Family study of affective spectrum disorder

Background: Affective spectrum disorder (ASD) represents a group of psychiatric and medical conditions, each known to respond to several chemical families of antidepressant medications and hence possibly linked by common heritable abnormalities. Forms of ASD include major depressive disorder (MDD), attention-deficit/ hyperactivity disorder, bulimia nervosa, cataplexy, dysthymic disorder, fibromyalgia, generalized anxiety disorder, irritable bowel syndrome, migraine, obsessive-compulsive disorder, panic disorder, posttraumatic stress disorder, premenstrual dysphoric disorder, and social phobia. Two predictions of the ASD hypothesis were tested: that ASD, taken as a single entity, would aggregate in families and that MDD would coaggregate with other forms of ASD in families. Methods: Probands with and without MDD, together with their first-degree relatives, were interviewed using the Structured Clinical Interview for DSM-IV and a supplemental interview for other forms of ASD. The familial aggregation and coaggregation of disorders were analyzed using proband predictive logistic regression models, including a novel bivariate model for the presence or absence of each of 2 disorders in a relative as predicted by the presence or absence of each, of 2 disorders in the associated proband. Results: In the 178 interviewed relatives of 64 probands with MDD and 152 relatives of 58 probands without MDD, the estimated odds ratio (95% confidence interval) for the familial aggregation of ASD as a whole was 2.5 (1.4-4.3; P=.001) and for the familial coaggregation of MDD with at least one other form of ASD was 1.9 (1.1-3.2; P=.02). Conclusions: Affective spectrum disorder aggregates strongly in families, and MDD displays a significant familial coaggregation with other forms of ASD, taken collectively. These results suggest that forms of ASD may share heritable pathophysiologic features.