Short telomeres in patients with chronic schizophrenia who show a poor response to treatment

Short telomeres in patients with chronic schizophrenia who show a poor response to treatment

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J Psychiatry Neurosci 2008;33(3):218-26

Wu-Yang Yu, MD, MSc; Hsueh-Wen Chang, PhD; Ching-Hua Lin, MD, MSc; Chung-Lung Cho, PhD

Yu — Yu’s Psychiatric Clinic; Chang, Cho — Department of Biological Sciences, National Sun Yat-sen University; Lin — Kai-Suan Psychiatric Hospital, Kaohsiung, Taiwan

Abstract

Objective: Telomere shortening has been observed in many human diseases, including atherosclerosis, cancer, aging syndromes, Alzheimer disease and vascular dementia. The present study aimed to investigate the mean telomere lengths of patients with schizophrenia.

Methods: We analyzed the lengths of telomeric DNA, comparing 2 groups of patients with schizophrenia (34 good responders and 34 poor responders). A control group of 76 healthy volunteers was also included. Blood samples were obtained, and telomere length was measured by Southern blot analysis on the mean length of terminal restriction fragment (TRF).

Results: Compared with the control group, a significant amount of telomere shortening was found in peripheral blood leukocytes from patients with schizophrenia who experienced poor response to antipsychotics (p < 0.001). Conclusion: Shortened telomere length in chronic schizophrenia may be a trait marker caused by oxidative stress, and the ensuing cellular dysfunction may be a factor contributing to the progressive deterioration in treatment-resistant schizophrenia.

Résumé

Objectif : On a observé un raccourcissement des télomères dans beaucoup de maladies humaines, y compris l’athérosclérose, le cancer, les syndromes du vieillissement, la maladie d’Alzheimer et la démence vasculaire. L’étude visait à analyser la longueur moyenne des télomères chez les patients atteints de schizophrénie.

Méthodes : Nous avons analysé la longueur de l’ADN télomérique en comparant deux groupes de patients atteints de schizophrénie (34 qui réagissaient bien et 34 qui réagissaient mal). L’étude comportait aussi un groupe témoin de 76 volontaires en bonne santé. On a prélevé des échantillons de sang et mesuré la longueur des télomères par transfert de Southern portant sur la longueur moyenne du fragment de restriction terminal (FRT).

Résultats : Comparativement au groupe témoin, on a constaté un raccourcissement important des télomères dans les leucocytes du sang périphérique des patients atteints de schizophrénie qui réagissaient mal aux antipsychotiques (p < 0,001). Conclusion : Le raccourcissement des télomères dans les cas de schizophrénie chronique peut constituer un marqueur caractéristique causé par le stress oxydatif , et le dysfonctionnement cellulaire qui en découle peut contribuer à la détérioration progressive dans les cas de schizophrénie résistant au traitement.


Medical subject headings: telomere; DNA restriction enzymes; blotting, Southern; schizophrenia.

Competing interests: None declared.

Submitted May 28, 2007; Revised Sep. 12, Oct. 29, Dec. 20, 2007; Accepted Dec. 20, 2007

Contributors: Drs. Yu and Cho contributed equally to the work. Drs. Yu and Cho designed the study. Dr. Yu acquired the data, which Drs. Chang, Lin and Cho analyzed. Drs. Yu, Lin and Cho wrote the article, which Drs. Chang and Cho reviewed. All authors gave final approval for publication.

Acknowledgements: Thanks to Dr. Hay-Yan Jack Wang for critical reading and editing and to Mr. Chien-Ming Chen for computer art work for figures.

Correspondence to: Dr. C.-L. Cho, Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, 804, Taiwan; clcho@mail.nsysu.edu.tw