No abstract

Delineating longitudinal relationships between early developmental markers, adult cognitive function, and adult brain structure could clarify the pathogenesis of neurodevelopmental disorders such as schizophrenia. We aimed to identify brain structural correlates of infant motor development (IMD) and adult executive function in nonpsychotic adults and to test for abnormal associations between these measures in people with schizophrenia. Representative samples of nonpsychotic adults (n ‫؍‬ 93) and people with schizophrenia (n ‫؍‬ 49) were drawn from the Northern Finland 1966 general population birth cohort. IMD was prospectively assessed at age 1 year; executive function testing and MRI were completed at age 33-35 years. We found that earlier motor development in infancy was correlated with superior executive function in nonpsychotic subjects. Earlier motor development was also normally associated with increased gray matter density in adult premotor cortex, striatum, and cerebellum and increased white matter density in frontal and parietal lobes. Adult executive function was normally associated with increased gray matter density in a fronto-cerebellar system that partially overlapped, but was not identical to, the gray matter regions normally associated with IMD. People with schizophrenia had relatively delayed IMD and impaired adult executive function in adulthood. Furthermore, they demonstrated no normative associations between frontocerebellar structure, IMD, or executive function. We conclude that frontal cortico-cerebellar systems correlated with adult executive function are anatomically related to systems associated with normal infant motor development. Disruption of this anatomical system may underlie both the early developmental and adult cognitive abnormalities in schizophrenia.L ittle is known about how the early development of the human brain predicts its adult structure. Several twin studies have established that adult brain structure is heritable (1, 2), but these designs cannot address questions concerning the timing of genetic effects on neuroanatomical variation in adults. Hypothetically, the responsible genetic differences may be expressed during early brain development with anatomical effects being conserved over the course of childhood and adolescence, albeit conditioned by environmental factors and gene ϫ environment interactions (3).It would be useful to know more about (dis)continuities between early developmental markers and adult brain structure as a basis for better understanding of the pathogenesis of psychiatric disorders such as schizophrenia, which typically present in young adults but may be predicted, at least in part, by earlier neurodevelopmental aberration. Longitudinal epidemiological studies of schizophrenia show early developmental adversity imparting increased risk of adult psychosis, with the emergence of psychotic symptoms preceded by subtle abnormalities of motor coordination (developmental dysmetria), social function, and cognition in childhood and adolescence (4-6). Typic...