Massachusetts General Hospital
Harvard T.H. Chan School of Public Health
logo artistic effects M

RESEARCH

Depression and Comorbidity with Cardiometabolic Disorders

 MDD has a high rate of comorbidity with general medical disorders such as cardiovascular disease & metabolic syndrome, which exhibit significant sex differences. Thus there is a high cost to the medical system and society associated with depression that differs for men and women.

depression and mood reg

The Background 

The incidence of major depressive disorder (MDD) in women is twice that of men and sex differences emerge post-puberty or early adulthood Depression is the primary leading cause of disease burden worldwide.  We believe that risk factors for MDD occur prenatally during mid-to-late gestation.

Our current work focuses on investigating the pathophysiology of sex differences in the comorbidity of MDD and cardiometabolic disorders. Our hypotheses are based on the assumption that some of the key brain regions involved in the regulation of mood also regulate metabolism, the hypothalamic-pituitary-adrenal (HPA) axis, inflammatory responses, and autonomic nervous system (ANS), which controls heart rate and blood pressure. We propose that hormones and peptides that these shared brain regions express are important links in understanding the comorbidity of MDD and risk for cardiometabolic disorders.

We study fetal and neonatal neurodevelopmental pathways that we hypothesize are implicated in sex-dependent adult brain abnormalities and physiologic dysfunctions.

In a previous multi-site, collaborative, interdisciplinary, basic and translational research center examining the biological causes of sex differences in depression, we tested hypotheses regarding the roles of adrenal and gonadal signaling pathways regulating growth factors and their interactions with GABA-ergic, glutamatergic, and nitric oxide (NO) mechanisms in the development of regions in the stress response circuitry (known to be abnormal in depression). The human studies in this project involved functional brain imaging, endocrinology, immunology, and genetics. Currently, we are exploring the degree to which relationships between HPA- and HP-gonadal-axis hormones, GABA, and brain activity in response to psychosocial stress contribute to explaining sex differences in the emergence of MDD in young adults (age 18-25) using multimodal imaging. We believe that findings from this work will lead to the development of novel sex-dependent treatments and/or prevention strategies