Neurobiology of the dorsolateral prefrontal cortex in GAD: Aberrant neurometabolic correlation to hippocampus and relationship to anxiety sensitivity and IQ

J Affect Disord. 2018 Mar 15;229:1-13. doi: 10.1016/j.jad.2017.12.001. Epub 2017 Dec 12.


Introduction: The neurometabolism underlying the cognitive and affective symptoms associated with generalized anxiety disorder (GAD) remain poorly understood. After we have linked worry to intelligence in patients with GAD, we hypothesized that aberrant neurometabolic correlations between hippocampus and neocortical regions may underlie a shared substrate in GAD patients for both anxiety sensitivity and intelligence.

Methods: GAD patients (n = 16; F = 11) and healthy volunteers (n = 16; F = 10) were assessed using 1H-MRSI. Co-axial planes I [hippocampus (HIPP)] and co-axial plane III [dorsolateral prefrontal cortex (DLPFC), central gyrus (CG)] were examined. Using general linear models, we examined resting metabolite concentrations using HIPP as a hub to CG and DLPFC. Neocortical ROIs were related to Anxiety Sensitivity Index (ASI) and Full Scale IQ (FSIQ) in GAD patients versus controls.

Results: Right hippocampal Cho/Cr directly predicted left DLPFC Cho/Cr in GAD (r = 0.75), an effect distinguishable (p = 0.0004) from controls. Left HIPP Cho/Cr positively predicted left CG Cho/Cr in GAD, an effect distinguishable from controls. In patients, both left and right DLPFC Cho/Cr positively predicted ASI but only left DLPFC Cho/Cr inversely predicted IQ. By contrast, IQ in controls correlated directly with left CG Cho/Cr.

Limitations: Small sample size precluded us from investigating how gender and FSIQ subscales related to neurochemical correlations in the ROIs examined.

Conclusions: Aberrant resting state neurochemical correlation between left DLPFC and right HIPP may contribute to GAD symptomatology. Unlike controls, in GAD, IQ and worry may share a common yet inverse neurometabolic substrate in left DLPFC.

Keywords: Choline/creatine ratio; Dorsolateral prefrontal cortex; Generalized anxiety disorder; Hippocampus; Intelligence quotient; Proton magnetic resonance spectroscopy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anxiety / diagnostic imaging
  • Anxiety / metabolism*
  • Anxiety Disorders / diagnostic imaging
  • Anxiety Disorders / metabolism*
  • Anxiety Disorders / psychology
  • Case-Control Studies
  • Female
  • Gyrus Cinguli / diagnostic imaging
  • Gyrus Cinguli / metabolism
  • Hippocampus / diagnostic imaging
  • Hippocampus / metabolism*
  • Humans
  • Intelligence / physiology*
  • Linear Models
  • Magnetic Resonance Spectroscopy / methods
  • Male
  • Middle Aged
  • Prefrontal Cortex / diagnostic imaging
  • Prefrontal Cortex / metabolism*