Review article Pathophysiological mechanisms involved in the relationship between diabetes and major depressive disorder Gislaine Z. Réus a, ⁎, Maria Augusta B. dos Santos a , Ana Paula Strassi a , Helena M. Abelaira a , Luciane B. Ceretta b , João Quevedo a,c,d,e a Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil b Programa de Pós-graduação em Saúde Coletiva, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil c Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA d Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA e Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA abstract article info Article history: Received 23 May 2017 Received in revised form 28 June 2017 Accepted 30 June 2017 Available online 01 July 2017 Diabetes mellitus (DM) and major depressive disorder (MDD) are diseases that are expanding globally. Separate- ly, each presents with several comorbidities for patients. When the two diseases present simultaneously in the same subject, there is a drastic worsening in the quality of life of the patient. This study reviewed the literature relating to the relationship between MDD and DM, bringing forward studies showing that DM develops due to MDD, and others that report the opposite. According to the studies reviewed, DM and MDD are both debilitating conditions that are associated with significant morbidity, mortality, and healthcare costs. When these two dis- eases coexist, the association results in a decreased adherence to treatment, poor metabolic control, higher rates of complications, a decrease in the quality of life for the patient, increased healthcare use and cost, increased disability and lost productivity, and an increased risk of death. Therefore, it becomes essential that there are larg- er studies targeting the association of these two diseases, as for the patient, preventing even one of them will en- sure improvements in their quality of life. © 2016 Elsevier Inc. All rights reserved. Keywords: Diabetes mellitus Hypothalamic-pituitary-adrenal axis Monoamines Major depressive disorder Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 1.1. Major depressive disorder (MDD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 1.2. Diabetes mellitus (DM) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 1.3. MDD and DM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 2. Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 Conflicts of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 1. Introduction It is estimated that in 2020, chronic disease will be responsible for the majority of deaths and disabilities worldwide. However, one of the main challenges for the scientific community is comorbidity, which is a clinical condition where two or more diseases occur simultaneously in the same person. For example, MDD and DM that are both highly prevalent conditions, with DM having already affected around 346 mil- lion people around the world [1], and MDD affecting over 350 million people worldwide, both of which have a significant impact on health outcomes [2]. Both MDD and DM are extremely disabling, since they are closely associated with other diseases such as; Diabetic retinopathy, Life Sciences 183 (2017) 78–82 ⁎ Corresponding author at: Laboratory of Neurosciences, University of Southern Santa Catarina, Criciuma, SC 88806-000, Brazil. E-mail address: gislainereus@unesc.net (G.Z. Réus). http://dx.doi.org/10.1016/j.lfs.2017.06.025 0024-3205/© 2016 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Life Sciences journal homepage: www.elsevier.com/locate/lifescie