NEUROBIOLOGY OF ANXIOUS DEPRESSION: A REVIEW

Authors

  • Dawn F. Ionescu M.D.,

    Corresponding author
    • Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland
    Search for more papers by this author
  • Mark J. Niciu M.D., Ph.D.,

    1. Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland
    Search for more papers by this author
  • Daniel C. Mathews M.D.,

    1. Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland
    Search for more papers by this author
  • Erica M. Richards M.D., Ph.D.,

    1. Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland
    Search for more papers by this author
  • Carlos A. Zarate Jr M.D.

    1. Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland
    Search for more papers by this author

  • Resubmitted as a Review Article to Depression and Anxiety, February 2013.

  • Contract grant sponsor: Intramural Research Program at the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH).

Correspondence to: Dr. Dawn F. Ionescu, Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Building 10, CRC Room 7-5545, 10 Center Drive, MSC 1282, Bethesda, MD 20892. E-mail: dawn.ionescu@nih.gov

Abstract

Anxious depression is a common, distinct clinical subtype of major depressive disorder (MDD). This review summarizes current neurobiological knowledge regarding anxious depression. Peer-reviewed articles, published January 1970 through September 2012, were identified via PUBMED, EMBASE, and Cochrane Library, using the following key words: anxious depression electroencephalography (EEG), anxious depression functional magnetic resonance imaging (fMRI), anxious depression genetics, anxious depression neurobiology, and anxious melancholia neurobiology. Despite a general dearth of neurobiological research, the results suggest that anxious depression—when defined either syndromally or dimensionally—has distinct neurobiological findings that separate it from nonanxious depression. Structural neuroimaging, EEG, genetics, and neuropsychiatric studies revealed differences in subjects with anxious depression compared to other groups. Endocrine differences between individuals with anxious depression and those with nonanxious depression have also been noted, as evidenced by abnormal responses elicited by exogenous stimulation of the system. Despite these findings, heterogeneity in the definition of anxious depression complicates the results. Because exploring the neurobiology of this depressive subtype is important for improving diagnosis, prognosis, and treatment, enrichment strategies to decrease heterogeneity within the field should be employed for future research.

Ancillary