Low Reward and Heightened Threat Neural Activity are Both Associated with Heightened Anhedonia: A Transdiagnostic Perspective.

Psychiatric neuroscience typically examines categorical diagnoses and brain systems in isolation. This approach is complicated by comorbidity and within-diagnosis heterogeneity and fails to evaluate whether relationships are unique to, or common across, neural circuits. To address this, we examined associations between reward and threat neural activity and symptoms of General Distress, Fears, and Anhedonia-Apprehension from the tri-level model of depression and anxiety. Data were collected on 339 participants aged 18-19; 272 completed a monetary incentive delay task (MID) assessing reward neural activity and a Pavlovian fear learning task assessing threat neural activity. We used full-information maximum likelihood to handle missing data and thus retained all 339 participants in each analysis. As predicted, heightened Anhedonia-Apprehension was associated with lower orbitofrontal cortex activity during reward receipt in the MID task (b = -.34, se = .147, p = .021). This relationship was specific to Anhedonia-Apprehension relative to other symptom dimensions and to orbitofrontal activity during reward receipt relative to threat-related neural activity. Heightened Anhedonia-Apprehension was also associated with lower ventral striatal activation during reward anticipation in the MID reward task (b = -.53, se = .218, p = .015). Unexpectedly, heightened Anhedonia-Apprehension was also associated with heightened threat neural activity during the extinction phase of the Pavlovian fear learning task (b = .21, se = .066, p = .001). Findings highlight the importance of examining associations between specific brain systems and empirically derived symptom dimensions to better understand mental health problems and develop targeted interventions.