Structural and functional models of depression: from sub-types to substrates

OBJECTIVE: To present a functional model of depression facilitating research and clinical understanding. METHOD: The authors conducted a systematic literature search and reviewed articles pertaining to the neurochemistry and pathophysiology of depressive disorders, focusing on the contribution made by the principal monoamines to three differing depressive structural sub-types (i.e. psychotic, melancholic and non-melancholic). RESULTS: We suggest that the three structural depressive subtypes appear functionally underpinned by differential contributions of serotonergic, noradrenergic and dopaminergic neurotransmitters, so influencing phenotypic distinction (our structural model) and allowing an aetiological model to be derived with treatment specificity implications. CONCLUSION: The functional model logically iterates with the structural model of depression and provides a useful framework for conceptualizing the depressive disorders. This model provides a logic for distinguishing between principal depressive subtypes, pursuing their functional underpinnings and explaining treatment differential effects across the three sub-types.