Evidence of Brain Overgrowth in the First Year of Life in Autism

Abstract

Context Autism most commonly appears by 2 to 3 years of life, at which time the brain is already abnormally large. This raises the possibility that brain overgrowth begins much earlier, perhaps before the first clinically noticeable behavioral symptoms. Objectives To determine whether pathological brain overgrowth precedes the first clinical signs of autism spectrum disorder (ASD) and whether the rate of overgrowth during the first year is related to neuroanatomical and clinical outcome in early childhood. Design, Setting, and Participants Head circumference (HC), body length, and body weight measurements during the first year were obtained from the medical records of 48 children with ASD aged 2 to 5 years who had participated in magnetic resonance imaging studies. Of these children, 15 (longitudinal group) had measurements at 4 periods during infancy: birth, 1 to 2 months, 3 to 5 months, and 6 to 14 months; and 33 (partial HC data group) had measurements at birth and 6 to 14 months (n=7), and at birth only (n=28). Main Outcome Measures Age-related changes in infants with ASD who had multiple-age measurements, and the relationship of these changes to brain anatomy and clinical and diagnostic outcome at 2 to 5 years were evaluated by using 2 nationally recognized normative databases: cross-sectional normative data from a national survey and longitudinal data of individual growth. Results Compared with normative data of healthy infants, birth HC in infants with ASD was significantly smaller (z=-0.66, PϽ.001); after birth, HC increased 1.67 SDs and mean HC was at the 84th percentile by 6 to 14 months. Birth HC was related to cerebellar gray matter volume at 2 to 5 years, although the excessive increase in HC between birth and 6 to 14 months was related to greater cerebral cortex volume at 2 to 5 years. Within the ASD group, every child with autistic disorder had a greater increase in HC between birth and 6 to 14 months (mean [SD], 2.19 [0.98]) than infants with pervasive developmental disorder-not otherwise specified (0.58 [0.35]). Only 6% of the individual healthy infants in the longitudinal data showed accelerated HC growth trajectories (Ͼ2.0 SDs) from birth to 6 to 14 months; 59% of infants with autistic disorder showed these accelerated growth trajectories. Conclusions The clinical onset of autism appears to be preceded by 2 phases of brain growth abnormality: a reduced head size at birth and a sudden and excessive increase in head size between 1 to 2 months and 6 to 14 months. Abnormally accelerated rate of growth may serve as an early warning signal of risk for autism.

Modeling early cortical serotonergic deficits in autism

“…These results suggest that forebrain neonatal 5-HT depletion causes permanent morphologic changes in the structure of the cerebral cortex, and these developmental alterations are evident within one week of serotonergic manipulation, at PND 7. This age in mouse is similar, in terms of cortical maturation, to the youngest children with autism who have increased cortical volumes [36][37][38]111].…”

“…-stereotypical behaviors, impaired verbal and nonverbal communication and blunted social interaction) are accompanied by structural and functional changes in cortex, cerebellum and amygdala [3,4,7,8,[19][20][21][22]37,38,49,55,67,101,125]. Structural and functional changes apparent in early childhood suggest that autism is a disorder of brain development [4,19,20,[37][38][39]111].…”

Proteomic studies identified a single nucleotide polymorphism in glyoxalase I as autism susceptibility factor

“…Since autism in an early developmental disorder, molecules that affect cell growth can be possible sites of biological defects. Courchesne et al [2003] have recently shown that autistic children have abnormal growth of the brain in the first year of life.…”

The ups and downs of Wnt signaling in prevalent neurological disorders

“…Neuroanatomical observations, along with data from functional magnetic resonance imaging, have shown that a major pathological hallmark in autistic individuals may be a premature brain overgrowth affecting structures such as the cerebral cortex, the limbic system, including the hippocampal formation and the amygdala, and the cerebellum (Courchesne et al, 2001(Courchesne et al, , 2003Sparks et al, 2002;Schumann et al, 2004). Such overgrowth would happen early before clinical diagnosis is made consistent with the possibility that growth factors, which normally regulate cell differentiation, proliferation and survival, having a functional role in the disease.…”