Dorsolateral prefrontal cortical pathology in generalized anxiety disorder: a proton magnetic resonance spectroscopic imaging study

Am J Psychiatry. 2004 Jun;161(6):1119-21. doi: 10.1176/appi.ajp.161.6.1119.


Objective: Few neuroimaging studies of generalized anxiety disorder have been conducted. The present study used proton magnetic resonance spectroscopy to assess concentrations of N-acetylaspartate, often considered a marker of neuronal viability, in generalized anxiety disorder patients.

Method: N-Acetylaspartate/creatine resonance ratios were measured in the left and right dorsolateral prefrontal cortex and hippocampus of 15 medication-free generalized anxiety disorder patients and 15 age- and sex-matched healthy volunteers.

Results: Generalized anxiety disorder patients had a 16.5% higher N-acetylaspartate/creatine ratio in the right dorsolateral prefrontal cortex compared with healthy participants; 13 of 15 matched patient-comparison subject pairs displayed a difference in this direction. In addition, generalized anxiety disorder patients reporting childhood abuse had lower N-acetylaspartate/creatine ratios in the right dorsolateral prefrontal cortex than did nonabused patients. Metabolite differences were not detected in other regions.

Conclusions: Generalized anxiety disorder is associated with asymmetric increases in the N-acetylaspartate/creatine ratio, a suggested marker of neuronal viability, in the prefrontal cortex. The findings also support prior research linking childhood abuse to reduced neuronal viability.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Anxiety Disorders / diagnosis
  • Anxiety Disorders / metabolism*
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / metabolism*
  • Biomarkers
  • Child
  • Child Abuse / diagnosis
  • Creatine / metabolism
  • Female
  • Functional Laterality
  • Hippocampus / metabolism
  • Humans
  • Magnetic Resonance Spectroscopy*
  • Male
  • Prefrontal Cortex / metabolism*


  • Biomarkers
  • Aspartic Acid
  • N-acetylaspartate
  • Creatine