Journal
PSYCHIATRY AND CLINICAL NEUROSCIENCES
Volume 69, Issue 10, Pages 597-608Publisher
WILEY
DOI: 10.1111/pcn.12299
Keywords
dopamine; hypothalamic-pituitary-adrenal axis; inflammation; stress; tryptophan
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Funding
- NCNP [24-11]
- Japan Society for the Promotion of Science (JSPS) [25253075]
- Grants-in-Aid for Scientific Research [25253075] Funding Source: KAKEN
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The pathophysiology of major depressive disorder (MDD) remains elusive, and there is no established biochemical marker used in the daily clinical setting. This situation may result in part from the heterogeneity of MDD, which might include heterogeneous subgroups with different biological mechanisms. In this review, we discuss three promising biological systems/markers to potentially subtype MDD: the dopamine system, the hypothalamic-pituitary-adrenal axis, and chronic inflammatory markers. Several lines of evidence suggest that a facet of MDD is a dopamine agonist-responsive subtype. Focusing on the hypothalamic-pituitary-adrenal axis, depressive spectrum disorders show hypercortisolism to hypocortisolism, which could be detected by hormonal challenge tests, such as the dexamethasone/corticotrophin-releasing hormone test. Finally, accumulating evidence suggests that at least some MDD patients show characteristics similar to those of chronic inflammatory diseases, including neuroinflammatory markers and reduced tryptophan due to the increased activation of the tryptophan-kynurenine pathway. Future studies should examine the inter-relations between these systems/markers to subtype and integrate the pathophysiology of MDD.
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