JOURNAL OF PSYCHIATRIC RESEARCH 19

GENETICS OF PANIC DISORDER

MYRNA M. WEISSMAN

College of Physicians and Surgeons of Columbia University, 722 West 168th Street, Box 14, New York, New York 10132, U.S.A.

There is good evidence that panic disorder is a familial disease; however, the extent to which the transmission among family members is genetic has not been resolved. Although there are a number of family studies of anxiety disorders, most have not separated panic from other anxiety disorders, and some use family history, not direct interview methods.

Three family studies have included probands with panic disorder and have used direct interviews and specific diagnostic criteria (Cloninger, Martin, Clayton, & Guze, 1981; Crowe, Noyes, Harris, Slymen, & Chaudhry, 1984; Harris, Noyes, Crowe, & Chaudhry, 1983). These studies confirm the highly familial nature of panic disorder. The rates of illness were higher than those reported in the earlier family history studies, but the patterns were similar. The first-degree relatives of probands with panic disorder had markedly elevated rates of panic disorder.

Attempts have been made to explain the familial patterns of panic disorder using genetic models. However, no specific patterns of genetic transmission have been conclusively or consistently established (Pauls, Bucher, Crowe, & Noyes, 1980).

Only one twin study of panic disorder has been conducted using DSM-III criteria (Torgersen, 1983). In a study of 29 adult, same-sex twins, the monozygotic twins were found to have a significantly higher rate of panic disorder or agoraphobia with panic attacks than the dizygotic twins. The monozygotic concordance rate was 31%, compared with no concordance in dizygotic twins.

Recent advances in molecular genetics have led to the discovery of a growing number of genetic markers, which can be used to examine linkage of a disorder to a marker on a chromosome. The ultimate goal is the eventual identification and study of the gene itself. Using red-cell antigens and protein polymorphisms as genetic markers, Crowe reported preliminary findings from a linkage study of panic disorders in November 1987 (Crowe, Noyes, & Persico, 1987; Crowe, Noyes, Wilson, Elston, & Ward, 1987). Twenty-nine markers in 26 families with panic disorder provided suggestive linkage at one locus mapped to chromosome 16 or chromosome 22. The maximum loci score for haptoglobin was 2.27 at a recombinant fraction of 0.0. Linkage was excluded at 18 loci. Currently, at least three groups--Crowe, Fyer, Weissman

- - are engaged in ongoing linkage studies of panic disorder using modern DNA techniques. In this presentation, available family and twin studies will be reviewed, and preliminary findings from our ongoing family study of panic disorder will be reported.

20 PANIC AND ANXIETY

REFERENCES Cloninger, C. R., Martin, R. L., Clayton, P. J., & Guze, S. B. (1981). A blind follow-up and

family study of anxiety neurosis: preliminary analysis of the St. Louis 500, In D. F. Klein & J. G. Rabkin (Eds.), Anxiety: new research and changing concepts. New York: Raven Press.

Crowe, R. R., Noyes, R., Harris, E., Slymen, D., & Chaudhry, D. R. (1984). Family study methodology (letter). Archives of General Psychiatry 41, 919.

Crowe, R. R., Noyes, R., & Persico, A. M. (1987). Pro-opiomelanocortin (POCM) gene excluded as a cause of panic disorder in a large family. Journal of Affective Disorders 12, 23-27.

Crowe, R. R., Noyes, R. Jr., Wilson, A. F., Elston, R. C., & Ward L .J. (1987). A linkage study of panic disorder. Archives of General Psychiatry 44, 933-937.

Harris, E. L., Noyes, R. Jr., Crowe, R. R., & Chaudhry, D. R. (1983). Family study of agoraphobia. Report of a pilot study. Archives of General Psychiatry 40, 1061-1064.

Pauls, D. L., Bucher, K.D., Crowe, R. R., & Noyes, R. Jr. (1980). A genetic study of panic disorder pedigrees. American Journal of Human Genetics 32, 639-644.

Torgersen, S. (1983). Genetic factors in anxiety disorders. Archives of General Psychiatry 40, 1085-1089.