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Leukocyte telomere length in patients with schizophrenia and related disorders: a meta-analysis of case-control studies

Molecular Psychiatry volume 27, pages 2968–2975 (2022)Cite this article

Subjects

Abstract

Context

Telomere length may serve as a biomarker of cellular aging. The literature assessing telomere length in schizophrenia contains conflicting results.

Objective

To assess differences in leukocyte telomere length (LTL) in peripheral blood in patients with schizophrenia and related disorders and healthy controls and to explore the effect of potential confounding variables.

Data sources

A search of Ovid MEDLINE, and Proquest databases was conducted to identify appropriate studies published from database inception through December 2020. The review protocol was registered with PROSPERO-ID: CRD42021233280.

Study selection

The initial literature search yielded 192 studies. After study selection in 3 phases, we included 29 samples from 22 studies in the meta-analysis database.

Data extraction

We used random effects and meta-regression models to derive Cohen d values with pooled 95% confidence intervals (CI) as estimates of effect size (ES) and to test effects of potential moderators.

Results

The overall meta-analysis included 4145 patients with schizophrenia and related disorders and 4184 healthy controls and showed that LTL was significantly shorter in patients, with a small to medium effect size (ES, −0.388; 95% CI, −0.492 to −0.283; p < 0.001). Subgroup meta-analyses did not find a significant effect of age or illness duration on differences in LTL in patients with psychosis relative to controls. Meta-regression analyses showed that none of the putative moderators had a significant effect on effect size estimates.

Conclusions

This meta-analysis find further support for the hypothesis of accelerated cellular aging in schizophrenia and related disorders and highlights the need for large longitudinal studies with repeated LTL measurements over time and appropriate assessments of associated factors.

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Acknowledgements

Supported by the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (PI14/00397, PI17/00481, PIE16/00055, PI20/00216, PI20/00721, JR19/00024), co-financed by ERDF Funds from the European Commission, “A way of making Europe”, CIBERSAM, Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), EU Structural Funds, EU Seventh Framework Program under grant agreement FP7-HEALTH-2013-2.2.1-2-603196 (Project PSYSCAN); EU H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking under grant agreements 115916 (Project PRISM), and 777394 (project AIMS-2-TRIALS), Fundación Familia Alonso, Fundación Alicia Koplowitz and Fundación Mutua Madrileña. Research in the Blasco lab is funded by Spanish State Research Agency (AEI), Ministry of Science and Innovation, cofunded by the European Regional Development Fund (ERDF) (SAF2017-82623-R and SAF2015-72455-EXP), the Comunidad de Madrid Project (S2017/BMD-3770), the World Cancer Research (WCR) Project (16-1177), the European Research Council (ERC-AvG Shelterines GA882385) and the Fundación Botín (Spain).

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Author notes

  1. These authors contributed equally: Miriam Ayora, David Fraguas.

Authors and Affiliations

  1. Department of (Child and Adolescent) Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), School of Medicine, Universidad Complutense, Madrid, Spain

    Miriam Ayora, Renzo Abregú-Crespo, Sandra Recio, Celso Arango & Covadonga M. Díaz-Caneja

  2. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain

    Miriam Ayora, David Fraguas, Celso Arango & Covadonga M. Díaz-Caneja

  3. Institute of Psychiatry and Mental Health, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain

    David Fraguas

  4. Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, Madrid, E-28029, Spain

    María A. Blasco, Ana Moises & Aksinya Derevyanko

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Contributions

MA and DF had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: MA, DF, CDC, RAC, and CA. Acquisition, analysis, or interpretation of data: MA, DF, RAC, SR, MB, AM, AD, CA, and CDC. Drafting of the manuscript: MA, DF, and CDC. Critical revision of the manuscript for important intellectual content: MA, DF, RAC, SR, MB, AM, AD, CA, and CDC. Statistical analysis: MA and DF. Obtained funding: DF, CDC, and CA. Administrative, technical, or material support: MA, DF, RAC, CDC, and SR. Supervision: MA, DF, MB, CA, and CDC.

Corresponding author

Correspondence to David Fraguas.

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Competing interests

MA has held a Río Hortega grant from Instituto de Salud Carlos III (Spanish Ministry of Science and Innovation). DF has been a consultant and/or has received fees from Angelini, Casen Recordati, Janssen, Lundbeck, and Otsuka. He has also received grant support from Instituto de Salud Carlos III (Spanish Ministry of Science and Innovation) and from Fundación Alicia Koplowitz. RAC has received grant support from Instituto de Salud Carlos III. SR has no conflicts of interest. MB is founder and owns stock from Life Length, SL, a biotechnology company focussed on telomere length determinations for biomedical use. Aksinya Derevyanko has no conflicts of interest. CA has been a consultant to or has received honoraria or grants from Acadia, Abbot, AMGEN, AstraZeneca, Bristol-Myers Squibb, Caja Navarra, CIBERSAM, Dainippon Sumitomo Pharma, Fundación Alicia Koplowitz, Forum, Instituto de Salud Carlos III, Gedeon Richter, Janssen Cilag, Lundbeck, Merck, Ministerio de Ciencia e Innovación, Ministerio de Sanidad, Ministerio de Economía y Competitividad, Mutua Madrileña, Otsuka, Pfizer, Roche, Servier, Shire, Schering Plough, Sunovio and Takeda. CDC has received grant support from Instituto de Salud Carlos III (Spanish Ministry of Science and Innovation) and honoraria from Exeltis and Angelini.

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Ayora, M., Fraguas, D., Abregú-Crespo, R. et al. Leukocyte telomere length in patients with schizophrenia and related disorders: a meta-analysis of case-control studies. Mol Psychiatry 27, 2968–2975 (2022). https://doi.org/10.1038/s41380-022-01541-7

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