Schizophrenia Genetic Risk Peaks During Early Childhood Development

Schizophrenia is frequently diagnosed in adulthood, yet its biological roots often stretch back to the earliest stages of brain formation. A recent study has illuminated the role of FOXP1, a critical transcription factor—a protein that acts like a switch to turn other genes on or off—in this developmental timeline. By analysing transcriptomic data from mouse models and human brain organoids, researchers mapped how genes regulated by FOXP1 contribute to schizophrenia risk across different life stages.

The findings reveal that genetic vulnerability is highly dynamic rather than constant. The research team compared developmental time points in mice to human equivalents: the third trimester, early childhood, and adolescence. While significant links to schizophrenia heritability were found in the prenatal stage and adolescence, the data uncovered a distinct spike in risk during the period mapping to early childhood (P7 in mice). Conversely, the stage equivalent to the third trimester showed no significant enrichment.

Further investigation highlighted that these FOXP1-regulated genes are crucial for the function of synapses, the junctions where neurons communicate. The risk was predominantly located within glutamatergic excitatory neurons during childhood, expanding to include GABAergic inhibitory neurons by adolescence. This suggests that the molecular pathways influencing schizophrenia susceptibility are most active and potentially vulnerable during the specific wiring phases of early childhood.