Pharmacological interventions and telomere length in patients with schizophrenia and bipolar disorder: A systematic review and meta-analysis

Background: Patients with schizophrenia and bipolar disorder have a life expectancy shorter than the general population. Cellular mechanisms underlying accelerated ageing, such as telomere shortening, may contribute to this premature mortality. We aimed to provide a comprehensive evaluation of the impact of pharmacological treatments for schizophrenia and bipolar disorder on telomere length. Method: PRISMA/MOOSE systematic review and meta-analysis from inception to June 2024. PubMed, Cochrane Library, SCOPUS, Web of Science, Embase and PsycInfo databases were searched for eligible studies. Methodological quality and risk of bias were evaluated with the Newcastle-Ottawa Scale and the Risk of Bias In Non-randomized Studies - of Exposure (ROBINS-E) respectively. Results: An initial search retrieved 2133 articles. However, only 28 studies were finally included in qualitative synthesis and 19 in meta-analysis. All studies identified in the review were observational. Random-effects model analysis was used to quantify the difference in telomere length between cohorts of patients with schizophrenia or bipolar disorder and healthy control groups. The meta-analysis confirmed that telomere length was shorter in patients with schizophrenia (SMD = 0.35, 95 % CI 0.11 to 0.60; p=<0.0001) and bipolar disorder (SMD = 0.18, 95 % CI -0.04 to 0.39 p=<0.0001) than in healthy controls. This difference was not modified by predominant treatment with either lithium (SMD = 0.37, 95 % CI 0.04 to 0.69; p=<0.0001) or antipsychotics (SMD = 0.20, 95 % CI 0.02 to 0.38; p=<0.0001) at cohort level across studies. Conclusions: Patients with schizophrenia or bipolar disorder have shorter telomeres than healthy populations. Predominant treatment with lithium or antipsychotics at cohort level did not have an impact on such shortening difference.