Long-term effect of prenatal exposure to malnutrition on risk of schizophrenia in adulthood: Evidence from the Chinese famine of 1959–1961

Schizophrenia is a common major mental disorder and prenatal nutritional deficiency may increase its risk. We aimed to investigate long-term impact of prenatal exposure to malnutrition on risk of schizophrenia in adulthood using the Chinese famine of 1959-1961 as a natural experiment.We obtained data from the Second National Sample Survey on Disability implemented in 31 provinces in 2006, and restricted our analysis to 387,093 individuals born from 1956 to 1965. Schizophrenia was ascertained by psychiatrists based on the International Statistical Classification of Diseases, Tenth Revision. Famine severity was defined as cohort size shrinkage index. The famine effect on adult schizophrenia was estimated by difference-in-difference models, established by examining the variations of famine exposure across birth cohorts.Compared with the reference cohort of 1965, famine cohorts (1959-1962) had significantly higher odds (OR: 1.84; 95% CI: 1.13, 3.00; P = 0.014) of schizophrenia in the rural population. After adjusting for multiple covariates, this association remained significant (OR: 1.82; 95% CI: 1.11, 2.98; P = 0.018). We did not observe statistically significant differences in odds of schizophrenia among famine cohorts compared with the reference cohort in the urban population.Prenatal malnutrition exposure has a detrimental impact on risk of schizophrenia in adulthood in the rural population. Further studies were needed to investigate corresponding mechanisms on this topic.