Neural Processing Dysfunctions During Fear Learning but Not Reward-Related Processing Characterize Depressed Individuals With High Levels of Repetitive Negative Thinking

Background: Repetitive negative thinking (RNT) is a symptom dimension of depression that is associated with a poorer prognosis in terms of higher recurrence, treatment resistance, residual symptoms, and disability. This investigation examined whether RNT is associated with aberrant reward processing and fear learning.

Methods: Very high RNT (VH-RNT) (n = 60) and high RNT (H-RNT) (n = 60) propensity-matched individuals with depression (age, sex, race/ethnicity, income/employment, body mass index, depressive and anxiety symptom severity) participated in this study along with matched healthy comparison volunteers (n = 30). This propensity-matched sample was selected from the larger Tulsa 1000 study. Participants performed two functional magnetic resonance imaging tasks: the monetary incentive delay task probing reward processing and the fear conditioning task probing aversive learning and extinction.

Results: Both VH-RNT and H-RNT groups showed lower neural activity than healthy comparison subjects in reward circuitry, including the inferior frontal gyrus (VH-RNT: β = -1.24, H-RNT: β = -1.28) and the cerebellum (VH-RNT: β = -0.93, H-RNT: β = -1.14). However, individuals with VH-RNT exhibited lower activation than those with H-RNT in central autonomic network components during fear conditioning (β = -0.84) and continued conditioned responses during early extinction in the postcentral cortex (β = 0.71).

Conclusions: VH-RNT showed aberrant processing in fear conditioning during both learning and extinction phases compared with H-RNT. These findings demonstrate that dysfunctions of negative valence associated with RNT may be domain specific, which should be taken into account for identifying potential specific targets of intervention.