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 journalArticle

Abstract

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
Volume29
Issue number3
DOIs
StatePublished - Mar 2012
Externally publishedYes

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Multimodal Imaging
Twin Studies
Anxiety Disorders
Amygdala
Frontal Lobe
Fear
Diffusion Magnetic Resonance Imaging
Monozygotic Twins
Creatine
Anisotropy
Brain
Inositol
Glutamine
Genetic Markers
Neuroimaging
gamma-Aminobutyric Acid
Psychiatry
Glutamic Acid
Hippocampus
Anxiety

Keywords

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

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Clinical Psychology

Cite this

Hettema, J. M., Kettenmann, B., Ahluwalia, V., McCarthy, C., Kates, W. R., Schmitt, J. E., ... Fatouros, P. (2012). Pilot multimodal twin imaging study of generalized anxiety disorder. Depression and Anxiety, 29(3), 202-209. https://doi.org/10.1002/da.20901

Pilot multimodal twin imaging study of generalized anxiety disorder. / Hettema, John M.; Kettenmann, Birgit; Ahluwalia, Vishwadeep; McCarthy, Christopher; Kates, Wendy R.; Schmitt, James E.; Silberg, Judy L.; Neale, Michael C.; Kendler, Kenneth S.; Fatouros, Panos.

In: Depression and Anxiety, Vol. 29, No. 3, 03.2012, p. 202-209.

Research output: Contribution to journalArticle

Hettema, JM, Kettenmann, B, Ahluwalia, V, McCarthy, C, Kates, WR, Schmitt, JE, Silberg, JL, Neale, MC, Kendler, KS & Fatouros, P 2012, 'Pilot multimodal twin imaging study of generalized anxiety disorder', Depression and Anxiety, vol. 29, no. 3, pp. 202-209. https://doi.org/10.1002/da.20901
Hettema JM, Kettenmann B, Ahluwalia V, McCarthy C, Kates WR, Schmitt JE et al. Pilot multimodal twin imaging study of generalized anxiety disorder. Depression and Anxiety. 2012 Mar;29(3):202-209. https://doi.org/10.1002/da.20901
Hettema, John M. ; Kettenmann, Birgit ; Ahluwalia, Vishwadeep ; McCarthy, Christopher ; Kates, Wendy R. ; Schmitt, James E. ; Silberg, Judy L. ; Neale, Michael C. ; Kendler, Kenneth S. ; Fatouros, Panos. / Pilot multimodal twin imaging study of generalized anxiety disorder. In: Depression and Anxiety. 2012 ; Vol. 29, No. 3. pp. 202-209.
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