Increased Extra-axial Cerebrospinal Fluid in High-Risk Infants Who Later Develop Autism.

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TitleIncreased Extra-axial Cerebrospinal Fluid in High-Risk Infants Who Later Develop Autism.
Publication TypeJournal Article
Year of Publication2017
AuthorsShen, MD, Kim, SHyung, Mckinstry, RC, Gu, H, Hazlett, HC, Nordahl, CW, Emerson, RW, Shaw, D, Elison, JT, Swanson, MR, Fonov, VS, Gerig, G, Dager, SR, Botteron, KN, Paterson, S, Schultz, RT, Evans, AC, Estes, AM, Zwaigenbaum, L, Styner, MA, Amaral, DG, Piven, J, Piven, J, Hazlett, HC, Chappell, C, Dager, S, Estes, A, Shaw, D, Botteron, K, McKinstry, R, Constantino, J, Pruett, J, Schultz, R, Zwaigenbaum, L, Elison, J, Evans, AC, Collins, DL, Pike, GB, Fonov, V, Kostopoulos, P, Das, S, Gerig, G, Styner, M, Gu, H
Corporate AuthorsInfant Brain Imaging Study Network, Infant Brain Imaging Study Network, The Infant Brain Imaging Study (IBIS) Network is a National Institutes of Health–funded Autism Center of Excellence project and consists of a consortium of eight universities in the United States and Canada
JournalBiol Psychiatry
Volume82
Issue3
Pagination186-193
Date Published2017 Aug 01
ISSN1873-2402
KeywordsAutism Spectrum Disorder, Axis, Cervical Vertebra, Cerebral Ventricles, Cerebrospinal Fluid, Child, Preschool, Female, Genetic Predisposition to Disease, Humans, Image Processing, Computer-Assisted, Infant, Longitudinal Studies, Magnetic Resonance Imaging, Male, Motor Skills, Organ Size, Pattern Recognition, Automated, Prodromal Symptoms, Prognosis, Sensitivity and Specificity, Severity of Illness Index, Siblings, Subarachnoid Space
Abstract

BACKGROUND: We previously reported that infants who developed autism spectrum disorder (ASD) had increased cerebrospinal fluid (CSF) in the subarachnoid space (i.e., extra-axial CSF) from 6 to 24 months of age. We attempted to confirm and extend this finding in a larger independent sample.METHODS: A longitudinal magnetic resonance imaging study of infants at risk for ASD was carried out on 343 infants, who underwent neuroimaging at 6, 12, and 24 months. Of these infants, 221 were at high risk for ASD because of an older sibling with ASD, and 122 were at low risk with no family history of ASD. A total of 47 infants were diagnosed with ASD at 24 months and were compared with 174 high-risk and 122 low-risk infants without ASD.RESULTS: Infants who developed ASD had significantly greater extra-axial CSF volume at 6 months compared with both comparison groups without ASD (18% greater than high-risk infants without ASD; Cohen's d = 0.54). Extra-axial CSF volume remained elevated through 24 months (d = 0.46). Infants with more severe autism symptoms had an even greater volume of extra-axial CSF from 6 to 24 months (24% greater at 6 months, d = 0.70; 15% greater at 24 months, d = 0.70). Extra-axial CSF volume at 6 months predicted which high-risk infants would be diagnosed with ASD at 24 months with an overall accuracy of 69% and corresponding 66% sensitivity and 68% specificity, which was fully cross-validated in a separate sample.CONCLUSIONS: This study confirms and extends previous findings that increased extra-axial CSF is detectable at 6 months in high-risk infants who develop ASD. Future studies will address whether this anomaly is a contributing factor to the etiology of ASD or an early risk marker for ASD.

DOI10.1016/j.biopsych.2017.02.1095
Alternate JournalBiol. Psychiatry
PubMed ID28392081
PubMed Central IDPMC5531051
Grant ListU54 HD083091 / HD / NICHD NIH HHS / United States
T32 HD040127 / HD / NICHD NIH HHS / United States
K99 MH108700 / MH / NIMH NIH HHS / United States
U54 HD086984 / HD / NICHD NIH HHS / United States
R01 HD059854 / HD / NICHD NIH HHS / United States
AS6020 / / Autism Speaks / United States
R01 HD055741 / HD / NICHD NIH HHS / United States