The genetics of the mood disorder spectrum:genome-wide association analyses of over 185,000 cases and 439,000 controls

Background Mood disorders (including major depressive disorder and bipolar disorder) affect 10-20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Despite their diagnostic distinction, multiple approaches have shown considerable sharing of risk factors across the mood disorders. Methods To clarify their shared molecular genetic basis, and to highlight disorder-specific associations, we meta-analysed data from the latest Psychiatric Genomics Consortium (PGC) genome-wide association studies of major depression (including data from 23andMe) and bipolar disorder, and an additional major depressive disorder cohort from UK Biobank (total: 185,285 cases, 439,741 controls; non-overlapping N = 609,424). Results Seventy-three loci reached genome-wide significance in the meta-analysis, including 15 that are novel for mood disorders. More genome-wide significant loci from the PGC analysis of major depression than bipolar disorder reached genome-wide significance. Genetic correlations revealed that type 2 bipolar disorder correlates strongly with recurrent and single episode major depressive disorder. Systems biology analyses highlight both similarities and differences between the mood disorders, particularly in the mouse brain cell-types implicated by the expression patterns of associated genes. The mood disorders also differ in their genetic correlation with educational attainment – positive in bipolar disorder but negative in major depressive disorder. Conclusions The mood disorders share several genetic associations, and can be combined effectively to increase variant discovery. However, we demonstrate several differences between these disorders. Analysing subtypes of major depressive disorder and bipolar disorder provides evidence for a genetic mood disorders spectrum

Effect of gabapentin on pain after cardiac surgery: a randomised, double-blind, placebo-controlled trial

This study evaluated whether perioperative administration of gabapentin in cardiac surgery patients could reduce postoperative opioid consumption, postoperative sleep or perceived quality of recovery. This randomised controlled trial assigned 60 patients undergoing cardiac surgery to receive 1200 mg of gabapentin or placebo two hours preoperatively, and then 600 mg of gabapentin or placebo twice a day for the next two postoperative days. Postoperative opioid use was measured by the amount of fentanyl used in the first 48 hours postoperatively. Pain at rest and with movement at 12, 24, 48 and 72 hours after surgery, sleep scores on postoperative days two and three and patient-perceived quality of recovery were also assessed. Fentanyl use, visual analog pain scores, sleep scores, adjunctive pain medication use and number of anti-emetics given were not significantly different between the gabapentin and placebo groups. The incidence of side-effects was similar between the gabapentin and placebo groups, and no difference was found between groups in relation to quality of recovery. These findings indicate that preoperative use of gabapentin followed by postoperative dosing for two days did not significantly affect the postoperative pain, sleep, opioid consumption or patient-perceived quality of recovery for patients undergoing cardiac surgery

The conditional relationship between beta and returns: a re-assessment.

NoSeveral recent empirical tests of the Capital Asset Pricing Model have been based on the conditional relationship between betas and market returns. This paper shows that this method needs reconsideration. An adjusted version of this test is presented. It is then demonstrated that the adjusted technique has similar, or lower, power to the more easily implemented CAPM test of Fama and MacBeth (1973) if returns are normally distributed