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.

Symptoms, psychosocial functioning, and familial lineage overlap across the three DSM-IV psychosis diagnoses used in B-SNIP. The comingling of psychosis diagnoses within families suggests overlapping genetic determinants across psychoses. These data provide scant evidence for distinct phenotypic clustering around traditional phenomenological diagnoses.

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

Background Depression is prevalent in long-term dialysis patients and is associated with death and hospitalization. Whether depression is present through all chronic kidney disease (CKD) stages or appears after dialysis therapy initiation is not clear. We determined the prevalence of a major depressive episode and other psychiatric illnesses by using a structured gold-standard clinical interview and demographic and clinical variables associated with major depressive episode in patients with CKD. Study Design Observational cross-sectional study using a Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition)-based structured interview administered by trained persons to 272 consecutive participants. Multivariable logistic regression was used to determine demographic and clinical variables associated with major depressive episode. Setting & Participants Patients with stages 2 to 5 CKD not treated by using dialysis were consecutively approached and enrolled from a Veterans Affairs CKD clinic. Predictors Demographic and clinical variables. Outcome Major depressive episode diagnosed by using a structured Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition)-based interview, the Mini International Neuropsychiatric Interview. Results The cohort had a mean age of 64.5 ± 12.0 years. Thirty-eight percent were African American, and 55% had diabetes mellitus. Percentages of patients with stages 2, 3, 4, and 5 CKD were 6%, 38%, 41%, and 14%, respectively. Mean hemoglobin level was 12.5 ± 2.0 g/dL. The prevalence of a major depressive episode was 21% and did not vary significantly among different CKD stages. Variables associated with a major depressive episode were diabetes mellitus, comorbid psychiatric illness, and history of drug or alcohol abuse. Limitations Single-center study composed of primarily male veterans. Conclusions One in 5 patients with CKD had a major depressive episode. Patients with CKD should be screened routinely for depression given this high prevalence and the independent association of depression with poor outcomes in patients with end-stage renal disease receiving maintenance dialysis.

Background There is increasing evidence for phenomenological, biological and genetic overlap between schizophrenia and bipolar disorder, bringing into question the traditional dichotomy between them. Neurobiological models linked to dimensional clinical data may provide a better foundation to represent diagnostic variation in neuropsychiatric disorders. Method To capture the interaction between psychosis and affective symptoms dimensionally, we devised a brief descriptive scale based on the type and relative proportions of psychotic and affective symptoms over the illness course. The scale was administered to a series of 762 patients with psychotic disorders, including schizophrenia, schizoaffective and psychotic bipolar disorder assessed as part of the Bipolar- Schizophrenia Network for Intermediate Phenotypes (B-SNIP) study. Results The resulting Schizo-Bipolar Scale scores across these disorders showed neither a clear dichotomy nor a simple continuous distribution. While the majority of cases had ratings close to prototypic schizophrenia or bipolar disorder, a large group (45% of cases) fell on the continuum between these two prototypes. . Conclusions Our data suggest a hybrid conceptualization model with a representation of cases with prototypic schizophrenia or bipolar disorder at the extremes, but a large group of patients on the continuum between them that traditionally would be considered schizoaffective. A dimensional approach, using the Schizo-Bipolar Scale, characterized patients across a spectrum of psychopathology. This scale may provide a valuable means to examine the relationships between schizophrenia and psychotic bipolar disorder.