DNA Damage and Repair in Schizophrenia and Autism: Implications for Cancer Comorbidity and Beyond.
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.
Institute of Pharmacology and Toxicology, Vetsuisse Faculty, University of Z&#252;rich, Winterthurerstrasse 260, Z&#252;rich 8057, Switzerland. enni.markkanen@vetpharm.uzh.ch.
Enni
E
Markkanen
Institute of Pharmacology and Toxicology, Vetsuisse Faculty, University of Z&#252;rich, Winterthurerstrasse 260, Z&#252;rich 8057, Switzerland. urs.meyer@vetpharm.uzh.ch.
Urs
U
Meyer
Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK. grigory.dianov@oncology.ox.ac.uk.|Institute of Cytology and Genetics, Russian Academy of Sciences, Lavrentyeva 10, Novosibirsk 630090, Russia. grigory.dianov@oncology.ox.ac.uk.
Grigory L
GL
Dianov
D000818:Animals; D000067877:Autism Spectrum Disorder / Q000175:diagnosis / Q000209:etiology / Q000235:genetics; D001321:Autistic Disorder / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D015897:Comorbidity; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D009369:Neoplasms / Q000209:etiology / Q000378:metabolism; D018384:Oxidative Stress; D012306:Risk; D012559:Schizophrenia / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism
DNA base excision repair; XRCC1; autism; cancer; neurodevelopmental disorders; oxidative DNA damage; oxidative stress; schizophrenia