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

Abstract

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

Presence and acquired origin of reduced recall for fear extinction in PTSD: Results of a twin study

“…The impaired extinction retention in the PTSD subjects in the present study is consistent with studies reporting deficient activation of this brain region in PTSD (Shin et al, 2004;Bremner et al, 2005;Liberzon et al, 2003;Phan et al, 2006;Britton et al, 2005;Shin et al, 2001). Moreover, a recent twin study reported acquired gray matter reduction in an area of vmPFC (rostral anterior cingulate cortex) in PTSD (Kasai et al, 2007). This is consistent with our present data showing that the extinction retention deficiency appears to be acquired.…”

Structural magnetic ressonance imaging in anxiety disorders: an update of research findings

“…[22][23][24][25][26][27] However, as shown in our previous review, 10 there is also some disagreement about laterality 21,[28][29][30] and even about the presence of this reduction, 13,[31][32][33][34] in both ROI and VBM-based studies. These contrasting findings, in addition to being due to possible neurobiological abnormalities, may also be due to methodological limitations such as differences in the selection of the hippocampus by manual methods.…”

“…[17][18][19][20] Hippocampal abnormalities in association with PTSD may represent pre-trauma vulnerability to the development of the disorder or may be the consequence of exposure to trauma, of PTSD or even of comorbidities associated with the disorder. 21 The morphometric MRI studies of PTSD discussed in our previous review 10 showed important disagreement in respect to hippocampal volume, having some studies reported volumetric reduction and others indicated absence of alterations in this brain region. Patients with PTSD also presented reduced total brain volume, reduction in the corpus callosum, and ventricular enlargement.…”

“…Several studies later confirmed a volumetric reduction of the anterior cingulate cortex in association with PTSD, although there has been disagreement regarding laterality since differences were detected in the right 37 and left 29 pregenual region 21 and in the anterior cingulated region as a whole. 37 Of particular interest is the fact that the anterior cingulate cortex has close neuroanatomical relations with subcortical components of the "central fear system", including the amygdala and locus coeruleus.…”

“…8,37 The insula, another region functionally related to the amygdala, has been found to be repeatedly reduced in volume in PTSD patients in recent voxel-based morphometric studies. 21,29,38 There is evidence indicating that the insula is involved both in emotional processing and in cognition, with connections linked to the prefrontal cortex, limbic system and temporal pole. 39 In a meta-analysis of 43 studies using PET and of 12 studies using functional MRI (fMRI), Phan et al suggested that the anterior cingulate cortex and the insula may be involved in emotional induction in association with cognitive demands.…”