Pilot multimodal twin imaging study of generalized anxiety disorder

John M. Hettema, Birgit Kettenmann, Vishwadeep Ahluwalia, Christopher McCarthy, Wendy R. Kates, James E. Schmitt, Judy L. Silberg, Michael C. Neale, Kenneth S. Kendler, Panos Fatouros

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


Background Generalized anxiety disorder (GAD) is a common chronic condition that is relatively understudied compared to other psychiatric syndromes. Neuroimaging studies have begun to implicate particular neural structures and circuitry in its pathophysiology; however, no genetically informative research has examined the potential sources of reported brain differences. Methods We acquired spectroscopic, volumetric, and diffusion tensor magnetic resonance imaging data from a pilot study of 34 female subjects selected from monozygotic twin pairs based upon their affection status for GAD, and examined brain regions previously implicated in fear and anxiety for their relationship with affection status and genetic risk. Results Lifetime GAD associated with increased creatine levels in the amygdala, smaller left hippocampal volume, and lower fractional anisotropy in the uncinate fasciculus which connects amygdala and frontal cortex. In addition, GAD genetic risk predicted increases in myo-inositol in the amygdala and, possibly, glutamate/glutamine/GABA alterations in the hippocampus. The association of lifetime GAD with smaller hippocampal volume was independent of major depression and might represent a common genetic risk marker for internalizing disorders. Conclusions These preliminary data suggest that GAD and its genetic risk factors are likely correlated with volumetric and spectroscopic changes in fear-related limbic structures and their connections with the frontal cortex.

Original languageEnglish (US)
Pages (from-to)202-209
Number of pages8
JournalDepression and anxiety
Issue number3
StatePublished - Mar 2012
Externally publishedYes


  • anxiety disorders
  • depressive disorder
  • diffusion tensor imaging
  • magnetic resonance spectroscopy
  • twin study

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health


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