This Program Project Grant is a multidisciplinary attempt to deal with the complexities of the anxiety disorders. Our original effort to validate the DSM-III disorders in terms of physioloqy, response to provocation, and family study, is now extended to deal also with the complex issue of cross sectional and developmental co-morbidity. Our team now includes Rachel Gittelman Klein and Myrna Weissman; experts in the developmental and longitudinal study of clinical samples, family studies, and epidemiological samples. Rachel Klein will pursue the systematic study of the offspring of patients with panic disorder, social phobia, agoraphobia, simple phobia and normals. Myrna Weissman will study the already gathered ECA data, which is now ready for complete cross-site analyses, thus applying the variables of epidemiological aggregation and risk factors to the problem of syndromal validation. Jack Gorman's project grant on hyperventilation and carbon dioxide sensitivity in panic disorders is amplified by this grant to include social phobics and obsessive compulsives. Thirty-five percent carbon dioxide challenges allow for yet further study of the carbon dioxide dose response curve in patients with panic disorder, social phobia, obsessive compulsive disorder and normal controls. To control for cognitive and expectation effects a comparison with increased airway resistance will be conducted. The family study will pursue the issue of comorbidity and heterogeneity in panic disorder, social phobia, agoraphobia, simple phobia and two classes of normals (acquaintances and relatives of normal acquaintances). Blind followup of first degree relatives of anxiety disorders will provide information concerning onset of this high risk group as well as the natural history of untreated sick people. DNA analyses of selected pedigrees will be conducted in collaboration with James Gusella and Jurg Ott.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Program Projects (P01)
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Treatment Development and Assessment Research Review Committee (TDA)
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Columbia University (N.Y.)
Schools of Medicine
New York
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Hodges, Laura M; Fyer, Abby J; Weissman, Myrna M et al. (2014) Evidence for linkage and association of GABRB3 and GABRA5 to panic disorder. Neuropsychopharmacology 39:2423-31
Hodge, Susan E; Subaran, Ryan L; Weissman, Myrna M et al. (2012) Designing case-control studies: decisions about the controls. Am J Psychiatry 169:785-9
Fyer, Abby J; Costa, Ramiro; Haghighi, Fatemeh et al. (2012) Linkage analysis of alternative anxiety phenotypes in multiply affected panic disorder families. Psychiatr Genet 22:123-9
Subaran, Ryan L; Talati, Ardesheer; Hamilton, Steven P et al. (2012) A survey of putative anxiety-associated genes in panic disorder patients with and without bladder symptoms. Psychiatr Genet 22:271-8
Logue, Mark W; Bauver, Sarah R; Knowles, James A et al. (2012) Multivariate analysis of anxiety disorders yields further evidence of linkage to chromosomes 4q21 and 7p in panic disorder families. Am J Med Genet B Neuropsychiatr Genet 159B:274-80
Brisbin, Abra; Weissman, Myrna M; Fyer, Abby J et al. (2010) Bayesian linkage analysis of categorical traits for arbitrary pedigree designs. PLoS One 5:e12307
Hodges, Laura M; Weissman, Myrna M; Haghighi, Fatemeh et al. (2009) Association and linkage analysis of candidate genes GRP, GRPR, CRHR1, and TACR1 in panic disorder. Am J Med Genet B Neuropsychiatr Genet 150B:65-73
Logue, Mark W; Durner, Martina; Heiman, Gary A et al. (2009) A linkage search for joint panic disorder/bipolar genes. Am J Med Genet B Neuropsychiatr Genet 150B:1139-46
Fyer, Abby J; Hamilton, Steven P; Durner, Martina et al. (2006) A third-pass genome scan in panic disorder: evidence for multiple susceptibility loci. Biol Psychiatry 60:388-401
Fyer, Abby J; Lipsitz, Joshua D; Mannuzza, Salvatore et al. (2005) A direct interview family study of obsessive-compulsive disorder. I. Psychol Med 35:1611-21

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