Shared metabolic and neuroimmune mechanisms underlying Type 2 Diabetes Mellitus and Major Depressive Disorder

Eduardo Duarte-Silva; Michel Gomes de Melo; Michael Maes; Adriano José Maia Chaves Filho; Danielle Macedo; Christina Alves Peixoto

doi:10.1016/j.pnpbp.2021.110351

Shared metabolic and neuroimmune mechanisms underlying Type 2 Diabetes Mellitus and Major Depressive Disorder

Prog Neuropsychopharmacol Biol Psychiatry. 2021 Dec 20:111:110351. doi: 10.1016/j.pnpbp.2021.110351. Epub 2021 May 14.

Authors

Eduardo Duarte-Silva¹, Michel Gomes de Melo², Michael Maes³, Adriano José Maia Chaves Filho⁴, Danielle Macedo⁵, Christina Alves Peixoto⁶

Affiliations

¹ Laboratory of Ultrastructure, Aggeu Magalhães Institute (IAM), PE, Brazil; Postgraduate Program in Biosciences and Biotechnology for Health (PPGBBS), Oswaldo Cruz Foundation (FIOCRUZ-PE)/Aggeu Magalhães Institute (IAM), Recife, PE, Brazil; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Recife, PE, Brazil. Electronic address: eduardo.pduartesilva@gmail.com.
² Laboratory of Ultrastructure, Aggeu Magalhães Institute (IAM), PE, Brazil; Postgraduate Program in Biological Sciences (PPGCB), Federal University of Pernambuco (UFPE), Brazil.
³ Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria; IMPACT Strategic Research Center, Deakin University, Geelong, Australia.
⁴ Neuropsychopharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
⁵ Neuropsychopharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil; National Institute for Translational Medicine (INCT-TM, CNPq), Ribeirão Preto, Brazil.
⁶ Laboratory of Ultrastructure, Aggeu Magalhães Institute (IAM), PE, Brazil; National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM, CNPq), Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. Electronic address: peixoto.christina@gmail.com.

PMID: 34000290
DOI: 10.1016/j.pnpbp.2021.110351

Abstract

Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disease with symptoms that go beyond the domain of glucose metabolism. In fact, research has shown that T2DM is accompanied by neurodegeneration and neuroinflammation. Interestingly, Major Depressive Disorder (MDD), a mood disorder characterized mainly by depressed mood and anhedonia is a key feature of T2DM. A body of evidence demonstrates that there are many shared neuroimmune mechanisms underlying the pathophysiology of T2DM and MDD. Therefore, here we review the state-of-art regarding the underlying factors common to both T2DM and MDD. Furthermore, we briefly discuss how depressive symptoms in diabetic patients could be tackled by using novel therapeutic approaches uncovered by these shared mechanisms. Understanding the comorbidity of depression in diabetic patients is essential to fully address T2DM pathophysiology and treatment.

Keywords: Major Depressive Disorder; Pathogenesis; Therapies; Type 2 Diabetes Mellitus.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Anhedonia / physiology
Blood-Brain Barrier / physiopathology
Comorbidity*
Depressive Disorder, Major* / immunology
Depressive Disorder, Major* / physiopathology
Diabetes Mellitus, Type 2* / immunology
Diabetes Mellitus, Type 2* / physiopathology
Endocannabinoids / immunology
Gastrointestinal Microbiome / immunology
Humans
Inflammation / immunology*
Metabolic Diseases / physiopathology
Neuroimmunomodulation*

Substances

Endocannabinoids