Childhood maltreatment increases schizophrenia risk 5-fold

Childhood maltreatment increases the risk of schizophrenia by five-fold, attention deficit hyperactivity disorder (ADHD) by 10-fold, and major depressive disorder (MDD) by nearly two-fold. It also leaves lasting genetic markers linked to neurodegenerative conditions, including Alzheimer’s disease and Parkinson’s disease, a Mendelian randomization study has shown.

According to the Social Welfare Department in Hong Kong, newly reported cases of childhood maltreatment surged from 940 in 2020 to 1,504 in 2024, representing a 60 percent increase. [www.swd.gov.hk/vs/index_e.html#s3]

Mendelian randomization

“Observational studies suggested an association between childhood maltreatment and neuropsychiatric disorders, but these studies rely mainly on long-term follow-ups and questionnaires, which are susceptible to confounding factors, such as environment and social background,” said the research team lead, Dr Brian Hon-Yin Chung of the Department of Paediatrics and Adolescent Medicine at the University of Hong Kong (HKU).

Using genomic data from the UK Biobank and the Psychiatric Genomics Consortium, HKU’s researchers performed Mendelian randomization to evaluate the effect of childhood maltreatment (n=143,473) on the risks of six neuropsychiatric disorders (up to n=500,199). [Br J Psychiatry 2025; doi:10.1192/bjp.2025.10433]

“By applying the rigorous Mendelian randomization method, which is ranked just below randomized controlled trials in the evidence hierarchy, our team has established a causal relationship linking childhood maltreatment to common neuropsychiatric conditions,” said Professor Yiu-Fai Cheung, Chairperson of the Department of Paediatrics and Adolescent Medicine, HKU.

Elevated neuropsychiatric risk

Childhood maltreatment was significantly associated with higher risks of ADHD (odds ratio [OR], 10.09; 95 percent confidence interval [CI], 4.76–21.40), MDD (OR, 1.89; 95 percent CI, 1.32–2.70), and schizophrenia (OR, 5.89; 95 percent CI, 1.46–23.78).

Beyond direct psychological harm, childhood maltreatment leaves epigenetic changes in DNA methylation at 10 genetic locations near nine critical genes. Of note, three of these genes — CLU, MAPT, and HNRNPK — were associated with neurodegenerative conditions, including Alzheimer’s disease and Parkinson’s disease.

“By identifying specific DNA methylation markers, we aim to develop early biomarker screening for high-risk populations in the future and even explore novel therapeutic targets for drug development to reduce disease risk at its source,” highlighted Chung.

Modifiable risk factors

Approximately 4–22 percent of the effect of childhood maltreatment was mediated by addiction-related behaviours (eg, smoking initiation, prolonged screen time, and substance abuse), cognitive traits (eg, executive functioning, intelligence, and risk tolerance), and educational attainment.

“While the influence of these factors varies across different neuropsychiatric disorders, they are all modifiable,” pointed out Chung. “Interventions aimed at improving behaviours, enhancing cognitive ability, and providing educational support during development can effectively lower the risk of neuropsychiatric disorders.”

Prevention remains key

“The long-term epigenetic markers left by childhood maltreatment may be difficult to reverse,” Chung pointed out. “Therefore, preventing childhood maltreatment remains the most fundamental strategy to protect children.”

Effective from 20 January 2026, Hong Kong’s Mandatory Reporting of Child Abuse Ordinance requires professionals in the healthcare, education, and social welfare sectors to report suspected serious child abuse or risk of harm, to enhance child protection measures further. [www.elegislation.gov.hk/hk/cap650]