 We are currently not in a position to sufficiently homogenize subgroups of adults with mood disorder on the basis of any single or combinatorial biomarkers. It is also unlikely that alterations in GLP-1 receptor function, and the proposed model herein, is sufficiently explanatory to all sub-populations of adults with mood disorders. Instead, we propose that adults with mood disorders, who have co-existing metabolic disorders e.g. type 2 diabetes mellitus, would be more likely to have a brain illness that is influenced by i.e. cause, consequence or both alterations in cellular bioenergetics. Moreover, convergent evidence suggest that GLP-1 receptor function may be, at least partially, dependent on glucose levels andor insulin sensibility. It is a separate, yet testable, hypothesis that subpopulations enriched on the basis of having metabolic comorbidity i.e. insulin resistance may be more responsive to an intervention that targets a metabolic pathway. 