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Major depressive disorder arises from complex interactions between genetic variation, environmental influences, and receptor-mediated signaling that regulate mood, cognition, and stress resilience. This review synthesizes recent empirical evidence examining how genetic and epigenetic variation intersect with receptor function, binding, and expression to shape depressive phenotypes and treatment outcomes. Findings are organized into ten interconnected biochemical domains: monoaminergic, glutamatergic, GABAergic, neuropeptidergic, hormonal-metabolic, immuno-inflammatory, neurotrophic-plasticity, epigenetic/gene–environment, opioidergic and emerging therapeutics, with summary tables included for most domains to aid cross-system interpretation. Across these pathways, convergent receptor–gene relationships highlight integrative themes such as multi-omics approaches, in vivo receptor imaging, single-cell resolution mapping, and circuit-level analyses. Collectively, these findings position receptor systems as central hubs linking genetic risk and environmental modulation, providing a translational framework for receptor-centric, precision-psychiatry interventions.
Oatu et al. (Sun,) studied this question.