Should Depressive Syndromes Be Reclassified as "Metabolic Syndrome Type II"?

• Published in: Annals of clinical psychiatry 2007-10, Vol.19 (4), p.257-264
• Main Authors: McIntyre, Roger S, Soczynska, Joanna K, Konarski, Jakub Z, Woldeyohannes, Hanna O, Law, Candy W Y, Miranda, Andrew, Fulgosi, Don, Kennedy, Sidney H
• Format: Article
• Language: English
• Subjects: Aged; Bipolar Disorder - classification; Bipolar Disorder - diagnosis; Bipolar Disorder - metabolism; Brain - anatomy & histology; Brain - diagnostic imaging; Brain - physiopathology; Depressive Disorder - diagnosis; Depressive Disorder - metabolism; Depressive Disorder - physiopathology; Diagnosis, Differential; Diagnostic and Statistical Manual of Mental Disorders; Female; Glucocorticoids - metabolism; Humans; Insulin - metabolism; Magnetic Resonance Imaging; Male; Metabolic Syndrome - diagnosis; Metabolic Syndrome - metabolism; Metabolic Syndrome - physiopathology; Oxidative Stress - physiology; Positron-Emission Tomography; Signal Transduction - physiology
• ISSN: 1040-1237; 1547-3325; 1573-3238
• DOI: 10.1080/10401230701653377

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. 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. 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. 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.