Results of a genome-wide genetic screen for panic disorder.

Panic disorder is characterized by spontaneous and recurrent panic attacks, often accompanied by agoraphobia. The results of family, twin, and segregation studies suggest a genetic role in the etiology of the illness. We have genotyped up to 23 families that have a high density of panic disorder with 540 microsatellite DNA markers in a first-pass genomic screen. The thirteen best families (ELOD > 6.0 under the dominant genetic model) have been genotyped with an ordered set of markers encompassing all the autosomes, at an average marker density of 11 cM. Over 110,000 genotypes have been generated on the whole set of families, and the data have been analyzed under both a dominant and a recessive model, and with the program SIBPAIR. No lod scores exceed 2.0 for either parametric model. Two markers give lod scores over 1.0 under the dominant model (chromosomes 1p and 20p), and four do under the recessive model (7p, 17p, 20q, and X/Y). One of these (20p) may be particularly promising. Analysis with SIBPAIR yielded P values equivalent to a lod score of 1.0 or greater (i.e., P < .016, one-sided, uncorrected for multiple tests) for 11 marker loci (2, 7p, 8p, 8q, 9p, 11q, 12q, 16p, 20p and 20q).

The DSM-IV panic disorder field trial: panic attack frequency and functional disability.

The goal of the DSM-IV panic disorder field trial was to provide an empirical basis for choosing between alternate proposals (DSM-III-R and proposed DSM-IV) for the diagnostic threshold for panic disorder, in particular the number and frequency of panic attacks required for diagnosis. The two criteria sets were compared with respect to their ability to identify individuals whose panic attacks were associated with distress, impairment, or help-seeking. Subjects were a convenience sample screened in three geographically diverse primary care clinics for presence (past 6 months) or absence (lifetime) of panic attacks. Each underwent a clinician-administered semistructured interview which included assessment of panic frequency, panic-related impairment, psychiatric diagnosis, health services utilization, and medical illness. Self-perceived health-related quality of life was assessed using the Medical Outcome Study SF-36 Health Survey Questionnaire. Although both proposals diagnosed the same proportion of panic-impaired individuals, they were not completely overlapping. Twenty percent of subjects diagnosed by each criteria set were excluded by the other. Subjects who had been excluded by the DSM-III-R but included by the DSM-IV proposal were those with fewer than 4 attacks in 4 weeks who also denied worry about the "next" attack. Broadening the worry criterion to include concerns about the health implications of attacks enabled diagnosis of this group. Subjects who met DSM-III-R, but not the proposed DSM-IV criteria, had 4 attacks in 4 weeks but denied any panic related worry. Modification of the DSM-IV proposal to include a month of worry or "a significant change in behavior related to the attacks" allowed inclusion of this group in the diagnostic category. These data suggest that the finalized DSM-IV panic disorder criteria will diagnose a greater proportion of individuals whose panic attacks are associated with impairment without inflating the diagnostic category or significantly reducing specificity.