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

Ayora, Miriam; Fraguas, David; Abregú-Crespo, Renzo; Recio, Sandra; Blasco, Marı́a A.; Moisés, Ana Carolina; Derevyanko, Aksinya; Arango, Celso; Díaz‐Caneja, Covadonga M.

doi:10.1038/s41380-022-01541-7

Cited by 18 publications

(10 citation statements)

References 54 publications

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“…Across diagnostic groups of psychiatric illness, aging-like anatomical and biochemical alterations, such as progressive atrophic changes in the brain, systemic inflammation and immune dysregulation, insulin resistance, and osteoporosis, have been documented. Telomeres, the nucleotide repeat sequences that cap chromosomal ends and are shortened with cell division and increased age, undergo accelerated attrition in several psychiatric disorders, such as schizophrenia, bipolar disorder, and unipolar depression (although conflicting data exist). Finally, medical conditions that occur at higher rates and at an earlier age among patients with psychiatric disorders (eg, circulatory, pulmonary, nervous, and endocrine system disorders) are also prevalent with increasing age in the general population .…”

Section: Introductionmentioning

confidence: 99%

Association of Oxidative Stress–Induced Nucleic Acid Damage With Psychiatric Disorders in Adults

et al. 2022

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IMPORTANCE Nucleic acid damage from oxidative stress (NA-OXS) may be a molecular mechanism driving the severely increased morbidity and mortality from somatic causes in adults with psychiatric disorders.OBJECTIVE To systematically retrieve and analyze data on NA-OXS across the psychiatric disorder diagnostic spectrum.DATA SOURCES The PubMed, Embase, and PsycINFO databases were searched from inception to November 16, 2021. A hand search of reference lists of relevant articles was also performed.STUDY SELECTION Key study inclusion criteria in this meta-analysis were as follows: adult human study population, measurement of any marker of DNA or RNA damage from oxidative stress, and either a (1) cross-sectional design comparing patients with psychiatric disorders (any diagnosis) with a control group or (2) prospective intervention. Two authors screened the studies, and 2 senior authors read the relevant articles in full and assessed them for eligibility. DATA EXTRACTION AND SYNTHESISThe Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Two authors performed data extraction independently, and a senior coauthor was consulted in cases of disagreement. Data were synthesized with random-effects and multilevel meta-analyses. MAIN OUTCOMES AND MEASURESThe predefined hypothesis was that individuals with psychiatric disorders have increased NA-OXS levels. The main outcome was the standardized mean differences (SMDs) among patients and controls in nucleic acid oxidation markers compared across diagnostic groups. Analyses were divided into combinations of biological matrices and nucleic acids.RESULTS Eighty-two studies fulfilled the inclusion criteria, comprising 205 patient vs control group comparisons and a total of 10 151 patient and 10 532 control observations. Overall, the data showed that patients with psychiatric disorders had higher NA-OXS levels vs controls across matrices and molecules. Pooled effect sizes ranged from moderate for urinary DNA markers (SMD = 0.44 [95% CI, 0.20-0.68]; P < .001) to very large for blood cell DNA markers (SMD = 1.12 [95% CI, 0.69-1.55; P < .001). Higher NA-OXS levels were observed among patients with dementias followed by psychotic and bipolar disorders. Sensitivity analyses excluding low-quality studies did not materially alter the results. Intervention studies were few and too heterogenous for meaningful meta-analysis. CONCLUSIONS AND RELEVANCEThe results of this meta-analysis suggest that there is an association with increased NA-OXS levels in individuals across the psychiatric disorder diagnostic spectrum. NA-OXS may play a role in the somatic morbidity and mortality observed among individuals with psychiatric disorders.

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Section: Introductionmentioning

confidence: 99%

Association of Oxidative Stress–Induced Nucleic Acid Damage With Psychiatric Disorders in Adults

et al. 2022

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“…Many studies found cellular and molecular evidence of accelerated aging in schizophrenia patients. Telomere attrition is a feature of aging, and significantly shorter leukocyte telomere length is observed in patients with schizophrenia and related disorders when compared to age-matched healthy individuals 12,13 . The free radical theory attributes the accumulation of oxidative damages in cells and tissues to the functional decline in aging 14 .…”

Section: Introductionmentioning

confidence: 99%

Associations of Systemic Inflammation and Senescent Cell Biomarkers with Clinical Outcomes in Older Adults with Schizophrenia

Chui,

Schneider,

Miclau

et al. 2024

Preprint

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Individuals with schizophrenia suffer from higher morbidity and mortality throughout life partly due to acceleration of aging-related diseases and conditions. Systemic inflammation is a hallmark of aging and is also observed in schizophrenia. An improved understanding of how inflammation and accelerated aging contribute to long-term health outcomes in schizophrenia could provide more effective treatments to preserve long-term cognitive and physical function. In this pilot cross-sectional study, 24 older adults (≥55 years old) with schizophrenia were assessed on symptoms (Positive and Negative Syndrome Scale), neurocognition (Matrics Consensus Cognitive Battery), mobility (Timed Get Up and Go), and general health (SF-12). Serum levels of 112 different cytokines were measured, from which we derived estimated senescence-associated secretory phenotype (SASP) scores for each participant. Two-tailed Pearson's bivariate correlations were computed to test the associations between schizophrenia clinical outcomes with individual cytokines, and SASP. Higher levels of eotaxin, IL-1α, IL-1β, and IFNα are associated with both worse PANSS negative and depressive symptoms scores. IL-1α and IL-1β negatively associated with general physical health whereas eotaxin negatively associated with mobility and global cognition. Overall, we found that specific inflammatory cytokines, but not composite measurements of SASP, are associated with clinical outcomes in older adults with schizophrenia.

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“…LTL is known as the ”molecular clock” related to the senescence of cells and organisms ( Vaiserman & Krasnienkov, 2020 ). Epidemiological studies have shown evidence that shortened LTL is linked to several psychiatric disorders, including major depressive disorder ( Monroy-Jaramillo, Dyukova & Walss-Bass, 2018 ; Pisanu et al, 2020a ; Pisanu et al, 2020b ; Wang et al, 2017 ), anxiety ( Monroy-Jaramillo, Dyukova & Walss-Bass, 2018 ; Wang et al, 2017 ), schizophrenia ( Ayora et al, 2022 ; Wolkowitz et al, 2017 ). The occurrence of BD may be closely related to these diseases, which may all be affected by shortened LTL.…”

Section: Introductionmentioning

confidence: 99%

Leukocyte telomere length and bipolar disorder risk: evidence from Mendelian randomization analysis

Zeng

Wan

et al. 2023

PeerJ

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Objective We aim to test whether leukocyte telomere length (LTL) is causally associated with the risk of bipolar disorder (BD) using the Mendelian randomization (MR) method. Methods Results of a genome-wide association study (GWAS) conducted with 472,174 individuals of European descent were used to screen for single-nucleotide polymorphisms (SNPs) related with LTL traits. Summary-level data for BD (7,647 cases and 27,303 controls) were obtained from UK Biobank. An inverse-variance-weighted (IVW) method was employed as the primary MR analysis. Sensitivity analyses were conducted via MR-Egger, maximum likelihood, MR-pleiotropy residual sum outlier (MR-PRESSO), and MR-robust adjusted profile score (MR-RAPS) methods. Finally, the MR Steiger test was utilized to validate the hypothesized relationship between exposure and outcome. Results Two-sample MR analysis revealed inverse relationships between genetically predicted LTL and BD risk (IVW OR [odds ratio] = 0.800, 95% CI [0.647–0.989] P = 0.039). Genetically predicted LTL exhibits a consistent connection with BD across five MR methods. Sensitivity analyses showed that the genetically determined effect of LTL on BD was stable and reliable. Furthermore, the MR Steiger test demonstrated that LTL was causal for BD rather than the opposite (P < 0.001). Conclusion Our findings show that genetically determined LTL reduces the risk of BD. More research is required to clarify the mechanisms underlying this apparent causal connection. In addition, these findings may be useful for developing strategies for the prevention and treatment of BD.

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

Cited by 18 publications

References 54 publications

Association of Oxidative Stress–Induced Nucleic Acid Damage With Psychiatric Disorders in Adults

Association of Oxidative Stress–Induced Nucleic Acid Damage With Psychiatric Disorders in Adults

Associations of Systemic Inflammation and Senescent Cell Biomarkers with Clinical Outcomes in Older Adults with Schizophrenia

Leukocyte telomere length and bipolar disorder risk: evidence from Mendelian randomization analysis

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