Authors: McIntyre, Roger¹; Soczynska, Joanna²; Konarski, Jakub²; Woldeyohannes, Hanna³; Law, Candy³; Miranda, Andrew³; Fulgosi, Don; Kennedy, Sidney⁴

Source: Annals of Clinical Psychiatry (after Jan 1, 2004), Volume 19, Number 4, October 2007 , pp. 257-264(8)

Publisher: Informa Healthcare

Abstract:

Background. A nascent explanatory theory regarding the pathophysiology of major depressive disorder posits that alterations in metabolic networks (e.g., insulin and glucocorticoid signaling) mediate allostasis. Method. We conducted a PubMed search of all English-language articles published between January 1966 and September 2006. The search terms were: neurobiology, cognition, neuroprotection, inflammation, oxidative stress, glucocorticoids, metabolic syndrome, diabetes mellitus, insulin, and antidiabetic agents, cross-referenced with the individual names of DSM-III-R/IV/-TR-defined mood disorders. The search was augmented with a manual review of article reference lists; articles selected for review were determined by author consensus. Results. Disturbances in metabolic networks: e.g., insulin-glucose homeostasis, immuno-inflammatory processes, adipokine synthesis and secretion, intra-cellular signaling cascades, and mitochondrial respiration are implicated in the pathophysiology, brain volumetric changes, symptomatic expression (e.g., neurocognitive decline), and medical comorbidity in depressive disorders. The central nervous system, like the pancreas, is a critical modulator of the metabolic milieu and is endangered by chronic abnormalities in metabolic processes. We propose the notion of "metabolic syndrome type II" as a neuropsychiatric syndrome in which alterations in metabolic networks are a defining pathophysiological component. Conclusion. A comprehensive management approach for depressive disorders should routinely include opportunistic screening and primary prevention strategies targeting metabolically mediated comorbidity (e.g., cardiovascular disease). Innovative treatments for mood disorders, which primarily target aberrant metabolic networks, may constitute potentially novel, and disease-modifying, treatment avenues.

Keywords: Major depressive disorder; Bipolar disorder; Diabetes mellitus; Pathophysiology; Metabolic syndrome

Document Type: Research article

DOI: http://dx.doi.org/10.1080/10401230701653377

Affiliations: 1: Mood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, Canada 2: Mood Disorders Psychopharmacology Unit, University Health Network, and Institute of Medical Science, University of Toronto, Toronto, ON, Canada 3: Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada 4: Department of Psychiatry and Institute of Medical Science, University of Toronto, and Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada

Publication date: 2007-10-01

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