Neurochemical and Energetic Alterations in Depression: A Narrative Review of Potential PET Biomarkers

Depression is a heterogeneous neuropsychiatric disorder with variable clinical presentation and response to treatment. This variability has motivated interest in neuroimaging biomarkers capable of disease characterization and therapeutic prediction. Positron emission tomography (PET) enables in vivo assessment of cerebral glucose utilization, neurochemical targets, inflammatory markers, and cerebral blood flow. This narrative review synthesizes PET studies conducted predominantly in adults with major depressive disorder diagnosed using DSM-based criteria, with bipolar disorder included only when imaging was performed during a depressive episode. Studies were identified through a structured, non-systematic literature search of major databases. Depression is consistently associated with regionally specific PET alterations within cortico-limbic and cortico-striatal circuits; studies most frequently report reduced glucose-derived PET measures in prefrontal and anterior cingulate regions at baseline, with treatment responders showing relative increases or redistribution of these measures following interventions. Neurochemical PET studies demonstrate altered receptor, transporter, or enzyme-related binding in serotonergic, dopaminergic, and noradrenergic systems, while neuroinflammatory and perfusion studies reveal regionally increased PET signals in subsets of patients. Overall, PET findings indicate convergent, region-specific and neurochemical alterations associated with depressive episodes and treatment response. Interpretation is constrained by methodological and clinical heterogeneity, underscoring the need for harmonized, longitudinal PET studies.