Neurobiological Signatures of Major Depressive Disorder: A Narrative Review of Brain Structure and Function

Major Depressive Disorder (MDD) represents a multifactorial psychiatric condition characterized by complex neurobiological alterations involving frontostriatal circuits, limbic structures, and specialized neural networks. This narrative review synthesizes recent scientific evidence on the neural correlates of depression, focusing on functional and structural alterations documented through advanced neuroimaging techniques, with particular attention to neurobiological differences across major depressive subtypes. Recent studies have consistently identified dysfunctions primarily within the dorsolateral and ventromedial prefrontal cortex, accompanied by amygdala hyperactivation, hippocampal volume reduction, and anterior cingulate cortex alterations. Significant neural network modifications include hyperconnectivity of the Default Mode Network, impairment of the Executive Control Network, and dysfunction of the Salience Network. Neurophysiological markers reveal frontal alpha asymmetries and frontostriatal metabolic alterations. Emerging evidence demonstrates distinct neurobiological signatures across depressive subtypes, with melancholic depression showing pronounced reward circuit dysfunction, atypical depression displaying unique metabolic patterns, and persistent depressive disorder (dysthymia) exhibiting chronic structural alterations. These neural correlates are essential for advancing MDD understanding and developing personalized therapeutic interventions, including non-invasive neurostimulation techniques and target-specific pharmacological therapies, opening new avenues for translational research in neuropsychiatric contexts.