Hudson's Family Study of Affective Spectrum Disorder

Hudson's Family Study of Affective Spectrum Disorder -...

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Family Study of Affective Spectrum Disorder James I. Hudson, MD, ScD; Barbara Mangweth, PhD; Harrison G. Pope, Jr, MD, MPH; Christine De Col, MD; Armand Hausmann, MD; Sarah Gutweniger, MA; Nan M. Laird, PhD; Wilfried Biebl, MD; Ming T. Tsuang, MD, PhD, DSc Background: Affective spectrum disorder (ASD) rep- resents 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, dys- thymic disorder, fibromyalgia, generalized anxiety dis- order, irritable bowel syndrome, migraine, obsessive- compulsive disorder, panic disorder, posttraumatic stress disorder, premenstrual dysphoric disorder, and social pho- bia. Two predictions of the ASD hypothesis were tested: that ASD, taken as a single entity, would aggregate in fami- lies 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 supple- mental interview for other forms of ASD. The familial ag- gregation and coaggregation of disorders were analyzed using proband predictive logistic regression models, in- cluding a novel bivariate model for the presence or ab- sence of each of 2 disorders in a relative as predicted by the presence or absence of each of 2 disorders in the as- sociated proband. Results: In the 178 interviewed relatives of 64 pro- bands with MDD and 152 relatives of 58 probands with- out MDD, the estimated odds ratio (95% confidence in- terval) 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 fa- milial coaggregation with other forms of ASD, taken col- lectively. These results suggest that forms of ASD may share heritable pathophysiologic features. Arch Gen Psychiatry. 2003;60:170-177 C ERTAIN PSYCHIATRIC dis- orders commonly occur together in individuals (co-occurrence) and in families (coaggrega- tion), an observation suggesting that such disorders may share causal factors. Among proposed groups are the obsessive- compulsive spectrum of disorders, 1 the ex- ternalizing and internalizing disorders, 2 the bipolar spectrum of disorders, 3 disorders characterized by serotonin disturbance, 4 and schizotaxia. 5,6 In 1990, we 7 proposed the affective spectrum disorder (ASD) hypothesis, sug- gesting that major depressive disorder (MDD) shares a causal factor (or set of fac- tors) with 7 other psychiatric and medical disorders: attention-deficit/hyperactivity dis- order, bulimia nervosa, cataplexy, irritable bowel syndrome, migraine, obsessive- compulsive disorder, and panic disorder.
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Hudson's Family Study of Affective Spectrum Disorder -...

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