional sample of first-episode psychosis (FEP) patients, we investigated if the relationship between serum lipid levels (total cholesterol, HDL-C, LDL-C, and triglycerides), BMI, and symptoms differs between the sexes. Methods: We included 435 FEP patients (males: N = 283, 65%) from the ongoing Thematically Organized Psychosis (TOP) study. Data on clinical status, antipsychotics, lifestyle, serum lipid levels, and BMI were obtained. The Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS) were used to assess psychotic and depressive symptoms. General linear models were employed to examine the relationship between metabolic variables and symptomatology. Results: We observed a female-specific association between serum HDL-C levels and negative symptoms (B = −2.24, p = 0.03) and between triglycerides levels (B = 1.48, p = 0.04) and BMI (B = 0.27, p = 0.001) with depressive symptoms. When controlling for BMI, only the association between serum HDL-C levels and negative symptoms remained significant. Moreover, the HDL-C and BMI associations remained significant after controlling for demography, lifestyle, and illness-related factors. Conclusion: We found a relationship between metabolic factors and psychiatric symptoms in FEP patients that was sex-dependent. [ABSTRACT FROM AUTHOR]

Background: Childhood maltreatment is a well‐known risk factor for developing a more severe and complex form of bipolar disorders (BD). However, knowledge is scarce about the interactions between childhood maltreatment and underlying genetic vulnerability on the clinical expression of BD. Method: We assigned a BD‐polygenic risk score (BD‐PRS), calculated from the Psychiatric Genomics Consortium, to each individual in a sample of 402 cases with BD. The lifetime clinical expression of BD was characterized using structured interviews and patients completed the Childhood Trauma Questionnaire (CTQ) to assess the severity of childhood maltreatment. Results: Cases who reported more severe childhood maltreatment had a lower BD‐PRS (rho = −0.12, P =.01), especially when considering emotional abuse (rho = −0.16, P =.001). An interaction between BD‐PRS and childhood maltreatment was observed for the risk of rapid cycling (P =.01). No further interactions between BD‐PRS and childhood maltreatment were observed for other clinical characteristics (age at onset, suicide attempts, number of mood episodes, mixed features, substance use disorders and psychotic symptoms). Conclusion: Our study is the first to show that less genetic risk may be needed to develop a more unstable form of BD when exposed to childhood maltreatment. Our study supports childhood trauma as an independent risk factor for BD. [ABSTRACT FROM AUTHOR]

To investigate whether changes in serum lipids are associated with cognitive performance in first episode psychosis (FEP) patients during their first year of antipsychotic drug treatment. One hundred and thirty-two antipsychotic-treated FEP patients were included through the TOP study along with 83 age- and gender-matched healthy controls (HC). Information regarding cognitive performance, psychotic symptoms, lifestyle, body mass index, serum lipids [total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, and triglycerides] and antipsychotic treatment was obtained at baseline and after 1 year. The cognitive test battery is comprised of assessments for verbal learning, processing speed, working memory, verbal fluency, and inhibition. Mixed-effects models were used to study the relationship between changes over time in serum lipids and cognitive domains, controlling for potential confounders. There was a significant group by HDL interaction effect for verbal learning (F = 11.12, p = 0.001), where an increase in HDL levels was associated with improvement in verbal learning in FEP patients but not in HC. Practice effects, lifestyle, and psychotic symptoms did not significantly affect this relationship. Antipsychotic-treated FEP patients who increased in HDL levels during the first year of follow-up exhibited better verbal learning capacity. Further investigations are needed to clarify the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: Common variants in the Vaccinia-related kinase 2 (VRK2) gene have been associated with schizophrenia, but the relevance of its encoded protein VRK2 in the disorder remains unclear.Aims: To identify potential differences in VRK2 gene expression levels between schizophrenia, bipolar disorder, psychosis not otherwise specified (PNOS) and healthy controls.Method: VRK2 mRNA level was measured in whole blood in 652 individuals (schizophrenia, n = 201; bipolar disorder, n = 167; PNOS, n = 61; healthy controls, n = 223), and compared across diagnostic categories and subcategories. Additionally, we analysed for association between 1566 VRK2 single nucleotide polymorphisms and mRNA levels.Results: We found lower VRK2 mRNA levels in schizophrenia compared with healthy controls (P<10(-12)), bipolar disorder (P<10(-12)) and PNOS (P = 0.0011), and lower levels in PNOS than in healthy controls (P = 0.0042) and bipolar disorder (P = 0.00026). Expression quantitative trait loci in close proximity to the transcription start site of the short isoforms of the VRK2 gene were identified.Conclusions: Altered VRK2 gene expression seems specific for schizophrenia and PNOS, which is in accordance with findings from genome-wide association studies. These results suggest that reduced VRK2 mRNA levels are involved in the underlying mechanisms in schizophrenia spectrum disorders. [ABSTRACT FROM AUTHOR]

Aims The aim of this study was to investigate the associations between recent cannabis use, current symptomatology and age at onset of first manic, depressive and psychotic episodes in a large sample with first-treatment bipolar I disorder ( BD I). Methods One hundred one patients with first-treatment Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition ( DSM- IV) bipolar I disorder were included as part of the Thematically Organized Psychosis study. The Structural Clinical Interview for DSM- IV was used for DSM- IV diagnosis and identification of episodes of illness. Earlier suicide attempts were recorded. Manic, depressive and psychotic symptoms were rated using the Young Mania Rating Scale, Inventory of Depressive Symptoms and Positive and Negative Syndrome Scale correspondingly. Cannabis use within the six last months was recorded. Results After controlling for confounders, recent cannabis use was significantly associated with lower age at onset of first manic and psychotic episode, but not with onset of first depressive episode (both P < 0.05). Recent use was also associated with more lifetime suicide attempts ( P < 0.01). No group differences were found on symptom levels. Conclusions The present study confirms earlier findings of an association between cannabis use and a lower age at onset. Recent cannabis use was also associated with more lifetime suicide attempts. The current findings suggest that recent cannabis use is associated with a more severe course of illness in the early phase of BD I. [ABSTRACT FROM AUTHOR]

Background: Immigration status is a significant risk factor for psychotic disorders, and a number of studies have reported more severe positive and affective symptoms among immigrant and ethnic minority groups. We investigated if perceived discrimination was associated with the severity of these symptoms among immigrants in Norway with psychotic disorders. Methods: Cross-sectional analyses of 90 immigrant patients (66% first-generation, 68% from Asia/Africa) in treatment for psychotic disorders were assessed for DSM-IV diagnoses with the Structured Clinical Interview for DSM Disorders (SCID-I, sections A-E) and for present symptom severity by The Structured Positive and Negative Syndrome Scale (SCI-PANSS). Perceived discrimination was assessed by a self-report questionnaire developed for the Immigrant Youth in Cultural Transition Study. Results: Perceived discrimination correlated with positive psychotic (r = 0.264, p < 0.05) and depression/anxiety symptoms (r = 0.282, p < 0.01), but not negative, cognitive, or excitement symptoms. Perceived discrimination also functioned as a partial mediator for symptom severity in African immigrants. Multiple linear regression analyses controlling for possible confounders revealed that perceived discrimination explained approximately 10% of the variance in positive and depression/anxiety symptoms in the statistical model. Conclusions: Among immigrants with psychotic disorders, visible minority status was associated with perceived discrimination and with more severe positive and depression/anxiety symptoms. These results suggest that context-specific stressful environmental factors influence specific symptom patterns and severity. This has important implications for preventive strategies and treatment of this vulnerable patient group. [ABSTRACT FROM AUTHOR]

Abstract: Both schizophrenia (SCZ) and bipolar disorder (BD) are associated with disturbances in emotion processing. Previous studies suggest that patients with SCZ assess unpleasant pictures as less arousing than healthy controls (HC), while patients with BD assess neutral pictures as more arousing than HC. No previous studies have investigated whether there is a difference in emotional response across all three groups. Our aim was to explore whether there was a difference in the evaluation of valence and in arousal between SCZ, BD and HC for aversive and neutral pictures. We showed 72 pictures (neutral, non-socially aversive and socially aversive) from the International Affective Picture System (IAPS) to 347 subjects. There was a clear interaction effect between the diagnostic group and increasing picture aversiveness for both valence and arousal. There were no significant differences in valence ratings between the different groups or in arousal ratings on any type of stimuli between BD patients and HC. However, SCZ patients reported significantly lower arousal for aversive stimuli, particularly with a social content, when compared to BD patients and HC. This was more pronounced in females. The presence of lifetime psychotic symptoms did not influence emotional responses. [Copyright &y& Elsevier]

Background: A potential link between increase in total cholesterol and triglycerides and clinical improvement has been observed during antipsychotic drug treatment in chronic schizophrenia patients, possibly due to drug related effects on lipid biosynthesis. We examined whether changes in serum lipids are associated with alleviation of psychosis symptoms after one year of antipsychotic drug treatment in a cohort of first-episode psychosis (FEP) patients.Methods: A total of 132 non-affective antipsychotic-treated FEP patients were included through the Norwegian Thematically Organized Psychosis (TOP) project. Data on antipsychotic usage, serum lipids (total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides (TG)), body mass index (BMI) and clinical state were obtained at baseline and after 12months. The Positive and Negative Syndrome Scale (PANSS) was used to assess psychotic symptoms. Mixed-effects models were employed to examine the relationship between serum lipids and psychotic symptoms while controlling for potential confounders including BMI.Results: An increase in HDL during one year of antipsychotic treatment was associated with reduction in PANSS negative subscores (B=-0.48, p=0.03). This relationship was not affected by concurrent change in BMI (adjusted HDL: B=-0.54, p=0.02). No significant associations were found between serum lipids, BMI and PANSS positive subscores.Conclusion: We found that an increase in HDL level during antipsychotic treatment is associated with improvement in negative symptoms in FEP. These findings warrant further investigation to clarify the interaction between lipid pathways and psychosis. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Our objective was to examine the cortisol release during a mental challenge in severe mental disorders versus healthy controls (HC), analyzing effects of sex, clinical characteristics and medication, and comparing Bipolar Disorder (BD) to Schizophrenia (SCZ). Methods: Patients with BD and SCZ (n =151) were recruited from a catchment area. HC (n =98) were randomly selected from the same area. Salivary samples were collected before and after a mental challenge and cortisol levels determined. Results: During the challenge there was an interaction between group and sex (P =0.015) with male patients having a blunted cortisol release compared to male HC (P =0.037). Cortisol change did not differ significantly between BD and SCZ. In all patients, the cortisol change correlated with number of psychotic episodes (r=−0.23, P =0.025), and in females patients, with number of depressive episodes (r=−0.33, P =0.015). Patients using antidepressants had a greater cortisol release during challenge than those not using antidepressants (P =0.043). Conclusions: Male patients with severe mental disorders seem to have a uniform abnormal cortisol release during mental challenges which associates with clinical course, and with beneficial effects of antidepressants. [Copyright &y& Elsevier]

Abstract: Objective: Patients with schizophrenia exhibit distorted beliefs and experiences, and their own evaluation of this is labeled cognitive insight. We examined the relationship between cognitive insight and neurocognition, as well as the contribution of neurocognition in explaining cognitive insight. Method: Clinically characterized patients with schizophrenia (n=102) were assessed with a measure of cognitive insight, Beck Cognitive Insight Scale (BCIS) and a neuropsychological test battery. The contribution of neurocognition to the explained variance in BCIS components self-reflectiveness (i.e. objectivity and reflectiveness) and self-certainty (i.e. overconfidence in own beliefs) was examined controlling for current affective and psychotic symptoms. Results: A significant negative correlation was found between self-certainty and verbal learning, whereas no associations were found between self-reflectiveness and any of the neuropsychological tests. Verbal learning was added significantly to the explained variance in self-certainty after controlling for potential confounders. Conclusion: High self-certainty was associated with poor verbal learning. This suggests that overconfidence in own beliefs is associated with cognitive dysfunction in schizophrenia. [Copyright &y& Elsevier]

While a growing literature links cardiac autonomic dysregulation to a variety of psychiatric disorders, the relationship between cardiac autonomic functioning and specific symptoms in schizophrenia (SZ) and bipolar disorder (BD) remains elusive. Thus, we investigated heart rate variability (HRV), a proxy for vagal activity, as a biological marker for symptom severity in patients with SZ and BD. HRV was calculated in 35 patients with SZ and 52 patients with BD, as well as in 149 healthy controls. In the patient groups, symptom severity and function were measured by the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF) scale. Results showed that HRV was significantly lower in both clinical groups compared to the healthy controls, with no significant HRV differences between patient groups. PANSS general psychopathology scores, GAF symptom scores, and GAF function scores showed statistically significant associations with HRV across groups. These results suggest that disease severity is associated with autonomic dysfunction and that HRV may provide a potential biomarker of disease severity in SZ and BD. [Display omitted] • Heart rate variability (HRV) approximates autonomic control of the heart rate. • HRV is reduced in in patients with in schizophrenia (SZ) and bipolar disorder (BD). • There is no significant difference in HRV between SZ and BD groups. • Disease severity is associated with autonomic dysfunction across SZ and BD groups. [ABSTRACT FROM AUTHOR]

Highlights from the article: Sa62identification of molecular mechanisms following cannabis exposure in patients with psychosis B Methods: b We have carried out a whole genome DNA methylation study on 1000 blood samples from patients with schizophrenia, bipolar disorder and non-psychiatric persons and compared the methylation profiles of those who are using cannabis to those who do not. Comparing the methylation profiles of current and never users of cannabis to former users show some methylation sites that are closer in methylation level to that of current cannabis users, while other sites are closer to never users.