Guilt-selective functional disconnection of anterior temporal and subgenual cortices in major depressive disorder.
BACKGROUND
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.


METHODS
Case-control study from May 1, 2008, to June 1, 2010.


METHODS
Clinical research facility.


METHODS
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.


METHODS
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 ofMDD vulnerability that accounts for self-blaming biases.
Neuroscience and Aphasia Research Unit, School of Psychological Sciences, The University of Manchester & Manchester Academic Health Sciences Centre, Manchester, England.
Sophie
S
Green
Matthew A
MA
Lambon Ralph
Jorge
J
Moll
John F W
JF
Deakin
Roland
R
Zahn
D000328:Adult; D015415:Biomarkers; D001921:Brain / Q000503:physiopathology*; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000503:physiopathology*; D005260:Female; D006167:Guilt; D006179:Gyrus Cinguli / Q000503:physiopathology; D006624:Hippocampus / Q000503:physiopathology; D006801:Humans; D007031:Hypothalamus / Q000503:physiopathology; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D008297:Male; D009415:Nerve Net / Q000503:physiopathology*; D017397:Prefrontal Cortex / Q000503:physiopathology; D020665:Septum of Brain / Q000503:physiopathology; D013702:Temporal Lobe / Q000503:physiopathology; D055815:Young Adult
D015415:Biomarkers