Neuroanatomical differences in toddler boys with fragile x syndrome and idiopathic autism.
BACKGROUND
Autism is an etiologically heterogeneous neurodevelopmental disorder for which there is no known unifying etiology or pathogenesis. Many conditions of atypical development can lead to autism, including fragile X syndrome (FXS), which is presently the most common known single-gene cause of autism.


OBJECTIVE
To examine whole-brain morphometric patterns that discriminate young boys with FXS from those with idiopathic autism (iAUT) as well as control participants.


METHODS
Cross-sectional, in vivo neuroimaging study.


METHODS
Academic medical centers.


METHODS
Young boys (n = 165; aged 1.57-4.15 years) diagnosed as having FXS or iAUT as well as typically developing and idiopathic developmentally delayed controls.


METHODS
Univariate voxel-based morphometric analyses, voxel-based morphometric multivariate pattern classification (linear support vector machine), and clustering analyses (self-organizing map).


RESULTS
We found that frontal and temporal gray and white matter regions often implicated in social cognition, including the medial prefrontal cortex, orbitofrontal cortex, superior temporal region, temporal pole, amygdala, insula, and dorsal cingulum, were aberrant in FXS and iAUT as compared with controls. However, these differences were in opposite directions for FXS and iAUT relative to controls; in general, greater volume was seen in iAUT compared with controls, who in turn had greater volume than FXS. Multivariate analysis showed that the overall pattern of brain structure in iAUT generally resembled that of the controls more than FXS, both with and without AUT.


CONCLUSIONS
Our findings demonstrate that FXS and iAUT are associated with distinct neuroanatomical patterns, further underscoring the neurobiological heterogeneity of iAUT.
Center for Interdisciplinary Brain Sciences Research (CIBSR), Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine 401 Quarry Rd. Stanford CA 94305-5795.
Fumiko
F
Hoeft
Center for Interdisciplinary Brain Sciences Research (CIBSR), Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine 401 Quarry Rd. Stanford CA 94305-5795.
Elizabeth
E
Walter
Center for Interdisciplinary Brain Sciences Research (CIBSR), Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine 401 Quarry Rd. Stanford CA 94305-5795.
Amy A
AA
Lightbody
The Carolina Institute for Developmental Disabilities, CB# 3366, University of North Carolina, Chapel Hill, NC 27514.
Heather C
HC
Hazlett
Department of Radiology, Stanford University, Lucas MRI/S Center, MC 5488, 1201 Welch Road, Stanford, CA 94305-5488.
Catie
C
Chang
The Carolina Institute for Developmental Disabilities, CB# 3366, University of North Carolina, Chapel Hill, NC 27514.
Joseph
J
Piven
Center for Interdisciplinary Brain Sciences Research (CIBSR), Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine 401 Quarry Rd. Stanford CA 94305-5795.
Allan L
AL
Reiss
D000679:Amygdala / Q000473:pathology / Q000503:physiopathology; D001321:Autistic Disorder / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology* / Q000523:psychology; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology; D002675:Child, Preschool; D003142:Communication; D002658:Developmental Disabilities / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D005600:Fragile X Syndrome / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology* / Q000523:psychology; D005625:Frontal Lobe / Q000473:pathology / Q000503:physiopathology; D030342:Genetic Diseases, Inborn / Q000235:genetics; D006179:Gyrus Cinguli / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D015999:Multivariate Analysis; D012016:Reference Values; D012919:Social Behavior; D013239:Stereotyped Behavior / Q000502:physiology; D013702:Temporal Lobe / Q000473:pathology / Q000503:physiopathology