title: Pilot multimodal twin imaging study of generalized anxiety disorder.
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.
authors: Departments of Psychiatry, State University of New York Upstate Medical University, Syracuse, New York, USA. jhettema@vcu.edu
authors: John M
authors: JM
authors: Hettema
authors: Birgit
authors: B
authors: Kettenmann
authors: Vishwadeep
authors: V
authors: Ahluwalia
authors: Christopher
authors: C
authors: McCarthy
authors: Wendy R
authors: WR
authors: Kates
authors: James E
authors: JE
authors: Schmitt
authors: Judy L
authors: JL
authors: Silberg
authors: Michael C
authors: MC
authors: Neale
authors: Kenneth S
authors: KS
authors: Kendler
authors: Panos
authors: P
authors: Fatouros
mesh_terms: D000328:Adult; D000368:Aged; D000679:Amygdala / Q000503:physiopathology; D001008:Anxiety Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D006624:Hippocampus / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010865:Pilot Projects; D014430:Twins, Monozygotic