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

Abstract

<h4>Background</h4>Telomere shortening is shared by all psychiatric disorders and is hypothesized as resulting from decreased telomerase activity (TA) or expression of the <i>TERT</i> (Telomerase Reverse Transcriptase) gene.<h4>Methods</h4>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 <i>TERT</i> gene expression in peripheral blood. We performed two separate meta-analyses to generate pooled effect size (ES) for TA and <i>TERT</i> gene expression, followed by meta-regression.<h4>Results</h4>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], <i>p</i> = 0.78 - <i>I</i>-squared = 95%), nor <i>TERT</i> gene expression (ES = 0.00 [-0.56-0.57], <i>p</i> = 0.99 - <i>I</i>-squared = 91%). However, TA was elevated in mood disorders (ES = 0.61 [0.06-1.16] - <i>p</i> = 0.03), while decreased in non-mood disorders (ES = -0.70 [-1.37 - -0.03] - <i>p</i> = 0.04). ES for TA were larger in mood disorders as compared to other disorders (<i>p</i> = 0.003).<h4>Conclusions</h4>This meta-analysis shows that psychiatric disorders - taken together - are not associated with peripheral blood TA or <i>TERT</i> 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 <i>TERT</i> gene expression. Further research is needed, incorporating a broader spectrum of psychiatric disorders and larger sample sizes.