Neural sensitivity following stress predicts anhedonia symptoms: a 2-year multi-wave, longitudinal study.

Animal models of depression show that acute stress negatively impacts functioning in neural regions sensitive to reward and punishment, often manifesting as anhedonic behaviors. However, few human studies have probed stress-induced neural activation changes in relation to anhedonia, which is critical for clarifying risk for affective disorders. Participants (N = 85, 12-14 years-old, 53 female), oversampled for risk of depression, were administered clinical assessments and completed an fMRI guessing task during a baseline (no-stress) period to probe neural response to receipt of rewards and losses. After the initial task run of the fMRI guessing task, participants received an acute stressor and then, were re-administered the guessing task. Including baseline, participants provided up to 10 self-report assessments of life stress and symptoms over a 2 year period. Linear mixed-effects models estimated whether change in neural activation (post- vs. pre-acute stressor) moderated the longitudinal associations between life stress and symptoms. Primary analyses indicated that adolescents with stress-related reductions in right ventral striatum response to rewards exhibited stronger longitudinal associations between life stress and anhedonia severity (β = -0.06, 95%CI[-0.11, -0.02], p = 0.008, p = 0.048). Secondary analyses showed that longitudinal positive associations between life stress and depression severity were moderated by stress-related increases in dorsal striatum response to rewards (left caudate β = 0.11, 95%CI[0.07,0.17], p < 0.001, p = 0.002; right caudate β = 0.07, 95%CI[0.02,0.12], p = 0.002, p = 0.003; left putamen β = 0.09, 95%CI[0.04, 0.14], p < 0.001, p = 0.002; right putamen β = 0.08, 95%CI[0.03, 0.12], p < 0.001, p = 0.002). Additionally, longitudinal positive associations among life stress and anxiety severity were moderated by stress-related reductions in dorsal anterior cingulate cortex (β = -0.07, 95%CI[-0.12,.02], p = 0.008, p = 0.012) and right anterior insula (β = -0.07, 95%CI[-0.12,-0.02], p = 0.002, p = 0.006) response to loss. All results held when adjusting for comorbid symptoms. Results show convergence with animal models, highlighting mechanisms that may facilitate stress-induced anhedonia as well as a separable pathway for the emergence of depressive and anxiety symptoms.