Markkanen Enni, Meyer Urs, Dianov Grigory L
Institute of Pharmacology and Toxicology, Vetsuisse Faculty, University of Zürich, Winterthurerstrasse 260, Zürich 8057, Switzerland.
Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK.
Int J Mol Sci. 2016 Jun 1;17(6):856. doi: 10.3390/ijms17060856.
Schizophrenia and autism spectrum disorder (ASD) are multi-factorial and multi-symptomatic psychiatric disorders, each affecting 0.5%-1% of the population worldwide. Both are characterized by impairments in cognitive functions, emotions and behaviour, and they undermine basic human processes of perception and judgment. Despite decades of extensive research, the aetiologies of schizophrenia and ASD are still poorly understood and remain a significant challenge to clinicians and scientists alike. Adding to this unsatisfactory situation, patients with schizophrenia or ASD often develop a variety of peripheral and systemic disturbances, one prominent example of which is cancer, which shows a direct (but sometimes inverse) comorbidity in people affected with schizophrenia and ASD. Cancer is a disease characterized by uncontrolled proliferation of cells, the molecular origin of which derives from mutations of a cell's DNA sequence. To counteract such mutations and repair damaged DNA, cells are equipped with intricate DNA repair pathways. Oxidative stress, oxidative DNA damage, and deficient repair of oxidative DNA lesions repair have been proposed to contribute to the development of schizophrenia and ASD. In this article, we summarize the current evidence of cancer comorbidity in these brain disorders and discuss the putative roles of oxidative stress, DNA damage and DNA repair in the aetiopathology of schizophrenia and ASD.
精神分裂症和自闭症谱系障碍(ASD)是多因素、多症状的精神疾病,全球发病率均为0.5%-1%。二者均以认知功能、情感和行为受损为特征,破坏人类基本的感知和判断过程。尽管经过数十年广泛研究,精神分裂症和自闭症谱系障碍的病因仍知之甚少,对临床医生和科学家而言仍是重大挑战。更糟糕的是,精神分裂症或自闭症谱系障碍患者常出现各种外周和全身紊乱,其中一个突出例子是癌症,在精神分裂症和自闭症谱系障碍患者中呈现直接(但有时相反)的共病关系。癌症是一种以细胞不受控制增殖为特征的疾病,其分子起源源于细胞DNA序列突变。为对抗此类突变并修复受损DNA,细胞具备复杂的DNA修复途径。氧化应激、氧化性DNA损伤及氧化性DNA损伤修复缺陷被认为与精神分裂症和自闭症谱系障碍的发病有关。在本文中,我们总结了这些脑部疾病中共病癌症的现有证据,并讨论了氧化应激、DNA损伤和DNA修复在精神分裂症和自闭症谱系障碍病因病理中的潜在作用。