Insulin dysfunction and allostatic load in bipolar disorder

Abstract

Bipolar disorder (BD) is associated with substantial morbidity, as well as premature mortality. Available evidence indicates that ‘stress-sensitive’ chronic medical disorders, such as cardiovascular disease, obesity and Type 2 diabetes mellitus, are critical mediators and/or moderators of BD. Changes in physiologic systems implicated in allostasis have been proposed to impact brain structures and neurocognition, as well as medical comorbidity in this population. For example, abnormalities in insulin physiology, for example, insulin resistance, hyperinsulinemia and central insulinopenia, are implicated as effectors of allostatic load in BD. Insulin’s critical role in CNS physiological (e.g., neurotrophism and synaptic plasticity) and pathophysiological (e.g., neurocognitive deficits, pro-apoptosis and amyloid deposition) processes is amply documented. This article introduces the concept that insulin is a mediator of allostatic load in the BD and possibly a therapeutic target.

Keywords::

• allostatic load
• bipolar disorder
• cognition
• cytokines
• early life stress
• general medical comorbidities
• HPA
• insulin
• neuroplasticity
• oxidative stress

Financial & competing interests disclosure

Roger S McIntyre has received research grants from the Stanley Medical Research Institute, the National Alliance for Research on Schizophrenia and Depression (NARSAD), Eli Lilly, Janssen-Ortho, Shire, AstraZeneca and Pfizer. He is on the advisory boards for the following: AstraZeneca, Bristol-Myers Squibb, France Foundation, GlaxoSmithKline, Janssen-Ortho, Solvay/Wyeth, Eli Lilly, Organon, Lundbeck, Biovail, Pfizer, Shire, Schering-Plough and Merck, and on the speakers bureau for the following: Janssen-Ortho, Astra-Zeneca, Eli Lilly, Lundbeck, Biovail and Merck. He has also carried out CME activities for the following: AstraZeneca, Bristol-Myers Squibb, France Foundation, I3CME, Solvay/Wyeth, Physicians’ Postgraduate Press, CME Outfitters, Optum Health, Schering-Plough, Merck and Eli Lilly and received travel funds from Bristol-Myers Squibb. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.