Table 1.

Revising the Original Self-Regulation Risk Phenotype with Hypotheses Generated From a Macroscale Brain Organization Perspective

Regulatory Focus and Depression: Hypotheses for the Original Risk Phenotype
H1: Vulnerability to depression under circumstances involving cumulative or catastrophic loss of promotion goal pursuit success requires: (a) a functional genetic variation in dopamine signaling leading to perseverative responses to reward omission, (b) a socialization history emphasizing promotion goals in self-evaluation, and (c) a premorbid history of consistent promotion goal attainment. H2: The core symptoms of self-regulation-based depression reflect promotion hypoactivation (anhedonia, dysphoric mood, energy, concentration, worthlessness, hopelessness, low self-esteem) as well as dysregulation of dynamic reciprocal inhibition between promotion and prevention (sleep disturbance, guilt, agitation/anxiety, HPA axis dysfunction). H3: Promotion system hypoactivation is correlated with attenuated BOLD signal in left prefrontal cortex/middle frontal gyrus in response to priming of promotion goals, detectable both prior to and during a depressive episode. H4: As episodes of depression accumulate, self-regulatory mechanisms (behavioral as well as neurobiological) are permanently altered, leading to further difficulties with flexibility in response to varying degrees of success/failure feedback in promotion goal pursuit.
Revised Hypotheses from a Macroscale Brain Organization Perspective
H1*: There is a reliably reproducible macroscale hierarchical gradient pattern, identifiable prior to the onset of a first episode of depression, associated with covariation of the hypothesized individual difference components of the risk phenotype (dopamine signaling, socialization history, reinforcement history). H2*: The same macroscale hierarchical gradient pattern is characteristic of depressive episodes associated with promotion system hypoactivation and, in cases of depressive/anxious comorbidity, corresponding prevention system hyperactivation. H3*: The hypothesized macroscale gradient pattern features associated with vulnerability to self-regulation-based depression and episodes of depression are discriminantly correlated with the circuit-specific and location-specific findings from previous task-based fMRI studies of self-regulation failure and depression. That is, they reflect both promotion and prevention system dysfunction but specifically under conditions of continuous promotion goal pursuit failure feedback. H4*: The greater the number of previous episodes, the greater the resistance to intervention that will be manifested at the level of the overall vulnerability-linked macroscale gradient pattern.