Elsevier

Biological Psychiatry

Volume 59, Issue 7, 1 April 2006, Pages 582-587
Biological Psychiatry

Original article
Decreased Anterior Cingulate Volume in Combat-Related PTSD

https://doi.org/10.1016/j.biopsych.2005.07.033Get rights and content

Background

Neuroanatomical data point to functional relationships between the anterior cingulate cortex (ACC) and subcortical centers regulating fear, in particular, the amygdala. Functional brain imaging has disclosed divergent patterns of ACC activation in persons with posttraumatic stress disorder (PTSD). In addition, two preliminary structural imaging studies have found evidence of smaller ACC volume in PTSD. We explored associations between PTSD and ACC volume in a relatively large sample of adult combat veterans in which PTSD, lifetime alcohol abuse/dependence, and Vietnam versus Gulf War service were crossed.

Methods

Subjects were US military combat veterans of the Vietnam and Gulf Wars recruited from two metropolitan areas served by allied Department of Veterans Affairs PTSD treatment/research centers. Anterior cingulate cortex volume was analyzed as a function of grouping factors with and without adjustment for body size.

Results

Posttraumatic stress disorder was associated with smaller anterior cingulate cortex volume. This effect persisted in subjects without histories of alcoholism, did not interact with cohort effects, and was not modified by adjustment for body size.

Conclusions

Anterior cingulate cortex volume is substantially smaller in association with combat-related PTSD, a finding broadly consistent with cingulate hypofunctionality in that disorder.

Section snippets

Recruitment and Screening

Subjects provided written informed consent in accordance with procedures of the Institutional Review Boards of either Stanford University Medical School/VA Palo Alto Healthcare System or Boston VA Medical Center and the McLean Hospital. Subjects were recruited through a combination of advertising and word-of-mouth contacts with current and past patients and research volunteers. Initial screening established that subjects were US military veterans of the Vietnam Conflict or the Persian Gulf War

Results

The ACC was larger in the right hemisphere while the posterior cingulate cortex (PCC) was larger on the left [interaction of hemisphere and anterior-posterior dimension: F(1,91) = 25.6, p < .001]. There was no main effect of hemisphere and no interaction between hemisphere and any grouping factor. The ACC [F(1,91) = 11.7, p = .001] but not the PCC [F(1,91) = .056, n.s.] was smaller in subjects diagnosed with PTSD [interaction of PTSD and anterior-posterior factor: F(1,91) = 5.28, p = .024; see

Discussion

This analysis of 99 combat veterans confirmed and extended previous findings. Anterior cingulate cortex volume was observed to be smaller in persons with combat-related PTSD whether or not they were diagnosed with lifetime alcoholism or belonged to one of two military/aging cohorts. Statistical adjustment for body size did not modify the results. We did not find that the effect of PTSD was limited to pregenual ACC. Our data suggested instead that dorsal ACC, often associated with more cognitive

References (62)

  • E. Jodo et al.

    Activation of locus coeruleus by prefrontal cortex is mediated by excitatory amino acid inputs

    Brain Res

    (1997)
  • W.R. Kates et al.

    Automated Talairach atlas-based parcellation and measurement of cerebral lobes in children

    Psychiatry Res

    (1999)
  • R.A. Lanius et al.

    Brain activation during script-driven imagery induced dissociative responses in PTSDA functional magnetic resonance imaging investigation

    Biol Psychiatry

    (2002)
  • R.A. Lanius et al.

    Recall of emotional states in posttraumatic stress disorderAn fMRI investigation

    Biol Psychiatry

    (2003)
  • I. Liberzon et al.

    Brain activation in PTSD in response to trauma-related stimuli

    Biol Psychiatry

    (1999)
  • D.H. Mathalon et al.

    Anatomy of an errorERP and fMRI

    Biol Psychol

    (2003)
  • A.J. McDonald et al.

    Projections of the medial and lateral prefrontal cortices to the amygdalaA Phaseolus vulgaris leucoagglutinin study in the rat

    Neuroscience

    (1996)
  • W.H. Miltner et al.

    Implementation of error-processing in the human anterior cingulate cortexA source analysis of the magnetic equivalent of the error-related negativity

    Biol Psychol

    (2003)
  • J.J. Radley et al.

    Chronic behavioral stress induces apical dendritic reorganization in pyramidal neurons of the medial prefrontal cortex

    Neuroscience

    (2004)
  • N. Raz et al.

    Aging, sexual dimorphism, and hemispheric asymmetry of the cerebral cortexReplicability of regional differences in volume

    Neurobiol Aging

    (2004)
  • L.M. Shin et al.

    An fMRI study of anterior cingulate function in posttraumatic stress disorder

    Biol Psychiatry

    (2001)
  • J.K. Zubieta et al.

    Medial frontal cortex involvement in PTSD symptomsA SPECT study

    J Psychiatr Res

    (1999)
  • A.T. Beck et al.

    An inventory for measuring depression

    Arch Gen Psychiatry

    (1961)
  • D. Blake et al.

    Clinician-Administered PTSD Scale (CAPS) Instructional Manual

    (2000)
  • D.D. Blake et al.

    Clinician-Administered PTSD Scale for DSM-IVCurrent and Lifetime Version

    (1997)
  • J.D. Bremner et al.

    Neural correlates of memories of childhood sexual abuse in women with and without posttraumatic stress disorder

    Am J Psychiatry

    (1999)
  • J.D. Bremner et al.

    MRI-based measurement of hippocampal volume in patients with combat- related posttraumatic stress disorder

    Am J Psychiatry

    (1995)
  • S.T. Carmichael et al.

    Limbic connections of the orbital and medial prefrontal cortex in macaque monkeys

    J Comp Neurol

    (1995)
  • M.B. First et al.

    Structured Clinical Interview for the DSM-IV Axis-I Disorders

    (1995)
  • A. Gevins et al.

    High-resolution EEG mapping of cortical activation related to working memoryEffects of task difficulty, type of processing, and practice

    Cereb Cortex

    (1997)
  • M.B. Hamner et al.

    Potential role of the anterior cingulate cortex in PTSDReview and hypothesis

    Depress Anxiety

    (1999)
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