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.
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 autisticpatients. METHODS: Fronto-occipital head circumference was measured in 241 nonsyndromic autisticpatients, 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.
Authors: Pauline Chaste; Lambertus Klei; Stephan J Sanders; Michael T Murtha; Vanessa Hus; Jennifer K Lowe; A Jeremy Willsey; Daniel Moreno-De-Luca; Timothy W Yu; Eric Fombonne; Daniel Geschwind; Dorothy E Grice; David H Ledbetter; Catherine Lord; Shrikant M Mane; Christa Lese Martin; Donna M Martin; Eric M Morrow; Christopher A Walsh; James S Sutcliffe; Matthew W State; Bernie Devlin; Edwin H Cook; Soo-Jeong Kim Journal: Biol Psychiatry Date: 2013-06-06 Impact factor: 13.382
Authors: Wendy Froehlich; Sue Cleveland; Andrea Torres; Jennifer Phillips; Brianne Cohen; Tiffany Torigoe; Janet Miller; Angie Fedele; Jack Collins; Karen Smith; Linda Lotspeich; Lisa A Croen; Sally Ozonoff; Clara Lajonchere; Judith K Grether; Joachim Hallmayer Journal: J Autism Dev Disord Date: 2013-09
Authors: Armin Raznahan; Gregory L Wallace; Ligia Antezana; Dede Greenstein; Rhoshel Lenroot; Audrey Thurm; Marta Gozzi; Sarah Spence; Alex Martin; Susan E Swedo; Jay N Giedd Journal: Biol Psychiatry Date: 2013-05-23 Impact factor: 13.382