Decoding Parental Expression Patterns of Imprinted Genes: A Pathway to Regulate the Neuropsychiatric and Affective Disorders

Abstract Imprinted genes, expressed from only one parental allele, contribute to neurodevelopmental and mood disorders─including depression, bipolar disorder, and anxiety─through mechanisms such as dosage imbalance, early adversity, sex-specific epigenetic changes, and altered imprinting in the placenta or blood. Key imprinted genes including paternal IGF2 and DLK1, maternal H19, MEG3 and UBE3A, and complex GRB10 regulate neurogenesis, neuronal differentiation, and synaptic plasticity, suggesting that restoring imprint balance may serve as a therapeutic target. This review provides a comprehensive summary of the molecular mechanisms, regulatory characteristics, and methodologies associated with imprinted genes, emphasizing their parent-specific epigenetic roles in neural circuits and development. We also summarize their roles in neuropsychiatric and affective disorders. A deeper understanding of the complex interplay between imprinted genes and their regulatory networks is essential for developing targeted interventions for neural development and emotional neurological disorders.