White matter integrity alterations in first episode, treatment-naive generalized anxiety disorder

Yan Zhang, Lingjiang Li*, Rongjun Yu*, Jun Liu, Jinsong Tang, Liwen Tan, Mei Liao, Fan Yang, Baoci Shan

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

39 Citations (Scopus)


Background: Several neurobiological models of anxiety disorder posit a primary role for dysfunction of the amygdala and anterior cingulate cortex (ACC). This study tests the hypothesis that patients with generalized anxiety disorder (GAD) have abnormal white matter microstructure in the amygdala and ACC, as inferred from diffusion tensor imaging, compared with healthy controls.

Methods: Subjects were 16 right-handed, first-episode, treatment-naive GAD patients without comorbid disorders and 26 matched, healthy comparison controls. All subjects underwent diffusion tensor imaging and structural magnetic resonance imaging brain scanning. Fractional anisotropy (FA), a robust intravoxel measure of water self-diffusion, was compared between groups on a voxel-by-voxel basis. Associations between clinical ratings of symptom severity (i.e., the Hamilton Anxiety Scale and the Penn State Worry Questionnaire) and FA were assessed.

Results: Compared with healthy volunteers, patients demonstrated significantly higher FA in the right amygdala white matter and lower FA in the caudal ACC/mid-cingulate cortex white matter. Higher right amygdala FA correlated significantly with higher Hamilton Anxiety Scale scores and higher Penn State Worry Questionnaire scores.

Limitations: The sample size was modest and may contribute to false positive effects.

Conclusions: These findings provide the first evidence of an abnormality in white matter microstructure that involves the amygdala and the cingulate cortex in the pathogenesis of GAD, and are consistent with neurobiological models that posit a defect in emotion-related brain regions.
Original languageEnglish
Pages (from-to)196-201
Number of pages6
JournalJournal of Affective Disorders
Issue number2-3
Publication statusPublished - Jun 2013

User-Defined Keywords

  • Amygdala
  • Anterior cingulate cortex
  • Diffusion tensor imaging
  • Generalized anxiety disorder
  • Magnetic resonance imaging


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