Neurobiological signatures of anxiety and depression in resting-state functional magnetic resonance imaging

Biol Psychiatry. 2015 Feb 15;77(4):385-93. doi: 10.1016/j.biopsych.2014.08.006. Epub 2014 Aug 15.


Background: There is increasing interest in using neurobiological measures to inform psychiatric nosology. It is unclear at the present time whether anxiety and depression are neurobiologically distinct or similar processes. It is also unknown if the best way to examine these disorders neurobiologically is by contrasting categorical definitions or by examining symptom dimensions.

Methods: A cross-sectional neuroimaging study was conducted of patients with generalized anxiety disorder (GAD), major depressive disorder (MDD), comorbid GAD and MDD (GAD/MDD), or neither GAD nor MDD (control subjects). There were 90 participants, all medication-free (17 GAD, 12 MDD, 23 GAD/MDD, and 38 control subjects). Diagnosis/category and dimensions/symptoms were assessed to determine the best fit for neurobiological data. Symptoms included general distress, common to anxiety and depression, and anxiety-specific (anxious arousal) or depression-specific (anhedonia) symptoms. Low-frequency (.008-.1 Hz) signal amplitude and functional connectivity analyses of resting-state functional magnetic resonance imaging data focused on a priori cortical and subcortical regions of interest.

Results: Support was found for effects of diagnosis above and beyond effects related to symptom levels as well as for effects of symptom levels above and beyond effects of diagnostic categories. The specific dimensional factors of general distress and anxious arousal as well as a diagnosis of MDD explained unique proportions of variance in signal amplitude or functional connectivity.

Conclusions: Using resting-state functional magnetic resonance imaging, our data show that a single conceptual model alone (i.e., categorical diagnoses or symptom dimensions) provides an incomplete mapping of psychopathology to neurobiology. Instead, the data support an additive model that best captures abnormal neural patterns in patients with anxiety and depression.

Keywords: Anhedonia; Anxiety; Depression; Neuroimaging; Resting state; fMRI.

Publication types

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

MeSH terms

  • Adult
  • Anxiety Disorders / complications
  • Anxiety Disorders / diagnosis
  • Anxiety Disorders / physiopathology*
  • Brain / physiopathology*
  • Brain Mapping
  • Cross-Sectional Studies
  • Depressive Disorder, Major / complications
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / physiopathology*
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Models, Neurological
  • Rest