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Bringing a developmental perspective to anxiety genetics

Published online by Cambridge University Press:  15 October 2012

Lauren M. McGrath ,
Sydney Weill ,
Elise B. Robinson ,
Rebecca Macrae  and
Jordan W. Smoller
Lauren M. McGrath*
Affiliation:
Massachusetts General Hospital
Sydney Weill
Affiliation:
Massachusetts General Hospital
Elise B. Robinson
Affiliation:
Massachusetts General Hospital
Rebecca Macrae
Affiliation:
Massachusetts Institute of Technology
Jordan W. Smoller
Affiliation:
Massachusetts General Hospital
*
Address correspondence and reprint requests to: Lauren M. McGrath, Massachusetts General Hospital, Simches Research Building 6th floor, 185 Cambridge Street, Boston, MA 02114; E-mail: mcgrath@pngu.mgh.harvard.edu.
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Abstract

Despite substantial recent advancements in psychiatric genetic research, progress in identifying the genetic basis of anxiety disorders has been limited. We review the candidate gene and genome-wide literatures in anxiety, which have made limited progress to date. We discuss several reasons for this hindered progress, including small samples sizes, heterogeneity, complicated comorbidity profiles, and blurred lines between normative and pathological anxiety. To address many of these challenges, we suggest a developmental, multivariate framework that can inform and enhance anxiety phenotypes for genetic research. We review the psychiatric and genetic epidemiological evidence that supports such a framework, including the early onset and chronic course of anxiety disorders, shared genetic risk factors among disorders both within and across time, and developmentally dynamic genetic influences. We propose three strategies for developmentally sensitive phenotyping: examination of early temperamental risk factors, use of latent factors to model underlying anxiety liability, and use of developmental trajectories as phenotypes. Expanding the range of phenotypic approaches will be important for advancing studies of the genetic architecture of anxiety disorders.

Type
Articles
Information
Development and Psychopathology , Volume 24 , Issue 4: Contributions of the Genetic/Genomic Sciences to Developmental Psychopathology , November 2012 , pp. 1179 - 1193
Copyright
Copyright © Cambridge University Press 2012

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