Cross-cohort replicable resting-state functional connectivity in predicting symptoms and cognition of schizophrenia.

Schizophrenia (SZ) is a debilitating mental illness characterized by adolescence or early adulthood onset of psychosis, positive and negative symptoms, as well as cognitive impairments. Despite a plethora of studies leveraging functional connectivity (FC) from functional magnetic resonance imaging (fMRI) to predict symptoms and cognitive impairments of SZ, the findings have exhibited great heterogeneity. We aimed to identify congruous and replicable connectivity patterns capable of predicting positive and negative symptoms as well as cognitive impairments in SZ. Predictable functional connections (FCs) were identified by employing an individualized prediction model, whose replicability was further evaluated across three independent cohorts (BSNIP, SZ = 174; COBRE, SZ = 100; FBIRN, SZ = 161). Across cohorts, we observed that altered FCs in frontal-temporal-cingulate-thalamic network were replicable in prediction of positive symptoms, while sensorimotor network was predictive of negative symptoms. Temporal-parahippocampal network was consistently identified to be associated with reduced cognitive function. These replicable 23 FCs effectively distinguished SZ from healthy controls (HC) across three cohorts (82.7%, 90.2%, and 86.1%). Furthermore, models built using these replicable FCs showed comparable accuracies to those built using the whole-brain features in predicting symptoms/cognition of SZ across the three cohorts (r = .17-.33, p < .05). Overall, our findings provide new insights into the neural underpinnings of SZ symptoms/cognition and offer potential targets for further research and possible clinical interventions.

Neuroreceptor Inhibition by Clozapine Triggers Mitohormesis and Metabolic Reprogramming in Human Blood Cells.

The antipsychotic drug clozapine demonstrates superior efficacy in treatment-resistant schizophrenia, but its intracellular mode of action is not completely understood. Here, we analysed the effects of clozapine (2.5-20 µM) on metabolic fluxes, cell respiration, and intracellular ATP in human HL60 cells. Some results were confirmed in leukocytes of clozapine-treated patients. Neuroreceptor inhibition under clozapine reduced Akt activation with decreased glucose uptake, thereby inducing ER stress and the unfolded protein response (UPR). Metabolic profiling by liquid-chromatography/mass-spectrometry revealed downregulation of glycolysis and the pentose phosphate pathway, thereby saving glucose to keep the electron transport chain working. Mitochondrial respiration was dampened by upregulation of the F0F1-ATPase inhibitory factor 1 (IF1) leading to 30-40% lower oxygen consumption in HL60 cells. Blocking IF1 expression by cotreatment with epigallocatechin-3-gallate (EGCG) increased apoptosis of HL60 cells. Upregulation of the mitochondrial citrate carrier shifted excess citrate to the cytosol for use in lipogenesis and for storage as triacylglycerol in lipid droplets (LDs). Accordingly, clozapine-treated HL60 cells and leukocytes from clozapine-treated patients contain more LDs than untreated cells. Since mitochondrial disturbances are described in the pathophysiology of schizophrenia, clozapine-induced mitohormesis is an excellent way to escape energy deficits and improve cell survival.

Structural validity of the Rosenberg self-esteem scale in patients with schizophrenia in Indonesia.

BACKGROUND: The Rosenberg self-esteem scale (RSES) is a commonly employed instrument for measuring self-esteem in the general population and those with mental illness. However, confirmatory factor analyses (CFA) to determine the structural validity of the RSES for schizophrenia patients in Indonesia are limited. OBJECTIVES: We examined the structural validity of the RSES as a measurement for patients with schizophrenia in Indonesia through confirmatory factor analyses (CFA), as well as assessing internal consistency and reliability. METHODS: The sample comprised 260 participants. Over two weeks, 30 subjects were added to investigate test-retest reliability. The structural validity analyzed was based on a CFA to determine the model fit. We used internal consistency (Ordinal alpha) to evaluate the reliability evidence. RESULTS: Four different models were analyzed in this study. Considering the single-factor model (Model 1a), the overall fit criteria were inadequate. However, after some modification indices, all fit criteria were significantly adequate (Model 1b). The adequacy of all fit standards remained satisfactory when the two-factor model (Model 2) and hierarchical model (Model 3) were applied. The RSES had an ordinal alpha coefficient of 0.75. While 0.89 and 0.88 for the positive and negative self-esteem subscale, respectively. Test-retest reliability yielded adequate results with an interclass correlation score ranging from 0.87 to 0.93. CONCLUSIONS: The current investigation provided evidence supporting the structural validity, internal consistency, and reliability of the RSES, indicating that the RSES can be considered a valid and reliable measurement. A two-factor model of RSES was an appropriate model to measure self-esteem in our study. This finding suggests that the use of the RSES is beneficial and applicable in assessing levels of self-esteem in individuals diagnosed with schizophrenia in Indonesia.

Behavioral evidence of impaired self-referential processing in patients with affective disorders and first-episode schizophrenia.

Despite the critical role of self-disturbance in psychiatric diagnosis and treatment, its diverse behavioral manifestations remain poorly understood. This investigation aimed to elucidate unique patterns of self-referential processing in affective disorders and first-episode schizophrenia. A total of 156 participants (41 first-episode schizophrenia [SZ], 33 bipolar disorder [BD], 44 major depressive disorder [MDD], and 38 healthy controls [HC]) engaged in a self-referential effect (SRE) task, assessing trait adjectives for self-descriptiveness, applicability to mother, or others, followed by an unexpected recognition test. All groups displayed preferential self- and mother-referential processing with no significant differences in recognition scores. However, MDD patients showed significantly enhanced self-referential recognition scores and increased bias compared to HC, first-episode SZ, and BD. The present study provides empirical evidence for increased self-focus in MDD and demonstrates that first-episode SZ and BD patients maintain intact self-referential processing abilities. These findings refine our understanding of self-referential processing impairments across psychiatric conditions, suggesting that it could serve as a supplementary measure for assessing treatment response in first-episode SZ and potentially function as a discriminative diagnostic criterion between MDD and BD.

Sex affects transcriptional associations with schizophrenia across the dorsolateral prefrontal cortex, hippocampus, and caudate nucleus.

Schizophrenia is a complex neuropsychiatric disorder with sexually dimorphic features, including differential symptomatology, drug responsiveness, and male incidence rate. Prior large-scale transcriptome analyses for sex differences in schizophrenia have focused on the prefrontal cortex. Analyzing BrainSeq Consortium data (caudate nucleus: n = 399, dorsolateral prefrontal cortex: n = 377, and hippocampus: n = 394), we identified 831 unique genes that exhibit sex differences across brain regions, enriched for immune-related pathways. We observed X-chromosome dosage reduction in the hippocampus of male individuals with schizophrenia. Our sex interaction model revealed 148 junctions dysregulated in a sex-specific manner in schizophrenia. Sex-specific schizophrenia analysis identified dozens of differentially expressed genes, notably enriched in immune-related pathways. Finally, our sex-interacting expression quantitative trait loci analysis revealed 704 unique genes, nine associated with schizophrenia risk. These findings emphasize the importance of sex-informed analysis of sexually dimorphic traits, inform personalized therapeutic strategies in schizophrenia, and highlight the need for increased female samples for schizophrenia analyses.

Australian trial of behavioural activation for people with schizophrenia experiencing negative symptoms: a feasibility randomised controlled trial protocol.

INTRODUCTION: Negative symptoms are frequently experienced by people with schizophrenia. People with negative symptoms often have impaired social functioning and reduced quality of life. There is some evidence that cognitive-behavioural therapy results in a modest reduction in negative symptoms. Behavioural activation may be an effective alternative treatment for negative symptoms.The study aims to examine the feasibility and acceptability of implementing a behavioural activation trial delivered in three community mental health services in South Australia to support adult consumers experiencing negative symptoms of schizophrenia. METHOD AND ANALYSIS: This randomised controlled study will recruit a total of 60 consumers aged 18 years or above with mild-moderate negative symptoms of schizophrenia. The consumers will be randomly allocated to receive behavioural activation plus usual mental healthcare or usual mental healthcare alone. The intervention group will receive twelve 30 min sessions of behavioural activation, which will be delivered twice weekly over 6 weeks. In addition, we aim to recruit nine mental health workers from the three rural mental health services who will complete a 10-week online training programme in behavioural activation. Changes in negative symptoms of schizophrenia and depressive symptoms will be assessed at three time points: (a) at baseline, at 6 weeks and 3 month follow-ups. Changes in health-related quality of life (Short Form F36; secondary outcome) will be assessed at two time points: (a) at baseline and (b) immediately at postintervention after 6 weeks. At the end of the trial, interviews will be conducted with purposively selected mental health workers and consumers. Descriptive statistics and thematic analysis will be used to assess feasibility and acceptability. ETHICS AND DISSEMINATION: The findings from our feasibility study will inform the design of a fully powered randomised controlled trial to test the effectiveness of behavioural activation as a treatment for negative symptoms in schizophrenia. The study protocol was approved by the Central Adelaide Local Health Network Human Research Ethics Committee. The findings from this study will be disseminated through peer-reviewed scientific journals and conferences. TRIAL REGISTRATION NUMBER: ACTRN12623000348651p.

Schizophrenia and medication adherence: Associated factors.

BACKGROUND: Schizophrenia is a chronic condition that requiring maintenance treatment with antipsychotic medication. Medication adherence is essential to improve the symptoms of this health problem reduce relapses and readmissions and achieve treatment goals. The rate of challenges associated with medication adherence in schizophrenia is reported to be 26.5-85.1 %. PURPOSE: This study was conducted to determine factors associated with medication adherence in individuals diagnosed with schizophrenia. METHODS: A descriptive correlational research design was used. The study was completed with a total of 162 participants diagnosed with schizophrenia, between February-June 2021, at a Community Mental Health Center. Regression analysis (Model: enter and stepwise) was used to determine associated factors. RESULTS: The mean medication adherence score of individual diagnosed with schizophrenia indicated that more than half of the participants (52 %) had poor medication adherence. In individual diagnosed with schizophrenia, medication attitudes, level of internalized stigma, the status of regular attendance to appointments, belief in recovery, and using medicines as prescribed were complicating factors for medication adherence (p < 0.05). CONCLUSIONS: Medication adherence in individuals with diagnosed schizophrenia may be multifactorial. Mental health professionals should consider associated factors and implement a personalized treatment plan in this direction for strengthening adherence to medication treatment.

Development of family resource indicators for people with schizophrenic disorder in community by modified Delphi method in Beijing, China.

INTRODUCTION: Most people with schizophrenia in China are supported by their family members in community. The patient's family is confronted with severe care burden and pressure, which directly affects the caregiver's own health and social life, and indirectly affects the patient's rehabilitation. Adequate family resources can reduce the burden and pressure on families. But there is an absence of systematic family resource indicators for people with schizophrenic disorder in China. OBJECTIVES: This study aimed to develop a set of family resource indicators for people with schizophrenic disorder in China. DESIGN: Preliminary family resource indicators were generated and refined by literature review and an expert consultation meeting. Two rounds of email-based Delphi survey were carried out to identify family resource indicators. SETTING: Two rounds of email-based Delphi survey were performed from July to September 2021 in Beijing, China. PARTICIPANTS: There were 15 mental health doctors from community health service centres and four psychiatrists from tertiary hospitals, and two primary care researchers from universities in the first and second rounds Delphi survey. RESULTS: All the 21 experts participated in both rounds of Delphi survey. A total of 46 indicators achieved consensus for inclusion in the final set of indicators after two rounds of Delphi survey. The final set of indicators was grouped into 10 domains: financial support (three indicators), psychological and spiritual support (eight indicators), medical treatment (three indicators), information and education (three indicators), structural support (two indicators), external family resources included social resources (five indicators), cultural resources (two indicators), economic resources (seven indicators), environmental resources (four indicators) and medical resources (nine indicators). CONCLUSIONS: A set of 46 family resource indicators for people with schizophrenic disorder in community was identified by an iterative Delphi process in Beijing, China. However, the indicators still need to be validated by testing in further studies.

In Vivo Reactive Astrocyte Imaging in Patients With Schizophrenia Using Fluorine 18-Labeled THK5351.

Importance: In vivo imaging studies of reactive astrocytes are crucial for understanding the pathophysiology of schizophrenia because astrocytes play a critical role in glutamate imbalance and neuroinflammation. Objective: To investigate in vivo reactive astrocytes in patients with schizophrenia associated with positive symptoms using monoamine oxidase B (MAO-B)-binding fluorine 18 ([18F])-labeled THK5351 positron emission tomography (PET). Design, Setting, and Participants: In this case-control study, data were collected from October 1, 2021, to January 31, 2023, from the internet advertisement for the healthy control group and from the outpatient clinics of Seoul National University Hospital in Seoul, South Korea, for the schizophrenia group. Participants included patients with schizophrenia and age- and sex-matched healthy control individuals. Main Outcomes and Measures: Standardized uptake value ratios (SUVrs) of [18F]THK5351 in the anterior cingulate cortex (ACC) and hippocampus as primary regions of interest (ROIs), with other limbic regions as secondary ROIs, and the correlation between altered SUVrs and Positive and Negative Syndrome Scale (PANSS) positive symptom scores. Results: A total of 68 participants (mean [SD] age, 32.0 [7.0] years; 41 men [60.3%]) included 33 patients with schizophrenia (mean [SD] age, 32.3 [6.3] years; 22 men [66.7%]) and 35 healthy controls (mean [SD] age, 31.8 [7.6] years; 19 men [54.3%]) who underwent [18F]THK5351 PET scanning. Patients with schizophrenia showed significantly higher SUVrs in the bilateral ACC (left, F = 5.767 [false discovery rate (FDR)-corrected P = .04]; right, F = 5.977 [FDR-corrected P = .04]) and left hippocampus (F = 4.834 [FDR-corrected P = .04]) than healthy controls. Trend-level group differences between the groups in the SUVrs were found in the secondary ROIs (eg, right parahippocampal gyrus, F = 3.387 [P = .07]). There were positive correlations between the SUVrs in the bilateral ACC and the PANSS positive symptom scores (left, r = 0.423 [FDR-corrected P = .03]; right, r = 0.406 [FDR-corrected P = .03]) in patients with schizophrenia. Conclusions and Relevance: This case-control study provides novel in vivo imaging evidence of reactive astrocyte involvement in the pathophysiology of schizophrenia. Reactive astrocytes in the ACC may be a future target for the treatment of symptoms of schizophrenia, especially positive symptoms.

Minimum spanning tree analysis of EEG resting-state functional networks in schizophrenia.

Schizophrenia is a serious and complex mental disease, known to be associated with various subtle structural and functional deviations in the brain. Recently, increased attention is given to the analysis of brain-wide, global mechanisms, strongly altering the communication of long-distance brain areas in schizophrenia. Data of 32 patients with schizophrenia and 28 matched healthy control subjects were analyzed. Two minutes long 64-channel EEG recordings were registered during resting, eyes closed condition. Average connectivity strength was estimated with Weighted Phase Lag Index (wPLI) in lower frequencies: delta and theta, and Amplitude Envelope Correlation with leakage correction (AEC-c) in higher frequencies: alpha, beta, lower gamma and higher gamma. To analyze functional network topology Minimum Spanning Tree (MST) algorithms were applied. Results show that patients have weaker functional connectivity in delta and alpha frequency bands. Concerning network differences, the result of lower diameter, higher leaf number, and also higher maximum degree and maximum betweenness centrality in patients suggest a star-like, and more random network topology in patients with schizophrenia. Our findings are in accordance with some previous findings based on resting-state EEG (and fMRI) data, suggesting that MST network structure in schizophrenia is biased towards a less optimal, more centralized organization.

Risk assessment for aggressive behaviour in schizophrenia.

BACKGROUND: Aggressive or violent behaviour is often associated with people with schizophrenia in common perceptions of the disease. Risk assessment methods have been used to identify and evaluate the behaviour of those individuals who are at the greatest risk of perpetrating aggression or violence or characterise the likelihood to commit acts. Although many different interventions have been developed to decrease aggressive or violent incidences in inpatient care, staff working in inpatient settings seek easy-to-use methods to decrease patient aggressive events. However, many of these are time-consuming, and they require intensive training for staff and patient monitoring. It has also been recognised in clinical practice that if staff monitor patients' behaviour in a structured manner, the monitoring itself may result in a reduction of aggressive/violent behaviour and incidents in psychiatric settings. OBJECTIVES: To assess the effects of structured aggression or violence risk assessment methods for people with schizophrenia or schizophrenia-like illnesses. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, PubMed, ISRCTN registry, ClinicalTrials.gov, and WHO ICTRP, on 10 February 2021. We also inspected references of all identified studies. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing structured risk assessment methods added to standard professional care with standard professional care for the evaluation of aggressive or violent behaviour among people with schizophrenia. DATA COLLECTION AND ANALYSIS: At least two review authors independently inspected citations, selected studies, extracted data, and appraised study quality. For binary outcomes, we calculated a standard estimation of the risk ratio (RR) and its 95% confidence interval (CI). For continuous outcomes, we calculated the mean difference (MD) and its 95% CI. We assessed risk of bias in the included studies and created a summary of findings table using the GRADE approach. MAIN RESULTS: We included four studies in the review. The total number of participants was not identifiable, as some studies provided number of participants included, and some only patient days. The studies compared a package of structured assessment methods with a control group that included routine nursing care and drug therapy or unstructured psychiatric observations/treatment based on clinical judgement. In two studies, information about treatment in control care was not available. One study reported results for our primary outcome, clinically important change in aggressive/violent behaviour, measured by the rate of severe aggression events. There was likely a positive effect favouring structured risk assessment over standard professional care (RR 0.59, 95% CI 0.41 to 0.85; 1 RCT; 1852 participants; corrected for cluster design: RR 0.59, 95% CI 0.37 to 0.93; moderate-certainty evidence). One trial reported data for the use of coercive measures (seclusion room). Compared to standard professional care, structured risk assessment may have little or no effect on use of seclusion room as days (corrected for cluster design: RR 0.92, 95% CI 0.27 to 3.07; N = 20; low-certainty evidence) or use of seclusion room as secluded participants (RR 1.83, 95% CI 0.39 to 8.7; 1 RCT; N = 20; low-certainty evidence). However, seclusion room may be used less frequently in the standard professional care group compared to the structured risk assessment group (incidence) (corrected for cluster design: RR 1.63, 95% CI 0.49 to 5.47; 1 RCT; N = 20; substantial heterogeneity, Chi2 = 0.0; df = 0.0; P = 0.0; I2 = 100%; low-certainty evidence). There was no evidence of a clear effect on adverse events of escape (RR 0.2, 95% CI 0.01 to 4.11; 1 RCT; n = 200; very low-certainty evidence); fall down (RR 0.33, 95% CI 0.04 to 3.15; 1 RCT; n = 200; very low-certainty evidence); or choking (RR 0.2, 95% CI 0.01 to 4.11; 1 RCT; n = 200; very low-certainty evidence) when comparing structured risk assessment to standard professional care. There were no useable data for patient-related outcomes such as global state, acceptance of treatment, satisfaction with treatment, quality of life, service use, or costs. AUTHORS' CONCLUSIONS: Based on the available evidence, it is not possible to conclude that structured aggression or violence risk assessment methods are effective for people with schizophrenia or schizophrenia-like illnesses. Future work should combine the use of interventions and structured risk assessment methods to prevent aggressive incidents in psychiatric inpatient settings.

Correlation of Serum High-Sensitivity C-Reactive Protein, Homocysteine, and Macrophage Migration Inhibitory Factor Levels With Symptom Severity and Cognitive Function in Patients With Schizophrenia.

OBJECTIVE: This trial analyzed high-sensitivity C-reactive protein (hs-CRP), homocysteine (Hcy), and macrophage migration inhibitory factor (MIF) level in serum and their correlation with symptom severity and cognitive function in patients with schizophrenia (SP). METHODS: Sixty-eight SP patients were enrolled in the SP group, and 68 healthy volunteers were in the control (CN) group. Serum hs-CRP, Hcy, and MIF were measured, and symptom severity was assessed with the Positive and Negative Symptom Scale (PANSS). Cognitive function was determined with the MATRICS Consensus Cognitive Battery (MCCB). The SP group was divided into high PANSS score (PANSS ≥70 points) and low PANSS score (PANSS <70 points), or the mild cognitive dysfunction group and severe cognitive dysfunction group according to the median MCCB score. The correlation between serum hs-CRP, Hcy, and MIF levels and PANSS and MCCB scores in SP patients was examined by Pearson correlation analysis. RESULTS: SP patients had higher serum hs-CRP, Hcy, and MIF levels and showed higher PANSS scores and lower MCCB total score. Serum hs-CRP, Hcy, and MIF levels in the high PANSS group were higher than those in the low PANSS group and in the severe cognitive dysfunction group than in the mild cognitive dysfunction group. Serum hs-CRP, Hcy, and MIF levels in SP patients were positively correlated with PANSS total score and negatively correlated with MCCB total score. CONCLUSION: High serum hs-CRP, Hcy, and MIF levels in SP patients are correlated with symptom severity and cognitive dysfunction.

ZO-1 Serum Levels as a Potential Biomarker for Psychotic Disorder.

OBJECTIVE: There are limited studies in the literature on the relationship between intestinal and blood-brain barrier permeability and the etiology of schizophrenia. We hypothesized that the difference in serum ZO-1 levels in patients with schizophrenia may affect the severity of the disease. The aim of this study was to investigate the role of changes in serum ZO-1 concentrations in the etiopathogenesis of patients with schizophrenia. METHODS: A total of 46 patients, 34 with schizophrenia, 12 with a first psychotic attack, and 37 healthy controls, were included in the study. Symptom severity was determined by applying the Positive and Negative Syndrome Scale and the Clinical Global Impression-Severity Scale. Serum ZO-1 levels were measured from venous blood samples. RESULTS: Serum ZO-1 levels were higher in patients with psychotic disorder compared to healthy controls. There was no statistically significant difference between the groups in the first psychotic attack group and the schizophrenia patients. There was a statistically significant positive correlation between serum ZO-1 levels and Positive and Negative Syndrome Scale positive symptom score. CONCLUSIONS: These findings regarding ZO-1 levels suggest that dysregulation of the blood-brain barrier in psychotic disorder may play a role in the etiology of the disorder.

Collaborative care approaches for people with severe mental illness.

BACKGROUND: Collaborative care for severe mental illness (SMI) is a community-based intervention that promotes interdisciplinary working across primary and secondary care. Collaborative care interventions aim to improve the physical and/or mental health care of individuals with SMI. This is an update of a 2013 Cochrane review, based on new searches of the literature, which includes an additional seven studies. OBJECTIVES: To assess the effectiveness of collaborative care approaches in comparison with standard care (or other non-collaborative care interventions) for people with diagnoses of SMI who are living in the community. SEARCH METHODS: We searched the Cochrane Schizophrenia Study-Based Register of Trials (10 February 2021). We searched the Cochrane Common Mental Disorders (CCMD) controlled trials register (all available years to 6 June 2016). Subsequent searches on Ovid MEDLINE, Embase and PsycINFO together with the Cochrane Central Register of Controlled Trials (with an overlap) were run on 17 December 2021. SELECTION CRITERIA: Randomised controlled trials (RCTs) where interventions described as 'collaborative care' were compared with 'standard care' for adults (18+ years) living in the community with a diagnosis of SMI. SMI was defined as schizophrenia, other types of schizophrenia-like psychosis or bipolar affective disorder. The primary outcomes of interest were: quality of life, mental state and psychiatric admissions at 12 months follow-up. DATA COLLECTION AND ANALYSIS: Pairs of authors independently extracted data. We assessed the quality and certainty of the evidence using RoB 2 (for the primary outcomes) and GRADE. We compared treatment effects between collaborative care and standard care. We divided outcomes into short-term (up to six months), medium-term (seven to 12 months) and long-term (over 12 months). For dichotomous data we calculated the risk ratio (RR) and for continuous data we calculated the standardised mean difference (SMD), with 95% confidence intervals (CIs). We used random-effects meta-analyses due to substantial levels of heterogeneity across trials. We created a summary of findings table using GRADEpro. MAIN RESULTS: Eight RCTs (1165 participants) are included in this review. Two met the criteria for type A collaborative care (intervention comprised of the four core components). The remaining six met the criteria for type B (described as collaborative care by the trialists, but not comprised of the four core components). The composition and purpose of the interventions varied across studies. For most outcomes there was low- or very low-certainty evidence. We found three studies that assessed the quality of life of participants at 12 months. Quality of life was measured using the SF-12 and the WHOQOL-BREF and the mean endpoint mental health component scores were reported at 12 months. Very low-certainty evidence did not show a difference in quality of life (mental health domain) between collaborative care and standard care in the medium term (at 12 months) (SMD 0.03, 95% CI -0.26 to 0.32; 3 RCTs, 227 participants). Very low-certainty evidence did not show a difference in quality of life (physical health domain) between collaborative care and standard care in the medium term (at 12 months) (SMD 0.08, 95% CI -0.18 to 0.33; 3 RCTs, 237 participants). Furthermore, in the medium term (at 12 months) low-certainty evidence did not show a difference between collaborative care and standard care in mental state (binary) (RR 0.99, 95% CI 0.77 to 1.28; 1 RCT, 253 participants) or in the risk of being admitted to a psychiatric hospital at 12 months (RR 5.15, 95% CI 0.67 to 39.57; 1 RCT, 253 participants). One study indicated an improvement in disability (proxy for social functioning) at 12 months in the collaborative care arm compared to usual care (RR 1.38, 95% CI 0.97 to 1.95; 1 RCT, 253 participants); we deemed this low-certainty evidence. Personal recovery and satisfaction/experience of care outcomes were not reported in any of the included studies. The data from one study indicated that the collaborative care treatment was more expensive than standard care (mean difference (MD) international dollars (Int$) 493.00, 95% CI 345.41 to 640.59) in the short term. Another study found the collaborative care intervention to be slightly less expensive at three years. AUTHORS' CONCLUSIONS: This review does not provide evidence to indicate that collaborative care is more effective than standard care in the medium term (at 12 months) in relation to our primary outcomes (quality of life, mental state and psychiatric admissions). The evidence would be improved by better reporting, higher-quality RCTs and the assessment of underlying mechanisms of collaborative care. We advise caution in utilising the information in this review to assess the effectiveness of collaborative care.

Digital Mental Health for Schizophrenia and Other Severe Mental Illnesses: An International Consensus on Current Challenges and Potential Solutions.

BACKGROUND: Digital approaches may be helpful in augmenting care to address unmet mental health needs, particularly for schizophrenia and severe mental illness (SMI). OBJECTIVE: An international multidisciplinary group was convened to reach a consensus on the challenges and potential solutions regarding collecting data, delivering treatment, and the ethical challenges in digital mental health approaches for schizophrenia and SMI. METHODS: The consensus development panel method was used, with an in-person meeting of 2 groups: the expert group and the panel. Membership was multidisciplinary including those with lived experience, with equal participation at all stages and coproduction of the consensus outputs and summary. Relevant literature was shared in advance of the meeting, and a systematic search of the recent literature on digital mental health interventions for schizophrenia and psychosis was completed to ensure that the panel was informed before the meeting with the expert group. RESULTS: Four broad areas of challenge and proposed solutions were identified: (1) user involvement for real coproduction; (2) new approaches to methodology in digital mental health, including agreed standards, data sharing, measuring harms, prevention strategies, and mechanistic research; (3) regulation and funding issues; and (4) implementation in real-world settings (including multidisciplinary collaboration, training, augmenting existing service provision, and social and population-focused approaches). Examples are provided with more detail on human-centered research design, lived experience perspectives, and biomedical ethics in digital mental health approaches for SMI. CONCLUSIONS: The group agreed by consensus on a number of recommendations: (1) a new and improved approach to digital mental health research (with agreed reporting standards, data sharing, and shared protocols), (2) equal emphasis on social and population research as well as biological and psychological approaches, (3) meaningful collaborations across varied disciplines that have previously not worked closely together, (4) increased focus on the business model and product with planning and new funding structures across the whole development pathway, (5) increased focus and reporting on ethical issues and potential harms, and (6) organizational changes to allow for true communication and coproduction with those with lived experience of SMI. This study approach, combining an international expert meeting with patient and public involvement and engagement throughout the process, consensus methodology, discussion, and publication, is a helpful way to identify directions for future research and clinical implementation in rapidly evolving areas and can be combined with measurements of real-world clinical impact over time. Similar initiatives will be helpful in other areas of digital mental health and similarly fast-evolving fields to focus research and organizational change and effect improved real-world clinical implementation.

Association between genetic variants of GRM7 (rs1396409 and rs9883258) and treatment outcomes in Schizophrenic Egyptian patients.

BACKGROUND AND AIM: This study evaluated the association between rs1396409 and rs9883258 and the risk of schizophrenia (SCZ) and treatment outcomes in Egyptian patients. METHODS: This study included 88 patients with SCZ and 88 healthy controls. Lipid profile was assayed. Genotyping of rs1396409 and rs9883258 polymorphisms was analyzed using real-time PCR. RESULTS: The rs1396409 AG genotype frequency was significantly associated with SCZ risk (p = 0.002). Also, significant increased risk of SCZ was observed under allelic (p = 0.001), dominant (p = 0.001) and overdominant (p = 0.001) genetic model of rs1396409. However, rs9883258 AA genotype revealed nonsignificant association with SCZ. Cases with the rs1396409AG genotype exhibited hypertriglyceridemia (p < 0.001) and hypercholesterolemia (p = 0.001). In total, 72.3% and 74.5% of the cases presented with rs1396409 AG have negative symptoms (p = 0.022) and exhibited poor drug response (p = 0.023), respectively; all cases with rs1396409 GG genotype attempted suicide (p = 0.002) and are drug-free (p = 0.003). SCZ patients with negative symptoms had hypercholesterolemia (p = 0.008) mainly low-density lipoproteins (LDLc) (p = 0.016), and those with cognitive symptoms presented with low level of high-density lipoprotein (HDLc) (p = 0.023). Moreover, the multivariate regression analysis revealed that both rs1396409 G allele and HDLc were predictors of SCZ (p = 0.003 and 0.001, resp.). CONCLUSION: The current study concluded that metabotropic glutamate receptor 7 (GRM7) rs1396409 AG could be a potential biomarker for SCZ diagnosis. It also revealed an independent association between the GRM7 rs1396409 G allele, HDLc and SCZ development.

Changes in cognitive function after a 12-week POWER rehabilitation in older adults with schizophrenia and frailty.

BACKGROUND: The effectiveness of isolated resistance training (RT) on cognitive function among older adults with schizophrenia is insufficiently investigated. This study investigated the effectiveness of 12-weeks POWER rehabilitation, a novel RT regimen, on cognitive function among older patients with schizophrenia and frailty. METHODS: Thirty-two older adults with schizophrenia and frailty were enrolled and randomized to receive either a 12-week, twice weekly POWER rehabilitation, or without add-on training. Cognitive functioning was assessed using mini-mental state examination (MMSE), digit symbol substitution test, color trail task (CTT), and digit span task (DST). Physical performance was assessed by walking speed and hand grip strength. The generalized estimating equations was used to compare pre- and post-training outcome measure between groups. RESULTS: Between-group analysis revealed significant improvement in CTT1 and hand grip strength in the intervention group compared to the controls. Subgroup analyses showed CTT1 performance significantly improved after 12 weeks of POWER rehabilitation in the intervention group (time, p < .001), independent of age, educational level, global cognition, depressive symptoms, and psychotropic medication use. Increased hand grip strength was significantly associated with improved performance in MMSE, CTT1, and DST forward at study endpoint. CONCLUSION: A 12-week POWER rehabilitation for older patients with schizophrenia and frailty is safe and feasible, and may benefit physical and some domains of cognitive functioning.

Sex-related cortical asymmetry in antipsychotic-naïve first-episode schizophrenia.

Schizophrenia has been considered to exhibit sex-related clinical differences that might be associated with distinctly abnormal brain asymmetries between sexes. One hundred and thirty-two antipsychotic-naïve first-episode patients with schizophrenia and 150 healthy participants were recruited in this study to investigate whether cortical asymmetry would exhibit sex-related abnormalities in schizophrenia. After a 1-yr follow-up, patients were rescanned to obtain the effect of antipsychotic treatment on cortical asymmetry. Male patients were found to show increased lateralization index while female patients were found to exhibit decreased lateralization index in widespread regions when compared with healthy participants of the corresponding sex. Specifically, the cortical asymmetry of male and female patients showed contrary trends in the cingulate, orbitofrontal, parietal, temporal, occipital, and insular cortices. This result suggested male patients showed a leftward shift of asymmetry while female patients showed a rightward shift of asymmetry in these above regions that related to language, vision, emotion, and cognition. Notably, abnormal lateralization indices remained stable after antipsychotic treatment. The contrary trends in asymmetry between female and male patients with schizophrenia together with the persistent abnormalities after antipsychotic treatment suggested the altered brain asymmetries in schizophrenia might be sex-related disturbances, intrinsic, and resistant to the effect of antipsychotic therapy.