Neural cell-derived plasma exosome protein abnormalities implicate mitochondrial impairment in first episodes of psychosis.

Neuroprotective and other functional proteins of mitochondria were quantified in extracts of plasma neural-derived exosomes from ten first-episode psychosis (FP) patients and ten matched psychiatrically normal controls (ctls). Astrocyte-derived extracellular vesicles (ADEVs) and neuron-derived extracellular vesicles (NDEVs) were immunoabsorbed separately from physically precipitated plasma total EVs. Extracted mitochondrial ATP synthase was specifically immunofixed to plastic wells for quantification of catalytic activity based on conversion of NADH to NAD+ . Other extracted mitochondrial functional proteins were quantified by ELISAs. All protein levels were normalized with EV content of the CD81 exosome marker. FP patient ADEV level but not NDEV level of mitochondrial ATP synthase activity was significantly lower than that of ctls. FP patient ADEV and NDEV levels of the functionally critical mitochondrial proteins mitofusin 2 and cyclophilin D, but not of transcription factor A of mitochondria, and of the mitochondrial short open-reading frame neuroprotective and metabolic regulatory peptides humanin and MOTS-c were significantly lower than those of ctls. In contrast, FP patient NDEV, but not ADEV, level of the mitochondrial-tethering protein syntaphilin, but not of myosin VI, was significantly higher than that of ctls. The distinctively different neural levels of some mitochondrial proteins in FP patients than ctls now should be correlated with diverse clinical characteristics. Drugs that increase depressed levels of proteins and mimetics of deficient short open-reading frame peptides may be of therapeutic value in early phases of schizophrenia.

First help-seeking attempt before and after psychosis onset: measures of delay and aversive pathways to care.

PURPOSE: Delay in receiving effective treatment for psychosis adversely impacts outcomes. We investigated the timing of the first help-seeking attempt in individuals with recent onset non-affective psychosis by comparing those who sought help during the prodrome to those who sought help after psychosis onset across sociodemographic and clinical characteristics, overall functioning, and occurrence of aversive events during their pathways to care. METHODS: Patients were admitted from February 1st, 2014 to January 31st, 2019 to the Program for Specialized Treatment Early in Psychosis (STEP) in New Haven, CT. Psychosis-onset date was ascertained using the Structured Interview for Psychosis-risk Syndromes. Key dates before and after psychosis onset, along with initiators and aversive events, were collected via semi-structured interview. RESULTS: Within 168 individuals, 82% had their first help-seeking episode after psychosis onset and did not differ in terms of sociodemographic characteristics from prodrome help seekers. When the first help-seeking episode started before (i.e., during prodrome) vs after psychosis onset it was mostly initiated by patients vs family members (Cramer's V = 0.23, p = 0.031) and led to a faster prescription of an antipsychotic once full-blown psychosis emerged (time to antipsychotic since psychosis onset = 21 vs 56 days, p = 0.03). No difference in aversive events before STEP enrollment was detected across groups. CONCLUSION: Help seeking during the prodrome is associated with faster initiation of antipsychotic treatment and is more likely to be self-initiated, compared to help seeking after psychosis onset. Early detection efforts that target prodromal samples may improve the length and experience of pathways to care.

An Economic Evaluation of Coordinated Specialty Care (CSC) Services for First-Episode Psychosis in the U.S. Public Sector.

BACKGROUND: Schizophrenia spectrum disorders exert a large and disproportionate economic impact. Early intervention services may be able to alleviate the burden of schizophrenia spectrum disorders on diagnosed individuals, caregivers, and society at large. Economic analyses of observational studies have supported investments in specialized team-based care for early psychosis; however, questions remain regarding the economic viability of first-episode services in the fragmented U.S. healthcare system. The clinic for Specialized Treatment Early in Psychosis (STEP) was established in 2006, to explicitly model a nationally-relevant U.S. public-sector early intervention service. The purpose of this study was to conduct an economic evaluation of STEP, a Coordinated Specialty Care service (CSC) based in a U.S. State-funded community mental health center, relative to usual treatment (UT). METHODS: Eligible patients were within 5 years of psychosis onset and had no more than 12 weeks of lifetime antipsychotic exposure. Participants were randomized to STEP or UT. The annual per-patient cost of the STEP intervention per se was estimated assuming a steady-state caseload of 30 patients. A cost-offset analysis was conducted to estimate the net value of STEP from a third-party payer perspective. Participant healthcare service utilization was evaluated at 6 months and over the entire 12 months post randomization. Generalized linear model multivariable regressions were used to estimate the effect of STEP on healthcare costs over time, and generate predicted mean costs, which were combined with the per-patient cost of STEP. RESULTS: The annual per-patient cost of STEP was $1,984. STEP participants were significantly less likely to have any inpatient or ED visits; among individuals who did use such services in a given period, the associated costs were significantly lower for STEP participants at month 12. We did not observe a similar effect with regard to other healthcare services. The predicted average total costs were lower for STEP than UT, indicating a net benefit for STEP of $1,029 at month 6 and $2,991 at month 12; however, the differences were not statistically significant. CONCLUSIONS: Our findings are promising with regard to the value of STEP to third-party payers.

High rates of obstructive sleep apnea symptoms among patients with schizophrenia.

BACKGROUND: Patients with schizophrenia have high rates of obesity and cardiovascular morbidity, which are strongly associated with obstructive sleep apnea (OSA). The prevalence and risk factors for OSA are not well studied in patients with schizophrenia. OBJECTIVE: The purpose of this study was to evaluate the frequency of OSA symptoms in a sample of outpatients with schizophrenia. METHODS: This cross-sectional study was a secondary analysis of data generated from an insomnia study that evaluated 175 outpatients with schizophrenia or schizoaffective disorder in a single, large urban community mental health center. Results of scales evaluating insomnia were used to complete the STOP questionnaire, which is a screening tool for OSA validated in surgical populations. Appropriate statistical analysis was done to compare participants across groups. RESULTS: Patients were classified into high risk for OSA (STOP ≥ 2) (57.7%), and low risk for OSA (STOP score < 2) (42.3%). We also identified patients with a known diagnosis of OSA (14.9%). Patients with diagnosed OSA had significantly higher STOP scores (mean 2.7 vs. 1.6 [t = 6.3; p < 0.001]). Only 23.8% of patients in the high-risk group were diagnosed with OSA. Body mass index was significantly higher in the diagnosed group (F[2,169] = 25; p < 0.001) as was diabetes (χ2 [2, N = 175] = 35, p < 0.001). CONCLUSION: A large number of outpatients with severe mental illness are at high risk for OSA. The STOP questionnaire is easy to use and appears to have a very high clinical utility to detect OSA. Based on our findings, further studies are warranted to validate the tool in patients with severe mental illness.

A randomized, double-blind, placebo-controlled pilot study of naltrexone to counteract antipsychotic-associated weight gain: proof of concept.

Patients with schizophrenia experience higher rates of obesity as well as related morbidity and mortality than the general population does. Women with schizophrenia are at particular risk for antipsychotic-associated weight gain, obesity, and related medical disorders such as diabetes and cardiovascular disease. Given preclinical studies revealing the role of the endogenous opioid systems in human appetite and the potential of antipsychotic medications to interfere with this system, we hypothesized that opioid antagonists may be beneficial in arresting antipsychotic-associated weight gain and promoting further weight loss in women with schizophrenia. In the present study, 24 overweight women with a diagnosis of schizophrenia or schizoaffective disorder were randomized to placebo or naltrexone (NTX) 25 mg/d for 8 weeks. The primary outcome measure was a change in body weight from baseline. The patients in the NTX group had significant weight loss (-3.40 kg) compared with weight gain (+1.37 kg) in the patients in the placebo group. Mainly, nondiabetic subjects lost weight in the NTX arm. These data support the need to further investigate the role of D2 blockade in reducing food reward-based overeating. A larger study addressing the weaknesses of this pilot study is currently underway.

Reducing the duration of untreated psychosis and its impact in the U.S.: the STEP-ED study.

BACKGROUND: Early intervention services for psychotic disorders optimally interlock strategies to deliver: (i) Early Detection (ED) to shorten the time between onset of psychotic symptoms and effective treatment (i.e. Duration of Untreated Psychosis, DUP); and (ii) comprehensive intervention during the subsequent 2 to 5 years. In the latter category, are teams ('First-episode Services' or FES) that integrate several empirically supported treatments and adapt their delivery to younger patients and caregivers. There is an urgent need to hasten access to established FES in the U.S. Despite improved outcomes for those in treatment, these FES routinely engage patients a year or more after psychosis onset. The Scandinavian TIPS study was able to effectively reduce DUP in a defined geographic catchment. The guiding questions for this study are: can a U.S. adaptation of the TIPS approach to ED substantially reduce DUP and improve outcomes beyond existing FES? METHODS/DESIGN: The primary aim is to determine whether ED can reduce DUP in the US, as compared to usual detection. ED will be implemented by one FES (STEP) based in southern Connecticut, and usual detection efforts will continue at a comparable FES (PREP(R)) serving the greater Boston metropolitan area. The secondary aim is to determine whether DUP reduction can improve presentation, engagement and early outcomes in FES care. A quasi-experimental design will compare the impact of ED on DUP at STEP compared to PREP(R) over 3 successive campaign years. The campaign will deploy 3 components that seek to transform pathways to care in 8 towns surrounding STEP. Social marketing approaches will inform a public education campaign to enable rapid and effective help-seeking behavior. Professional outreach and detailing to a wide variety of care providers, including those in the healthcare, educational and judicial sectors, will facilitate rapid redirection of appropriate patients to STEP. Finally, performance improvement measures within STEP will hasten engagement upon referral. DISCUSSION: STEP-ED will test an ED campaign adapted to heterogeneous U.S. pathways to care while also improving our understanding of these pathways and their impact on early outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02069925 . Registered 20 February 2014.

Reliability and practicality of measuring waist circumference to monitor cardiovascular risk among community mental health center patients.

The aim of this study was to evaluate the clinical utility of measuring waist circumference (WC) in obese individuals with severe psychiatric disabilities. Reliability of the measure and researchers' comfort were assessed. Thirty outpatients with a diagnosis of schizophrenia or schizoaffective disorder were recruited from an urban community mental health center and WC was measured using two methods by three different raters. Inter- and intra-rater reliability was calculated. Raters reported on their comfort with obtaining WC. There was good inter-rater reliability and an acceptable rate of error independent of measurement location. Overall, raters were not comfortable with the WC measurement process for multiple reasons and reported difficulty with the measurement process. Our findings suggest that non-medical staff can reliably and validly measure WC within a typical outpatient mental health treatment setting, but discomfort with the procedure and difficulty with the measurement process may interfere with this practice as part of usual care.

Clinical features of night eating syndrome among depressed patients.

OBJECTIVE: The aim of this study was to investigate the frequency and clinical features of night eating syndrome (NES) in a sample of patients with depression. METHODS: The study sample consisted of 155 depressed outpatients. Socio-demographic Form, Beck Depression Inventory, Beck Anxiety Inventory, Maudsley Obsessive-Compulsive Inventory, Pittsburgh Sleep Quality Index (PSQI) and Night Eating Questionnaire were utilised for data collection. RESULTS: Night eating syndrome was identified in 21.3% of the patients. Comparisons between NES and non-NES patients revealed significant differences in BMI, smoking status, Beck Depression Inventory, Beck Anxiety Inventory, rumination and PSQI sub-scores for sleep quality, latency, disturbances and daytime dysfunction. In our sample, the predictors of NES were BMI, smoking and the subject's score on the PSQI sleep disturbances subscale. CONCLUSIONS: Night eating syndrome is negatively associated with sleep, severity of anxiety and depression. Our findings suggest that there is a complex relation between NES and depression, and it is recommended that depressed patients be evaluated for NES.

The impact of early detection (ED) campaigns on care presentations: Beyond DUP reduction.

We examined the effects of an early detection (ED) campaign (Mindmap), that successfully shortened the duration of untreated psychosis (DUP), on patient presentation profiles at two receiving coordinated specialty care (CSC) services. Data were collected between 2015 and 2019 during a test of ED delivered at one CSC (STEP, n = 147) compared to usual detection at another CSC (PREP, n = 63). Regression models were used to test the effects of ED and DUP on presentation. Before the launch of ED, there were no differences in presentation between STEP and PREP. However, the ED changed the profile of presentations to STEP such that patients were admitted with better negative and total symptoms scores, but worse GAF current and GAF social and with a greater decline in function over the prior year (GAF-Δ). Site-by-time interaction effects were not significant. During the campaign years, STEP vs. PREP recruited patients with better negative and total symptoms, GAF role, and pre-morbid adjustment scores but with worse positive symptoms, GAF current, and GAF-Δ. Nonetheless, mediation analysis revealed that DUP reduction accounted for very little (<8 %) of these differences in presentation. Early detection campaigns while successfully reducing access delays, can have salutary effects on presentation independent of DUP reduction.

Obese schizophrenia spectrum patients have significantly higher 10-year general cardiovascular risk and vascular ages than obese individuals without severe mental illness.

BACKGROUND: Individuals with schizophrenia have a life expectancy that is 20 years less than the general population, along with high rates of obesity and cardiovascular disease (CVD) mortality. OBJECTIVE: This study assessed the 10-year general CVD risk and vascular ages of 106 obese schizophrenia spectrum patients and 197 demographically matched obese controls without severe mental illness (SMI) from the National Health and Nutrition Examination Survey (NHANES). METHODS: Vascular age and general CVD risk were calculated using the Framingham global CVD calculator, which incorporates age, sex, total and HDL cholesterol levels, systolic blood pressure, smoking status, and diabetes or hypertension treatment. RESULTS: Obese schizophrenia spectrum patients had a mean vascular age that was 14.1 years older than their mean actual age, whereas obese NHANES participants had only a 6.7-year difference. The probability of experiencing a CVD event within the next 10 years was 10.7% for obese patients and 8.5% for obese NHANES participants. CONCLUSION: These findings suggest that schizophrenia spectrum patients experience increased metabolic risk independent of weight. Primary care clinicians can utilize general CVD risk and vascular age scores to communicate metabolic risk more easily and to help make treatment decisions.

Investigating the safety and efficacy of naltrexone for anti-psychotic induced weight gain in severe mental illness: study protocol of a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Obesity is a growing health problem leading to high rates of mortality and morbidity in patients with severe mental illness (SMI). The increased rate of obesity is largely attributed to antipsychotic use. The effect of antipsychotic medications on H1 and 5HT2 receptors has been associated with weight gain, but there is also a substantial amount of evidence showing that D2 receptor blockade may be responsible for weight gain by interacting with the dopamine-opioid system. Unfortunately, current available medications for weight loss have limited efficacy in this population. Naltrexone, an opioid receptor antagonist, may be a promising agent to reduce antipsychotic induced weight gain by decreasing food cravings. We aim to investigate the safety and efficacy of two doses of naltrexone (25 mg & 50 mg) versus placebo for weight and health risk reduction in overweight and obese individuals (BMI ≥ 28) with SMI, who gained weight while being treated with antipsychotics. METHODS AND DESIGN: One hundred and forty four patients will be recruited throughout the greater New Haven area. The participants will be randomized to naltrexone 25 mg/day, naltrexone 50 mg/day, or placebo in a 1:1:1 ratio. Participants will be on the study medication for 52 weeks, and assessed weekly for the first 4 weeks and bi-weekly thereafter. The primary outcome measurements are weight reduction and percentage achieving clinically significant weight loss (5% of total body weight). Waist circumference, body mass index, serum lipid profile, fasting glucose, and glycosylated hemoglobin are the secondary outcome measures. The effect of naltrexone on other outcome measurements such as schizophrenia symptoms, depression, dietary consumption, quality of life, cognitive functioning, physical activity, metabolism/inflammation markers, serum leptin, ghrelin, peptide YY, adinopectin, high sensitivity CRP, interleukin 6, interleukin-1B, interleukin-18, and tumor necrosis factor alpha (TNF-α) will be evaluated. The data will be analyzed by applying linear mixed effect models. DISCUSSION: This is the first large scale study investigating the safety and efficacy of naltrexone in antipsychotic induced weight gain; and hopefully, this may lead to a novel pharmacological option for management of this major health problem. TRIAL REGISTRATION: This trial is registered in http://www.clinicaltrials.gov as NCT01866098.

Prevalence of night eating in obese individuals with schizophrenia and schizoaffective disorder.

The prevalence of Night Eating Syndrome (NES) in the general population is estimated to be 1.5%, however, the rates among individuals with schizophrenia and schizoaffective disorder are not yet established. This study sought to examine the frequency and correlates of NES-related behaviors in a sample of obese patients with schizophrenia. One-hundred outpatients diagnosed with schizophrenia or schizoaffective disorders completed the self-report Night Eating Questionnaire (NEQ) and were then interviewed as a follow-up for the specific assessment of NES. Based on a diagnostic interview, 12% of this sample met full criteria for NES, with an additional 10% meeting partial criteria for NES. Based on the NEQ alone, 8% met full criteria with an additional 8% meeting partial criteria. Night eating behaviors were associated with increased insomnia and depression. Our findings suggest that screening for NES among patients with serious mental illness may efficiently identify a subgroup with additional clinical needs.

Re-examining the utility and validity of benign ethnic neutropenia: A narrative literature review.

OBJECTIVE: To conduct a narrative literature review of published evidence documenting racial differences in white blood cells (WBCs) resulting in the legitimization of benign ethnic neutropenia (BEN) as a diagnosis. METHOD: A search of English-language U.S.-based articles was undertaken using the following electronic databases: Medline (1860 to 1990); PsycINFO (1860 to 1990); and EMBASE (1860 to 1990), which resulted in a total of eight studies. A narrative literature review of the eight studies was conducted to assess how race was utilized in the study methods. RESULTS: Of the eight studies, several themes emerged within the scientific literature that demonstrate imprecise, problematic use of race in research practice. 1) Researchers embedded flawed notions of biological differences between racial groups (mostly focused on Black people compared to white people) within the research hypotheses, methods, and conclusions, 2) studies were unclear on how racial group membership was defined and identified within the study samples, 3) studies did not adequately account for structural or historical determinants of health that may drive racial differences in immune status (i.e., neutropenia). CONCLUSIONS: Given the limitations in this U.S.-based scientific literature, BEN is a diagnosis of limited construct validity that reinforces false notions of biological race, warrants renaming to remove "ethnic" language (to include "familial" or "hereditary"), and suggests a need for global expansion of the existing absolute neutrophil count reference ranges in the clozapine monitoring guidelines.

The effect of duration of untreated psychosis (DUP) on the risk for hospitalization after admission to a first episode service.

Engagement with a first episode-psychosis service (FES) reduces the risk of psychiatric hospitalization. However, the role of the duration of untreated psychosis (DUP) in impacting this outcome is disputed. This study aimed to examine whether DUP was an effect modifier of the post-FES reduction of risk of hospitalization, and to explore associations between patients' characteristics and hospitalization post-FES. Individuals aged 16-35 with recent onset (< 3 years) of non-affective psychosis, admitted to the Program for Specialized Treatment Early in Psychosis (STEP), a FES serving the Greater New Haven area, Connecticut, between 2014 and 2019 were included (N = 189). Medical records were queried from 2013 through 2020 for number and duration of psychiatric hospitalizations. Poisson regression models were used to estimate incidence rate ratios for hospitalization rates across all explanatory variables. Negative binomial regression was used to compare the length of stay (LOS) before vs after STEP enrollment. STEP admission was associated with a significant 90 % reduction in the frequency and duration of hospitalizations. This effect was moderated by DUP: with 30-day prolongations in components of DUP (supply, demand, and total) there was less reduction in hospitalizations and LOS after FES enrollment (p < .0001). Only DUP supply (time from first antipsychotic use to STEP admission) differentiated those who were hospitalized during the first year after STEP enrollment from those who were not (median: 35 vs. 15 weeks, p = .003). To fully harness the positive impact of FES on hospitalization, a detailed effort should be pursued to reduce all DUP components.

The effect of dietary and physical activity pattern on metabolic profile in individuals with schizophrenia: a cross-sectional study.

OBJECTIVE: With the rate of obesity on the rise worldwide, individuals with schizophrenia represent a particularly vulnerable population. The aim of this study was to assess the metabolic profile of individuals with schizophrenia in relation to dietary and physical activity habits compared with healthy controls. METHODS: Dietary and physical activity habits of 130 individuals with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of schizophrenia or schizoaffective disorder were compared with 250 body mass index-, age-, and sex-matched and racially matched controls from the 2005-2008 National Health and Nutrition Examination Surveys using a 24-hour diet recall and a self-report physical activity questionnaire. RESULTS: Individuals with schizophrenia had significantly higher levels of glycosylated hemoglobin and insulin compared with matched controls. In addition, these individuals had an increased waist circumference and diastolic blood pressure than did the comparison group. Daily energy intake was not different between groups; however, individuals with schizophrenia consumed significantly greater amounts of sugar and fat. Individuals with schizophrenia reported engaging in moderate physical activity less frequently compared with the National Health and Nutrition Examination Surveys group, but there was no difference in reported vigorous physical activity. CONCLUSIONS: These findings suggest that the dietary and physical activity habits of individuals with schizophrenia contribute to an adverse metabolic profile. Increased opportunities for physical activity and access to healthy foods for individuals with schizophrenia may ease the burden of disease.

Reducing the Duration of Untreated Psychosis (DUP) in a US Community: A Quasi-Experimental Trial.

Objective: Duration of Untreated Psychosis (DUP) remains unacceptably long and limits effectiveness of care. To determine whether an early detection campaign ("Mindmap") can reduce DUP in a US community setting. Methods: In this nonrandomized controlled trial, Mindmap targeted the catchment of one specialty first-episode service or FES (STEP, Greater New Haven) from 2015 to 2019, while usual detection efforts continued at a control FES (PREP, Greater Boston). Mindmap targeted diverse sources of delay through mass & social media messaging, professional outreach & detailing, and rapid enrollment of referrals. Both FES recruited 16-35 years old with psychosis onset ≤3 years. Outcome measures included DUP-Total (onset of psychosis to FES enrollment), DUP-Demand (onset of psychosis to first antipsychotic medication), and DUP-Supply (first antipsychotic medication to FES enrollment). Results: 171 subjects were recruited at STEP and 75 at PREP. Mindmap was associated with an increase in the number of referrals and in efficiency of engagement at STEP. Pre-campaign DUP (2014-2015) was equivalent, while Mindmap was associated with DUP reductions at STEP but not PREP. DUP-Total fell significantly in both the first and the second quartile (11.5 and 58.5 days reduction per campaign year, respectively). DUP-Demand and DUP-Supply fell in the third quartiles only (46.3 and 70.3 days reduction per campaign year, respectively). No reductions were detectable across all quartiles at PREP, but between site comparisons were not significant. Conclusions: This is the first controlled demonstration of community DUP reduction in the US, and can inform future early detection efforts across diverse settings.

Implications of weight-based stigma and self-bias on quality of life among individuals with schizophrenia.

Obesity has been associated with significant stigma and weight-related self-bias in community and clinical studies, but these issues have not been studied among individuals with schizophrenia. A consecutive series of 70 obese individuals with schizophrenia or schizoaffective disorder underwent assessment for perceptions of weight-based stigmatization, self-directed weight bias, negative affect, medication compliance, and quality of life. The levels of weight-based stigmatization and self-bias were compared with levels reported for nonpsychiatric overweight/obese samples. Weight measures were unrelated to stigma, self-bias, affect, and quality of life. Weight-based stigmatization was lower than published levels for nonpsychiatric samples, whereas levels of weight-based self-bias did not differ. After controlling for negative affect, weight-based self-bias predicted an additional 11% of the variance in the quality of life measure. Individuals with schizophrenia and schizoaffective disorder reported weight-based self-bias to the same extent as nonpsychiatric samples despite reporting less weight stigma. Weight-based self-bias was associated with poorer quality of life after controlling for negative affect.

Systematic review of racial disparities in clozapine prescribing.

OBJECTIVE: To conduct a systematic review of published evidence on clozapine prescribing disparities across racial and ethnic categories, estimate the size of these disparities, and assess possible causes to inform future monitoring and intervention. METHODS: Electronic databases (MEDLINE, Embase, PsycINFO, Web of Science) were searched for directly relevant studies. Three independent reviewers selected studies: (1) of US samples; (2) directly addressed ethnic and/or racial disparities in prescribing of antipsychotic medications; (3) identified specific ethnic and/or racial groups (e.g. White, Blacks, Hispanics, non-Hispanic etc.); (4) reported clozapine prescription rates and (5) reported relevant covariates (i.e. gender, age, co-morbidities etc.). FINDINGS: 16 studies met our eligibility criteria. All studies reported clozapine underutilization in ethnic and racial minority patients when compared to their white counterparts. These findings remained consistent despite different time periods, designs, data set types, and after controlling for relevant covariates such as: length of hospital stay, institutional setting, and disease severity. CONCLUSION: The reasons for underutilization of clozapine in minority patients remain unclear. Various contributors can be categorized as: clinician-related factors (e.g. prescriber lack of experience), patient-related factors (e.g. distrust or suspicion of clinician), and institution-related factors (e.g. state operated facilities). Direct examination of these factors can help inform efforts to reduce clozapine prescription disparities.

Decreased mitochondrial electron transport proteins and increased complement mediators in plasma neural-derived exosomes of early psychosis.

Potentially neurotoxic systems involved in traumatic and degenerative diseases of the brain were assessed in acute psychosis. Astrocyte-derived exosomes (ADEs) and neuron-derived exosomes (NDEs) were immunoprecipitated from plasma of ten untreated first-episode psychotics (FPs) and ten matched normal controls (Cs). Neural mitochondrial electron transport and complement proteins were extracted, quantified by ELISAs and normalized with levels of CD81 exosome marker. Levels of subunits 1 and 6 of NADH-ubiquinone oxidoreductase (complex I) and subunit 10 of cytochrome b-c1 oxidase (complex III), but not of subunit 1 of cytochrome C oxidase (complex IV) or superoxide dismutase 1 (SOD1) were significantly lower in ADEs and NDEs of FPs than Cs. This dysregulated pattern of electron transport proteins is associated with increased generation of reactive oxygen species. ADE glial fibrillary acidic protein levels were significantly higher in FPs than Cs, indicating a higher percentage of inflammatory astrocytes in FPs. ADE levels of C3b opsonin were significantly higher and those of C5b-9 attack complex was marginally higher in FPs than Cs. A significantly lower ADE level of the C3 convertase inhibitor CD55 may explain the higher levels of C3 convertase-generated C3b. ADE levels of the neuroprotective protein leukemia inhibitory factor (LIF) were significantly lower in FPs than Cs, whereas levels of IL-6 were no different. Plasma neural exosome levels of electron transport and complement proteins may be useful in predicting FP and guiding therapy. SOD mimetics, C3 convertase inhibitors and LIF receptor agonists also may have therapeutic benefits in FP.