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

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.