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It is unknown how smoking behavior polygenic scores (PRS) relate to psychosis and psychotic symptoms. To elucidate this, genotype and phenotype data were collected from patients with schizophrenia, their unaffected siblings, and healthy controls in a six-year follow-up prospective cohort study. Associations between smoking behaviors, PRS and schizophrenia symptoms were explored using linear mixed-effect models. The mean number of cigarettes smoked per day were 18 for patients, 13 for siblings and 12 for controls. In the overall sample, PRSs-smoking initiation (i.e., ever smoking as a binary phenotype, PRS-SI) were positively associated with positive symptoms, negative symptoms, and depressive symptoms, whereas PRSs-AI (age at regular smoking initiation) were negatively associated with all symptom dimensions, with similar effect sizes. When considering groups separately, PRS were only associated with psychotic symptoms in siblings and controls. In conclusion, unaffected siblings show smoking behaviors at an intermediate level between patients and healthy controls. Additionally, PRS-SI and PRS-AI are associated with all symptom dimensions only in unaffected siblings and healthy controls, possibly owing to the dominant role of other (genetic) risk factors in patients. Future studies may examine mechanisms via which genetic risk for smoking affects mental health symptoms., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: Antipsychotics (APs) can cause weight gain. Little is known about changes in weight when APs are combined with other psychotropics. This study examines the weight change in patients undergoing long-term treatment with APs or with AP combined with other psychotropics., Methods: Patients with non-affective psychotic disorder from the GROUP study were divided into three groups: AP medication group (APm) (n = 100), AP in combination with other psychotropics (APc) (n = 73), and medication-free (Meds-free) (n = 100). Weight change was examined at inclusion and after three years using a paired-sample t-test. An Independent-sample t-test was performed to evaluate weight change among patients taking clozapine, olanzapine, and quetiapine and individuals not taking these medications. Linear regression was performed to evaluate the association between covariates and weight., Results: Patients in the APm group [mean = 1.800 kg, t(99)=2.849, 95% CI(0.546, 3.054), p = 0.005] and the APc group [mean = 1.877 kg, t(72)=2.688, 95% CI(0.485, 3.268), p = 0.009] showed significant weight gain. Patients taking clozapine, olanzapine or quetiapine showed significant weight gain compared to those not taking these medications [mean difference=1.707 kg, t(271)= 2.061, 95% CI(0.077, 3.337), p = 0.040)]., Conclusion: Patients receiving APs and APs with other psychotropics gain weight during long-term treatment. It is possible that weight gain is mainly driven by APs., (Copyright © 2022. Published by Elsevier B.V.)

Objective: Life expectancy in patients suffering from affective disorders is considerably diminished. We investigated whether skin autofluorescence (SAF), indicating concentration of advanced glycation end products in the skin and oxidative stress, mediates the association between affective disorders and excess mortality., Methods: Included were 81,041 participants of the Lifelines cohort study. Presence of major depressive disorder, dysthymia, generalised anxiety disorder, panic disorder or social phobia was assessed with the Mini-International Neuropsychiatric Interview. SAF was assessed as mediator in Cox proportional hazards models for all-cause or natural-cause mortality., Results: Mortality was increased in cases with major depression compared to controls (36.4 vs. 22.5 per 100,000 person years). Partial mediation by SAF of the association between affective disorders and mortality was shown (9.0-10.5%, P<.001-.002), although attenuated by cardiometabolic parameters and history of physical illness. For major depressive disorder, partial mediation by 5.5-10.3% was shown (crude model: P<.001; fully adjusted model: P=.03)., Limitations: The relatively short duration of follow-up and the relatively young cohort resulted in a lack of power to detect an association between mortality and dysthymia, social phobia and two or more comorbid disorders., Conclusion: Evidence of partial mediation by SAF of the association between affective disorders and all-cause and natural-cause mortality was demonstrated, although attenuated by health factors. For major depression, mediation by SAF was largest and remained significant after adjustment for sociodemographic and health factors, identifying oxidative stress as possible determinant of premature death., (Copyright © 2021. Published by Elsevier B.V.)

Sleep disturbances in patients with psychotic disorders are common and associated with poor clinical outcomes, but research on negative symptoms is limited. This study aimed to examine the association between subjective sleep disturbances and negative symptoms in 525 patients with non-affective psychotic disorders, 569 unaffected siblings and 265 healthy controls (HC) from the Genetic Risk and Outcome of Psychosis (GROUP) study. Several aspects of subjective sleep disturbances were assessed: sleep satisfaction, sleep onset insomnia, midnocturnal insomnia, early morning insomnia, and hypersomnia. Regression analyses revealed significant negative associations between sleep satisfaction and negative symptoms in all three groups. In addition, significant associations with sleep onset insomnia and hypersomnia were found in patients and with early morning insomnia and hypersomnia in siblings. Exploratory mediation analyses showed that depressive symptoms partly mediated all associations on the subclinical level in siblings and healthy controls, whereas only the association with sleep onset insomnia was mediated in patients. The results of this study implicate specific sleep disturbances and depressive symptoms as potential targets in prevention or intervention strategies focussed on negative symptoms in individuals suffering from, or at risk of non-affective psychotic disorders., (Copyright © 2021. Published by Elsevier B.V.)

Background: Skin autofluorescence (SAF), indicating concentration of advanced glycation end products in the skin and oxidative stress, is cross-sectionally associated with affective disorders. Prospective studies of oxidative stress markers will help to clarify the pathophysiological role of oxidative stress., Methods: Data of a population-based cohort study were used. Presence of major depressive disorder, dysthymia, generalised anxiety disorder, panic disorder or social phobia was assessed at baseline and at 5-year follow-up with the Mini-International Neuropsychiatric Interview. Associations between SAF at baseline and incidence and persistence/recurrence of affective disorders were assessed with logistic regression., Results: Of 43,267 participants with no disorder at baseline, 2885 (6.7%) developed an incident disorder during follow-up. In 1360 of 3648 participants (37.3%) with an affective disorder at baseline, a persisting/recurrent disorder was present at follow-up. A modest association existed between SAF and incident affective disorders (OR=1.07 [95%CI 1.03-1.12], P<.001), specifically major depressive disorder (OR=1.11 [95%CI 1.04-1.19], P=.003); this association lost statistical significance after adjustment for sociodemographic factors. Associations between SAF and persistence/recurrence were not significant., Limitations: Many confounders might also act as intermediate: extensive adjustment for confounders caused overfitting and possibly masked effects of SAF on course of affective disorders. Relatively small sample sizes for analyses of SAF and persistence/recurrence of affective disorders resulted in a low power., Conclusions: Increased SAF modestly raises the odds of incident affective disorders, particularly major depressive disorder, providing evidence that oxidative stress plays a role in subsequent occurrence of affective disorders. However, significance of effects faded after adjustment for socioeconomic status., (Copyright © 2020. Published by Elsevier B.V.)

Background: Oxidative stress may be a mechanistic link between affective disorders (depressive and anxiety disorders) and somatic disease. Advanced glycation end products are produced under the influence of oxidative stress and in the skin (measured by skin autofluorescence [SAF]) serve as marker for cumulative oxidative stress. Aim of study was to determine whether SAF is associated with presence of affective disorders., Methods: Participants in the Lifelines cohort study who had completed the Mini-International Neuropsychiatric Interview for affective disorders and a SAF-measurement were included. Cross-sectional associations between SAF and presence of the following psychiatric disorders were investigated through logistic regression analyses adjusted for sociodemographic factors, cardiometabolic parameters, and somatic morbidities: major depressive disorder, dysthymia, generalised anxiety disorder, panic disorder or social phobia., Results: Of 81,041 included participants (41.7% male, aged 18-91 years), 6676 (8.2%) were cases with an affective disorder. SAF was associated with presence of affective disorders (OR=1.09 [95%CI 1.07-1.12], P<.001 adjusted for sociodemographic factors). Association with major depressive disorder was strongest and significant after adjustment for all confounders (OR=1.31 [95%CI 1.25-1.36], P<.001 in the crude model; OR=1.12 [95%CI 1.07-1.17], P<.001 in the fully adjusted model). For other disorders, associations lost significance after adjustment for cardiometabolic parameters and somatic morbidities., Limitations: Persons of non-Western descent and severely (mentally or physically) ill individuals were underrepresented., Conclusions: SAF was associated with presence of affective disorders, suggesting a link between these disorders and cumulative oxidative stress. For major depressive disorder, this association was strongest and independent of sociodemographic, cardiometabolic factors, and somatic morbidities., Competing Interests: Declaration of Competing Interest Access to the Lifelines data by our research group was funded by the Amsterdam University Fund. Dr. A. Lok is a member of the advisory board on suicidality for Janssen Netherlands. Other authors report no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Coping styles are associated with levels of subjective well-being. Negative life events and reduced subjective well-being are more prevalent in patients with psychotic disorders. The aims of the current study were to test a mediation model, with coping styles as potential mediators of the relation between negative life events and subjective well-being in patients with psychotic disorders (N = 259), and aimed to repeat the potential mediation model in patients' non-affected siblings (N = 309). Data pertains to a subsample of GROUP, a Dutch naturalistic cohort study. The Subjective Well-being under Neuroleptics-20 (SWN-20) scale was used to assess well-being. Coping styles were assessed with the Utrechtse Coping Lijst (UCL). Life events were assessed using an adaptation of the Interview of the Recent Life Event Scale (IRLES). Siblings, but not patients, who experienced negative life events in the previous three year period were more likely to experience a lower well-being. For both groups passive coping styles mediated the relation between negative life events and subjective well-being. Severity of positive, negative or affective symptoms did not change this relationship. Our findings point to a better recognition of copings styles as a therapeutic target to promote well-being and recovery., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Research has found that Obsessive Compulsive Symptoms (OCS) in schizophrenia are associated with either more or less negative symptoms and either better or poorer cognitive functioning. In order to explain these contradictory results, (Lysaker et al., 2004), performed a cluster analysis resulting in 2 OCS positive (OCSpos) clusters, one with higher functioning (HF) and one with poorer functioning (PF) compared to 2 OCS negative (OCSneg) clusters. The OCSpos/HF cluster had less negative symptoms compared to all other clusters, while the OCSpos/PF cluster showed poorer executive functioning. We performed a replication study, in an almost 10 times larger, representative sample, using both a longitudinal and cross-sectional design. Similar to Lysaker et al., we found a group with mild OCS and HF (OCSmild/HF) showing less negative symptoms compared to the PF groups. We also found an OCSmild/PF group, which did not significantly differ in executive functioning from the other groups. Moreover, we did not find evidence for a better prognosis in the OCSmild/HF group, and thus found no support for the assumption that for some patients OCS might be an effective coping mechanism., (Copyright © 2018. Published by Elsevier B.V.)

One in five patients with a psychotic disorder has persistent low subjective well-being (SWB), which is associated with a poorer prognosis. In schizophrenia patients, personality traits are associated with SWB. The present study aims to evaluate whether neuroticism and extraversion influence SWB in patients with a psychotic disorder and healthy controls over the course of time. In 186 patients and 126 healthy control subjects, SWB was measured with the Subjective Well-being under Neuroleptics-20 (SWN) scale at baseline, three years and six years. We used the Five-Factor Inventory to assess neuroticism and extraversion. Mixed model analyses were conducted to investigate moderating associations of positive, negative and depressive symptoms, cannabis use, illness insight, weak social support and antipsychotic medication in patients. Higher neuroticism and lower extraversion were associated with lower SWB over six years in both groups. Personality traits did not have a differential effect on the course of SWB over time. In patients, a stable low SWB was found in 15.1% of the subjects. This group scored highest on neuroticism and lowest on extraversion compared to subjects with an increase in SWB or a stable high SWB. Our findings underline that personality traits are correlated to subjective well-being regardless of psychotic or depressive symptoms., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Subjective well-being (SWB) is associated with treatment adherence and symptom outcome in people with psychotic disorders. Also, it is associated with psychosis susceptibility and it is partly hereditable. The SWN-20 is a widely used tool to assess subjective well-being in patients; it was also found to be suitable for assessing SWB in healthy populations. Yet it is unclear how this retrospectively measured construct may be associated with momentary affective state, which is the proposed underlying mechanism of subjective well-being. This study therefore investigated the ecological validity of the SWN-20 in people at different risk for psychosis. In 63 patients with a psychotic disorder and 61 siblings of patients with a psychotic disorder we assessed whether subjective well-being as measured with the SWN-20, was associated with momentary positive affect, negative affect, reward experience and stress-sensitivity as measured by the experience sample method (ESM). Higher subjective well-being was associated with higher momentary positive affect and lower negative affect, and this association was not conditional on psychosis vulnerability. Subjective well-being was not associated with stress-sensitivity or reward-experience. SWN-20 is an easy-to-use and ecologically valid tool to measure subjective well-being in people with different vulnerability for psychosis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Various studies reported remarkably high prevalence rates of obsessive-compulsive symptoms (OCS) in patients with a psychotic disorder. Little is known about the pathogenesis of this co-occurrence. The current study aimed to investigate the contribution of shared underlying risk factors, such as childhood trauma and neuroticism, to the onset and course of OCS in patients with psychosis. Data were retrieved from 161 patients with psychosis included in the 'Genetic Risk and Outcome in Psychosis' project. Patients completed measures of OCS and psychotic symptoms at study entrance and three years later. Additionally, childhood maltreatment and neuroticism were assessed. Between-group comparisons revealed increased neuroticism and positive symptoms in patients who reported comorbid OCS compared to OCS-free patients. Subsequent mediation analyses suggested a small effect of childhood abuse on comorbid OCS severity at baseline, which was mediated by positive symptom severity. Additionally, results showed a mediating effect of neuroticism as well as a moderating effect of positive symptoms on the course of OCS severity over time. OCS severity in patients with psychosis might thus be associated with common vulnerability factors, such as childhood abuse and neuroticism. Furthermore, the severity of positive symptoms might be associated with more severe or persistent comorbid OCS., (Copyright © 2017. Published by Elsevier B.V.)

Prior studies with schizophrenia patients described a reduced ability to discriminate between correct and false memories in terms of confidence compared to control groups. This metamemory bias has been associated with the emergence and maintenance of delusions. The relation to neuropsychological performance and other clinical dimensions is incompletely understood. In a cross-sectional study, metamemory functioning was explored in 32 schizophrenia patients and 25 healthy controls. Metamemory was assessed using a verbal recognition task combined with retrospective confidence level ratings. Associations of metamemory performance with six neuropsychological domains (executive functioning/problem solving, speed of processing, working memory, verbal and visual learning, and attention/vigilance) and psychopathological measures were analyzed. Results revealed a significantly smaller discrepancy between confidence ratings for correct and incorrect recognitions in the patient group. Furthermore, patients showed significantly lower recognition accuracy in the metamemory task and marked deficits in all neuropsychological domains. Across all participants, metamemory performance significantly correlated with executive functioning and working memory. No associations with delusions were found. This data confirms prior findings of metamemory biases in schizophrenia. Selective neuropsychological abilities seem to be modulating factors of metamemory functioning. Longitudinal studies in at risk mental state and first-episode patients are needed to reveal causal interrelations., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

High rates of obsessive-compulsive symptoms (OCS) in schizophrenia require pathogenic explanations. Personality traits may represent risk and resiliency factors for the development of mental disorders and their comorbidities. The aim of the present study was to explore the associations between Five-Factor Model (FFM) personality traits and the liability for OCS in patients with psychotic disorders and in their un-affected siblings. FFM traits, occurrence and severity of OCS and (subclinical) psychotic symptoms were assessed in 208 patients and in 281 siblings. Differences in FFM traits between participants with vs. without comorbid OCS were examined and the predictive value of FFM traits on group categorization was evaluated. Associations between FFM traits and OCS severity were investigated. Patients and siblings with OCS showed significantly higher Neuroticism compared to their counterparts without OCS. Neuroticism was positively associated with higher OCS severity and significantly predicted group assignment in both patients and in siblings. Patients with comorbid OCS presented with lower scores on Extraversion and Conscientiousness. Higher Neuroticism, and to a lesser degree lower Extraversion and Conscientiousness might add to the vulnerability of patients with a psychotic disorder to also develop OCS. Future prospective studies are needed to elucidate proposed personality-psychopathology interrelations and possible mediating factors., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Previous studies have demonstrated a cognitive bias in the integration of disconfirmatory evidence (BADE) in patients with schizophrenia. This bias has been associated with delusions. So far, it is unclear how the integration of evidence is associated with neurocognitive capabilities. In the current study, 31 patients with schizophrenia and 29 healthy controls, matched on age, gender, education and premorbid verbal intelligence, underwent a BADE task. Written scenarios of three consecutive sentences each were presented, which progressively reduced the ambiguity of situations. Participants were asked to rate the plausibility of four possible interpretations and adjust their ratings in response to the provided sentences. Psychometric rating scales and a neuropsychological test battery were applied. Patients displayed a bias in the integration of confirmatory, but not disconfirmatory evidence and a liberal acceptance of belief formation. Correlation analyses revealed no associations of evidence integration with the severity of positive symptoms, but with neurocognitive domains, especially with processing speed, executive functioning, vigilance and working memory. In conclusion, patients with schizophrenia show a bias in evidence integration. Neurocognitive functioning emerged as a modulatory factor that should be considered in further research. Studies investigating BADE in earlier stages of psychosis will be necessary to reveal causal relationships., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)