RT Journal
A1 Green S, Lambon Ralph MA, Moll J, Deakin JW, Zahn R
T1 GUilt-selective functional disconnection of anterior temporal and subgenual cortices in major depressive disorder
JF Archives of General Psychiatry
JO Archives of General Psychiatry
YR 2012
FD October 1
VO 69
IS 10
SP 1014
OP 1021
DO 10.1001/archgenpsychiatry.2012.135
UL http://dx.doi.org/10.1001/archgenpsychiatry.2012.135
AB Context 
                  Proneness to overgeneralization of self-blame is a core part of cognitive vulnerability to major depressive disorder (MDD) and remains dormant after remission of symptoms. Current neuroanatomical models of MDD, however, assume general increases of negative emotions and are unable to explain biases toward emotions entailing self-blame (eg, guilt) relative to those associated with blaming others (eg, indignation). Recent functional magnetic resonance imaging (fMRI) studies in healthy participants have shown that moral feelings such as guilt activate representations of social meaning within the right superior anterior temporal lobe (ATL). Furthermore, this area was selectively coupled with the subgenual cingulate cortex and adjacent septal region (SCSR) during the experience of guilt compared with indignation. Despite its psychopathological importance, the functional neuroanatomy of guilt in MDD is unknown.Objective 
                  To use fMRI to test the hypothesis that, in comparison with control individuals, participants with remitted MDD exhibit guilt-selective SCSR-ATL decoupling as a marker of deficient functional integration.Design 
                  Case-control study from May 1, 2008, to June 1, 2010.Setting 
                  Clinical research facility.Participants 
                  Twenty-five patients with remitted MDD (no medication in 16 patients) with no current comorbid Axis I disorders and 22 controls with no personal or family history of MDD.Main Outcome Measures 
                  Between-group difference of ATL coupling with a priori SCSR region of interest for guilt vs indignation.Results 
                  We corroborated the prediction of a guilt-selective reduction in ATL-SCSR coupling in MDD vs controls (familywise error–corrected P = .001 over the region of interest) and revealed additional medial frontopolar, right hippocampal, and lateral hypothalamic areas of decoupling while controlling for medication status and intensity of negative emotions. Lower levels of ATL-SCSR coupling were associated with higher scores on a validated measure of overgeneralized self-blame (67-item Interpersonal Guilt Questionnaire).Conclusions 
                  Vulnerability to MDD is associated with temporofrontolimbic decoupling that is selective for self-blaming feelings. This provides the first neural mechanism of MDD vulnerability that accounts for self-blaming biases.