Epigenetic clock analysis reveals increased plasma cystatin C levels based on DNA methylation in major depressive disorder

• Published in: Psychiatry research 2023-04, Vol.322, p.115103-115103, Article 115103
• Main Authors: Tanifuji, Takaki, Okazaki, Satoshi, Otsuka, Ikuo, Mouri, Kentaro, Horai, Tadasu, Shindo, Ryota, Shirai, Toshiyuki, Hishimoto, Akitoyo
• Format: Article
• Language: English
• Subjects: Aging - genetics; Cystatin C; Depressive Disorder, Major - genetics; DNA Methylation; Epigenesis, Genetic; Epigenetic clock; Humans; Major depressive disorder
• ISSN: 0165-1781; 1872-7123
• DOI: 10.1016/j.psychres.2023.115103

•DNA methylation (DNAm) is associated with biological aging and health risks.•Epigenetic changes have been reported to be related to depression.•We assessed five epigenetic clocks, DNAmTL, and DNAm-based age-predictive factors.•Specific DNAm changes were related to plasma cystatin C levels in MDD.•The plasma cystatin C level may be an independent risk factor for developing MDD. Major depressive disorder (MDD) is a common mental illness and a major public health concern worldwide. Depression is associated with epigenetic changes that regulate gene expression, and analyzing these changes may help elucidate the pathophysiology of MDD. Genome-wide DNA methylation (DNAm) profiles can function as ‘epigenetic clocks’ that can help estimate biological aging. Here, we assessed biological aging in patients with MDD using various DNAm-based indicators of epigenetic aging. We used a publicly available dataset containing data obtained from the whole blood samples of MDD patients (n = 489) and controls (n = 210). We analyzed five epigenetic clocks (HorvathAge, HannumAge, SkinBloodAge, PhenoAge, and GrimAge) and DNAm-based telomere length (DNAmTL). We also investigated seven DNAm-based age-predictive plasma proteins (including cystatin C) and smoking status, which are components of GrimAge. Following adjustment for confounding factors such as age and sex, patients with MDD showed no significant difference in epigenetic clocks and DNAmTL. However, DNAm-based plasma cystatin C levels were significantly higher in patients with MDD than controls. Our findings revealed specific DNAm changes predicting plasma cystatin C levels in MDD. These findings may help elucidate the pathophysiology of MDD, leading to the development of new biomarkers and medications.