A significant health burden associated with major depressive disorder (MDD), such as changes in appetite and body weight, is present. The development of biomarkers that may be reliably generalized to most patients has been complicated by the heterogeneity of depressive symptoms, necessitating symptom-based mapping. Using resting-state functional connectivity (FC) to specify contributions and effects on disease biomarkers, characterize the functional architecture of the reward circuit serving rises vs. reductions in hunger and body weight in individuals with MDD.

Functional magnetic resonance imaging (fMRI) data from the Marburg-Münster FOR 2107 Affective Disorder Cohort Research (MACS), gathered between September 2014 and November 2016, were used in the case-control study. From March 2018 to June 2022, cross-sectional data from patients with MDD (n = 407) and healthy control individuals (n = 400) were evaluated. fMRI was used to study changes in hunger during the depressed episode and their relationship to FC. A sparse symptom-specific elastic-net model was constructed with 10-fold cross-validation using the nucleus accumbens (NAcc) as the seed of the reward circuit. Associations with opposing changes in appetite were mapped using this method.

The mean (SD) age of the 407 patients with MDD was 36.79 (13.4) years, and 249 (61.2%) of them were female. A decrease in NAcc-based FC to the hippocampus and ventromedial prefrontal cortex (vmPFC) was linked to a decrease in hunger (vmPFC: bootstrap r = -0.15; 95% CI, 0.05-0.26). Contrarily, greater hunger was linked to decreased NAcc-based FC to the insular ingestive cortex (bootstrap r = -0.14; 95% CI, 0.24 to 0.04). Importantly, the cross-validated elastic-net model captured variations in appetite based on NAcc FC and increased explained variance with increasing symptom severity (all patients: bootstrap r = 0.24; 95% CI, 0.16-0.31; patients with Beck Depression Inventory score of 28 or higher: bootstrap r = 0.42; 95% CI, 0.25-0.58). However, NAcc FC did not categorize diagnosis (MDD vs. healthy control).

In the study, NAcc-based FC captured significant individual variations in appetite and body weight in depressed individuals that can be used for customized prediction. NAcc-based FC did not outperform chance levels in the categorization of diagnoses, nevertheless. Such symptom-specific relationships underlined the need to map biomarkers onto more focused aspects of psychopathology to enhance the diagnosis and care of MDD.

Reference: jamanetwork.com/journals/jamapsychiatry/article-abstract/2795624