Elsevier

Biological Psychiatry

Volume 63, Issue 6, 15 March 2008, Pages 550-556
Biological Psychiatry

Original Article
Evidence for Acquired Pregenual Anterior Cingulate Gray Matter Loss from a Twin Study of Combat-Related Posttraumatic Stress Disorder

https://doi.org/10.1016/j.biopsych.2007.06.022Get rights and content

Background

Controversy exists over the nature and origin of reduced regional brain volumes in posttraumatic stress disorder (PTSD). At issue is whether these reductions represent preexisting vulnerability factors for developing PTSD upon traumatic exposure or acquired PTSD signs due to the traumatic stress that caused the PTSD or the chronic stress of having the disorder (or both). We employed a case–control design in monozygotic twin pairs discordant for combat exposure to address the preexisting versus acquired origin of brain morphometric abnormalities in PTSD.

Methods

We used voxel-based morphometry to search for gray matter density reductions in magnetic resonance imaging (MRI) data obtained in a previous study of combat-exposed Vietnam veteran twins with (n = 18) versus without (n = 23) PTSD and their “high-risk” versus “low-risk” (respectively) identical combat-unexposed cotwins.

Results

Compared with the combat-exposed twins without PTSD, the combat-exposed twins with PTSD showed significant gray matter density reductions in four predicted brain regions: right hippocampus, pregenual anterior cingulate cortex (ACC), and left and right insulae. There was a significant PTSD Diagnosis × Combat Exposure interaction in pregenual ACC in which combat-exposed PTSD twins had lower gray matter density than their own combat-unexposed cotwins as well as than the combat-exposed twins without PTSD and their cotwins.

Conclusions

The results point to gray matter volume diminutions in limbic and paralimbic structures in PTSD. The pattern of results obtained for pregenual ACC suggests that gray matter reduction in this region represents an acquired sign of PTSD consistent with stress-induced loss.

Section snippets

Subjects

The strategy for subject ascertainment and recruitment has been presented elsewhere (16). The sample was described in detail in the report of our previous hippocampus manual tracing study (15). This study reanalyzed the same MRI scans from the same subjects. In the previous study, one combat-exposed twin with PTSD and his combat-unexposed cotwin were removed from the analysis because the former was an extreme, asymmetrical outlier for manually traced hippocampal volume. This subject and his

Demographics and Psychometrics

Group mean age, Combat Severity Score (26), total Clinician-Administered PTSD Scale (CAPS) score (27), number of potentially traumatic lifetime noncombat events (16), total Michigan Alcoholism Screening Test (MAST) score (28), and Symptom Check List-90-Revised (SCL-90-R) Depression scale score (29), along with statistical analyses, are presented in Table 1. It may be seen that age was similar among subject groups. Combat-exposed twins with PTSD had more severe combat exposure than

Discussion

Of the seven loci at which combat-exposed twins with PTSD had lower gray matter density than combat-exposed twins without PTSD at a liberal threshold of p < .001, four were located in predicted brain regions, namely, right hippocampus, pregenual ACC, and left anterior and right midinsula, even though the predicted brain regions occupy less than 10% of total gray matter volume. This regional specificity supports the validity of our results and implicates limbic and paralimbic structures as the

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