Bipolar disorder (BD) is a heritable mental illness with complex etiology. We performed a genome-wide association study (GWAS) of 41,917 BD cases and 371,549 controls, which identified 64 associated genomic loci. BD risk alleles were enriched in genes in synaptic and calcium signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers and antiepileptics. Integrating eQTL data implicated 15 genes robustly linked to BD via gene expression, including druggable genes such as HTR6, MCHR1, DCLK3 and FURIN. This GWAS provides the best-powered BD polygenic scores to date, when applied in both European and diverse ancestry samples. Together, these results advance our understanding of the biological etiology of BD, identify novel therapeutic leads and prioritize genes for functional follow-up studies.

Abstract:A retrospective data analysis was conducted to evaluate the usefulness of baseline characteristics in predicting treatment response to antidepressant medication in 97 outpatients with nonpsychotic major depression treated for up to sixteen weeks with nefazodone. Baseline demographics (gender), illness features (symptom severity, length of illness, length of current episode, number of episodes, age of onset, longitudinal subtype, endogenicity, melancholia, family history of mood disorders), and social features (living status) were evaluated. Response to treatment was defined as a ≥ 50% reduction in the 17-item Hamilton Rating Scale for Depression (HRSD 17 ) score. The results of a survival analysis indicated that patients with shorter histories of illness (< 4 years), a negative family history of depression, and those who were either married or were living with someone were more likely to have a positive outcome during the acute phase treatment of depression. The main findings are consistent with extensive previous literature indicating a better short-term outcome of depression where illness is shorter, where there is no family history, and where there is better social support.

In 39 hospitalized patients with suspected gastrointestinal bleeding and given intravenous 51Cr-labeled red cells, reactions of three chemical spot tests for fecal occult blood were compared with the "true" blood loss as determined by stool radioassay. Guaiac reagent and orthotolidine (Hematest) tablets were extremely sensitive, but yielded false-positive reaction rates of 72% and 76%, respectively on the 240 stool specimens compared. A modified guaiac test (Hemoccult) exhibited a false positive rate of 12%. Of the 27 patients entering the study due to positive guaiac or Hematest screening tests, 17 (63%) were not bleeding. Hemoccult, approximately 1/4 as sensitive as guaiac and Hematest, could miss lesions with low rates of bleeding unless multiple stools were tested. While barium had no effect, iron therapy or laxatives tended to lower both false-positive and false-negative reactions for all reagents. A positive Hemoccult test usually indicated significant gastrointestinal bleeding and would appear to be the test of choice provided at least 3 stools are tested to minimize false-negative results.

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