A Two-Factor Model of Relapse/Recurrence Vulnerability in Unipolar Depression

The substantial health burden associated with major depressive disorder (MDD) is a product of both its high prevalence and the significant risk of relapse, recurrence, and chronicity. Establishing recurrence vulnerability factors (VFs) could improve the long-term management of MDD by identifying the need for further intervention in seemingly recovered patients. We present a model of sensitization in depression vulnerability, with an emphasis on the integration of behavioral and neural systems accounts. Evidence suggests that VFs fall into 2 categories: dysphoric attention and dysphoric elaboration. Dysphoric attention is driven by fixation on negative life events, and is characterized behaviorally by reduced executive control, and neurally by elevated activity in the brain's salience network. Dysphoric elaboration is driven by rumination that promotes overgeneral self-and contextual appraisals, and is characterized behaviorally by dysfunctional attitudes, and neurally by elevated connectivity within normally distinct prefrontal brain networks. Although few prospective VF studies exist from which to catalogue a definitive neurobehavioral account, extant data support the value of the proposed 2-factor model. Measuring the continued presence of these 2 VFs during recovery may more accurately identify remitted patients who would benefit from targeted prophylactic intervention.