Depression is common in persons with MS (PwMS), substantially contributing to morbidity and mortality. Depression can dually impact PwMS as both a psychosocial reaction to living with the disease and a neurological effect of it. Cardinal features of depression include reduced ability to seek and experience pleasure, often attributed to dysregulation of the brain's reward system. People with depression exhibit atypical reward processing, as do fatigued PwMS. However, it is unclear whether MS itself affects reward processing, and whether it interacts with depression. The current study explored the associations of depression, MS, and their interaction on reward responsiveness. We hypothesized that depression and MS would independently be associated with poorer reward responsiveness and that they would interact synergistically to impair reward responsiveness.

Forty PwMS and 40 healthy age- and education-matched healthy controls (HC) participated in a computerized switching task with high- and low-reward manipulations. The Chicago Multiscale Depression Inventory (CMDI) Mood subscale measured depressive symptoms. The Behavioral Inhibition/Activation Scales (BIS/BAS) measured self-reported reward responsiveness and behavioral inhibition. Switching task performance was measured as response time (RT) and accuracy. Performance differences between the high- and low-reward conditions represented performance-based reward responsiveness. Linear mixed effects models were used to estimate the associations of MS and depression with reward responsiveness, behavioral inhibition, and task performance.

Depression, but not MS, was associated with higher BIS scores (p=.007). Neither depression nor MS was associated with BAS subscales. On the switching task, participants who reported lower depression responded to reward such that they were slightly faster in the high-reward condition compared to the low-reward condition (p=.07). By contrast, in participants who reported higher depression, there was no effect of reward on response time. Additionally, MS (p=.009) and depression (p=.018) were each associated with slower response times. Regarding accuracy, no effects of reward were observed; however, there was an interaction between MS and depression. Among HC participants, depression was not related to accuracy. In comparison, PwMS who reported higher depression were more accurate than PwMS who reported less depression (p=.043).

Consistent with hypotheses, higher depressive symptoms were associated with increased behavioral inhibition. Depression was not associated with self-reported reward responsiveness, but it was associated with reduced reward responsiveness on a cognitive task. Contrary to hypotheses, MS was not associated with reduced reward responsiveness. Additionally, higher depression and an MS diagnosis were related to slower response time, consistent with prior findings that psychomotor slowing is a hallmark feature of both disorders. Interestingly, we observed a unique behavioral trend in PwMS, such that PwMS with higher depressive symptoms were more accurate than PwMS with lower depressive symptoms, whereas this relationship was not present among HCs. Altogether, depression in both PwMS and cognitively healthy individuals may be associated with blunted reward responsiveness, but MS does not exacerbate this relationship. In fact, PwMS with depression may be more conscientious in their functioning and therefore perform better on cognitive task accuracy. Continued work should examine how reward processing and its underlying mechanisms may differ in depressed PwMS.