Clinical, Morphological, and Biochemical Correlates of Head Circumference in Autism

Background: Head growth rates are often accelerated in autism. This study is aimed at defining the clinical, morphological, and biochemical correlates of head circumference in autistic patients. Methods: Fronto-occipital head circumference was measured in 241 nonsyndromic autistic patients, 3 to 16 years old, diagnosed according to DSM-IV criteria. We assessed 1) clinical parameters using the Autism Diagnostic Observation Schedule, Autism Diagnostic Interview-Revised, Vineland Adaptive Behavioral Scales, intelligence quotient measures, and an ad hoc clinical history questionnaire; 2) height and weight; 3) serotonin (5-HT) blood levels and peptiduria. Results: The distribution of cranial circumference is significantly skewed toward larger head sizes (p .00001). Macrocephaly (i.e., head circumference97th percentile) is generally part of a broader macrosomic endophenotype, characterized by highly significant correlations between head circumference, weight, and height (p .001). A head circumference 75th percentile is associated with more impaired adaptive behaviors and with less impairment in IQ measures and motor and verbal language development. Surprisingly, larger head sizes are significantly associated with a positive history of allergic/immune disorders both in the patient and in his/her first-degree relatives. Conclusions: Our study demonstrates the existence of a macrosomic endophenotype in autism and points toward pathogenetic links with immune dysfunctions that we speculate either lead to or are associated with increased cell cycle progression and/or decreased apoptosis.