TY - JOUR
T1 - Self-blame-selective hyper-connectivity between anterior temporal and subgenual cortices predicts prognosis in major depressive disorder
AU - Fennema, Diede
AU - Barker, Gareth
AU - O'Daly, Owen
AU - Duan, Suqian
AU - Carr, Ewan
AU - Goldsmith, Kimberley
AU - Young, Allan
AU - Moll, Jorge
AU - Zahn, Roland
N1 - Funding Information:
This study represents independent research funded by the National Institute for Health and Care Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG-0416-20039) and independent research part funded by the National Institute for Health and Care (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London (RZ, AHY, KG, EC). This study was also supported by the Rosetrees Trust (M816) awarded to RZ. RZ was partly funded by a Medical Research Council grant (ref. MR/T017538/1). KG was supported by the National Institute for Health and Care Research (NIHR) Applied Research Collaboration South London (NIHR ARC South London) at King’s College Hospital NHS Foundation Trust. DF was funded by a Medical Research Council Doctoral Training Partnership Studentship (ref. 2064430) and partly supported by a KCL/IDOR Pioneer Science Fellowship. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Additional support was provided to the study by the South London Clinical Research Network and sponsorship by Lambeth CCG. The funding sources had no involvement in the study design, the collection, analysis and interpretation of data, in the writing of the report, or in the decision to submit the article for publication.
Funding Information:
We are grateful to Drs Mark Ashworth and Barbara Barrett who contributed to the trial study design, and to Dr Phillippa Harrison who collected trial data. We thank the participants of this study for their support. This study represents independent research funded by the National Institute for Health and Care Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG-0416-20039) and independent research part funded by the National Institute for Health and Care (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London (RZ, AHY, KG, EC). This study was also supported by the Rosetrees Trust (M816) awarded to RZ. RZ was partly funded by a Medical Research Council grant (ref. MR/T017538/1). KG was supported by the National Institute for Health and Care Research (NIHR) Applied Research Collaboration South London (NIHR ARC South London) at King's College Hospital NHS Foundation Trust. DF was funded by a Medical Research Council Doctoral Training Partnership Studentship (ref. 2064430) and partly supported by a KCL/IDOR Pioneer Science Fellowship. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Additional support was provided to the study by the South London Clinical Research Network and sponsorship by Lambeth CCG. The funding sources had no involvement in the study design, the collection, analysis and interpretation of data, in the writing of the report, or in the decision to submit the article for publication. The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. For the purposes of open access, the author has applied a Creative Commons Attribution (CC BY) licence to any Accepted Author Manuscript version arising from this submission.
Publisher Copyright:
© 2023
PY - 2023/6/16
Y1 - 2023/6/16
N2 - Background: Self-blame-related fMRI measures were shown to predict subsequent recurrence in remitted major depressive disorder (MDD). Their role in current MDD, however, is unknown. We hypothesised that these neural signatures reflect a highly recurrent but remitting course of MDD and therefore predict favourable outcomes over a four-month follow-up period in current MDD. Methods: Forty-five participants with current MDD and non-responders to at least two serotonergic antidepressants, were encouraged to optimise their medication and followed up after receiving four months of primary care treatment-as-usual. Prior to their medication review, participants completed an fMRI paradigm in which they viewed self- and other-blame emotion-evoking statements. Thirty-nine participants met pre-defined fMRI data minimum quality thresholds. Psychophysiological interaction analysis was used to determine baseline connectivity of the right superior anterior temporal lobe (RSATL), with an a priori BA25 region-of-interest for self-blaming vs other-blaming emotions, using Quick Inventory of Depressive Symptomatology (16-item) percentage change as a covariate. Results: We corroborated our pre-registered hypothesis that a favourable clinical outcome was associated with higher self-blame-selective RSATL-BA25 connectivity (Family-Wise Error-corrected p <.05 over the a priori BA25 region-of-interest; r
s(34) = −0.47, p =.005). This generalised to the sample including participants with suboptimal fMRI quality (r
s(39) = −0.32, p =.05). Conclusions: This study shows that neural signatures of overgeneralised self-blame are relevant for prognostic stratification of current treatment-resistant MDD. Future studies need to confirm whether this neural signature indeed represents a trait-like feature of a fully remitting subtype of MDD, or whether it is also modulated by depressive state and related to treatment effects.
AB - Background: Self-blame-related fMRI measures were shown to predict subsequent recurrence in remitted major depressive disorder (MDD). Their role in current MDD, however, is unknown. We hypothesised that these neural signatures reflect a highly recurrent but remitting course of MDD and therefore predict favourable outcomes over a four-month follow-up period in current MDD. Methods: Forty-five participants with current MDD and non-responders to at least two serotonergic antidepressants, were encouraged to optimise their medication and followed up after receiving four months of primary care treatment-as-usual. Prior to their medication review, participants completed an fMRI paradigm in which they viewed self- and other-blame emotion-evoking statements. Thirty-nine participants met pre-defined fMRI data minimum quality thresholds. Psychophysiological interaction analysis was used to determine baseline connectivity of the right superior anterior temporal lobe (RSATL), with an a priori BA25 region-of-interest for self-blaming vs other-blaming emotions, using Quick Inventory of Depressive Symptomatology (16-item) percentage change as a covariate. Results: We corroborated our pre-registered hypothesis that a favourable clinical outcome was associated with higher self-blame-selective RSATL-BA25 connectivity (Family-Wise Error-corrected p <.05 over the a priori BA25 region-of-interest; r
s(34) = −0.47, p =.005). This generalised to the sample including participants with suboptimal fMRI quality (r
s(39) = −0.32, p =.05). Conclusions: This study shows that neural signatures of overgeneralised self-blame are relevant for prognostic stratification of current treatment-resistant MDD. Future studies need to confirm whether this neural signature indeed represents a trait-like feature of a fully remitting subtype of MDD, or whether it is also modulated by depressive state and related to treatment effects.
KW - fMRI
KW - self-blame
KW - depression
KW - biomarker
KW - prognosis
UR - http://www.scopus.com/inward/record.url?scp=85163152620&partnerID=8YFLogxK
U2 - 10.1016/j.nicl.2023.103453
DO - 10.1016/j.nicl.2023.103453
M3 - Article
SN - 2213-1582
VL - 39
JO - NeuroImage: Clinical
JF - NeuroImage: Clinical
M1 - 103453
ER -