A Potential Role for MAGI-1 in the Bi-Directional Relationship Between Major Depressive Disorder and Cardiovascular Disease

Curr Atheroscler Rep. 2024 Sep;26(9):463-483. doi: 10.1007/s11883-024-01223-5. Epub 2024 Jul 3.

Abstract

Purpose of review: Major Depressive Disorder (MDD) is characterized by persistent symptoms such as fatigue, loss of interest in activities, feelings of sadness and worthlessness. MDD often coexist with cardiovascular disease (CVD), yet the precise link between these conditions remains unclear. This review explores factors underlying the development of MDD and CVD, including genetic, epigenetic, platelet activation, inflammation, hypothalamic-pituitary-adrenal (HPA) axis activation, endothelial cell (EC) dysfunction, and blood-brain barrier (BBB) disruption.

Recent findings: Single nucleotide polymorphisms (SNPs) in the membrane-associated guanylate kinase WW and PDZ domain-containing protein 1 (MAGI-1) are associated with neuroticism and psychiatric disorders including MDD. SNPs in MAGI-1 are also linked to chronic inflammatory disorders such as spontaneous glomerulosclerosis, celiac disease, ulcerative colitis, and Crohn's disease. Increased MAGI-1 expression has been observed in colonic epithelial samples from Crohn's disease and ulcerative colitis patients. MAGI-1 also plays a role in regulating EC activation and atherogenesis in mice and is essential for Influenza A virus (IAV) infection, endoplasmic reticulum stress-induced EC apoptosis, and thrombin-induced EC permeability. Despite being understudied in human disease; evidence suggests that MAGI-1 may play a role in linking CVD and MDD. Therefore, further investigation of MAG-1 could be warranted to elucidate its potential involvement in these conditions.

Keywords: Bi-directional relationship; Cardiovascular disease; Endothelial permeability; MAGI-1; Major depressive disorder; Post-translational modifications.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing* / genetics
  • Adaptor Proteins, Signal Transducing* / metabolism
  • Animals
  • Cardiovascular Diseases* / genetics
  • Cardiovascular Diseases* / metabolism
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Depressive Disorder, Major* / genetics
  • Depressive Disorder, Major* / metabolism
  • Guanylate Kinases* / genetics
  • Guanylate Kinases* / metabolism
  • Humans
  • Polymorphism, Single Nucleotide

Substances

  • Adaptor Proteins, Signal Transducing
  • Guanylate Kinases
  • MAGI1 protein, human
  • Cell Adhesion Molecules