Background: Individuals with appetite-related divergent phenotypes of major depressive disorder (MDD) exhibit differences in clinical outcomes and medical comorbidities. Preclinical evidence suggests that stress-related disruption in mesolimbic brain regions may lead to altered eating behaviors, but the mechanism underlying interactions between stress and reward processing in MDD is largely understudied. The current study examined the effects of acute stress on mesolimbic reward responsivity to a monetary incentive delay (MID) task in MDD phenotypes and healthy controls.
Methods: Forty healthy control subjects (HC; 20F/20M), 29 Hypophagic MDD (Hypo – decreased appetite/weight loss; 15F/14M), and 21 Hyperphagic MDD (Hyper – increased appetite/weight gain; 9F/12M) (all unmedicated) completed two study visits: one including a stress (S) version and the other including a no-stress (NS) version of the Maastricht Acute Stress Test (MAST). Both visits involved pre- and post-MAST measurements of cortisol, mood ratings, and an fMRI scan including a monetary incentive delay task. Data were analyzed using SPSS and SPM12.
Results: For cortisol responsivity, there was a Time x Visit interaction (p<0.001), driven by higher cortisol response to the MAST during the S visit, but not at the NS visit. During the MID, for anticipation of monetary reward vs. neutral, there a main effect of Group in the caudate (p<0.001; Hyper>HC), insula (p=0.007; Hyper, Hypo>HC), and NAcc (p<0.001; Hyper, Hypo>HC), of Visit during anticipation in the VMPFC (p=0.05; S>NS in HC and Hypo), and a Group x Visit interaction trend in the hypothalamus (p=0.06; NS>S in Hyper). During receipt of monetary reward vs. neutral, there was a main effect of Group in the left pallidum (p=0.023; HC, Hypo>Hyper), of Visit in the VMPFC (p=0.049; S>NS in HC), and a Group x Visit interaction in the right pallidum (p=0.009; NS>S in HC; S>NS in Hypo).
Conclusions: These data indicate stress-induced alterations of mesolimbic circuitry activation in appetite phenotypes of MDD, particularly in the hypothalamus and right pallidum, which provide insight into novel neuroanatomical targets in the development of treatments for MDD phenotypes.
Live Zoom Session – March 9th
Julia Hall, Hyeon Min Ahn, PhD, Jill M. Goldstein, PhD, Daniel G. Dillon, PhD, Diego A. Pizzagalli, PhD, Laura M. Holsen, PhD
Laura M. Holsen, PhD