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BackgroundSmoking rates among people living with behavioral health conditions (BHC) range from 30 to 65% and are 2-4 times higher than rates found in the general population. Starting tobacco treatment during a hospital stay is effective for smoking cessation, but little is known regarding treatment response among inpatients with BHC.ObjectiveThis study pooled data across multiple clinical trials to determine the relative success in quitting among participants with BHC compared to other study participants.ParticipantsAdults who smoke (≥ 18 years old) from five hospital-based smoking cessation randomized clinical trials.DesignA retrospective analysis using data from the electronic health record to identify participants with primary diagnoses related to BHC. Recruitment and data analysis were conducted from 2011 to 2016. We used propensity score matching to pair patients with BHC to those with similar characteristics and logistic regression to determine differences between groups.MeasuresThe main outcome was self-reported 30-day abstinence 6 months post-discharge.ResultsOf 6612 participants, 798 patients had a BHC-related primary diagnosis. The matched sample included 642 pairs. Nearly 1 in 3 reported using tobacco medications after hospitalization, with no significant difference between patients with and without BHC (29.3% vs. 31.5%; OR (95% CI) = 0.90 (0.71, 1.14), p = 0.40). Nearly 1 in 5 patients with BHC reported abstinence at 6 months; however, their odds of abstinence were 30% lower than among people without BHC (OR (95% CI) = 0.70 (0.53,0.92), p = 0.01).ConclusionWhen offered tobacco treatment, hospitalized patients with BHC were as likely as people without BHC to accept and engage in treatment. However, patients with BHC were less likely to report abstinence compared to those without BHC. Hospitals are a feasible and promising venue for tobacco treatment among inpatients with BHC. More studies are needed to identify treatment approaches that help people with BHC achieve long-term abstinence.

Objective: To compare rates of participation in the National Bowel Cancer Screening Program (NBCSP) and follow‐up for people with severe mental illness with those for people without severe mental illness or not prescribed antidepressants. Study design: Retrospective cohort study; analysis of de‐identified linked NBCSP, Pharmaceutical Benefits Scheme (PBS), and Medicare Benefits Schedule (MBS) data. Setting: Australia, 2006–2019. Participants: People aged 50–74 years (NBCSP‐eligible) with severe mental illness, defined as those dispensed two or more prescriptions for second generation antipsychotics or for lithium (PBS data), and a random sample of people aged 50–74 years eligible for Medicare‐subsidised services but never prescribed psychotropic medications (antipsychotics, lithium, antidepressants). Main outcome measures: NBCSP participation (returned faecal occult blood test sample), valid test result, positive test result, and follow‐up colonoscopy rates. Results: A total of 119 475 people with severe mental illness and 1 090 574 control group people were included in our analyses. The proportion of women was larger in the severe mental illness group (51.3%) than the control group (48.7%), as were the proportions who lived in inner regional areas (23.5% v 19.1%) or in areas in the lowest socio‐economic quintile (21.8% v 14.7%). The NBCSP participation rate was lower among people with severe mental illness (adjusted incidence rate ratio [IRR], 0.70; 95% confidence interval [CI], 0.69–0.84). The proportion of valid test results was smaller for people with severe mental illness (95.9% v 98.7%; adjusted IRR, 0.97; 95% CI, 0.96–0.99), and the positive test result proportion larger (12.3% v 6.6%; adjusted IRR, 2.01; 95% CI, 1.94–2.09). The proportion of positive test results followed by colonoscopy was smaller for people with severe mental illness (71.7% v 82.6%; adjusted IRR, 0.88; 95% CI, 0.85–0.92). Conclusions: People with severe mental illness were less likely to participate in the NBCSP or to undergo colonoscopy after a positive test result than other Australians. These differences may contribute to higher colorectal cancer mortality among people with severe mental illness. The contributions of differences in cancer stage at diagnosis and subsequent treatment to higher colorectal cancer mortality require further study. [ABSTRACT FROM AUTHOR]

Objective: The incidence of neuroleptic malignant syndrome (NMS), a rare, potentially fatal adverse effect of antipsychotics, among children and youth is unknown. This cohort study estimated NMS incidence in antipsychotic users age 5–24 years and described its variation according to patient and antipsychotic characteristics. Methods: We used national Medicaid data (2004–2013) to identify patients beginning antipsychotic treatment and calculated the incidence of NMS during antipsychotic current use. Adjusted hazard ratios (HRs) assessed the independent contribution of patient and antipsychotic characteristics to NMS risk. Results: The 1,032,084 patients had 131 NMS cases during 1,472,558 person-years of antipsychotic current use, or 8.9 per 100,000 person-years. The following five factors independently predicted increased incidence: age 18–24 years (HR [95% CI] = 2.45 [1.65–3.63]), schizophrenia spectrum and other psychotic disorders (HR = 5.86 [3.16–10.88]), neurodevelopmental disorders (HR = 7.11 [4.02–12.56]), antipsychotic dose >200mg chlorpromazine-equivalents (HR = 1.71 [1.15–2.54]), and first-generation antipsychotics (HR = 4.32 [2.74–6.82]). NMS incidence per 100,000 person-years increased from 1.8 (1.1–3.0) for those with none of these factors to 198.1 (132.8–295.6) for those with 4 or 5 factors. Findings were essentially unchanged in sensitivity analyses that restricted the study data to second-generation antipsychotics, children age 5–17 years, and the 5 most recent calendar years. Conclusion: In children and youth treated with antipsychotics, five factors independently identified patients with increased NMS incidence: age 18–24 years, schizophrenia spectrum and other psychotic disorders, neurodevelopmental disorders, first-generation drugs, and antipsychotic doses greater than 200 mg chlorpromazine-equivalents. Patients with 4 or 5 of these factors had more than 100 times the incidence of those with none. These findings could improve early identification of children and youth with elevated NMS risk, potentially leading to earlier detection and improved outcomes. [ABSTRACT FROM AUTHOR]

This article from the American Journal of Psychiatry provides a comprehensive overview of various topics related to schizophrenia spectrum disorders and psychosis. It includes studies on the use of antipsychotic medications, the potential adverse events of long-term clozapine treatment, the benefits of hormonal replacement therapy for menopausal women with schizophrenia, the risk of inducing psychosis or mania with prescribed stimulants, neural signatures associated with depressive versus negative symptoms in schizophrenia patients, and gene expression patterns in the prefrontal cortex. The article emphasizes the importance of monitoring and preventing adverse events related to clozapine treatment and highlights the potential benefits of hormonal replacement therapy for menopausal women with schizophrenia. It also discusses the increased risk of developing psychosis or mania with prescribed amphetamines and provides insights into the neural circuitry underlying depressive and negative symptoms in schizophrenia patients. Overall, this article offers valuable information for researchers and individuals interested in understanding and addressing schizophrenia spectrum disorders. [Extracted from the article]

This article explores the neurobiological aspects of schizophrenia, with a focus on the reduced functioning of the dorsolateral prefrontal cortex (DLPFC) and the loss of spines and dendrites on pyramidal cells in deep layer III of the DLPFC in individuals with schizophrenia. The study examines the transcriptional changes in macaque DLPFC during different stages of development and identifies the callosal projection (CP) cells as particularly vulnerable to genetic or environmental factors that cause dendritic spine loss during adolescence. The article also discusses the impact of stress on DLPFC function and its potential implications for understanding the causes of schizophrenia. Additionally, the study explores the expression of potassium channels in layer III spines and their potential role in dendritic spine loss, suggesting that high expression of SK3 channels in CUX2B pyramidal cells may contribute to overpruning of dendritic spines. The authors also speculate on the involvement of PACAP in driving spine loss through its effects on signaling pathways. Overall, these findings provide valuable insights into the molecular and connectional properties of cells affected in schizophrenia. [Extracted from the article]

Objective: Antipsychotic effectiveness in preventing relapse declines around menopausal age in women with schizophrenia or schizoaffective disorder (SSD). It is not known whether systemic menopausal hormone therapy (MHT) can help to prevent psychosis relapse. Methods: A within-subject study design was used to study the effectiveness of MHT in preventing relapse in a Finnish nationwide cohort of women with SSD between 40 and 62 years of age who used MHT during follow-up (1994–2017). Hazard ratios adjusted for age and psychotropic drug use were calculated for psychosis relapse as main outcome and any psychiatric hospitalization as secondary outcome. Results: The study population comprised 3,488 women using MHT. Use of MHT was associated with a 16% lower relapse risk (adjusted hazard ratio [aHR]=0.84, 95% CI=0.78–0.90) when compared to non-use. Stratified by age, MHT was associated with decreased relapse risks when used between ages 40–49 (aHR=0.86, 95% CI=0.78–0.95) and ages 50–55 (aHR=0.74, 95% CI=0.66–0.83), but not between ages 56–62 (aHR=1.11, 95% CI=0.91–1.37). Similar effectiveness was found for estrogen alone or combined with fixed or sequential progestogens (aHRs between 0.79 and 0.86), transdermal and oral formulations (aHRs 0.75–0.87), and for most specific formulations (aHRs 0.75–0.85), except tibolone (aHR=1.04, 95% CI=0.75–1.44) and formulations with dydrogesterone (aHR=1.05, 95% CI=0.85–1.30). Similar results were observed with any psychiatric hospitalization as outcome measure. Conclusions: The findings underscore the potential value of MHT in preventing psychosis relapse among women with SSD of menopausal age. These findings translate clinical evidence on the neuroprotective effects of estrogens to real-world settings, encompassing a group of women for whom current antipsychotic treatment options may be insufficient. [ABSTRACT FROM AUTHOR]

Objective: The authors used longitudinal biobank data with up to 25 years of follow-up on over 2,600 clozapine users to derive reliable estimates of the real-world burden of clozapine adverse drug events (ADEs). Methods: A total of 2,659 participants in the FinnGen biobank project had a schizophrenia diagnosis and clozapine purchases with longitudinal electronic health record follow-up for up to 25 years after clozapine initiation. Diseases and health-related events enriched during clozapine use were identified, adjusting for disease severity. The incidence and recurrence of ADEs over years of clozapine use, their effect on clozapine discontinuation and deaths, and their pharmacogenetics were studied. Results: Median follow-up time after clozapine initiation was 12.7 years. Across 2,157 diseases and health-related events, 27 were enriched during clozapine use, falling into five disease categories: gastrointestinal hypomotility, seizures, pneumonia, other acute respiratory tract infections, and tachycardia, along with a heterogeneous group including neutropenia and type 2 diabetes, among others. Cumulative incidence estimates for ileus (severe gastrointestinal hypomotility) and pneumonia were 5.3% and 29.5%, respectively, 20 years after clozapine initiation. Both events were significantly associated with increased mortality among clozapine users (ileus: odds ratio=4.5; pneumonia: odds ratio=2.8). Decreased genotype-predicted CYP2C19 and CYP1A2 activities were associated with higher pneumonia risk. Conclusions: Clozapine-induced ileus and pneumonia were notably more frequent than has previously been reported and were associated with increased mortality. Two CYP genes influenced pneumonia risk. Pneumonia and ileus call for improved utilization of available preventive measures. [ABSTRACT FROM AUTHOR]

Objective: Conceptual similarities between depressive and negative symptoms complicate biomarker and intervention development. This study employed a data-driven approach to delineate the neural circuitry underlying depressive and negative symptoms in schizophrenia spectrum disorders (SSDs). Methods: Data from three studies were analyzed (157 participants with SSDs) to assess brain-behavior relationships: two neuroimaging studies and a randomized trial of repetitive transcranial magnetic stimulation (rTMS). Partial least squares correlation (PLSC) was used to investigate associations between resting-state functional connectivity and depressive and negative symptoms. Secondary analyses of rTMS trial data (active, N=37; sham, N=33) were used to assess relationships between PLSC-derived symptom profiles and treatment outcomes. Results: PLSC identified three latent variables (LVs) relating functional brain circuitry with symptom profiles. LV1 related a general depressive symptom factor with positive associations between and within the default mode network (DMN), the frontoparietal network (FPN), and the cingulo-opercular network (CON). LV2 related negative symptoms (no depressive symptoms) via negative associations, especially between the FPN and the CON, but also between the DMN and the FPN and the CON. LV3 related a guilt and early wakening depression factor via negative rather than positive associations with the DMN, FPN, and CON. The secondary visual network had a positive association with general depressive symptoms and negative associations with guilt and negative symptoms. Active (but not sham) rTMS applied bilaterally to the dorsolateral prefrontal cortex (DLPFC) reduced general depressive but not guilt-related or negative symptoms. Conclusions: The results clearly differentiate the neural circuitry underlying depressive and negative symptoms, and segregated across the two-factor structure of depression in SSDs. These findings support divergent neurobiological pathways of depressive symptoms and negative symptoms in people with SSDs. As treatment options are currently limited, bilateral rTMS to the DLPFC is worth exploring further for general depressive symptoms in people with SSDs. [ABSTRACT FROM AUTHOR]

Objective: Amphetamine prescribing has increased in the United States in recent years. Previous research identified an increased risk of incident psychosis with prescription amphetamines. The purpose of this study was to examine the impact of dose levels of prescription amphetamines on the risk of this rare but serious adverse outcome. Methods: A case-control study using electronic health records was conducted to compare the odds of incident psychosis or mania with past-month exposure to prescription amphetamines. Case subjects were patients ages 16–35 hospitalized at McLean Hospital for incident psychosis or mania between 2005 and 2019. Control subjects were patients with an initial psychiatric hospitalization for other reasons, most commonly depression and/or anxiety. Amphetamine doses were converted to dextroamphetamine equivalents and divided into terciles. Secondary analyses evaluated the odds of psychosis or mania with methylphenidate use. Results: Among 1,374 case subjects and 2,748 control subjects, the odds of psychosis and mania were increased for individuals with past-month prescription amphetamine use compared with no use (adjusted odds ratio=2.68, 95% CI=1.90–3.77). A dose-response relationship was observed; high doses of amphetamines (>30 mg dextroamphetamine equivalents) were associated with 5.28-fold increased odds of psychosis or mania. Past-month methylphenidate use was not associated with increased odds of psychosis or mania compared with no use (adjusted odds ratio=0.91, 95% CI=0.54–1.55). Conclusions: Although use of hospitalized control subjects excludes individuals with less severe disease, leading to selection bias, the study results suggest that caution should be exercised when prescribing high doses of amphetamines, with regular screening for symptoms of psychosis or mania. [ABSTRACT FROM AUTHOR]

• Eggerthella is enriched in bipolar and schizophrenia spectrum disorders. • Lachnoclostridium is enriched in bipolar and schizophrenia spectrum disorders. • Balances are reproducible gut microbial signatures in psychiatric disorders. • Antipsychotic use is positively associated with the levels of Klebsiella in the gut. • Lithium use is positively associated with the gut levels of Anaeromassilibacillus. Numerous studies report gut microbiome variations in bipolar disorder (BD) and schizophrenia spectrum disorders (SSD) compared to healthy individuals, though, there is limited consensus on which specific bacteria are associated with these disorders. In this study, we performed a comprehensive metagenomic shotgun sequencing analysis in 103 Dutch patients with BD/SSD and 128 healthy controls matched for age, sex, body mass index and income, while accounting for diet quality, transit time and technical confounders. To assess the replicability of the findings, we used two validation cohorts (total n = 203), including participants from a distinct population with a different metagenomic isolation protocol. The gut microbiome of the patients had a significantly different β-diversity, but not α-diversity nor neuroactive potential compared to healthy controls. Initially, twenty-six bacterial taxa were identified as differentially abundant in patients. Among these, the previously reported genera Lachnoclostridium and Eggerthella were replicated in the validation cohorts. Employing the CoDaCoRe learning algorithm, we identified two bacterial balances specific to BD/SSD, which demonstrated an area under the receiver operating characteristic curve (AUC) of 0.77 in the test dataset. These balances were replicated in the validation cohorts and showed a positive association with the severity of psychiatric symptoms and antipsychotic use. Last, we showed a positive association between the relative abundance of Klebsiella and Klebsiella pneumoniae with antipsychotic use and between the Anaeromassilibacillus and lithium use. Our findings suggest that microbial balances could be a reproducible method for identifying BD/SSD-specific microbial signatures, with potential diagnostic and prognostic applications. Notably, Lachnoclostridium and Eggerthella emerge as frequently occurring bacteria in BD/SSD. Last, our study reaffirms the previously established link between Klebsiella and antipsychotic medication use and identifies a novel association between Anaeromassilibacillus and lithium use. [ABSTRACT FROM AUTHOR]

Objectives: In 2013, a cluster‐controlled pilot study found the 12‐week Keeping the Body in Mind (KBIM) lifestyle and life skills intervention was able to prevent weight gain in a small sample of youth experiencing first‐episode psychosis (FEP) with fewer than 4 weeks of antipsychotic exposure. This study aims to evaluate the effectiveness of KBIM as routine care on anthropometry and metabolic biochemistry in a larger sample of youth with FEP across three community mental health services. Method: This retrospective chart audit was conducted on youth with FEP, prescribed a therapeutic dose of antipsychotic medication, and who engaged with KBIM between 2015 and 2019. Primary outcomes were weight and waist circumference. Secondary outcomes were blood pressure, blood glucose, and blood lipids. Outcomes were collected in at baseline and at 12 weeks. Data on program engagement were obtained from the participant's medical file. Results: One‐hundred and eighty‐two people met inclusion criteria, and up to 134 people had baseline and 12‐week data on one or more outcome. Mean number of sessions attended was 11.1 (SD = 7.3). Increases in weight and waist circumference were limited to 1.5 kg (SD = 5.3, t(133) = 3.2, p =.002) and 0.7 cm (SD = 5.8, t(109) = 1.2, p =.23) respectively. Eighty‐one percent of participants did not experience clinically significant weight gain (>7% of baseline weight). There were no significant changes in blood pressure or metabolic biochemistry. Conclusion: The prevention of substantial gains in weight and waist circumference observed in the initial pilot study was maintained with implementation of KBIM as part of routine clinical care for youth with FEP. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. METHODS: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. RESULTS: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values

OBJECTIVE: Copy number variants (CNVs) are well-known genetic pleiotropic risk factors for multiple neurodevelopmental and psychiatric disorders (NPDs), including autism (ASD) and schizophrenia. Little is known about how different CNVs conferring risk for the same condition may affect subcortical brain structures and how these alterations relate to the level of disease risk conferred by CNVs. To fill this gap, the authors investigated gross volume, vertex-level thickness, and surface maps of subcortical structures in 11 CNVs and six NPDs. METHODS: Subcortical structures were characterized using harmonized ENIGMA protocols in 675 CNV carriers (CNVs at 1q21.1, TAR, 13q12.12, 15q11.2, 16p11.2, 16p13.11, and 22q11.2; age range, 6-80 years; 340 males) and 782 control subjects (age range, 6-80 years; 387 males) as well as ENIGMA summary statistics for ASD, schizophrenia, attention deficit hyperactivity disorder, obsessive-compulsive disorder, bipolar disorder, and major depression. RESULTS: All CNVs showed alterations in at least one subcortical measure. Each structure was affected by at least two CNVs, and the hippocampus and amygdala were affected by five. Shape analyses detected subregional alterations that were averaged out in volume analyses. A common latent dimension was identified, characterized by opposing effects on the hippocampus/amygdala and putamen/pallidum, across CNVs and across NPDs. Effect sizes of CNVs on subcortical volume, thickness, and local surface area were correlated with their previously reported effect sizes on cognition and risk for ASD and schizophrenia. CONCLUSIONS: The findings demonstrate that subcortical alterations associated with CNVs show varying levels of similarities with those associated with neuropsychiatric conditions, as well distinct effects, with some CNVs clustering with adult-onset conditions and others with ASD. These findings provide insight into the long-standing questions of why CNVs at different genomic loci increase the risk for the same NPD and why a single CNV increases the risk for a diverse set of NPDs.

Introduction Clozapine is the only antipsychotic approved for treatment-resistant schizophrenia, but without appropriate monitoring, it can be associated with potentially fatal outcomes. An International Adult Clozapine Titration Guideline categorizes patients into normal or slow metabolizers. Categorization provides clozapine titration schedules and recommends regular c-reactive protein (CRP) and clozapine concentration monitoring to reduce the risk of adverse drug reactions (ADRs). The impact of the guideline on clozapine ADRs has not been evaluated. Methods A retrospective chart review assessed clozapine titrations, laboratory monitoring, ADRs, and discontinuations for clozapine-naive adult inpatients at a single center from January 1, 2013, to June 1, 2022. Each patient’s cumulative weekly clozapine dosage was compared with their guideline recommended dosage to create a percent accordance. Linear logistic regression evaluated the relationship between titration speed and the presence of an ADR, while descriptive statistics analyzed laboratory monitoring. Results Forty-three patients were included, with the majority being White males with schizophrenia. An inverse relationship existed between the last inpatient week clozapine dose percent accordance and the probability of an ADR. Nonobese patients were less likely than obese patients to experience an ADR (odds ratio = 0.17; 95% CI, 0.03-0.99). CRP and clozapine concentration monitoring was suboptimal. Discussion Based on our small retrospective review of primarily White males, more aggressive clozapine titrations did not increase ADRs. Future studies with more diverse samples are needed and should focus on specific ADRs, which may have increased occurrence with rapid titrations. Obese patients were at higher risk of ADRs, correlating with the guideline-recommended slower titrations for these patients.

Objective: Cognitive remediation provides substantial improvements in cognitive performance and real-world functioning for people living with schizophrenia, but the durability of these benefits needs to be reassessed and better defined. The aims of this study were to provide a comprehensive assessment of the durability of the benefits of cognitive remediation for cognition and functioning in people living with schizophrenia and evaluating potential moderators of effects. Methods: A systematic search was conducted in PubMed, Scopus, and PsycINFO, and reference lists of included articles and Google Scholar were inspected. Eligible studies were randomized clinical trials of cognitive remediation in patients diagnosed with schizophrenia spectrum disorders in which follow-up assessments were included. Screening and data extraction were performed by at least two independent reviewers. Cohen's d was used to measure outcomes. Primary outcomes were changes in cognition and functioning from baseline to conclusion of follow-up. Moderators of the durability of effects were assessed. Results: Of 2,840 identified reports, 281 full texts were assessed and 130 reports on 67 studies with 5,334 participants were included. Cognitive remediation produced statistically significant positive effects that persisted at the end of follow-up in global cognition (d=0.23) and in global functioning (d=0.26). Smaller study samples and single-center studies were associated with better cognitive outcomes; longer treatment and follow-up duration, techniques for transferring cognitive gains to the real world, integration with psychiatric rehabilitation, group format of delivery, and more female participants in the sample were associated with better functional outcomes. Conclusions: Cognitive remediation provides durable improvements in cognition and functioning in schizophrenia. This finding corroborates the notion that cognitive remediation should be implemented more widely in clinical and rehabilitation practice. [ABSTRACT FROM AUTHOR]

Objective: Understanding prognosis is critical to anticipating public health needs and providing care to individuals with psychotic disorders. However, the long-term course of remission and recovery remains unclear. In this study, the most common trajectories of illness course are described for a cohort of individuals followed for 25 years since first admission for psychosis. Methods: Participants are from the Suffolk County Mental Health Project, an epidemiological study of first-admission psychosis. Data for the present study was collected from six follow-ups, with 311 individuals assessed at the 25-year follow-up. Common patterns of remission and recovery were assessed in the baseline cohort of 591 individuals and the subsample from the 25-year follow up. Results: In the baseline cohort and the 25-year subsample, the most common trajectory for individuals with schizophrenia spectrum disorders was no remission and no recovery. Among individuals with other psychotic disorders, in both the baseline and 25-year cohorts, the modal pattern was one of intermittent remission and recovery. Individuals with other psychotic disorders were more likely to experience stable remission (15.1%) and stable recovery (21.1%), outcomes that were rare among individuals with schizophrenia spectrum disorders (0% and 0.6%, respectively). Conclusions: The modal longitudinal pattern for individuals with other psychoses is one of multiple transitions into and out of symptomatic and functional recovery. Engagement in a long-term health care plan may help individuals detect and respond to these changes. Sustained remission and recovery are rare among people with schizophrenia spectrum disorders. Efforts should be directed toward developing more effective treatments for this population. [ABSTRACT FROM AUTHOR]

Objective: Markers for treatment resistance in schizophrenia are needed to reduce delays in effective treatment. Nigrostriatal hyperdopaminergic function plays a critical role in the pathology of schizophrenia, yet antipsychotic nonresponders do not show increased dopamine function. Neuromelanin-sensitive MRI (NM-MRI), which indirectly measures dopamine function in the substantia nigra, has potential as a noninvasive marker for nonresponders. Increased NM-MRI signal has been shown in psychosis, but has not yet been assessed in nonresponders. In this study, the authors investigated whether nonresponders show lower NM-MRI signal than responders. Methods: NM-MRI scans were acquired in 79 patients with first-episode psychosis and 20 matched healthy control subjects. Treatment response was assessed at a 6-month follow-up. An a priori voxel-wise analysis within the substantia nigra tested the relation between NM-MRI signal and treatment response in patients. Results: Fifteen patients were classified as nonresponders and 47 patients as responders. Seventeen patients were excluded, primarily because of medication nonadherence or change in diagnosis. Voxel-wise analysis revealed 297 significant voxels in the ventral tier of the substantia nigra that were negatively associated with treatment response. Nonresponders and healthy control subjects had significantly lower NM-MRI signal than responders. Receiver operating characteristic curve analysis showed that NM-MRI signal separated nonresponders with areas under the curve between 0.62 and 0.85. In addition, NM-MRI signal in patients did not change over 6 months. Conclusions: These findings provide further evidence for dopaminergic differences between medication responders and nonresponders and support the potential of NM-MRI as a clinically applicable marker for treatment resistance in schizophrenia. [ABSTRACT FROM AUTHOR]

Objective: Schizophrenia is a brain disorder that originates during neurodevelopment and has complex genetic and environmental etiologies. Despite decades of clinical evidence of altered striatal function in affected patients, studies examining its cellular and molecular mechanisms in humans are limited. To explore neurodevelopmental alterations in the striatum associated with schizophrenia, the authors established a method for the differentiation of induced pluripotent stem cells (iPSCs) into ventral forebrain organoids (VFOs). Methods: VFOs were generated from postmortem dural fibroblast–derived iPSCs of four individuals with schizophrenia and four neurotypical control individuals for whom postmortem caudate genotypes and transcriptomic data were profiled in the BrainSeq neurogenomics consortium. Individuals were selected such that the two groups had nonoverlapping schizophrenia polygenic risk scores (PRSs). Results: Single-cell RNA sequencing analyses of VFOs revealed differences in developmental trajectory between schizophrenia and control individuals in which inhibitory neuronal cells from the patients exhibited accelerated maturation. Furthermore, upregulated genes in inhibitory neurons in schizophrenia VFOs showed a significant overlap with upregulated genes in postmortem caudate tissue of individuals with schizophrenia compared with control individuals, including the donors of the iPSC cohort. Conclusions: The findings suggest that striatal neurons derived from high-PRS individuals with schizophrenia carry abnormalities that originated during early brain development and that the VFO model can recapitulate disease-relevant cell type–specific neurodevelopmental phenotypes in a dish. [ABSTRACT FROM AUTHOR]

Background: Mental capacity is a fundamental aspect that enables patients to fully participate in various healthcare procedures. To assist healthcare professionals (HCPs) in assessing patients' capacity, especially in the mental health field, several standardized tools have been developed. These tools include the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), and the Competence Assessment Tool for Psychiatric Advance Directives (CAT-PAD). The core dimensions explored by these tools include Understanding, Appreciation, Reasoning, and Expression of a choice. Objective: This meta-analysis aimed to investigate potential differences in decision-making capacity within the healthcare context among groups of patients with bipolar disorders (BD) and schizophrenia spectrum disorders (SSD). Methods: A systematic search was conducted on Medline/Pubmed, and Scopus. Additionally, Google Scholar was manually inspected, and a manual search of emerging reviews and reference lists of the retrieved papers was performed. Eligible studies were specifically cross-sectional, utilizing standardized assessment tools, and involving patients diagnosed with BD and SSD. Data from the studies were independently extracted and pooled using random-effect models. Hedges' g was used as a measure for outcomes. Results: Six studies were identified, with three studies using the MacCAT-CR, two studies the MacCAT-T, and one the CAT-PAD. The participants included 189 individuals with BD and 324 individuals with SSD. The meta-analysis revealed that patients with BD performed slightly better compared to patients with SSD, with the difference being statistically significant in the domain of Appreciation (ES = 0.23, 95% CI: 0.01 to 0.04, p = 0.037). There was no statistically significant difference between the two groups for Understanding (ES = 0.09, 95% CI:−0.10 to 0.27, p = 0.352), Reasoning (ES = 0.18, 95% CI: −0.12 to 0.47, p = 0.074), and Expression of a choice (ES = 0.23, 95% CI: −0.01 to 0.48, p = 0.60). In the sensitivity analysis, furthermore, when considering only studies involving patients in symptomatic remission, the difference for Appreciation also resulted in non-significant (ES = 0.21, 95% CI: −0.04 to 0.46, p = 0.102). Conclusions: These findings indicate that there are no significant differences between patients with BD and SSD during remission phases, while differences are minimal during acute phases. The usefulness of standardized assessment of capacity at any stage of the illness should be considered, both for diagnostic-therapeutic phases and for research and advance directives. Further studies are necessary to understand the reasons for the overlap in capacity between the two diagnostic categories compared in this study. [ABSTRACT FROM AUTHOR]

Introduction: Childhood trauma and adversities (CTA) and aberrant salience (AS) have a pivotal role in schizophrenia development, but their interplay with psychotic symptoms remains vague. We explored the mediation performed by AS between CTA and psychotic symptomatology in schizophrenia. Methods: We approached 241 adults suffering from schizophrenia spectrum disorders (SSDs), who have been in the unit for at least 12 consecutive months, excluding the diagnosis of dementia, and recent substance abuse disorder, and cross-sectional evaluated through the Aberrant Salience Inventory (ASI), Childhood Trauma Questionnaire Short-Form (CTQ-SF), and Positive and Negative Symptom Scale (PANSS). We tested a path-diagram where AS mediated the relationship between CTA and psychosis, after verifying each measure one-dimensionality through confirmatory factor analysis. Results: The final sample comprised 222 patients (36.9% female), with a mean age of 42.4 (± 13.3) years and an average antipsychotic dose of 453.6 (± 184.2) mg/day (chlorpromazine equivalents). The mean duration of untreated psychosis was 1.8 (± 2.0) years while the mean onset age was 23.9 (± 8.2) years. Significant paths were found from emotional abuse to ASI total score (β = 0.39; p

BackgroundThe conclusion that people with severe mental illness require involuntary care to protect their health (including threats due to physical-non-psychiatric-illness) is challenged by findings indicating that they often lack access to general healthcare and the assertion that they would access such care voluntarily if available and effective. Victoria, Australia's single-payer healthcare system provides accessible medical treatment; therefore, it is an excellent context in which to test these challenges.AimsThis study replicates a previous investigation in considering whether, in Australia's easy-access single-payer healthcare system, patients placed on community treatment orders, specifically involuntary community treatment, are more likely to access acute medical care addressing potentially life-threatening physical illnesses than voluntary patients with and without severe mental illness.MethodsReplicating methods used in 2000-2010, for the years 2010-2017, this study compared the acute medical care access of three new cohorts: 7826 hospitalised patients with severe mental illness who received a post-hospitalisation, community treatment order; 13 896 patients with severe mental illness released from the hospital without a community treatment order and 12 101 outpatients who were never psychiatrically hospitalised (individuals with less morbidity risk who were not considered to have severe mental illness) during periods when they were under versus outside community mental health supervision. Logistic regression was used to determine the influence of community-based community mental health supervision and the type of community mental health supervision (community treatment order vs non-community treatment order) on the likelihood of receiving an initial diagnosis of a life-threatening physical illness requiring acute care.ResultsValidating their shared elevated morbidity risk, 43.7% and 46.7%, respectively, of each hospitalised cohort (community treatment order and non-community treatment order patients) accessed an initial acute-care diagnosis for a life-threatening condition vs 26.3% of outpatients. Outside community mental health supervision, the likelihood that a community treatment order patient would receive a diagnosis of physical illness was 36% lower than non-community treatment order patients-1.30 times that of outpatients. Under community mental health supervision, their likelihood was two times greater than that of non-community treatment order patients and 6.6 times that of outpatients. Each community treatment order episode was associated with a 14.6% increase in the likelihood of a community treatment order patient receiving a diagnosis. The results replicate those found in an independent 2000-2010 cohort comparison.ConclusionsCommunity mental health supervision, notably community treatment order supervision, in two independent investigations over two decades appeared to facilitate access to physical healthcare in acute care settings for patients with severe mental illness who were refusing treatment-a group that has been subject to excess morbidity and mortality.

OBJECTIVE: Mental disorders are heritable and polygenic, and genome-wide genetic correlations (rg) have indicated widespread shared genetic risk across multiple disorders and related traits, mirroring their overlapping clinical characteristics. However, rg may underestimate the shared genetic underpinnings of mental disorders and related traits because it does not differentiate mixtures of concordant and discordant genetic effects from an absence of genetic overlap. Using novel statistical genetics tools, the authors aimed to evaluate the genetic overlap between mental disorders and related traits when accounting for mixed effect directions. METHODS: The authors applied the bivariate causal mixture model (MiXeR) to summary statistics for four mental disorders, four related mental traits, and height from genome-wide association studies (Ns ranged from 53,293 to 766,345). MiXeR estimated the number of causal variants for a given trait (polygenicity), the number of variants shared between traits, and the genetic correlation of shared variants (rgs). Local rg was investigated using LAVA. RESULTS: Among mental disorders, ADHD was the least polygenic (5.6K causal variants), followed by bipolar disorder (8.6K), schizophrenia (9.6K), and depression (14.5K). Most variants were shared across mental disorders (4.4K-9.3K) and between mental disorders and related traits (5.2K-12.8K), but with disorder-specific variations in rg and rgs. Overlap with height was small (0.7K-1.1K). MiXeR estimates correlated with LAVA local rg (r=0.88, p