Functional connectivity of the reward circuit predicts changes in appetite in depression

Importance: Major depressive disorder (MDD) is characterized by a substantial burden on health including changes in appetite and body weight. Heterogeneity of depressive symptoms has hampered the identification of robust biomarkers thus limiting the potential for personalized treatment. Objective: To define the functional architecture of the reward circuit subserving increases versus decreases in appetite and body weight in MDD by specifying their respective contributions and their influence on disease biomarkers using resting-state functional connectivity (FC).Design, Setting, & Participants: Functional magnetic resonance imaging (fMRI) data were from the Marburg-Münster FOR 2107 Affective Disorder Cohort (MACS) study, collected between September 2014 and November 2016. Cross-sectional data of patients with MDD (NMDD=407) and healthy control participants (NHC=400) were analyzed.Main outcomes and measures: We examined dimensional changes in appetite during the depressive episode and their association with functional connectivity of the reward circuit at rest using fMRI. By taking the nucleus accumbens (NAcc) as seed, we mapped associations with opposing changes in appetite and build a sparse symptom-specific prediction model using elastic net with tenfold cross-validation.Results: Among 407 MDD patients (mean [SD] age, 36.79 [13.4] years; 249 women [61%]), reduced NAcc-based FC to the ventromedial prefrontal cortex (vmPFC) and the hippocampus was associated with reduced appetite (bootstrap r [95% CI], vmPFC: r = .13 [.02, .23]; hippocampus r = .15 [.05, .26]). In contrast, reduced NAcc-based FC to the insular ingestive cortex was associated with increased appetite (bootstrap r [95% CI], r = -.14 [-.24, -.04]). Critically, the cross-validated elastic net model predicted changes in appetite based on NAcc FC and explained variance increased with increasing symptom severity (bootstrap mean [95% CI], all patients r = .24 [.16, .31, BDI ≥ 28 r = .42 [.25, .58]). In contrast, NAcc FC did not predict diagnosis (MDD vs. HC).Conclusions and relevance: Our results show that the FC of the reward circuit reflects important individual differences in appetite and body weight in depression that can be leveraged for personalized prediction. However, classification of diagnosis based on FC of the reward circuit did not exceed chance levels. Such symptom-specific associations emphasize the need to map biomarkers onto more confined facets of psychopathology to improve the classification and treatment of patients with MDD.