Psychological Medicine

Original Articles

Co-morbid anxiety disorders in bipolar disorder and major depression: familial aggregation and clinical characteristics of co-morbid panic disorder, social phobia, specific phobia and obsessive-compulsive disorder

F. S. Goesa1 c1, M. G. McCuskera1, O. J. Bienvenua1, D. F. MacKinnona1, F. M. Mondimorea1, B. Schweizera1, National Institute of Mental Health Genetics Initiative Bipolar Disorder Consortium, J. R. DePaulo Jr.a1 and J. B. Potasha2

a1 Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA

a2 Department of Psychiatry, University of Iowa, Iowa City, IA, USA


Background Co-morbidity of mood and anxiety disorders is common and often associated with greater illness severity. This study investigates clinical correlates and familiality of four anxiety disorders in a large sample of bipolar disorder (BP) and major depressive disorder (MDD) pedigrees.

Method The sample comprised 566 BP families with 1416 affected subjects and 675 MDD families with 1726 affected subjects. Clinical characteristics and familiality of panic disorder, social phobia, specific phobia and obsessive-compulsive disorder (OCD) were examined in BP and MDD pedigrees with multivariate modeling using generalized estimating equations.

Results Co-morbidity between mood and anxiety disorders was associated with several markers of clinical severity, including earlier age of onset, greater number of depressive episodes and higher prevalence of attempted suicide, when compared with mood disorder without co-morbid anxiety. Familial aggregation was found with co-morbid panic and OCD in both BP and MDD pedigrees. Specific phobia showed familial aggregation in both MDD and BP families, although the findings in BP were just short of statistical significance after adjusting for other anxiety co-morbidities. We found no evidence for familiality of social phobia.

Conclusions Our findings suggest that co-morbidity of MDD and BP with specific anxiety disorders (OCD, panic disorder and specific phobia) is at least partly due to familial factors, which may be of relevance to both phenotypic and genetic studies of co-morbidity.

(Received May 18 2011)

(Revised September 29 2011)

(Accepted October 17 2011)

(Online publication November 21 2011)


c1 Address for correspondence: F. S. Goes, M.D., Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Meyer 4-119, 600 N. Wolfe Street, Baltimore, MD, 21287, USA. (Email: