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 circumference >97th 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.
Sacco
Roberto
R
Laboratory of Molecular Psychiatry and Neurogenetics, University Campus Bio-Medico, and I.R.C.C.S. Fondazione Santa Lucia, Rome, Italy.
Militerni
Roberto
R
Frolli
Alessandro
A
Bravaccio
Carmela
C
Gritti
Antonella
A
Elia
Maurizio
M
Curatolo
Paolo
P
Manzi
Barbara
B
Trillo
Simona
S
Lenti
Carlo
C
Saccani
Monica
M
Schneider
Cindy
C
Melmed
Raun
R
Reichelt
Karl-Ludvig
KL
Pascucci
Tiziana
T
Puglisi-Allegra
Stefano
S
Persico
Antonio M
AM
D000293:Adolescent; D000367:Age Factors; D000704:Analysis of Variance; D001321:Autistic Disorder / Q000097:blood* / Q000473:pathology*; D001835:Body Weight; D002508:Cephalometry / Q000379:methods; D002648:Child; D002657:Child Development / Q000502:physiology; D002675:Child, Preschool; D019465:Craniofacial Abnormalities / Q000473:pathology; D005260:Female; D006257:Head / Q000254:growth & development* / Q000473:pathology*; D006801:Humans; D007360:Intelligence; D008297:Male; D010808:Physical Examination; D012016:Reference Values; D012044:Regression Analysis; D012701:Serotonin / Q000097:blood*
D012701:Serotonin