Impact of insulin and insulin resistance on brain dopamine signalling and reward processing – An underexplored mechanism in the pathophysiology of depression?
Gruber J, Hanssen R, Qubad M, Bouzouina A, Schack V, Sochor H, Schiweck C, Aichholzer M, Matura S, Slattery DA, Zopf Y, Borgland SL, Reif A, Thanarajah SE (2023)
Publication Type: Journal article, Review article
Publication year: 2023
Journal
Book Volume: 149
Article Number: 105179
DOI: 10.1016/j.neubiorev.2023.105179
Abstract
Type 2 diabetes and major depressive disorder (MDD) are the leading causes of disability worldwide and have a high comorbidity rate with fatal outcomes. Despite the long-established association between these conditions, the underlying molecular mechanisms remain unknown. Since the discovery of insulin receptors in the brain and the brain's reward system, evidence has accumulated indicating that insulin modulates dopaminergic (DA) signalling and reward behaviour. Here, we review the evidence from rodent and human studies, that insulin resistance directly alters central DA pathways, which may result in motivational deficits and depressive symptoms. Specifically, we first elaborate on the differential effects of insulin on DA signalling in the ventral tegmental area (VTA) - the primary DA source region in the midbrain - and the striatum as well as its effects on behaviour. We then focus on the alterations induced by insulin deficiency and resistance. Finally, we review the impact of insulin resistance in DA pathways in promoting depressive symptoms and anhedonia on a molecular and epidemiological level and discuss its relevance for stratified treatment strategies.
Authors with CRIS profile
Yurdagül Zopf
Professur für Integrative Medizin mit dem Schwerpunkt Ernährungsmedizin (Stiftungsprofessur der Hector Stiftung II gGmbH)
Involved external institutions
Universitätsklinikum Frankfurt am Main (KGU)
Germany (DE)
Universität zu Köln
Germany (DE)
University of Calgary
Canada (CA)
Germany (DE)
Universität zu Köln
Germany (DE)
University of Calgary
Canada (CA)
How to cite
APA:
Gruber, J., Hanssen, R., Qubad, M., Bouzouina, A., Schack, V., Sochor, H.,... Thanarajah, S.E. (2023). Impact of insulin and insulin resistance on brain dopamine signalling and reward processing – An underexplored mechanism in the pathophysiology of depression? Neuroscience and Biobehavioral Reviews, 149. https://doi.org/10.1016/j.neubiorev.2023.105179
MLA:
Gruber, Judith, et al. "Impact of insulin and insulin resistance on brain dopamine signalling and reward processing – An underexplored mechanism in the pathophysiology of depression?" Neuroscience and Biobehavioral Reviews 149 (2023).
BibTeX: Download