Abstract
Telomere length has emerged as a potential biomarker of cellular aging and has been implicated in various psychiatric disorders, including depression. However, recent studies investigating the association between depression and telomere length have yielded inconsistent findings. The objective of this study is to systematically review the current literature to evaluate the correlation between depression and telomere length, while also examining the influence of potential moderators such as age, gender, assessment techniques, tissue resources, and depression assessment protocols on this association. We systematically included studies measuring telomere length in individuals meeting clinical or rating scale thresholds for Major Depressive Disorder (MDD), employing a thorough search strategy across PubMed, Embase, PsycINFO, and Google Scholar. Using a structured data abstraction form, studies were meticulously assessed for inclusion or exclusion based on predetermined criteria. Analysis involved standardized mean differences within a random effects model framework, allowing for a comprehensive examination of the association between depression and telomere length while accounting for heterogeneity across studies. Following the meticulous screening of titles, abstracts, and full texts, a total of 71 articles meeting our inclusion criteria were identified and included in the meta-analysis. Our analysis revealed a significant association between depression and telomere length, with a Cohen's d effect size of -0.354 (p-value < 0.0001, I(2) = 80%). Subgroup analysis uncovered significant influences of various factors on the relationship between depression and telomere length, including depression assessment tools, measurement scales, telomere measurement techniques, source tissue, and the presence of comorbid medical conditions. Moreover, multivariable meta-regression showed that age, depression measurement technique, and telomere measurement technique significantly impacted this association. Our findings underscore the complexity of the relationship between depression and telomere length and emphasize the importance of considering multiple factors when interpreting study outcomes. Further studies are necessary to elucidate the potential causality underlying this association and to explore the bidirectional connection between depression severity and telomere shortening.