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ObjectiveDuration 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.MethodsIn 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).Results171 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.ConclusionsThis is the first controlled demonstration of community DUP reduction in the US, and can inform future early detection efforts across diverse settings.

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.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.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).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.

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.

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.

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.

The current study sought to expand on prior reports of the validity and reliability of the CAINS (CAINS) by examining its performance across diverse non-academic clinical settings as employed by raters not affiliated with the scale's developers and across a longer test-retest follow-up period. The properties of the CAINS were examined within the Management of Schizophrenia in Clinical Practice (MOSAIC) schizophrenia registry. A total of 501 participants with a schizophrenia spectrum diagnosis who were receiving usual care were recruited across 15 national Patient Assessment Centers and evaluated with the CAINS, other negative symptom measures, and assessments of functioning, quality of life and cognition. Temporal stability of negative symptoms was assessed across a 3-month follow-up. Results replicated the two-factor structure of the CAINS reflecting Motivation and Pleasure and expression symptoms. The CAINS scales exhibited high internal consistency and temporal stability. Convergent validity was supported by significant correlations between the CAINS subscales with other negative symptom measures. Additionally, the CAINS was significantly correlated with functioning and quality of life. Discriminant validity was demonstrated by small to moderate associations between the CAINS and positive symptoms, depression, and cognition (and these associations were comparable to those found with other negative symptom scales). Findings suggest that the CAINS is a reliable and valid tool for measuring negative symptoms in schizophrenia across diverse clinical samples and settings.

SummaryObjectives Obesity is associated with significant morbidity and mortality rates. Even modest weight loss may be associated with health benefits. Alpha-lipoic acid (ALA) is a naturally occurring antioxidant. Studies have suggested anti-obesity properties of ALA; however, results are inconsistent. The purpose of this study is to conduct a meta-analysis of the effect of ALA on weight and body mass index (BMI). Methods A comprehensive, systematic literature search identified 10 articles on randomized, double-blind, placebo-controlled studies involving ALA. We conducted a meta-analysis of mean weight and BMI change differences between ALA and placebo treatment groups. Results Alpha-lipoic acid treatment coincided with a statistically significant 1.27 kg (confidence interval = 0.25 to 2.29) greater mean weight loss compared with the placebo group. A significant overall mean BMI difference of −0.43 kg/ m2 (confidence interval = −0.82 to −0.03) was found between the ALA and placebo groups. Meta-regression analysis showed no significance in ALA dose on BMI and weight changes. Study duration significantly affected BMI change, but not weight change. Conclusions Alpha-lipoic acid treatment showed small, yet significant short-term weight loss compared with placebo. Further research is needed to examine the effect of different doses and the long-term benefits of ALA on weight management.

Background In the U.S., individuals affected by a first episode psychosis endure 74 mean weeks of delay in receiving effective treatment. Facilitating their access to care has become a public health priority. This delay has proven to have adverse consequences both in short and long-term outcomes. Moreover, aversive pathways to care can imperil subsequent engagement with treatment. A better understanding of how a patient’s characteristics might influence interactions with healthcare systems could help tailor early detection interventions and target delays in treatments. By comparing the timing of the first help seeking attempt initiated in a sample of first episode psychosis participants of an early detection campaign, we aim to investigate if people starting to seek help before psychosis will have shorter delays to care, and if an earlier help-seeking attempt correlates with a lower rate of adverse pathways to care (e.g. police involvement, involuntary admissions). Methods Participants were recruited starting February 1st, 2014 to January 31st, 2019, to STEP, a Coordinated Specialty Care Program in New Haven, CT. Based on the date of the first help-seeking episode, demographic, clinical, and socioeconomic data were used to compare participants who had their first help-seeking attempt before or after psychosis onset (psychosis onset defined using the POPS criteria at the SIPS Interview). Chi-square test was used to compare categorical variables; non-parametric or Student’s t test was used to compare the continuous variables. Results The sample comprised 168 subjects, the majority of which were male, African American, young adults (mean age was 22.4, SD=3.8), with a median time from psychosis onset to first antipsychotic of 52 days [IQ range, 15 – 196], and had their first help-seeking attempt after psychosis onset (70%). Between the two groups there was no difference in sociodemographic characteristics, in psychosis diagnosis, and in the global assessment of functioning (at baseline and 12 months prior). Help-seeking attempts made before psychosis onset were mostly initiated by the patients themselves, while attempts made after onset had the family as the prime initiator. Once the first help-seeking attempt was initiated, it took longer to get prescribed an antipsychotic for subjects seeking help before onset compared to those who sought help after (median 245 days [5 – 1400] vs. 1 day [0 – 999], p Help-seekers after psychosis onset had a trend of longer patient side delay (defined as the time interval from when patients noticed a change-patient’s term for psychotic symptoms- to the day they sought help) compared to participants seeking help before onset (median 75 days [0 – 3928] vs. 14 days [0 – 1093], p=0.09). Compared to those who had their first help seeking episode before psychosis onset, the group who sought help after onset had more contacts with the police (64 vs 10), more involuntary admissions (40 vs 6), and same median number of nights spent in a psychiatric hospital six months before STEP enrollment (n=14). Discussion Timing of first help seeking in early psychosis can be crucial in shaping the individual experience of care. Longer delays in receiving the appropriate treatment and aversive pathways might be associated with help seeking which started only after psychosis onset, compared to first help seeking started before psychosis onset. Tailored interventions are needed to improve psychosis detection and referral of first episodes to specialized services.

Background We have limited knowledge about the effects of antipsychotic exposure on the development of gestational diabetes mellitus (GDM). Aim of this study is to perform a systematic review and meta-analysis to assess GDM risk associated with antipsychotic exposure in pregnancy. Methods Systematic literature search was performed using PubMed, Science Direct, Scopus, and Web of Science databases up to August 22, 2018. No restrictions to language or date were applied. Randomized, controlled trials, case-control, or cohort studies reporting GDM risk in antipsychotic-exposed, healthy controls or antipsychotic-ceased patients were included in the meta-analysis. The primary outcomes were study defined GDM, including number of events, odds ratios, and/or risk ratios (RR) with confidence intervals (CI). Results Ten studies were included in the meta-analysis. The total number of subjects was 6213 for the antipsychotic-exposed group, 6836 for antipsychotic-ceased control group, and 1 677 087 for the healthy control group. Compared with the healthy controls, the unadjusted cumulative RR for GDM associated with antipsychotic use was 1.63 (95% CI = 1.20-2.22). Adjusted risk for GDM was significantly higher in antipsychotic exposure group than in healthy controls (RR = 1.30, 95% CI = 1.023-1.660). The adjusted RR for GDM was similar between the antipsychotic-exposed group and the antipsychotic-ceased group (RR = 0.78, 95% CI = 0.281-2.164). No significant association was found between study quality, smoking, alcohol use, gestational age, and cumulative GDM risk. Discussion Our results indicate an increased risk of GDM with antipsychotic exposure in pregnant women, who may benefit from close pregnancy monitoring, early testing for GDM, targeting modifiable risk factors, and lifestyle modifications.

BACKGROUND: Physical exercise (PE) is a safe, non-stigmatizing, and side-effect free intervention that has the potential to mitigate neurocognitive dysfunction in psychosis, as well as reduce anxiety and paranoia. Developing and promoting PE programs for people with SMI in the community where participants cannot be paid to participate requires an interdisciplinary approach to activate motivation for exercise. We report the initial development and pilot results of a PE community program developed to enhance motivation and engagement in adults with schizophrenia, merging expertise from the fields of exercise physiology, recreational therapy, virtual reality (VR) gaming technology, and neuropsychiatric rehabilitation. METHODS: Adult outpatients diagnosed with schizophrenia (N=29) were enrolled in 18 hours (40 min session, 3x/week for 3 months) of exergaming. Exergaming uses interactive exercise equipment connected to a computer and monitor so the patient is engaged in a virtual game while exercising. For example, while pedaling on an exergaming stationary bike, the can have the experience of racing or biking through the countryside, either using a virtual reality headset or simply looking at the monitor. The PE regimen was tailored for each participant based on input from a (1) exercise physiologist about optimal methods to achieve volitional exhaustion and reduce the risk for injury, (b) recreational therapist who set up the overall exercise milieu to promote enjoyment, (c) expert in VR technology who calibrated and tailored the virtual experience to each participant (d) psychiatrist who monitored medical risk for strenuous exercise, and (d) psychologist who collected outcome data. Cognition and symptoms were assessed at baseline and post (3 mo.) while motivation and treatment engagement were recorded biweekly. RESULTS: Large effects were seen in working memory from baseline to post (WASI WMI; ES=.53), with medium effects in overall symptoms (PANSS; ES=.30). Importantly, participants reported a high degree of motivation for PE throughout the treatment period (Intrinsic Motivation Inventory total score>35), and 27 out of 29 completed the entire PE regimen of 18 hours although they were not paid to attend. CONCLUSIONS: This study highlights the potential benefits of a PE program developed by an interdisciplinary team combing expertise in exercise, technology, recreation, and neuropsychiatry. Drawing from experience in other fields may help develop new treatments in psychiatric rehabilitation to maximize overall outcome. Funded by a Hartford Hospital Auxiliary Special Projects Grant to JC

The first-episode psychosis (FEP) represents a critical period to prevent cardiovascular and metabolic morbidity decades later. Antipsychotic (AP)-induced weight gain is one modifiable factor in this period. The purpose of this study is to conduct a meta-analysis of AP-induced weight and body mass index (BMI) change in FEP.A comprehensive literature search identified 28 articles that reported data on AP-specific weight or BMI change in FEP. We conducted a meta-analysis of short- and long-term mean weight and BMI differences between placebo and AP medications. We also performed subgroup and meta-regression analysis to examine weight, BMI outcomes and their relationship with location (Asian vs. Western), sponsorship and baseline weight and BMIs.Compared to placebo, AP-caused mean weight gain was 3.22 kg and 1.4 points BMI in the short-term, and 5.30 kg and 1.86 points BMI in the long term. Clinically significant weight gain risk increased about twofold with AP use. Weight gain was associated with duration of AP use. AP medications were associated with more weight gain in Western samples as opposed to Asian samples. Most AP medications were associated with significant body weight gain and BMI increase in FEP patients, except for ziprasidone. Olanzapine and clozapine caused the highest weight gain compared to placebo.Except for ziprasidone, most AP medications were associated with body weight gain and BMI increase in FEP patients. Early and continuing effects of various AP medications on weight gain and BMI increase should be taken into consideration by clinicians.

Background The Specialized Treatment Early in Psychosis (STEP) program has delivered a specialty-team based first-episode service (FES) since 2006 in New Haven. In 2015, STEP launched a 4-year early detection (ED) campaign (Mindmap), adapted from the Scandinavian TIPS approach, to shorten Duration of Untreated Psychosis (DUP) in a 10-town catchment (popn. 400,000). Methods Mindmap’s social-ecological model targeted demand (delays in identifying illness and help-seeking) and supply (delays in referring to and providing FES) side constituents of DUP. Mindmap used mass and social media messaging, professional detailing, and rapid triage of referrals. DUP was measured as the time between the onset of psychosis and initiation of antipsychotic treatment (DUP1) and FES care (DUP2). A control FES (PREP, Boston) supported the quasi-experimental design. Quantile regression was used to interrogate the impact of the campaign across the full range of DUP. The campaign was launched in 2015, after a one-year baseline. Results The third quartile of DUP1 fell significantly at the intervention site in the pre- vs. post-campaign period (329 to 185 days, p=0.03). A time-series analysis revealed a cumulative effect of the campaign over time i.e. for each year of campaigning a 46-day reduction was achieved at STEP. DUP1 at the other quartiles and DUP2 across all quartiles showed a consistent trend of reduction over time at STEP, but this did not reach conventional statistical significance. At PREP both DUP1 & DUP2 remain unchanged, and comparable to baseline levels at STEP. Discussion Mindmap has shown promise in reducing delays to care and this is the first controlled demonstration of DUP reduction in a U.S. community setting. Additional data on help-seeking events and pathways to care and social media metrics will be presented as mediating variables. Mindmap was an early detection campaign hosted by an established FES and targeting a defined geographic catchment to recruit all incident cases. As such, this effort included a wide range of community and clinical stakeholders and modeled a population health based approach to the care of early psychosis. The lessons are relevant for burgeoning FES implementations across the world, and these will be elaborated based on the data and experience of implementing this study.

BACKGROUND: Research in treatment-naïve, first episode patients with severe mental illnesses (SMIs) suggest a pre-diabetic condition at the onset of illness. However, we have limited knowledge on glucose metabolism differences across diagnostic categories of SMIs. AIMS: To compare the differences of glucose metabolism outcomes between treatment-naïve, patients with first episode psychosis (FEP) and mood disorders. METHOD: We conducted a systematic review and meta-analysis of glucose intolerance in treatment-naïve, first episode patients with SMIs. RESULTS: We identified 31 eligible studies. Compared to healthy controls, FEP group have higher insulin and insulin resistance levels, and both groups have higher glucose tolerance test results. No significant differences were found in glucose metabolism outcomes between FEP and mood disorder groups. CONCLUSIONS: Our results highlight impaired glucose metabolism at the onset of SMIs, suggesting both patients with psychosis and mood disorders are high-risk groups for diabetes development.

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.

This chapter provides a summary of a landmark study on schizophrenia. In patients hospitalized for the first time with a diagnosis of schizophrenia, what is the risk of rehospitalization, drug discontinuation, and total mortality? Also, which antipsychotics and routes of administration are most effective for maintenance after the first hospitalization for schizophrenia? Starting with these questions, it describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case.

This chapter provides a summary of a landmark study on adult patients with schizophrenia. Discussion here is based on the investigation from the Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE). What is the role of clozapine among patients with chronic schizophrenia who fail to respond to atypical antipsychotics? Starting with that question, it describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case.

This chapter provides a summary of a landmark study on schizophrenia. The study authors sought to compare the safety of typical and atypical antipsychotics with regard to a fatal adverse event. Are atypical antipsychotic drugs associated with a lower risk of sudden cardiac death compared to typical antipsychotics? Starting with that question, this chapter describes the basics of the study, including the funding source, study location, who was studied, how many patients, study design, study intervention, follow-up, study endpoints, results, as well as criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case.

Background The Management of Schizophrenia in Clinical Practice (MOSAIC), a disease-based registry of schizophrenia, was initiated in December 2012 to address important gaps in our understanding of the impact and burden of schizophrenia and to provide insight into the current status of schizophrenia care in the US. Recruitment began in December 2012 with ongoing assessment continuing through May 2014. Methods Participants were recruited from a network of 15 centralized Patient Assessment Centers supporting proximal care sites. Broad entry criteria included patients diagnosed with schizophrenia, schizophreniform or schizoaffective disorder, presenting within the normal course of care, in usual treatment settings, aged ≥ 18 years and able to read and speak English. Results By May 2014, 550 participants (65.8% male, 59.8% White, 64.4% single, mean age 42.9 years), were enrolled. The majority had a diagnosis of schizophrenia (62.0%). Mean illness duration at entry was 15.0 years. Common comorbidities at entry were high lipid levels (26.9%), hypertension (23.1%) and type II diabetes (13%). Participants were categorized by baseline overall Clinical Global Impression—Schizophrenia Severity Score as minimally (9.1%), mildly (25.3%), moderately (39.9%), markedly (22.3%) and severely (3.4%) ill. Most commonly used second generation antipsychotics at entry were risperidone (17.8%), clozapine (16.5%), olanzapine (14.0%), aripiprazole (13.6%) and quetiapine (5.6%). Conclusions No large-scale patient registry has been conducted in the US to longitudinally follow patients with schizophrenia and describe symptom attributes, support network, care access and disease burden. These data provide important epidemiological, clinical and outcome insights into the burden of schizophrenia in the US.

Aim The first-episode psychosis (FEP) represents a critical period to prevent cardiovascular and metabolic morbidity decades later. Antipsychotic (AP)-induced weight gain is one modifiable factor in this period. The purpose of this study is to conduct a meta-analysis of AP-induced weight and body mass index (BMI) change in FEP. Methods A comprehensive literature search identified 28 articles that reported data on AP-specific weight or BMI change in FEP. We conducted a meta-analysis of short- and long-term mean weight and BMI differences between placebo and AP medications. We also performed subgroup and meta-regression analysis to examine weight, BMI outcomes and their relationship with location (Asian vs. Western), sponsorship and baseline weight and BMIs. Results Compared to placebo, AP-caused mean weight gain was 3.22 kg and 1.4 points BMI in the short-term, and 5.30 kg and 1.86 points BMI in the long term. Clinically significant weight gain risk increased about twofold with AP use. Weight gain was associated with duration of AP use. AP medications were associated with more weight gain in Western samples as opposed to Asian samples. Most AP medications were associated with significant body weight gain and BMI increase in FEP patients, except for ziprasidone. Olanzapine and clozapine caused the highest weight gain compared to placebo. Conclusion Except for ziprasidone, most AP medications were associated with body weight gain and BMI increase in FEP patients. Early and continuing effects of various AP medications on weight gain and BMI increase should be taken into consideration by clinicians.

Aim To compare the prevalence of diabetes in patients with schizophrenia treated at a community mental health center with controls in the same metropolitan area and to examine the effect of antipsychotic exposure on diabetes prevalence in schizophrenia patients. Methods The study was a comprehensive chart review of psychiatric notes of patients with schizophrenia and schizoaffective disorder treated at a psychosis program in a community mental health center. Data collected included psychiatric diagnoses, diabetes mellitus diagnosis, medications, allergies, primary care status, height, weight, body mass index (BMI), substance use and mental status exam. Local population data was downloaded from the Centers for Disease Control Behavioral Risk Factor Surveillance System. Statistical methods used were χ2 test, Student's t test, general linear model procedure and binary logistic regression analysis. Results The study sample included 326 patients with schizophrenia and 1899 subjects in the population control group. Demographic data showed control group was on average 7.6 years older (P = 0.000), more Caucasians (78.7% vs 38.3%, P = 0.000), and lower percentage of males (40.7% vs 58.3%, P = 0.000). Patients with schizophrenia had a higher average BMI than the subjects in the population control (32.11, SD = 7.72 vs 27.62, SD = 5.93, P = 0.000). Patients with schizophrenia had a significantly higher percentage of obesity (58.5% vs 27%, P = 0.000) than the population group. The patients with schizophrenia also had a much higher rate of diabetes compared to population control (23.9% vs 12.2%, P = 0.000). After controlling for age sex, and race, having schizophrenia was still associated with increased risk for both obesity (OR = 3.25, P = 0.000) and diabetes (OR = 2.42, P = 0.000). The increased risk for diabetes remained even after controlling for obesity (OR = 1.82, P = 0.001). There was no difference in the distribution of antipsychotic dosage, second generation antipsychotic use or multiple antipsychotic use within different BMI categories or with diabetes status in the schizophrenia group. Conclusion This study demonstrates the high prevalence of obesity and diabetes in schizophrenia patients and indicates that antipsychotics may not be the only contributor to this risk.

Background: Prolonged duration of untreated psychosis (DUP) is associated with poor outcomes. The TIPS study halved DUP with an early detection (ED) campaign; however, conventional statistical analyses, focused on mean estimates, failed to reveal the effects of ED across the full DUP distribution, restricting inferences about ED's effectiveness. Utilizing a novel quantile regression based analysis, we examined the differential impact of ED across DUP. Secondary analysis explored possible predictors of DUP, and moderators of the effect of the campaign.Methods: The TIPS ED campaign was conducted in two health care sectors in Norway, with two equivalent health care sectors serving as controls. Quantile regression analysis was performed to analyze ED campaign's effect.Results: 281 patients with first episode psychosis were recruited, including 141 from the ED area. ED had no effect on the first quartile (Q1) of DUP, whereas a significant reduction in Q2 (11 weeks), and Q3 (41 weeks) of DUP was observed. The effect of ED was significantly stronger on reducing Q3 than Q1 or Q2, suggesting that the campaign was more effective in longerDUP samples. Male gender and single status predicted longerDUP inQ3: by 38 and 27 weeks, respectively. Single status, but not gender, emerged as a significant moderator of ED campaign effect.Conclusions: Quantile regression provided in depth information about the non-uniformity, and moderators, of TIPS's ED effort across the full distribution of DUP, demonstrating the value of this analytic approach to re-examine prior, and plan analyses for future, early detection efforts. (C) 2019 Published by Elsevier B.V.

Naltrexone, an opiate antagonist, and bupropion, a noradrenergic/dopaminergic antidepressant, have many effects on the reward systems of the brain. These medications impact eating behavior, presumably via their impact on food reward. However, only bupropion induces weight loss in obese individuals, while naltrexone does not have any appreciable effect. The combination of 32 mg of naltrexone and 360 mg of bupropion in a sustained-release combination pill form has been recently approved for obesity treatment. Studies have shown that the combination of these two medications is more effective in inducing weight loss, when combined with lifestyle intervention and calorie reduction, than each individual medicine alone. The naltrexone-bupropion combination, when combined with lifestyle intervention and modest calorie reduction, seems to be quite effective for 6-month and 1-year outcomes for clinically significant weight loss (over 5% of total body weight). These medications are not devoid of serious side effects, however, and careful patient selection can reduce dramatic complications and increase positive outcomes. This paper reviews existing weight loss clinical trials with bupropion and the bupropion-naltrexone combination. Additionally, the rationale for the suggested patient selection and clinical strategies for special patient populations are discussed.

Objectives In this proof-of-concept trial, we examined the feasibility and preliminary efficacy of Understanding Social Situations (USS), a new social-cognitive intervention that targets higher level social-cognitive skills using methods common to neurocognitive remediation, including drill and practice and hierarchically structured training, which may compensate for the negative effects of cognitive impairment on learning. Method Thirty-eight individuals with schizophrenia spectrum disorders completed the same baseline assessment of cognitive and social-cognitive functioning twice over a 1-month period to minimize later practice effects, then received 7-10 sessions of USS training, and then completed the same assessment again at posttreatment. Results USS training was well tolerated and received high treatment satisfaction ratings. Large improvements on the USS Skills Test, which contained items similar to but not identical to training stimuli, suggest that we were effective in teaching specific training content. Content gains generalized to improvements on some of the social-cognitive tasks, including select measures of attributional bias and theory of mind. Importantly, baseline neurocognition did not impact the amount of learning during USS (as indexed by the USS Skills Test) or the amount of improvement on social-cognitive measures. Conclusions and implications for practice USS shows promise as a treatment for higher level social-cognitive skills. Given the lack of relationship between baseline cognition and treatment effects, it may be particularly appropriate for individuals with lower range cognitive function. (PsycINFO Database Record

Suat Kucukgoncu, Margaretta Midura, Cenk Tek Department of Psychiatry, Yale University, New Haven, CT, USA Abstract: Night Eating Syndrome (NES) is a unique disorder characterized by a delayed pattern of food intake in which recurrent episodes of nocturnal eating and/or excessive food consumption occur after the evening meal. NES is a clinically important disorder due to its relationship to obesity, its association with other psychiatric disorders, and problems concerning sleep. However, NES often goes unrecognized by both health professionals and patients. The lack of knowledge regarding NES in clinical settings may lead to inadequate diagnoses and inappropriate treatment approaches. Therefore, the proper diagnosis of NES is the most important issue when identifying NES and providing treatment for this disorder. Clinical assessment tools such as the Night Eating Questionnaire may help health professionals working with populations vulnerable to NES. Although NES treatment studies are still in their infancy, antidepressant treatments and psychological therapies can be used for optimal management of patients with NES. Other treatment options such as melatonergic medications, light therapy, and the anticonvulsant topiramate also hold promise as future treatment options. The purpose of this review is to provide a summary of NES, including its diagnosis, comorbidities, and treatment approaches. Possible challenges addressing patients with NES and management options are also discussed. Keywords: night eating, obesity, psychiatric disorders, weight, depression

Diabetes is common and seen in one in five patients with schizophrenia. It is more prevalent than in the general population and contributes to the increased morbidity and shortened lifespan seen in this population. However, screening and treatment for diabetes and other metabolic conditions remain poor for these patients. Multiple factors including genetic risk, neurobiologic mechanisms, psychotropic medications, and environmental factors contribute to the increased prevalence of diabetes. Primary care physicians should be aware of adverse effects of psychotropic medications that can cause or exacerbate diabetes and its complications. Management of diabetes requires physicians to tailor treatment recommendations to address special needs of this population. In addition to behavioral interventions, medications such as metformin have shown promise in attenuating weight loss and preventing hyperglycemia in those patients being treated with antipsychotic medications. Targeted diabetes prevention and treatment is critical in patients with schizophrenia and evidence-based interventions should be considered early in the course of treatment. This paper reviews the prevalence, etiology, and treatment of diabetes in schizophrenia and outlines office based interventions for physicians treating this vulnerable population.

This study sought to determine the effectiveness of a comprehensive first-episode service, the clinic for Specialized Treatment Early in Psychosis (STEP), in an urban U.S. community mental health center by comparing it with usual treatment.This pragmatic randomized controlled trial enrolled 120 patients with first-episode psychosis within five years of illness onset and 12 weeks of antipsychotic exposure. Referrals were mostly from inpatient psychiatric units, and enrollees were randomly allocated to STEP or usual treatment. Main outcomes included hospital utilization (primary); the ability to work or attend age-appropriate schooling-or to actively seek these opportunities (vocational engagement); and general functioning. Analysis was by modified intent to treat (excluding only three who withdrew consent) for hospitalization; for other outcomes, only data for completers were analyzed.After one year, STEP participants had less inpatient utilization compared with those in usual treatment: no psychiatric hospitalizations, 77% versus 56% (risk ratio [RR]=1.38, 95% confidence interval [CI]=1.08-1.58); mean hospitalizations, .33±.70 versus .68±.92 (p=.02); and mean bed-days, 5.34±13.53 versus 11.51±15.04 (p=.05). For every five patients allocated to STEP versus usual treatment, one additional patient avoided hospitalization over the first year (number needed to treat=5; CI=2.7-26.5). STEP participants also demonstrated better vocational engagement (91.7% versus 66.7%; RR=1.40, CI=1.18-1.48) and showed salutary trends in global functioning measures.This trial demonstrated the feasibility and effectiveness of a U.S. public-sector model of early intervention for psychotic illnesses. Such services can also support translational research and are a relevant model for other serious mental illnesses.

Background: Emerging research highlights the potential cognitive benefits of physical fitness programs for schizophrenia. Physical exercise (PE) is a safe, nonstigmatizing, and side effect-free intervention that has the potential to mitigate neurocognitive dysfunction in psychosis. To date, only two recent studies have explored the possibility of combining PE and cognitive training therapy (CT). While both studies found a signal showing that combining PE and CT may improve cognition more than CT alone, the conclusions were limited by lack of randomization, no examination of biological factors, no study arm with PE only, low power due to small sample size (N < 22), or significant attrition during the physical exercise intervention (i.e., only 75% completed the PE regimen). Methods: In our randomized pilot with 82 outpatients, we examined the individual and synergistic effects of PE and/or CT using treatments designed to improve motivation for treatment and retain patients for the entire PE (and CT) intervention. This 3-arm study employed a self-determined PE regimen intended to improve motivation for exercising and neurofeedback-aided CT that monitored a biophysiologic gauge of motivation to maximize cognitive gains. Participants were allocated to 18 hours of either: (A) PE regimen where patients chose from a menu of activities for 12 weeks with each activity designed so participants would reach volitional exhaustion—a commonly accepted physiological gauge of strenuous exercise—at least twice per week; (B) tablet-based neurofeedback CT focused on processing speed and working memory, or (C) a combination of PE and CT, matched for total duration and treatment time. Assessments of cognition and symptoms were conducted at baseline, post (3 months), and follow-up (5 montha). Results: At post, all three groups showed significant improvements in working memory, with the PE group surpassing the other two in working memory and processing speed improvements. However, at 2-month follow-up, gains in the PE only group disappeared, and it was the PE+CT group that showed significant improvements in both cognition and negative symptoms. Notably, attrition for all three groups was only 4%–7% and even those with low baseline motivation attended as many sessions as those with high motivation while both saw improvements in cognition and negative symptoms. Conclusion: This pilot is the first study to show that combining PE and CT leads to lasting effects that are superior to those of either intervention alone. Moreover, our approach to PE and CT was well tolerated, and the low dropout rate may have further maximized the benefits of both types of interventions.

Background: Reducing excessive delays in care, as measured by Duration of Untreated Psychosis (DUP), can improve outcomes for schizophrenia spectrum disorders. The program for Specialized Treatment Early in Psychosis (STEP) has delivered a best practice approach to coordinated care for early psychosis since 2006 in greater New Haven, and in 2014 began studying an approach (the Mindmap campaign) to shorten DUP in a 10 town catchment of 400 000 people.

Night Eating Syndrome (NES) is a unique disorder characterized by a delayed pattern of food intake in which recurrent episodes of nocturnal eating and/or excessive food consumption occur after the evening meal. NES is a clinically important disorder due to its relationship to obesity, its association with other psychiatric disorders, and problems concerning sleep. However, NES often goes unrecognized by both health professionals and patients. The lack of knowledge regarding NES in clinical settings may lead to inadequate diagnoses and inappropriate treatment approaches. Therefore, the proper diagnosis of NES is the most important issue when identifying NES and providing treatment for this disorder. Clinical assessment tools such as the Night Eating Questionnaire may help health professionals working with populations vulnerable to NES. Although NES treatment studies are still in their infancy, antidepressant treatments and psychological therapies can be used for optimal management of patients with NES. Other treatment options such as melatonergic medications, light therapy, and the anticonvulsant topiramate also hold promise as future treatment options. The purpose of this review is to provide a summary of NES, including its diagnosis, comorbidities, and treatment approaches. Possible challenges addressing patients with NES and management options are also discussed.