Telomere length in bipolar disorder: An updated meta-analysis of observational studies

Telomere length, a biological marker related to cellular aging, has been associated with several psychiatric conditions, including bipolar disorder (BD). However, previous meta-analyses were limited by small sample sizes and substantial heterogeneity in measurement methods, sampling sources, and clinical characteristics.

We systematically searched Embase, MEDLINE, Cochrane CENTRAL, CINAHL, and Scopus for observational studies comparing telomere length between patients with BD and healthy controls. Random-effects models were used to estimate pooled effect sizes. Subgroup analyses were conducted according to sampling source, mood status, and measurement method. Meta-regression was performed to explore potential clinical moderators. The certainty of evidence was assessed using the GRADE approach.

Thirty studies were included, comprising 5639 patients with BD and 226,358 healthy controls. Overall, BD was associated with shorter telomere length compared with controls (Hedges' g = -0.309, 95% CI -0.437 to -0.181). This association was observed in studies using peripheral blood leukocytes and lymphoblastoid cell lines, but not in studies using post-mortem brain tissue. Shorter telomere length was observed across studies sampling different mood states at the group level and in studies using qPCR or Southern blot methods, but not Q-FISH. Meta-regression revealed that the sex distribution difference between patients and control significantly moderated the magnitude of telomere length differences.

This updated meta-analysis suggests an association between bipolar disorder and shorter telomere length at the group level. However, substantial heterogeneity and the observational nature of the included studies resulted in a very low certainty of evidence, warranting cautious interpretation.