Aperçu du projet

Individuals with depression are 60% more likely to develop type 2 diabetes (T2D) compared to the general population. Insulin resistance–a key feature of T2D–is associated with greater depressive symptom severity and worse cognition. This bidirectional relationship has shifted the understanding of depression as a metabolic disorder.

This project aims to understand the link between T2D and depression by studying insulin action in the brain. Researchers have only recently discovered that insulin has several important effects on the brain, such as mood, cognition, appetite, and blood sugar regulation. Each of these functions is related to the biology of depression. Hence, it is possible that impaired insulin action in the brain may be the mechanism that links T2D and depression. This is supported by early evidence that has shown that disrupting insulin action in the brain caused depression-like behaviour in mice and that common diabetes treatments show initial promise in reducing depressive symptoms through their effects on the brain.

Findings from our pilot study support this hypothesis. We utilized a validated neuroimaging protocol that leverages the property of intranasal (administered through the nose) insulin to induce changes in connectivity between brain regions. We identified adolescents with depression to have a weaker response to insulin administered through the nose, as measured through less connectivity between brain regions involved in cognitive and emotional regulation processes, when compared to controls without mental health disorders. Weaker responses to insulin in the brain were associated with lower subjective cognitive function and predicted greater depression severity in participants with depression, emphasizing the clinical significance of findings.

Utilizing a similar approach, this proposed study will seek to validate and expand these results and further delve into the biological underpinnings of this well-known association between diabetes and depression in 36 youth (age 15-24) with major depressive disorder (MDD) and 36 healthy controls. Overall, demonstrating disrupted brain insulin action can provide novel insights into mechanisms underlying the relationship between depression and T2D, and help uncover modifiable risk factors that can be targeted at the earliest stages of the illness.

Chef d'équipe

Mahavir Agarwal , Centre for Addiction and Mental Health Foundation

Partenaire et Donateurs

Diabetes Canada