Famine exposure during pregnancy induces changes in the DNA methylation of genes related to neuronal, neuroendocrine, and immune functions. These alterations are suggested to play a causal role in fostering the onset of mental disorders, particularly schizophrenia and depression, in the adult offspring.

This systematic review and meta-analysis sought to examine the relationship between exposure to prenatal famine, DNA methylation changes, and the occurrence of mental disorders in adult offspring. Additionally, the study explored whether modifications in DNA methylation resulting from prenatal famine exposure were prospectively linked to mental diseases.

A comprehensive search of the PubMed and PsycINFO databases was conducted to recognize relevant records up to September 2022. The focus was on individuals whose mothers encountered famine directly prior to and/or during their pregnancy phase. The assessment centered on the influence of prenatal famine exposure on the offspring's DNA methylation, mental illness, or related symptoms.

Adults exposed to famine in the womb had a heightened risk of developing schizophrenia and depression. Multiple studies indicated a connection between prenatal famine exposure and either increased or decreased methylation of specific genes. Among these, the IGF2 gene illustrated the most consistent differences in DNA methylation. The modified DNA methylation of the DUSP22 gene was identified as a mediator in the link between prenatal famine and schizophrenia in adult offspring.

The findings of the meta-analysis substantiated a heightened risk of schizophrenia after prenatal exposure to famine. However, due to variations in microarrays and data processing approaches, a meta-analysis for DNA methylation was deemed unsuitable.

Prenatal exposure to famine is linked to an escalated risk of mental disorders and shifts in DNA methylation. Hence, modifications in the DNA methylation of genes implicated in neuronal, neuroendocrine, and immune processes could be a mechanism contributing to the development of mental illnesses like depression and schizophrenia in the adult offspring.

Such insights are crucial given the global rise in undernutrition, which amplifies the risk of famine and, consequently, adverse effects on mental health.