Static and treatment-responsive brain biomarkers of depression relapse vulnerability following prophylactic psychotherapy: Evidence from a randomized control trial

Norman A S Farb; Philip Desormeau; Adam K Anderson; Zindel V Segal

doi:10.1016/j.nicl.2022.102969

Static and treatment-responsive brain biomarkers of depression relapse vulnerability following prophylactic psychotherapy: Evidence from a randomized control trial

Neuroimage Clin. 2022:34:102969. doi: 10.1016/j.nicl.2022.102969. Epub 2022 Feb 19.

Authors

Norman A S Farb¹, Philip Desormeau², Adam K Anderson³, Zindel V Segal²

Affiliations

¹ Department of Psychology, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, Ontario L5L 1C6, Canada; Graduate Department of Psychological Clinical Science, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada. Electronic address: norman.farb@utoronto.ca.
² Graduate Department of Psychological Clinical Science, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.
³ College of Human Ecology, Cornell University, Ithaca, NY 14853, USA.

Abstract

Background: Neural reactivity to dysphoric mood induction indexes the tendency for distress to promote cognitive reactivity and sensory avoidance. Linking these responses to illness prognosis following recovery from Major Depressive Disorder informs our understanding of depression vulnerability and provides engagement targets for prophylactic interventions.

Methods: A prospective fMRI neuroimaging design investigated the relationship between dysphoric reactivity and relapse following prophylactic intervention. Remitted depressed outpatients (N = 85) were randomized to 8 weeks of Cognitive Therapy with a Well-Being focus or Mindfulness Based Cognitive Therapy. Participants were assessed before and after therapy and followed for 2 years to assess relapse status. Neural reactivity common to both assessment points identified static biomarkers of relapse, whereas reactivity change identified dynamic biomarkers.

Results: Dysphoric mood induction evoked prefrontal activation and sensory deactivation. Controlling for past episodes, concurrent symptoms and medication status, somatosensory deactivation was associated with depression recurrence in a static pattern that was unaffected by prophylactic treatment, HR 0.04, 95% CI [0.01, 0.14], p < .001. Treatment-related prophylaxis was linked to reduced activation of the left lateral prefrontal cortex (LPFC), HR 3.73, 95% CI [1.33, 10.46], p = .013. Contralaterally, the right LPFC showed dysphoria-evoked inhibitory connectivity with the right somatosensory biomarker CONCLUSIONS: These findings support a two-factor model of depression relapse vulnerability, in which: enduring patterns of dysphoria-evoked sensory deactivation contribute to episode return, but vulnerability may be mitigated by targeting prefrontal regions responsive to clinical intervention. Emotion regulation during illness remission may be enhanced by reducing prefrontal cognitive processes in favor of sensory representation and integration.

Trial registration: ClinicalTrials.gov NCT01178424.

Keywords: Depression; Dysphoric reactivity; Mood challenge; Relapse vulnerability; Sensory deactivation; fMRI.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Brain / diagnostic imaging
Chronic Disease
Depression
Depressive Disorder, Major* / diagnostic imaging
Depressive Disorder, Major* / psychology
Depressive Disorder, Major* / therapy
Humans
Prospective Studies
Psychotherapy / methods
Recurrence

Substances

Biomarkers

Associated data

ClinicalTrials.gov/NCT01178424

Grants and funding

243812/CIHR/Canada