Brain enlargement is associated with regression in preschool-age boys with autism spectrum disorders

Journal List Proc Natl Acad Sci U S A v.108(50); 2011 Dec 13 PMC3250128

Brain enlargement is associated with regression in preschool-age boys with autism spectrum disorders

Christine Wu Nordahl, Nicholas Lange, Deana D. Li, Lou Ann Barnett, Aaron Lee, Michael H. Buonocore, Tony J. Simon, Sally Rogers, Sally Ozonoff, and David G. Amarala,

Neuroscience Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.) Institute and Department of Psychiatry and Behavioral Sciences, UC Davis School of Medicine,
University of California, Sacramento, CA 95817; Departments of Psychiatry and Biostatistics,
Harvard University Schools of Medicine and Public Health, McLean Hospital, Belmont, MA 02478; and
Department of Radiology, UC Davis School of Medicine, University of California, Sacramento, CA 95817

ABSTRACT

Autism is a heterogeneous disorder with multiple behavioral and biological phenotypes. Accelerated brain growth during early childhood is a well-established biological feature of autism. Onset pattern, i.e., early onset or regressive, is an intensely studied behavioral phenotype of autism. There is currently little known, however, about whether, or how, onset status maps onto the abnormal brain growth. We examined the relationship between total brain volume and onset status in a large sample of 2- to 4-y-old boys and girls with autism spectrum disorder (ASD) [n = 53, no regression (nREG); n = 61, regression (REG)] and a comparison group of age-matched typically developing controls (n = 66). We also examined retrospective head circumference measurements from birth through 18 mo of age. We found that abnormal brain enlargement was most commonly found in boys with regressive autism. Brain size in boys without regression did not differ from controls. Retrospective head circumference measurements indicate that head circumference in boys with regressive autism is normal at birth but diverges from the other groups around 4–6 mo of age. There were no differences in brain size in girls with autism (n = 22, ASD; n = 24, controls). These results suggest that there may be distinct neural phenotypes associated with different onsets of autism. For boys with regressive autism, divergence in brain size occurs well before loss of skills is commonly reported. Thus, rapid head growth may be a risk factor for regressive autism.