This Program Project Grant requests funds for the continuation of a multidisciplinary programmatic study of the anxiety disorders. The overall thrust is to both validate and refine the nosology of anxiety disorders using familial, developmental, epidemiologic, pharmacological challenge and molecular biologic criteria. The objective of the family study, under the direction of Dr. Abby Fyer, is to use patterns of longitudinal course of familial transmission to validate the distinctions between the anxiety disorders. We now also use the longitudinal sequences of anxiety disorder comorbidity as well as symptomatic heterogeneity within the anxiety disorders as dissecting tools. The child study, under the direction of Dr. Rachel Klein, will include prospective longitudinal studies, and the development of control groups of children of parents with pure as well as comorbid disorders and non-ill parents. This high risk study will cross validate the retrospective findings of the family study. The Hispanic study, under the direction of Dr. Michael Liebowitz will focus on the ataque syndrome as a marker of a culturally sanctioned label for anxiety and/or affective dysregulation in the Hispanic population. An informed systematic nosological appraisal will be uniquely validated for panic disorder by biological challenges. The epidemiologic component, under Dr. Myrna Weissman, will continue to analyze the already collected ECA data in consultation with clinicians from the Program. Analytic methods developed for panic disorder will be applied to other anxiety disorders. Further, crossnational comparisons should cast light on the variation of syndromes and risk factors. The linkage study, supervised by Dr. AbbyFyer in collaboration with Dr. Conrad Gilliam, will use highly polymorphic DNA markers spanning the entire human genome to test for linkage to disease phenotypes in a collection of extended pedigrees, augmented by genetic association studies.
| 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 |
| Lipsitz, Joshua D; Mannuzza, Salvatore; Chapman, Timothy F et al. (2005) A direct interview family study of obsessive-compulsive disorder. II. Contribution of proband informant information. Psychol Med 35:1623-31 |
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