TY - JOUR
T1 - In pursuit of neurophenotypes
T2 - The consequences of having autism and a big brain
AU - Amaral, David G.
AU - Li, Deana
AU - Libero, Lauren
AU - Solomon, Marjorie
AU - Van de Water, Judy
AU - Mastergeorge, Ann
AU - Naigles, Letitia
AU - Rogers, Sally
AU - Wu Nordahl, Christine
N1 - Funding Information:
We are indebted to the many families who have participated for many years in the Autism Phenome Project. We are also grateful to the many research assistants and colleagues who have dedicated time and effort to collecting data summarized in this Commentary. We are open to collaborations in the analysis of the Autism Phenome Project dataset and ask interested investigators to contact the first author for additional information. Grant sponsor NIH (1R01MH089626, 1R01MH103371, R01MH103284, U24MH081810, R01MH104438, R01MH104438-01S1, R00MH085099). Funding was also received from the MIND Institute. The authors have no conflict of interest regarding the contents of this manuscript.
Publisher Copyright:
© 2017 International Society for Autism Research, Wiley Periodicals, Inc.
PY - 2017/5
Y1 - 2017/5
N2 - A consensus has emerged that despite common core features, autism spectrum disorder (ASD) has multiple etiologies and various genetic and biological characteristics. The fact that there are likely to be subtypes of ASD has complicated attempts to develop effective therapies. The UC Davis MIND Institute Autism Phenome Project is a longitudinal, multidisciplinary analysis of children with autism and age-matched typically developing controls; nearly 400 families are participating in this study. The overarching goal is to gather sufficient biological, medical, and behavioral data to allow definition of clinically meaningful subtypes of ASD. One reasonable hypothesis is that different subtypes of autism will demonstrate different patterns of altered brain organization or development i.e., different neurophenotypes. In this Commentary, we discuss one neurophenotype that is defined by megalencephaly, or having brain size that is large and disproportionate to body size. We have found that 15% of the boys with autism demonstrate this neurophenotype, though it is far less common in girls. We review behavioral and medical characteristics of the large-brained group of boys with autism in comparison to those with typically sized brains. While brain size in typically developing individuals is positively correlated with cognitive function, the children with autism and larger brains have more severe disabilities and poorer prognosis. This research indicates that phenotyping in autism, like genotyping, requires a very substantial cohort of subjects. Moreover, since brain and behavior relationships may emerge at different times during development, this effort highlights the need for longitudinal analyses to carry out meaningful phenotyping. Autism Res 2017, 10: 711–722.
AB - A consensus has emerged that despite common core features, autism spectrum disorder (ASD) has multiple etiologies and various genetic and biological characteristics. The fact that there are likely to be subtypes of ASD has complicated attempts to develop effective therapies. The UC Davis MIND Institute Autism Phenome Project is a longitudinal, multidisciplinary analysis of children with autism and age-matched typically developing controls; nearly 400 families are participating in this study. The overarching goal is to gather sufficient biological, medical, and behavioral data to allow definition of clinically meaningful subtypes of ASD. One reasonable hypothesis is that different subtypes of autism will demonstrate different patterns of altered brain organization or development i.e., different neurophenotypes. In this Commentary, we discuss one neurophenotype that is defined by megalencephaly, or having brain size that is large and disproportionate to body size. We have found that 15% of the boys with autism demonstrate this neurophenotype, though it is far less common in girls. We review behavioral and medical characteristics of the large-brained group of boys with autism in comparison to those with typically sized brains. While brain size in typically developing individuals is positively correlated with cognitive function, the children with autism and larger brains have more severe disabilities and poorer prognosis. This research indicates that phenotyping in autism, like genotyping, requires a very substantial cohort of subjects. Moreover, since brain and behavior relationships may emerge at different times during development, this effort highlights the need for longitudinal analyses to carry out meaningful phenotyping. Autism Res 2017, 10: 711–722.
KW - brain development
KW - magnetic resonance imaging
KW - megalencephaly
KW - phenotype
KW - subtypes
UR - http://www.scopus.com/inward/record.url?scp=85013850411&partnerID=8YFLogxK
U2 - 10.1002/aur.1755
DO - 10.1002/aur.1755
M3 - Comment/debate
C2 - 28239961
AN - SCOPUS:85013850411
VL - 10
SP - 711
EP - 722
JO - Autism Research
JF - Autism Research
SN - 1939-3792
IS - 5
ER -