Peripheral blood telomerase activity and telomerase reverse transcriptase gene expression in psychiatric disorders: a systematic review and meta-analysis

Telomere shortening is shared by all psychiatric disorders and is hypothesized as resulting from decreased telomerase activity (TA) or expression of the TERT (Telomerase Reverse Transcriptase) gene.

A search in four English databases was conducted from inception to November 2024 to evaluate the association between psychiatric disorders and telomerase activity (TA) or TERT gene expression in peripheral blood. We performed two separate meta-analyses to generate pooled effect size (ES) for TA and TERT gene expression, followed by meta-regression.

The systematic review included 16 studies, 14 of which were included in the meta-analyses. When considering all psychiatric disorders, no associations were found for TA (ES = 0.08 [-0.50-0.67], p = 0.78 - I-squared = 95%), nor TERT gene expression (ES = 0.00 [-0.56-0.57], p = 0.99 - I-squared = 91%). However, TA was elevated in mood disorders (ES = 0.61 [0.06-1.16] - p = 0.03), while decreased in non-mood disorders (ES = -0.70 [-1.37 - -0.03] - p = 0.04). ES for TA were larger in mood disorders as compared to other disorders (p = 0.003).

This meta-analysis shows that psychiatric disorders - taken together - are not associated with peripheral blood TA or TERT gene expression. Nevertheless, we find that TA is increased in depressive disorders (unipolar or bipolar), whereas decreased in non-mood psychiatric disorders. The paucity of studies and small sample sizes are important limitations, especially for TERT gene expression. Further research is needed, incorporating a broader spectrum of psychiatric disorders and larger sample sizes.