Although the primary onset of schizophrenia is during adolescence to young adulthood, an early developmental origin of schizophrenia has been implied by improperly clustered immature neurons in cortical layers II, III, and V1, changes in the hippocampal nonpyramidal CA2 neurons2, as well as hypoplastic midbrain dopamine neurons3–6. Such changes in brain structure most likely develop in utero during the late first and early second trimester7–9. Additionally, disorganization of the white matter tract has been observed in schizophrenia10, suggesting that the disease affects not only the development and function of neurons, but also their projections. The variability in brain malformations are thought to underlie the variety of clinical findings: positive symptoms (delusions and hallucinations), negative symptoms (affective flattening, amotivation, and anhedonia)11,12, and cognitive symptoms (disorganized speech and cognitive deficits) (DSM 4th edition). Abnormal development during the first trimester is also consistent with minor physical anomalies associated with schizophrenia13.
