Leukocyte telomere length in patients with schizophrenia: A meta-analysis

Polho, Gabriel Berlingieri; Paula, Vanessa de; Cardillo, Giancarlo de Mattos; Santos, Bianca; Kerr, Daniel Shikanai

doi:10.1016/j.schres.2015.04.025

Cited by 60 publications

(26 citation statements)

References 40 publications

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“…Group Differences Ten studies of TL met our inclusion criteria. Consistent with previous meta-analyses, 17,19 findings were mixed. Five reports found that TL and telomerase activity were decreased in schizophrenia, 29,34,36,42,49 3 observed no difference in TL between schizophrenia and HC groups, 31,32,51 and one reported increased TL in schizophrenia.…”

Section: Characteristics Of Reviewed Studiessupporting

confidence: 87%

“…Several prior reviews have examined accelerated aging in schizophrenia from various perspectives, including metabolic disease, 2,13 cognition, 2,13 brain structure, [14][15][16] telomere length (TL), [17][18][19] and oxidative stress. 20 However, no publication, to our knowledge, has provided a comprehensive review of multiple biomarkers relevant to the hypothesis of accelerated biological aging in schizophrenia.…”

Section: "Besides the Psychic Disorders There Are Also In The Physicmentioning

confidence: 99%

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Systemic Biomarkers of Accelerated Aging in Schizophrenia: A Critical Review and Future Directions

Nguyen

Eyler

Jeste

2017

Schizophrenia Bulletin

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Background: Schizophrenia is associated with increased physical morbidity and early mortality, suggesting that the aging process may be accelerated in schizophrenia. However, the biological underpinnings of these alterations in aging in schizophrenia are unclear. Method: We conducted a detailed search of peer-reviewed empirical studies to evaluate evidence for accelerated biological aging in schizophrenia based on systemic, age-related biomarkers. We included studies that investigated differences between persons with schizophrenia and healthy comparison subjects in levels of biomarkers known to be associated with aging and examined the relationship of these biomarkers to age in the 2 groups. Results: Forty-two articles that met our selection criteria were reviewed. Nearly 75% reported abnormal biomarker levels among individuals with schizophrenia, including indices of inflammation, cytotoxicity, oxidative stress, metabolic health, gene expression, and receptor/synaptic function, with medium to large effect sizes reported in many studies. Twenty-nine percent of the studies observed differential age-related decline in schizophrenia. Markers of receptor/synaptic function and gene expression were most frequently differentially related to age in schizophrenia. Schizophrenia patients with greater disease severity and longer illness duration exhibited higher levels of inflammatory and oxidative stress biomarkers and shorter telomere length. Conclusions: Most studies show biomarker abnormalities in schizophrenia, and there is some suggestion for accelerated aging. Although definitive interpretation is limited by cross-sectional design of the published reports, findings in the area of gene expression and synaptic function are promising and pave the way for future longitudinal studies needed to fully test this hypothesis.

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Section: Characteristics Of Reviewed Studiessupporting

confidence: 87%

Section: "Besides the Psychic Disorders There Are Also In The Physicmentioning

confidence: 99%

Systemic Biomarkers of Accelerated Aging in Schizophrenia: A Critical Review and Future Directions

Nguyen

Eyler

Jeste

2017

Schizophrenia Bulletin

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“…Note that we have reversed the direction of our correlations compared to figure 3 where this is necessary for the comparison. TL, telomere length; SMD, standardized mean difference; OR, odds ratio; d , Cohen's d ; r , correlation coefficient.exposure categoryspecialist meta-analysis findingspresent findingscardiovascular diseasesignificant association between CVD and short TL, OR = 1.54 (1.30, 1.83) [12]significant negative correlation between CVD and TL, r = −0.13 (−0.23, −0.02)diabetessignificant association between diabetes and short TL, OR = 1.29 (1.11, 1.50) [13]significant negative correlation between diabetes and TL, r = −0.28 (−0.41, −0.15)Parkinson's diseaseno significant association between TL and disease, SMD = 0.36 (−0.25, 0.96) [14]no significant association between TL and disease, r = 0.09 (−0.26, 0.44)sleep apnoeasignificantly shorter TL in sleep apnoea, SMD = −0.03 (−0.06, −0.00) [15]association between TL and disease negative but not significant r = −0.07 (−0.27, 0.13)anxietysignificantly shorter TL in anxiety disorders, SMD = −0.53 (−1.05, −0.01) [16]significantly shorter TL in anxiety disorders, r = −0.05 (−0.08, −0.01)depressionsignificantly shorter TL in depressive disorders, SMD = −0.55 (−0.92, −0.18) [16]; d = −0.21 (−0.29, −0.12) [35]; r = −0.12 (−0.17, −0.07) [36]significantly shorter TL in depressive disorders, r = −0.12 (−0.20, −0.04), became marginally non-significant in reduced datasetPTSDsignificantly shorter TL in PTSD, SMD = −1.27 (−2.12, −0.43) [16]significantly shorter TL in PTSD, r = −0.17 (−0.31, −0.03); became non-significant in reduced datasetschizophreniano significant association between TL and psychosis/schizophrenia, SMD = −0.2 (−0.68, 0.21) [16]; SMD = 0.34 (0.77, 154) [37]significantly shorter TL in paranoid schizophrenia compared to controls SMD = −0.48 (−0.94, −0.03) [38]significant association between TL and schizophrenia, r = −0.30 (−0.50, −0.10); became non-significant in reduced datasetsmokingsmokers significantly shorter TL than non-smokers, SMD = −0.17 (−0.24, −0.09) [17]…”

Section: Discussionmentioning

confidence: 99%

Telomeres as integrative markers of exposure to stress and adversity: a systematic review and meta-analysis

Pepper¹,

Bateson²,

Nettle³

2018

R. Soc. open sci.

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Telomeres have been proposed as a biomarker that integrates the impacts of different kinds of stress and adversity into a common currency. There has as yet been no overall comparison of how different classes of exposure associate with telomeres. We present a meta-analysis of the literature relating telomere measures to stresses and adversities in humans. The analysed dataset contained 543 associations from 138 studies involving 402 116 people. Overall, there was a weak association between telomere variables and exposures (greater adversity, shorter telomeres: r = −0.15, 95% CI −0.18 to −0.11). This was not driven by any one type of exposure, because significant associations were found separately for physical diseases, environmental hazards, nutrition, psychiatric illness, smoking, physical activity, psychosocial and socioeconomic exposures. Methodological features of the studies did not explain any substantial proportion of the heterogeneity in association strength. There was, however, evidence consistent with publication bias, with unexpectedly strong negative associations reported by studies with small samples. Restricting analysis to sample sizes greater than 100 attenuated the overall association substantially (r = −0.09, 95% CI −0.13 to −0.05). Most studies were underpowered to detect the typical association magnitude. The literature is dominated by cross-sectional and correlational studies which makes causal interpretation problematic.

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“…Reasons for discrepancies in findings among these studies are not known, but may include inadequate sample sizes, differing gender distributions, quality of diagnostic evaluations, nature of the comparison sample, chronicity and severity of illness, medical illnesses, medication history, and history of treatment responsiveness, along with demographic and lifestyle factors such as age, diet, body-mass index (BMI), exercise, and tobacco use. Nonetheless, reviews and meta-analyses of these studies of LTL (Darrow et al, 2016;Lindqvist et al, 2015) support decreased LTL in schizophrenia compared to HCs, with an effect size of approximately d ¼ 0.34, with the effect size being larger in subgroups of subjects who were either drug-naïve (d ¼ 0.56) or poor responders to medication (d ¼ 0.97) (Darrow et al, 2016;Lin, 2015;Polho et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Leukocyte telomere length: Effects of schizophrenia, age, and gender

Wolkowitz

Jeste

Martin

et al. 2017

Journal of Psychiatric Research

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a b s t r a c tBackground: Schizophrenia is linked with early medical comorbidity and mortality. These observations indicate possible "accelerated biological aging" in schizophrenia, although prior findings are mixed, and few such studies have examined the role of gender. One putative marker of biological aging is leukocyte telomere length (LTL), which typically shortens with age. Methods: We assessed LTL in phenotypically well characterized 134 individuals with schizophrenia (60 women and 74 men) and 123 healthy comparison subjects (HCs) (66 women and 57 men), aged 26 to 65 years. Results: Overall, LTL was inversely associated with age (t(249) ¼ -6.2, p < 0.001), and a gender effect on the rate of LTL decrease with age was found (t(249) ¼ 2.20, p ¼ 0.029), with men declining more rapidly than women. No significant overall effect of diagnosis on the rate of decline was detected. However, at the average sample age (48 years), there was a significant gender effect in both schizophrenia and HC groups (t(249) ¼ 2.48, p ¼ 0.014), with women having longer LTL than men, and a significant gender X diagnosis effect (t(249) ¼ 2.43, p ¼ 0.016) -at the average sample age, women with schizophrenia had shorter LTL than HC women. Discussion: Gender, not the diagnosis of schizophrenia, was the major factor involved with LTL shortening across the age range studied. We discuss the constraints of a cross-sectional design and other methodological issues, and indicate future directions. Understanding the impact of schizophrenia on biological aging will require separate evaluations in men and women.Published by Elsevier Ltd.

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Leukocyte telomere length in patients with schizophrenia: A meta-analysis

Cited by 60 publications

References 40 publications

Systemic Biomarkers of Accelerated Aging in Schizophrenia: A Critical Review and Future Directions

Systemic Biomarkers of Accelerated Aging in Schizophrenia: A Critical Review and Future Directions

Telomeres as integrative markers of exposure to stress and adversity: a systematic review and meta-analysis

Leukocyte telomere length: Effects of schizophrenia, age, and gender

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