COMMENTARY

The Body and Mind Connection: The Latest Evidence

Nassir Ghaemi, MD, MPH

Disclosures

June 22, 2015

In This Article

Insulin, Inflammation, and the Link Between Body and Mind

At the recent American Psychiatric Association meeting in Toronto, Ontario, Canada, there was a presidential symposium[1] on how the mind affects the body and the body affects the mind—specifically, in terms of inflammation, depression, drugs, and disease.

The first presenter was Dr Roger S. McIntyre, professor of psychiatry and pharmacology, University of Toronto. His topic was "Cellular Energetics and Inflammation: Implications for Disease Modeling Opportunities for Common Connectopathies."

Dr McIntyre began by noting that from 1999 to 2009, mortality in bipolar illness and depression increased rather than decreased. Cognitive impairment may be an important barrier to health outcomes in mood illnesses. He noted that diabetes increases the risk for mild cognitive impairment (MCI). A new meta-analysis by his group showed that A1c is associated inversely with scores on the digit symbol substitution test, a measure of cognitive function; obesity also correlates with this measure. The Diabetes and Aging Study[2] showed that having both depression and diabetes markedly increased the risk for MCI, after correction for age, sex, and some clinical variables.

Insulin is a neurotrophic factor that has a major role in inhibiting apoptosis or cell death. Once it enters the brain, it is a critical neuropeptide. Ten percent to 20% of cases of Alzheimer disease are estimated to be the result of diabetes. Amyloid has proinflammatory and insulin-resistant effects—so once the process of dementia starts, the absence of insulin may hasten it.

Obesity also has been associated with reduced white-matter integrity, while insulin may be critical to normal brain circuitry. It's interesting to think that these biological relationships might have been the basis for past observation of benefit with insulin coma therapy in psychiatry in the early to mid-20th century. Recent studies indicate that intranasal insulin improves measures of cognitive function in amnestic MCI.

Glucagon-like peptide I is a drug given for diabetes, which is an insulin secretagogue. In the brain, it improves cognition in rat models. It gets into the brain much more effectively than other exogenously administered neurotrophic factors, such as brain-derived neurotrophic factor. It may have some potential as a new mood treatment.

Dr McIntyre also noted that obesity-related inflammation may be an important mechanism of worsening mood illnesses. The mechanism for how inflammation may worsen mood illness has to do with the kynurenine system. Tryptophan converts into kynurenine instead of serotonin under pathologic conditions of inflammation, which then produces harmful effects (via metabolites that are proinflammatory cytokines, such as quinolinic acid) that are directly toxic to dopaminergic neurons. Obese bipolar patients have been shown to have more kynurenine peripherally than nonobese bipolar patients, who are similar to healthy controls.

Minocycline, an antibiotic used for acne, improves executive function in schizophrenia.[3] A recent unpublished study by Dr McIntyre's group found that minocycline also improved bipolar depression in 27 persons, for both depressive and cognitive symptoms.[4]

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