Pawelczyk Tomasz, Szymanska Bozena, Grancow-Grabka Marta, Kotlicka-Antczak Magdalena, Pawelczyk Agnieszka
Department of Affective and Psychotic Disorders, Medical University of Lodz, Czechoslowacka, Lodz, Poland.
Central Scientific Laboratory, Medical University of Lodz, Mazowiecka, Lodz, Poland.
Neuropsychiatr Dis Treat. 2015 Jun 22;11:1493-503. doi: 10.2147/NDT.S82468. eCollection 2015.
Telomere shortening is strongly associated with higher mortality rates and has been shown in a number of age-related diseases, such as cardiovascular disorders, diabetes mellitus, Alzheimer's disease, and psychiatric disorders. Oxidative stress is known to induce DNA breaks and genome instability. Telomeric DNA rich in guanosine is particularly sensitive to such oxidative damages. Psychosis is associated with a disequilibrium between free radical production and antioxidative defense. Although telomere attrition has been demonstrated in schizophrenia, no relationship has been reported between telomere length and severity of schizophrenia.
The aim of the present study was to identify differences in telomere length in peripheral blood cells between patients with chronic schizophrenia (C-SCZ) and early schizophrenia (E-SCZ) and to identify any relationship between telomere length and disease chronicity and severity.
Relative average telomere lengths were determined using qPCR assay in patients with E-SCZ (n=42) and C-SCZ (n=44) hospitalized due to schizophrenia exacerbation. E-SCZ was diagnosed when less than 2 years had passed since the beginning of psychotic symptoms. The severity of symptoms was assessed using appropriate scales.
The severity of schizophrenia symptoms, as well as the number of psychotic episodes and hospital admissions, correlated significantly with telomere length in univariate analyses. Regression analysis revealed that a model incorporating study group (E-SCZ or C-ECZ), sex, and age, as well as the combined number of documented psychotic episodes and hospital admissions, can significantly predict the length of telomeres in patients with schizophrenia, with over 50% of variance in telomere length explained by the model (adjusted R (2)=0.512).
The results of the current study indicate that the recurrence of psychotic symptoms as well as their intensity and chronicity may be correlated with telomere attrition, which is well known to contribute to the development of premature senescence and age-related diseases.
端粒缩短与较高的死亡率密切相关,并且在许多与年龄相关的疾病中都有体现,如心血管疾病、糖尿病、阿尔茨海默病和精神疾病。已知氧化应激会导致DNA断裂和基因组不稳定。富含鸟苷的端粒DNA对这种氧化损伤尤为敏感。精神病与自由基产生和抗氧化防御之间的失衡有关。虽然在精神分裂症中已证实存在端粒损耗,但尚未有报道表明端粒长度与精神分裂症的严重程度之间存在关联。
本研究的目的是确定慢性精神分裂症(C-SCZ)患者和早期精神分裂症(E-SCZ)患者外周血细胞中端粒长度的差异,并确定端粒长度与疾病慢性程度和严重程度之间的任何关系。
使用qPCR测定法确定因精神分裂症加重而住院的E-SCZ患者(n = 42)和C-SCZ患者(n = 44)的相对平均端粒长度。自精神病症状开始起不到2年被诊断为E-SCZ。使用适当的量表评估症状的严重程度。
在单变量分析中,精神分裂症症状的严重程度以及精神病发作次数和住院次数与端粒长度显著相关。回归分析显示,一个包含研究组(E-SCZ或C-ECZ)、性别、年龄以及记录的精神病发作次数和住院次数总和的模型,可以显著预测精神分裂症患者的端粒长度,该模型解释了端粒长度超过50%的方差(调整后R(2)=0.512)。
本研究结果表明,精神病症状的复发及其强度和慢性程度可能与端粒损耗相关,而端粒损耗众所周知会导致早衰和与年龄相关疾病的发展。