Altered growth trajectory of head circumference during infancy and schizophrenia in a National Birth Cohort

Identification of abnormalities in the developmental trajectory during infancy of future schizophrenia cases offers the potential to reveal pathogenic mechanisms of this disorder. Previous studies of head circumference in pre-schizophrenia were limited to measures at birth. The use of growth acceleration of head circumference (defined as the rate of change in head circumference) provides a more informative representation of the maturational landscape of this measure compared to studies based on static head circumference measures. To date, however, no study has examined whether HC growth acceleration differs between pre-schizophrenia cases and controls. In the present study, we employed a nested case control design of a national birth cohort in Finland. Cases with schizophrenia or schizoaffective disorder (N=375) and controls (N=375) drawn from the birth cohort were matched 1:1 on date of birth (within 1month), sex, and residence in Finland at case diagnosis. Longitudinal data were obtained on head circumference from birth through age 1. Data were analyzed using a new nonparametric Bayesian inversion method which allows for a detailed understanding of growth dynamics. Adjusting for growth velocity of height and weight, and gestational age, there was significantly accelerated growth of head circumference in females with schizophrenia from birth to 2months; the findings remained significant following Bonferroni correction (p<0.0125). This is the first study to report abnormal HC growth acceleration, a more sensitive measure of somatic developmental deviation of this measure, in schizophrenia.