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Biol Psychiatry. 2017 Aug 1;82(3):186-193. doi: 10.1016/j.biopsych.2017.02.1095. Epub 2017 Mar 6.

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

Author information

1
Carolina Institute for Developmental Disabilities and Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina; MIND Institute and Department of Psychiatry and Behavioral Sciences, University of California, Davis, School of Medicine, Sacramento, California. Electronic address: mark_shen@med.unc.edu.
2
Carolina Institute for Developmental Disabilities and Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina.
3
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missourt.
4
Carolina Institute for Developmental Disabilities and Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina; Department of Biostatistics, School of Global Public Health, University of North Carolina at Chapel Hill School of Global Public Health, Chapel Hill, North Carolina.
5
MIND Institute and Department of Psychiatry and Behavioral Sciences, University of California, Davis, School of Medicine, Sacramento, California.
6
Department of Radiology, University of Washington Medical Center, Seattle, Washington.
7
Institute of Child Development, University of Minnesota, Minneapolis, Minnesota.
8
Montreal Neurological Institute, McGill University, Montreal, Quebec.
9
Computer Science & Engineering, New York University Tandon School of Engineering, New York, New York.
10
Department of Psychology, Temple University, Philadelphia, Pennsylvania.
11
Center for Autism Research, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
12
Department of Speech and Hearing Science, University of Washington, Seattle, Washington.
13
Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
14
Clinical sites-University of North Carolina.
15
University of Washington.
16
Washington University.
17
Children's Hospital of Philadelphia.
18
University of Alberta.
19
University of Minnesota.
20
Data Coordinating Center-Montreal Neurological Institute.
21
Image Processing Core-New York University.
22
University of North Carolina.
23
Statistical Analysis Core-University of North Carolina.

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.

KEYWORDS:

Autism; Brain development; CSF; Extra-axial fluid; Infancy; MRI

Comment in

PMID:
28392081
PMCID:
PMC5531051
DOI:
10.1016/j.biopsych.2017.02.1095
[Indexed for MEDLINE]
Free PMC Article

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