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The aim of this study was to estimate the effects of lifestyle interventions on bodyweight and other cardiometabolic risk factors in people with psychotic disorders. Additionally, the long-term effects on body weight and the effects on depressive symptoms were examined. We searched four databases for randomized controlled trials (RCTs) that compared lifestyle interventions to control conditions in patients with psychotic disorders. Lifestyle interventions were aimed at weight loss or weight gain prevention, and the study outcomes included bodyweight or metabolic parameters. The search resulted in 25 RCTs -only 4 were considered high quality- showing an overall effect of lifestyle interventions on bodyweight (effect size (ES)  =  -0.63, p<0.0001). Lifestyle interventions were effective in both weight loss (ES =  -0.52, p<0.0001) and weight-gain-prevention (ES =  -0.84, p = 0.0002). There were significant long-term effects, two to six months post-intervention, for both weight-gain-prevention interventions (ES =  -0.85, p = 0.0002) and weight loss studies (ES =  -0.46, p = 0.02). Up to ten studies reported on cardiometabolic risk factors and showed that lifestyle interventions led to significant improvements in waist circumference, triglycerides, fasting glucose and insulin. No significant effects were found for blood pressure and cholesterol levels. Four studies reported on depressive symptoms and showed a significant effect (ES =  -0.95, p = 0.05). Lifestyle interventions are effective in treating and preventing obesity, and in reducing cardiometabolic risk factors. However, the quality of the studies leaves much to be desired.

SignificanceFamily-based studies revealed that polycystic ovary syndrome (PCOS), a common endocrinopathy of women, has a genetic basis. Genome-wide association studies identified DENND1A as a PCOS locus, but its role in PCOS was unknown. We report that an alternatively spliced form of DENND1A (DENND1A.V2) is increased in PCOS theca cells, the source of the excess androgens that characterizes PCOS. Forced expression of DENND1A.V2 in normal theca cells increased expression of genes encoding steroidogenic enzymes, leading to augmented androgen biosynthesis, whereas silencing of DENND1A.V2 in PCOS theca cells reverts them to a normal phenotype. Our findings establish that increased DENND1A.V2 expression is sufficient to promote a PCOS phenotype in human theca cells, information that can inform development of diagnostic tests as well as novel therapeutic interventions. Polycystic ovary syndrome (PCOS), characterized by increased ovarian androgen biosynthesis, anovulation, and infertility, affects 5–7% of reproductive-age women. Genome-wide association studies identified PCOS candidate loci that were replicated in subsequent reports, including DENND1A, which encodes a protein associated with clathrin-coated pits where cell-surface receptors reside. However, these studies provided no information about functional roles for DENND1A in the pathogenesis of PCOS. DENND1A protein was located in the cytoplasm as well as nuclei of theca cells, suggesting a possible role in gene regulation. DENND1A immunostaining was more intense in the theca of PCOS ovaries. Using theca cells isolated and propagated from normal cycling and PCOS women, we found that DENND1A variant 2 (DENND1A.V2) protein and mRNA levels are increased in PCOS theca cells. Exosomal DENND1A.V2 RNA was significantly elevated in urine from PCOS women compared with normal cycling women. Forced overexpression of DENND1A.V2 in normal theca cells resulted in a PCOS phenotype of augmented CYP17A1 and CYP11A1 gene transcription, mRNA abundance, and androgen biosynthesis. Knock-down of DENND1A.V2 in PCOS theca cells reduced androgen biosynthesis and CYP17A1 and CYP11A1 gene transcription. An IgG specific to DENND1A.V2 also reduced androgen biosynthesis and CYP17 and CYP11A1 mRNA when added to the medium of cultured PCOS theca cells. We conclude that the PCOS candidate gene, DENND1A, plays a key role in the hyperandrogenemia associated with PCOS. These observations have both diagnostic and therapeutic implications for this common disorder.

Positive and negative symptoms are prominent but heterogeneous characteristics of schizophrenia spectrum disorder (SSD). Within the framework of the Genetic Risk and Outcome of Psychosis (GROUP) longitudinal cohort study, we aimed to distinguish and identify the genetic and non-genetics predictors of homogenous subgroups of the long-term course of positive and negative symptoms in SSD patients (n = 1119) and their unaffected siblings (n = 1059) in comparison to controls (n = 586). Data were collected at baseline, and after 3- and 6-year follow-ups. Group-based trajectory modeling was applied to identify latent subgroups using positive and negative symptoms or schizotypy scores. A multinomial random-effects logistic regression model was used to identify predictors of latent subgroups. Patients had decreasing, increasing, and relapsing symptoms course. Unaffected siblings and healthy controls had three to four subgroups characterized by stable, decreasing, or increasing schizotypy. PRS SCZ did not predict the latent subgroups. Baseline symptoms severity in patients, premorbid adjustment, depressive symptoms, and quality of life in siblings predicted long-term trajectories while were nonsignificant in controls. In conclusion, up to four homogenous latent subgroups of symptom course can be distinguished within patients, siblings, and controls, while non-genetic factors are the main factors associated with the latent subgroups.

This article explores the link between spirituality/religiosity and mental health from a clinical and neuroscience perspective, taking into account the advancements in neuroimaging. Specifically, it examines how spirituality influences the treatment of mental illness, emphasizing the importance of neuronal networks in cognitive and emotional processes, with a focus on the default mode network (DMN) of the brain. The discussion explores the role of spirituality/religiosity in managing mental disorders and how alterations in the DMN may provide insight into the impact of spirituality/religiosity on mental health. By also discussing spiritual and non-spiritual meditation, as well as spiritual experiences facilitated by the use of psychedelics in psychiatry and the associated brain networks, we aim to elaborate on the importance and limitations of spirituality within psychiatry.

To tackle the phenotypic heterogeneity of schizophrenia, data-driven methods are often applied to identify subtypes of its symptoms and cognitive deficits. However, a systematic review on this topic is lacking. The objective of this review was to summarize the evidence obtained from longitudinal and cross-sectional data-driven studies in positive and negative symptoms and cognitive deficits in patients with schizophrenia spectrum disorders, their unaffected siblings and healthy controls or individuals from general population. Additionally, we aimed to highlight methodological gaps across studies and point out future directions to optimize the translatability of evidence from data-driven studies. A systematic review was performed through searching PsycINFO, PubMed, PsycTESTS, PsycARTICLES, SCOPUS, EMBASE and Web of Science electronic databases. Both longitudinal and cross-sectional studies published from 2008 to 2019, which reported at least two statistically derived clusters or trajectories were included. Two reviewers independently screened and extracted the data. In this review, 53 studies (19 longitudinal and 34 cross-sectional) that conducted among 17,822 patients, 8729 unaffected siblings and 5520 controls or general population were included. Most longitudinal studies found four trajectories that characterized by stability, progressive deterioration, relapsing and progressive amelioration of symptoms and cognitive function. Cross-sectional studies commonly identified three clusters with low, intermediate (mixed) and high psychotic symptoms and cognitive profiles. Moreover, identified subgroups were predicted by numerous genetic, sociodemographic and clinical factors. Our findings indicate that schizophrenia symptoms and cognitive deficits are heterogeneous, although methodological limitations across studies are observed. Identified clusters and trajectories along with their predictors may be used to base the implementation of personalized treatment and develop a risk prediction model for high-risk individuals with prodromal symptoms.

Background Unhealthy lifestyle behaviours contribute to alarming cardiometabolic risk in patients with serious mental illness (SMI). Evidence-based practical lifestyle tools supporting patients and staff in improving patient lifestyle are lacking. Methods This multi-site randomized controlled pragmatic trial determined the effectiveness of a twelve-month multimodal lifestyle approach, including a web-based tool to improve patients’ cardiometabolic health, versus care-as-usual. Using the web tool, nurses (trained in motivational interviewing) assisted patients in assessing their lifestyle behaviours, creating a risk profile and constructing lifestyle goals, which were discussed during fortnightly regular care visits. Twenty-seven community-care and sheltered-living teams were randomized into intervention ( N  = 17) or control ( N  = 10) groups, including 244 patients (140 intervention/104 control, 49.2% male, 46.1 ± 10.8 years) with increased waist circumference (WC), BMI or fasting glucose. The primary outcomes concerned differences in WC after six and twelve months intervention, while BMI and metabolic syndrome Z-score were secondary outcome measures. Results General multilevel linear mixed models adjusted for antipsychotic medication showed that differences in WC change between intervention and control were − 0.15 cm (95%CI: − 2.49; 2.19) after six and − 1.03 cm (95%CI: − 3.42; 1.35) after twelve months intervention; however, the differences were not statistically significant. No intervention effects were found for secondary outcome measures. The intervention increased patients’ readiness to change dietary behaviour. Conclusion A multimodal web-based intervention facilitating nurses to address lifestyle changes in SMI patients did not improve patient cardiometabolic health. Web-tool use was lower than expected and nurses need more lifestyle coaching knowledge and skills. The type of intervention and delivery mode need optimization to realize effective lifestyle care for SMI patients. Trial registration Dutch Trial Registry, www.trialregister.nl , NTR3765, 21 December 2012.

Introduction Recognition of the value of involving relatives in mental health care is growing. This study explores the ambivalence surrounding their role, including formalisation, instrumental use, burden, and potential benefits. Collaboration between relatives, patients, and professionals is essential to recovery-based approaches. Thus, despite challenges, the involvement of relatives remains crucial. This study aims to understand perspectives on involving relatives in mental health care, within the larger context of collaboration across the triad of relatives, patients, and professionals. Methods We conducted a qualitative study using semi-structured interviews with relatives ( n  = 7), patients ( n  = 7), and professionals ( n  = 10) connected to various mental health care organizations. The study took place in The Netherlands. Data were analysed using thematic analysis. Results For collaboration in the triad, we found five aspects to be of importance: the significance of involving relatives, changing roles from relative to caregiver, relatives’ intermediary role in patient-professional relationship, negative experiences of relatives in the triad, and ambivalence about patient’s autonomy. Notably, because collaboration between professionals and relatives is often challenging, it often leads to tensions. Conclusion Our study uncovers varying perspectives both on involving relatives and on collaboration within the triad. Recovery-oriented approaches do not always align with patients’ and relatives’ intentions and values. Although relatives want to be involved, they often feel unheard and unseen by professionals. Relatives’ roles -especially the intermediary role- are surprisingly underrepresented in the recovery-oriented literature. This study reveals several tensions between the three perspectives, culminating in a so-called uneven triad. We conclude that although the concept of involving relatives is highly advocated in recovery-based approaches, actual practice is lagging behind.

Background Recent studies on the schizophrenia spectrum and other psychotic disorders showed that alternation of immune system components, particularly microRNAs (miRNAs) and pro-inflammatory compounds, plays a significant role in developing the illness. The study aimed to evaluate serum expression of the miRNA-26a, miRNA-106a, and miRNA-125b as genetic factors and serum levels of IL-6, IL-1β, and TNF-α as pro-inflammatory factors in an IranianAzeri population. Methods Forty patients with recent-onset non-affective psychosis and 40 healthy people as a control group were involved. Expression levels of miRNAs and serum levels of the cytokines were measured using RT-qPCR and ELISA, respectively. T-test, receiver operating characteristics (ROC), and spearman correlation coefficient were carried out data analysis. Results Findings showed higher levels of IL-6, IL-1β, TNF-α, miR-26a, and miR-106a in the plasma of the patients’ group compared with the control. miRNA-26a showed a statistically significant higher level ( p  < .003) compared to the control group, with AUC = 0.84 (95% CI: 0.77 to 0.93, P  < .001) and cut-off point = 0.17 in comparison to other miRNAs as mentioned above; in this regard, it might be a suggestive biomarker for schizophrenia in the early stage of the illness. Moreover, miRNAs’ expression level was not substantially associated with the level of any measured cytokines above. Conclusions miR-26a might be a suggestive biomarker for schizophrenia in the early stage of the illness. Given that the relationship between other miRNAs and cytokines is not yet well understood; accordingly, there are encouragement and support for continued research in this fascinating field.

Patients with schizophrenia spectrum disorders (SSD) have a shortened life expectancy related to cardiovascular diseases. We investigated the association of cognitive, positive, and negative symptoms with cardiometabolic dysregulations in SSD patients. Overall, 1,119 patients from the Genetic Risk and Outcome in Psychosis (GROUP) study were included. Cognitive function, positive and negative symptoms were assessed at baseline, 3-year, and 6-year. Cardiometabolic biomarkers were measured at 3-year follow-up. We used linear and multinomial logistic regression models to test the association between cardiometabolic biomarkers and clinical trajectories and performed mediation analyzes, while adjusting for clinical and demographic confounders. Cognitive performance was inversely associated with increased body mass index (mean difference [β], β  = -1.24, 95% CI = -2.28 to 0.20,  = 0.02) and systolic blood pressure (β  = 2.74, 95% CI = 0.11 to 5.37,  = 0.04). The severity of positive symptoms was associated with increased glycated hemoglobin (HbA1c) levels (β  = -2.01, 95% CI = -3.21 to -0.82,  = 0.001). Increased diastolic blood pressure (OR  = 1.04, 95% CI = 1.01 to 1.08,  = 0.02; OR  = 1.04, 95% CI = 1.00 to 1.08,  = 0.048) and decreased high-density lipoprotein (OR  = 6.25, 95% CI = 1.81 to 21.59,  = 0.004) were associated with more severe negative symptoms. Increased HbA1c (OR  = 1.05, 95% CI = 1.01 to 1.10,  = 0.024; OR  = 1.08, 95% CI = 1.02 to 1.14,  = 0.006) was associated with more severe positive symptoms. These associations were not mediated by antipsychotics. We showed an association between cardiometabolic dysregulations and clinical and cognitive symptoms in SSD patients. The observed associations underscore the need for early identification of patients at risk of cardiometabolic outcomes.

Financial problems are of influence on mental health, and vice versa. Indeed, finances are a key challenge for people with psychosis. To gain deeper insights into these challenges, a qualitative approach focusing on all perspectives within the therapeutic triad is needed. This study aims to investigate perspectives of people with psychosis, family members and mental healthcare professionals on people with psychosis' financial problems, and associated factors. Fourteen people with psychosis, 15 family members and 16 professionals were recruited using purposive sampling, and participated in semi-structured, one-on-one interviews. Data was analysed using iterative thematic data-analysis. Interviews revealed five themes of financial problems: Covering expenses, Financial performance, Living conditions and housing, Personal conflicts and victimization, and Regulations and legislation. Five themes were identified as factors associated with financial problems: Psychotic symptoms, Indirect factors related to psychosis, Substance use and addiction, Financial upbringing and life events, and Societal contextual factors. People in the therapeutic triad largely mentioned similar, wide-ranging, and often co-occurring (factors associated with) financial problems of people with psychosis, risking vicious cycles. Fostering awareness and collaborative efforts among stakeholders is essential to breaking these cycles of financial problems for individuals with psychosis.