#7098 Head circumference trajectories in autism and psychotic experiences

<h3>Funders</h3> Beatrice and Samuel Seaver Foundation (Seaver Autism Center, Icahn School of Medicine, Mount Sinai). <h3>Background</h3> Head circumference is a strong predictor of brain size and can offer important insights into neurodevelopment. Growing evidence suggests that autism is associated with early brain overgrowth and enlarged head size, however the timing and persistence of these differences is unclear. Similarly, psychotic disorders such as schizophrenia are associated with reduced brain volume in adulthood, however little is known about how the brain develops prior to clinical onset. Recruiting samples at risk for psychosis may help identify important biomarkers associated with the development of psychotic disorder. <h3>Method</h3> We charted head circumference from birth to 15 years using data from a longitudinal birth cohort (the Avon Longitudinal Study of Parents and Children [ALSPAC]). Linear mixed regressions compared trajectories in children with a clinical ASD diagnosis (N = 78), high autistic traits (N = 639), psychotic experiences (339), and controls (~N = 6,404), adjusting for several potential confounders. Exploratory analyses were conducted for a smaller sample of those with ASD and cognitive learning needs (CLN), as well as those with psychotic disorder. <h3>Results</h3> ASD was associated with increased head circumference across childhood and adolescence compared to controls (fully adjusted model: mean difference [MD] = 0.38 cm, 95% CI: 0.003 – 0.75, p = 0.048), emerging from 2 months of age. Interactions with sex were non-significant, and differences were more marked in those with ASD and CLN. In contrast, autistic traits were associated with smaller head circumference compared to controls (multivariable model 5: MD = -0.16 cm, CI: -0.28 – 0.03, p = 0.016). Psychotic experiences were associated with significantly smaller head circumference in females compared to female controls (MD = -0.25 cm, 95% CI: -0.46 to -0.04, p = 0.022), whereas males with psychotic experiences showed significantly larger head circumference than male controls. Those with psychotic experiences and social dysfunction and/or help-seeking (‘psychotic disorder’) had reduced head circumference (males and females) compared to controls (MD = -0.25 cm, 95% CI: -0.46 to -0.04, p = 0.022). <h3>Conclusions</h3> Head circumference trajectories are atypical in ASD as early as 2 months and persist until adolescence. Our results suggest distinct physiological differences between clinical cases and those with traits, as larger head circumference was seen in the former. Head circumference trajectories in those with psychotic experiences were differentiated by sex, whereas psychotic disorder was associated with reduced head circumference regardless of sex. These findings implicate altered trajectories of brain development specific to ASD and psychosis.