Objective The primary aim was to compare the impact of NAVIGATE, a comprehensive, multidisciplinary, team-based treatment approach for first episode psychosis designed for implementation in the U.S. healthcare system, to Community Care on quality of life. Methods Thirty-four clinics in 21 states were randomly assigned to NAVIGATE or Community Care. Diagnosis, duration of untreated psychosis and clinical outcomes were assessed via live, two-way video by remote, centralized raters masked to study design and treatment. Participants (mean age 23) with schizophrenia and related disorders and ≤6 months antipsychotic treatment (N=404) were enrolled and followed for ≥2 years. The primary outcome was the Total Score of the Heinrichs-Carpenter Quality of Life Scale, a measure that includes sense of purpose, motivation, emotional and social interactions, role functioning and engagement in regular activities. Results 223 NAVIGATE recipients remained in treatment longer, experienced greater improvement in quality of life, psychopathology and involvement in work/school compared to 181 Community Care participants. The median duration of untreated psychosis=74 weeks. NAVIGATE participants with duration of untreated psychosis <74 weeks had greater improvement in quality of life and psychopathology compared with those with longer duration of untreated psychosis and those in Community Care. Rates of hospitalization were relatively low compared to other first episode psychosis clinical trials and did not differ between groups. Conclusions Comprehensive care for first episode psychosis can be implemented in U.S. community clinics. and improves functional and clinical outcomes. Effects are more pronounced for those with shorter duration of untreated psychosis.

Twice-weekly and thrice-weekly administration of ketamine at 0.5 mg/kg similarly maintained antidepressant efficacy over 15 days.

Remission rates for Major Depressive Disorder (MDD) are low and unpredictable for any given antidepressant. No biological or clinical marker has demonstrated sufficient ability to match individuals to efficacious treatment. Biosignatures developed from the systematic exploration of multiple biological markers, which optimize treatment selection for individuals (moderators) and provide early indication of ultimate treatment response (mediators) are needed. The rationale and design of a multi-site, placebo-controlled randomized clinical trial of sertraline examining moderators and mediators of treatment response is described. The target sample is 400 participants with early onset (<30 years) recurrent MDD. Non-responders to an 8-week trial are switched double blind to either bupropion (for sertraline non-responders) or sertraline (for placebo non-responders) for an additional 8 weeks. Clinical moderators include anxious depression, early trauma, gender, melancholic and atypical depression, anger attacks, Axis II disorder, hypersomnia/fatigue, and chronicity of depression. Biological moderator and mediators include cerebral cortical thickness, task-based fMRI (reward and emotion conflict), resting connectivity, diffusion tensor imaging (DTI), arterial spin labeling (ASL), electroencephalograpy (EEG), cortical evoked potentials, and behavioral/cognitive tasks evaluated at baseline and week 1, except DTI, assessed only at baseline. The study is designed to standardize assessment of biomarkers across multiple sites as well as institute replicable quality control methods, and to use advanced data analytic methods to integrate these markers. A Differential Depression Treatment Response Index (DTRI) will be developed. The data, including biological samples (DNA, RNA, and plasma collected before and during treatment), will become available in a public scientific repository.

Neither medication combination outperformed monotherapy. The combination of extended-release venlafaxine plus mirtazapine may have a greater risk of adverse events.

In the last decade, many studies have used automated processes to analyze magnetic resonance imaging (MRI) data such as cortical thickness, which is one indicator of neuronal health. Due to the convenience of image processing software (e.g., FreeSurfer), standard practice is to rely on automated results without performing visual inspection of intermediate processing. In this work, structural MRIs of 40 healthy controls who were scanned twice were used to determine the test–retest reliability of FreeSurfer-derived cortical measures in four groups of subjects—those 25 that passed visual inspection (approved), those 15 that failed visual inspection (disapproved), a combined group, and a subset of 10 subjects (Travel) whose test and retest scans occurred at different sites. Test–retest correlation (TRC), intraclass correlation coefficient (ICC), and percent difference (PD) were used to measure the reliability in the Destrieux and Desikan–Killiany (DK) atlases. In the approved subjects, reliability of cortical thickness/surface area/volume (DK atlas only) were: TRC (0.82/0.88/0.88), ICC (0.81/0.87/0.88), PD (0.86/1.19/1.39), which represent a significant improvement over these measures when disapproved subjects are included. Travel subjects’ results show that cortical thickness reliability is more sensitive to site differences than the cortical surface area and volume. To determine the effect of visual inspection on sample size required for studies of MRI-derived cortical thickness, the number of subjects required to show group differences was calculated. Significant differences observed across imaging sites, between visually approved/disapproved subjects, and across regions with different sizes suggest that these measures should be used with caution.