Guilt-selective functional disconnection of anterior temporal and subgenual cortices in major depressive disorderCitation formats

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Guilt-selective functional disconnection of anterior temporal and subgenual cortices in major depressive disorder. / Green, Sophie; Lambon Ralph, Matthew A; Moll, Jorge; Deakin, John F W; Zahn, Roland.

In: Archives of General Psychiatry, Vol. 69, No. 10, 10.2012, p. 1014-1021.

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Green, Sophie ; Lambon Ralph, Matthew A ; Moll, Jorge ; Deakin, John F W ; Zahn, Roland. / Guilt-selective functional disconnection of anterior temporal and subgenual cortices in major depressive disorder. In: Archives of General Psychiatry. 2012 ; Vol. 69, No. 10. pp. 1014-1021.

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@article{5e929998687b430aa33eef64dd81943b,
title = "Guilt-selective functional disconnection of anterior temporal and subgenual cortices in major depressive disorder",
abstract = "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 ofMDD vulnerability that accounts for self-blaming biases.",
author = "Sophie Green and {Lambon Ralph}, {Matthew A} and Jorge Moll and Deakin, {John F W} and Roland Zahn",
note = "G0902304, Medical Research Council, United KingdomG0902304, Medical Research Council, United Kingdom, Wellcome Trust, United Kingdom",
year = "2012",
month = "10",
doi = "10.1001/archgenpsychiatry.2012.135",
language = "English",
volume = "69",
pages = "1014--1021",
journal = "Archives of General Psychiatry.",
issn = "0003-990X",
publisher = "American Medical Association",
number = "10",

}

RIS

TY - JOUR

T1 - Guilt-selective functional disconnection of anterior temporal and subgenual cortices in major depressive disorder

AU - Green, Sophie

AU - Lambon Ralph, Matthew A

AU - Moll, Jorge

AU - Deakin, John F W

AU - Zahn, Roland

N1 - G0902304, Medical Research Council, United KingdomG0902304, Medical Research Council, United Kingdom, Wellcome Trust, United Kingdom

PY - 2012/10

Y1 - 2012/10

N2 - 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 ofMDD vulnerability that accounts for self-blaming biases.

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 ofMDD vulnerability that accounts for self-blaming biases.

U2 - 10.1001/archgenpsychiatry.2012.135

DO - 10.1001/archgenpsychiatry.2012.135

M3 - Article

VL - 69

SP - 1014

EP - 1021

JO - Archives of General Psychiatry.

T2 - Archives of General Psychiatry.

JF - Archives of General Psychiatry.

SN - 0003-990X

IS - 10

ER -