Brain insulin resistance: A treatment target for cognitive impairment and anhedonia in depression

Julia A Hamer; Daniela Testani; Rodrigo B Mansur; Yena Lee; Mehala Subramaniapillai; Roger S McIntyre

doi:10.1016/j.expneurol.2019.01.016

Brain insulin resistance: A treatment target for cognitive impairment and anhedonia in depression

Exp Neurol. 2019 May:315:1-8. doi: 10.1016/j.expneurol.2019.01.016. Epub 2019 Jan 26.

Authors

Julia A Hamer¹, Daniela Testani², Rodrigo B Mansur¹, Yena Lee¹, Mehala Subramaniapillai², Roger S McIntyre³

Affiliations

¹ Mood Disorders Psychopharmacology Unit (MDPU), Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
² Mood Disorders Psychopharmacology Unit (MDPU), Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
³ Mood Disorders Psychopharmacology Unit (MDPU), Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada; Brain and Cognition Discovery Foundation (BCDF), Toronto, Ontario, Canada. Electronic address: roger.mcintyre@uhn.ca.

PMID: 30695707
DOI: 10.1016/j.expneurol.2019.01.016

Abstract

Type 2 Diabetes Mellitus (T2DM) and Major Depressive Disorder (MDD) are leading causes of disability worldwide. Indeed, both are costly and burdensome diseases at both individual and socio-economic levels. Notably, there are similar pathophysiological elements, which might explain the overlap in phenotypic symptoms and the high rate of comorbidity. Brain insulin resistance is a shared metabolic abnormality amongst many individuals with T2DM and MDD. Patients with either or both diseases often exhibit disturbances in cognition and mood, as well as the presence of anhedonia-like symptoms. However, individuals with T2DM with high glycemic control have reduced cognitive and depressive symptom burden. Based on this evidence, it is possible that repurposing therapies approved for treating insulin resistance may be useful in treating cognitive and anhedonia symptoms in depression. The objective of this review is to discuss the relationship between brain insulin resistance and depression, as well as possible disease modifying therapeutic agents targeting insulin signalling.

Keywords: Anhedonia; Brain insulin resistance; Cognition; Depression; Mood disorders.

Publication types

Review

MeSH terms

Anhedonia*
Brain Chemistry*
Cognitive Dysfunction / drug therapy*
Cognitive Dysfunction / etiology
Cognitive Dysfunction / metabolism*
Depression / complications
Depression / drug therapy*
Depression / metabolism*
Depressive Disorder, Major
Humans
Insulin Resistance*