Progress in the study of brain aging characteristics in autism and schizophrenia

Autism (ASD) and schizophrenia (SCZ) are common chronic psychiatric disorders with considerable overlapping features in behavioral, genetic, and neuropathological aspects, suggesting that autism and schizophrenia may share a common neuropathogenesis.

Aging is closely related to dynamic changes in epigenetic effects, and alterations in DNA methylation patterns have been observed in many age-related diseases. The tissue-specific “epigenetic clock” constructed on this basis can accurately predict the physiological age of the sample, so it is called “epigenetic age”. The deviation of epigenetic age from chronological age can be used as an indicator of the rate of aging of organisms.

Recent studies have found that there are systemic and age-related biological changes in the brains of patients with schizophrenia and other psychiatric diseases, but the aging characteristics of different brain regions of autism and schizophrenia patients are not clear. In response to the above problems, researchers at Xi’an Jiaotong University used the whole genome DNA methylation dataset of brain tissues and Horvath’s epigenetic clock algorithm to calculate the epigenetic ages of cerebellum, prefrontal cortex and temporal cortex in three brain regions of autistic patients and cerebellum, striatum and hippocampus in three brain regions in patients with schizophrenia. The Horvath epigenetic clock consists of 353 aging-related CpG sites and uses β Mixed Quantile Normalization (BMIQ) method to standardize DNA methylation data acquired by different platforms. Subsequently, the researchers established regression models of the methylation age and chronological age of each brain region to estimate the epigenetic age acceleration of each brain region. The study found that epigenetic age and chronological age were significantly correlated in different brain regions of autism and schizophrenia patients, suggesting that epigenetic age can be used as an indicator to evaluate the aging rate of brain tissue in autism and schizophrenia patients. The researchers further performed an age stratified analysis of the total sample and found that autistic patients over the age of 45 showed epigenetic aging acceleration in cerebellar tissue, and schizophrenia patients over 50 years old experienced epigenetic aging slowdown in cerebellar regions compared to the control group. After sex stratification of the total sample, no significant difference in epigenetic age acceleration between male and female patients was observed in different brain regions compared with normal controls. The above research results suggest that the cerebellar region of autism and schizophrenia deviates from the normal aging trajectory, which provides new important scientific clues for revealing the occurrence and development mechanism of autism and schizophrenia.

The results reveal the mechanism of the occurrence and development of autism and schizophrenia, and provide new important scientific clues. (Photo courtesy of Xi’an Jiaotong University)

Recently, the results were published online in the international authoritative journal “Molecular Psychosis” in the international authoritative journal of mental illness research entitled “Epigenetic analysis shows abnormal cerebellar aging in elderly people with autism spectrum disorder and schizophrenia”. Liu Li, a 2019 doctoral student at the School of Public Health of Xi’an Jiaotong University, is the first author, Qi Xin of the Precision Medicine Research Center of the First Affiliated Hospital is the co-first author of the paper, and Professor Zhang Feng of the School of Public Health of Xi’an Jiaotong University is the only corresponding author of the paper. (Source: Yan Tao, China Science News)

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