Psychiatric conditions affect multiple areas of psychosocial functioning, including functioning in the workplace. The purpose of this study was to establish norms for absenteeism (work days missed due to mental or physical illness) and work performance (quality of work performed when at work) for healthy individuals.

We selected 300 individuals without psychiatric or medical conditions from the National Comorbidity Survey Replication study (NCS-R). Absenteeism and work performance were assessed using the NCS-R version of the Health and Work Performance Questionnaire (HPQ).

Employees missed an average of 5.1 days of work in the past year. Absenteeism varied across occupations, with performers of routine tasks, office clerks, and professionals exhibiting the greatest variance in days missed. Work performance ratings were skewed toward high performance ratings and did not differ across occupations. Gender, age, race/ethnicity, and education level did not substantially moderate absenteeism and work performance norms.

Skewed ratings for work performance are consistent with previous findings using the HPQ. This may reflect a general tendency that individuals rate themselves favorably when they compare themselves to others.

This study provides normative tables for absenteeism and work performance in individuals without psychiatric or medical conditions, against which individuals with such conditions may be compared.

Despite consistently high discontinuation rates due to withdrawal of consent (WOC) and insufficient therapeutic effect (ITE) in schizophrenia trials, insight into the underlying factors contributing to poor satisfaction with treatment and dropout is limited. A better understanding of these factors could help to improve trial design and completion rates.

Using data from 1,136 trial participants with schizophrenia or schizoaffective disorder, we explored associations between predictor variables with (1) dropout due to WOC and ITE and (2) satisfaction with treatment among patients and investigators by means of hierarchic multiple regression analyses.

ITE was associated with poor clinical improvement, poor investigator satisfaction with treatment, and poor patient insight into their own disease, whereas WOC only showed a meaningful association with poor patient satisfaction with treatment. Investigator satisfaction with treatment appeared most strongly associated with Positive and Negative Syndrome Scale (PANSS) positive factor endpoint scores, whereas patient satisfaction with treatment was best predicted by the endpoint score on the PANSS emotional distress factor. The occurrence of severe side effects showed no meaningful association to satisfaction with treatment among investigators and patients, and neither did a patient’s experienced psychopathology, nor their self-rating of functional impairment.

Whereas trial discontinuation due to ITE is associated with poor treatment effectiveness, a patient’s decision to withdraw from an antipsychotic trial remains unpredictable and may occur even when the investigator observes a global clinical improvement and is satisfied with the treatment.

Alterations of the γ-aminobutyric acid (GABA) system have been implicated in the pathophysiology of major psychoses.

Restriction fragment length polymorphisms associated with the human γ-aminobutyric acid type A (GABAA) β2 and GABAA γ2 subunit genes on chromosome 5q32-q35 were tested to determine whether they confer susceptibility to major psychoses.

Thirty-two schizophrenic families and 25 bipolar families were tested for linkage.

Nonparametric linkage (NPL) analysis performed by GENEHUNTER showed no significant NPL scores for both genes in schizophrenia (GABAAβ2: NPL narrow=−0.450; NPL broad=−0.808; GABAA γ2: NPL narrow=0.177; NPL broad=−0.051) or bipolar disorder (GABAA β2: NPL narrow=0.834; NPL broad=0.783; GABAA γ2: NPL narrow=−0.159; NPL broad=0.070).

Linkage analysis does not support the hypothesis that variants within the GABAA β2 and GABAA γ2 genes are significantly linked to major psychoses in a Portuguese population.

SEP-363856 is a novel psychotropic agent that has shown broad efficacy in animal models of schizophrenia and depression. Its antipsychotic effects appear to be mediated by agonist activity at both trace amine-associated receptor 1 (TAAR1) and 5-HT1A receptors. Notably, SEP-363856 does not bind to any dopaminergic, serotonergic (except 5-HT1A), glutamatergic, or other neuroreceptors thought to mediate the effects of currently available antipsychotics. The aim of this study was to evaluate the efficacy and safety of SEP-363856 in acutely symptomatic patients with schizophrenia.

Patients aged 18-40 years meeting DSM-5 criteria for schizophrenia (PANSS total score ≥80) were randomized, double-blind, to 4-weeks of flexible-dose SEP-363856 (50 or 75 mg/d) or placebo. Efficacy measures included the Positive and Negative Syndrome Scale (PANSS) total score (primary), PANSS subscale scores, and the Clinical Global Impressions-Severity (CGI-S) score. Change from baseline in primary and secondary measures were analyzed using a mixed model for repeated measures (MMRM) analysis.

Study treatment groups were similar at baseline: SEP-363856 (N=120; male, 64.2%; mean age, 30.0 years; PANSS total score, 101.4) and placebo (N=125; male, 63.2%; mean age, 30.6 years; PANSS total score, 99.7). Least-squares (LS) mean reduction from baseline to week 4 was significantly greater for SEP-363856 vs. placebo on the PANSS total score (-17.2 vs. -9.7; P=0.001; effect size, 0.45), PANSS positive subscale score (-5.5 vs. -3.9; P=0.019; effect size, 0.32), PANSS negative subscale score (-3.1 vs. -1.6; P=0.008; effect size, 0.37), PANSS general psychopathology subscale score (-9.0 vs. -4.7; P<0.001; effect size, 0.51), and the CGI-Severity score (-1.0 vs. -0.5; P<0.001; effect size, 0.52). Discontinuation rates for SEP-363856 vs. placebo were similar overall (21.7% vs. 20.8%) and due to an adverse event (8.3% vs. 6.4%). Change in weight, lipids, glucose and prolactin was similar in SEP-363856 and placebo groups. Adverse events occurring with an incidence ≥2% on SEP-363856 or placebo (with SEP-363856 incidence higher than placebo) were: somnolence (6.7% vs. 4.8%), agitation (5.0% vs. 4.8%), nausea (5.0% vs. 3.2%), diarrhea (2.5% vs. 0.8%), and dyspepsia (2.5% vs. 0%). The proportion of patients who reported any extrapyramidal symptom was 3.3% on SEP-363856 and 3.2% on placebo.

In this placebo-controlled study, treatment with SEP-363856, a novel psychotropic agent, was associated with statistically significant and clinically meaningful improvement in schizophrenia symptoms as demonstrated by endpoint change in PANSS total and subscale scores, and CGI-Severity scores. Safety and tolerability findings for SEP-363856 were in general similar to placebo. In particular, SEP-363856 was not associated with extrapyramidal symptoms, akathisia, or hyperprolactinemia, consistent with its non-D2 mechanism of action.

NCT02969382

Supported by funding from Sunovion Pharmaceuticals Inc.

The importance of recognizing different kinds of autism spectrum presentations among adults, including subthreshold forms and the broad autism phenotype (BAP), has been increasingly highlighted in recent studies. Meanwhile, the possible involvement of immune system deregulation and altered methylation/trans-sulfuration processes in autism spectrum disorder (ASD) is gaining growing attention, but studies in this field are mainly focused on children. In this framework, the aim of this study was to compare plasmatic concentrations of IL-6 and homocysteine (HCY) among adults with ASD, their first-degree relatives, and healthy controls (CTLs), investigating also possible correlations with specific autism symptoms.

Plasma concentrations of IL-6 and HCY were measured in a group of adult subjects with ASD, their first-degree relatives (BAP group), and healthy controls (CTL). All participants were also evaluated with psychometric instruments.

IL-6 and HCY concentrations were significantly higher in the ASD group than in CTLs, while BAP subjects reported intermediate results. Significant correlations were reported between biochemical parameters and psychometric scales, particularly for the dimension of ruminative thinking.

These findings support the hypothesis of a key involvement of HCY-related metabolism and immune system alteration in autism spectrum pathophysiology. HCY and IL-6 seem to show different associations with specific autism dimensions.

Altered peripheral immune/inflammatory system and brain volumetric changes have been implicated in the pathophysiology of bipolar disorder (BD). This study aimed to evaluate how peripheral levels of cytokines are related to volumetric brain changes in euthymic patients with BD.

Euthymic patients with BD (n = 21) and healthy controls (n = 22) were enrolled in this exploratory study. Blood samples were collected on the same day of clinical assessment and neuroimaging. Cytokines were measured through cytometric bead array method. Neuroimaging data were acquired using a sagittal three-dimensional magnetic resonance imaging T1-weighted fast field echo sequence and was processed using FreeSurfer.

Compared to controls, BD patients had significantly lower volumes in the cingulate, medial-orbitofrontal (MOF) and parahippocampal regions. We found a negative correlation between right MOF volume and interferon-gamma levels (β = −0.431, P = .049) and a positive correlation between interleukin-10 levels and left posterior cingulate volume (β = 0.457, P = .048).

Our results support the involvement of inflammatory pathways in structural brain changes in BD.

The endogenous opioid system affects metabolism, including weight regulation. Evidence from preclinical and clinical studies provides a rationale for targeting this system to mitigate weight-related side effects of antipsychotics. This review describes the role of the opioid system in regulating weight and metabolism, examines the effects of opioid receptor antagonism on those functions, and explores the use of opioid antagonists to mitigate antipsychotic-associated weight gain and/or metabolic effects.

A PubMed literature search was conducted to identify representative opioid antagonists and associated preclinical and clinical studies examining their potential for the regulation of weight and metabolism.

The mu opioid receptor (MOR), delta opioid receptor (DOR), and kappa opioid receptor (KOR) types have overlapping but distinct patterns of central and peripheral expression, and each contributes to the regulation of body weight and metabolism. Three representative opioid antagonists (eg, naltrexone, samidorphan, and LY255582) were identified for illustration. These opioid antagonists differed in their receptor binding and pharmacokinetic profiles, including oral bioavailability, systemic clearance, and half-life, and were associated with varying effects on food intake, energy utilization, and metabolic dysregulation.

Preclinical and clinical data suggest that antagonism of the endogenous opioid system is a mechanism to address antipsychotic-associated weight gain and metabolic dysregulation. However, evidence suggests that the differing roles of MOR, DOR, and KOR in metabolism, together with the differences in receptor binding, pharmacokinetic, and functional activity profiles of the opioid receptor antagonists discussed in this review, likely contribute to their differential pharmacodynamic effects and clinical outcomes observed regarding antipsychotic-associated weight gain.