Abstract
To overview historical ascriptions and the current nosological status of melancholia, before reporting diagnostic strategy, biological marker and treatment studies. As melancholia has never been satisfactorily differentiated by reliance on symptoms, strategies that adopt a more prototypic approach and incorporate illness correlates in conjunction with symptoms appear to provide greater precision in differentiating melancholic and nonmelancholic depression. An early indicative biological marker--hyperactive Hypothalamic-Pituitary-Adrenal axis functioning--remains supported, whereas a number of other recently proposed candidate markers require clarification. Implications for treatment from recent clinical trials are also discussed. We note that the Diagnostic and Statistical Manual 5 (DSM-5) definition of melancholia [as for Diagnostic and Statistical Manual IV (DSM-IV)] may be limited in its differentiating capacity and so compromise research into melancholia's causes and treatments. Clarifying melancholia's status, primary causes and differential treatment responsiveness awaits more precise definition of this depressive condition.
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