Static and Treatment-Responsive Brain Biomarkers of Depression Relapse Vulnerability Following Prophylactic Psychotherapy

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. Objective: 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 either Cognitive Therapy or Mindfulness Based Cognitive Therapy and followed for 2 years to assess future relapse status. Findings: Dysphoric mood challenge evoked prefrontal activation and sensory inhibition. Controlling for number of past episodes and concurrent symptoms, somatosensory inhibition was significantly associated with depression recurrence in a static pattern that was unaffected by prophylactic treatment (HR ·05, 95% CI 0·02–0·17; p<·001). Treatment-related prophylaxis was, however, linked to reduced activation of the left lateral prefrontal cortex (LPFC; HR 3·35, CI 1·28–8·71; p =·013). Contralaterally, the right LPFC showed dysphoria-evoked inhibitory connectivity with the right somatosensory biomarker. Clinical Trial Registration Details: Registered at clinicaltrials.gov (NCT01178424). Interpretation: These findings support a two-factor model of depression relapse vulnerability, in which: i) enduring patterns of dysphoria-evoked sensory inhibition contribute to episode return, and ii) vulnerability may be mitigated by targeting prefrontal regions where reactivity is responsive to clinical intervention. Emotion regulation during illness remission may be optimized by reducing prefrontal cognitive processes in favor of sensory representation and integration. Funding Information: Canadian Institute of Health Research (Grant# 243812). Declaration of Interests: Dr. Segal reports personal fees from Guilford Press, personal fees from Centre for Mindfulness Studies, personal fees from Mindful Noggin Inc., outside the submitted work; all other authors have nothing to disclose. Ethics Approval Statement: The study protocol was approved by the institutional review board at the Centre for Addiction and Mental Health (CAMH). Participants were required to provide informed consent.