Rapid telomere erosion in schizophrenia

Kao, Hung‐Teh; Cawthon, Richard M.; DeLisi, L.E.; Bertisch, Hilary; Ji, Fei; Gordon, Derek; Li, P.; Benedict, Melissa M.; Greenberg, William M.; Porton, Barbara

doi:10.1038/sj.mp.4002105

Cited by 117 publications

(90 citation statements)

References 7 publications

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“…Similarly, lifetime numbers of depressive episodes were significantly correlated with telomere shortening in patients with bipolar II disorder (Elvsashagen et al, 2001). There is also rapid telomere erosion in patients with schizophrenia after 20 years of illness, indicating a premature biological aging of about 25 years (Kao et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Telomeres in the Brain Cortex of Patients with Major Depressive Disorder

et al. 2014

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Telomeres are complex structures formed by the end of the DNA molecule at the tip of each chromosomal arm. The repeated (TTAGGG) telomeric sequence progressively shortens during lifespan because it cannot be replicated as somatic cells divide, and is highly susceptible to breakage by free radicals. Critically shortened telomeres activate the genetic program of cell senescence and/or apoptosis. The telomere length measured in peripheral blood leucocytes is considered a reliable marker of biological age, mortality risk and exposure to various pathological conditions, including cardiovascular disease, dementia, and metabolic syndrome. Telomere erosion has been observed in psychiatric disorders including schizophrenia and mood disorders, suggesting an accelerated aging of 10 to 20 years. Whether this peripheral dynamic is reflected by a similar pattern in the brain remains unknown. To address this issue we have measured the telomere length in the occipital DNA cortex of 24 patients with major depressive disorder and 12 controls (donated by the Stanley Research Institute) by a real time quantitative PCR technique. The mean telomere lengths were identical in the depressed and control groups. Thus, although there is consistent evidence for the role of systemic inflammation and oxidative stress in depression, it must be concluded that the cerebral status of telomeres is not affected. This observation raises the issue of the relation between the psychiatric pathological process, and peripheral and central biomarkers.

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Section: Discussionmentioning

confidence: 99%

Telomeres in the Brain Cortex of Patients with Major Depressive Disorder

et al. 2014

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“…Age Relationships None of the TL studies reported differential age relationships between schizophrenia and HC groups. Five reports found no relationship between age and TL 29,31,32,51 or telomerase activity, 36 while 4 observed negative correlations between age and TL in both schizophrenia and comparison groups. 33,34,47,49 None of these studies statistically examined group differences in age-relationships.…”

Section: Characteristics Of Reviewed Studiesmentioning

confidence: 99%

“…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. 33 Wolkowitz et al 47 found a group × gender interaction, such that HC women had longer TL than women with schizophrenia.…”

Section: Characteristics Of Reviewed Studiesmentioning

confidence: 99%

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

Nguyen

Eyler

Jeste

2017

Schizophrenia Bulletin

105

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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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“…Thus far, cross-sectional studies have reported mixed results. Several investigations found shorter LTL in persons with schizophrenia than in healthy comparison subjects (HCs) (Fernandez-Egea et al, 2009;Kao et al, 2008) or at least in subgroups of individuals with more chronic, severely psychotic, or treatment-resistant illness (Kota et al, 2015;Li et al, 2015;Rao et al, 2016;Yu et al, 2008) (but see (Lin, 2015)), possibly suggesting accelerated biological aging Kirkpatrick et al, 2008). However, one large study reported longer LTL in schizophrenia than in HCs (Nieratschker et al, 2013).…”

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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Rapid telomere erosion in schizophrenia

Cited by 117 publications

References 7 publications

Telomeres in the Brain Cortex of Patients with Major Depressive Disorder

Telomeres in the Brain Cortex of Patients with Major Depressive Disorder

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

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

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