Key points Does the functional architecture of the reward circuit reflect whether patients with depression experience increases or decreases in appetite and weight? Findings In this case-control study, using neuroimaging, reduced appetite in patients with depression was associated with reduced functional connectivity between the nucleus accumbens and the ventromedial prefrontal cortex, as well as the hippocampus. In contrast, reduced connectivity of the nucleus accumbens with the insular ingestive cortex was associated with increased appetite, and cross-validated elastic network models reflected appetite-related symptoms if severity was high. Meaning Differential changes in appetite were reflected in the functional architecture of the reward circuit, but the associations increased with symptom severity. |
Importance
Major depressive disorder (MDD) is characterized by a substantial health burden, including changes in appetite and body weight. The heterogeneity of depressive symptoms has made it difficult to identify biomarkers that generalize robustly to most patients, requiring symptom-based mapping.
Aim
To define the functional architecture of the reward circuitry that favors increases versus decreases in appetite and body weight in patients with MDD by specifying its contributions and influence on disease biomarkers using resting-state functional connectivity (FC).
Design, environment and participants
In this case-control study, functional magnetic resonance imaging (fMRI) data were taken from the Marburg-Münster FOR 2107 Affective Disorders Cohort Study (MACS), collected between September 2014 and November 2016. Cross-sectional data of MDD patients (n = 407) and healthy control participants (n = 400) were analyzed from March 2018 to June 2022.
Main results and measures
Changes in appetite during the depressive episode and its association with HR were examined using fMRI. Taking the nucleus accumbens (NAcc) as the seed of the reward circuit, associations with opposite changes in appetite were mapped and a sparse symptom-specific elastic network model was constructed with 10-fold cross-validation.
Results
Among 407 patients with MDD, 249 (61.2%) were women and the mean (SD) age was 36.79 (13.4) years. Reduced NAcc-based FC in the ventromedial prefrontal cortex (vmPFC) and hippocampus was associated with reduced appetite (vmPFC: bootstrap r = 0.13; 95% CI, 0.02-0.23; hippocampus: bootstrap r = 0.15; 95% CI, 0.05-0.26).
In contrast, reduced NAcc-based FC in the insular ingestive cortex was associated with increased appetite (bootstrap r = −0.14; 95% CI, −0.24 to −0.04). Critically, the cross-validated elastic network model reflected changes in appetite based on NAcc FC and explained that the variance increased with increasing symptom severity (all patients: bootstrap r = 0.24; 95% CI, 0.16-0.31; patients with a Beck Depression Inventory score of 28 or more: bootstrap r = 0.42; 95% CI, 0.25-0.58). In contrast, NAcc FC did not classify diagnosis (MDD vs healthy control).
Conclusions and relevance
In this study, NAcc-based FC reflected important individual differences in appetite and body weight in patients with depression that can be exploited for personalized prediction. However, diagnostic classification using NAcc-based FC did not exceed chance levels. Such symptom-specific associations emphasize the need to map biomarkers to more confined facets of psychopathology to improve the classification and treatment of MDD.
