TABLE 1.
Sex Differences in Structural and Neural Connectivity in Autism
| Author | Year | Area | Country | Method | Sample Size |
|---|---|---|---|---|---|
| Piven et al | 1996 | Iowa | USA | sMRI | *26 males & 9 females with autism *20 males & 16 females as typical controls |
| Lainhart et al | 1997 | Baltimore | USA | sMRI | *70 males & 21 females with autism *used a reference sample of 354 volunteers from Britain for typical controls |
| Sparks et al | 2002 | Seattle Bethesda |
USA | sMRI | *38 boys & 7 girls with ASD *18 boys & 8 TD girls *6 boys & 8 girls with DD |
| Bloss & Courchesne |
2007 | San Diego | USA | sMRI | *9 girls & 27 boys with autism *14 girls & 13 TD boys |
| Craig et al | 2007 | London | UK | sMRI VBM |
*14 women with ASD *19 women as typical controls |
| Tepest et al (Tepest, Jacobi et al. 2010) |
2010 | Cologne | Germany | sMRI | *18 men & 11 women with high functioning autism *18 men & 11 women as typical controls |
| Schumann et al |
2010 | San Diego | USA | sMRI Longitudinal |
*32 boys & 9 girls with autism *32 boys & 12 TD girls |
| Calderoni et al | 2011 | Pisa | Italy | sMRI VBM SVM-RFE |
*19 girls with ASD *19 DD girls *19 TD girls |
| Beacher et al | 2012 | Brighton | UK | sMRI DTI |
*13 women & 15 men with high functioning autism *15 women & 15 men as typical controls |
| Lai et al | 2013 | Cambridge | UK | sMRI VBM |
*30 women & 30 men with autism *30 women & 30 men as typical controls |
| Nordahl et al | 2013 | Davis | USA | DTI Longitudinal |
*112 pre-school ASD boys & 27 preschool ASD girls *53 boys and 29 TD girls |
| Diagnostic Criteria |
Age | Brain Regions |
|---|---|---|
| *ADI *DSM-III-R |
Autistic subjects: 12 – 29 Typical subjects: 13 – 28 |
Enlarged TBV in autistic males, not females. Autistic vs. typical males: Enlarged temporal and parietal lobes in autistic males, compared to typical males. |
| *ADI *Clinical Observation |
3–38 |
8 autistic females vs. typical females from reference sample – greater mean birth head circumference in autistic females. 37 autistic males vs. typical males from reference sample – no significant difference in head circumference. |
| *MSEL *VABS *ADI-R *ADOS-G *DSM-IV |
3–4 | Both ASD girls and boys exhibited cerebrum enlargement, relative to controls. ASD vs. TD boys – Enlarged cerebellum, hippocampus, & amygdala, proportionate to cerebrum size. Enlarged right amygdala, controlling for cerebrum volume. ASD vs. TD girls – No such enlargement in cerebellum or subcortical structures. |
| *CARS *ADOS *ADI |
Autistic girls: 2.35 – 4.97 Autistic boys: 1.92 – 5.08 TD girls: 2.17 – 5.71 TD boys: 1.72 – 5.50 |
Autistic vs. TD girls: Enlarged intracranial, whole brain, cerebral GM, frontal GM, temporal GM, & cerebellar WM volumes. Reduced cerebellar GM. Autistic vs. TD boys: Enlarged whole brain, cerebral GM, frontal WM, frontal GM, & cerebellar WM volumes. Autistic boys vs. autistic girls: Enlarged cerebral WM, cerebral GM, frontal GM, & temporal GM volumes. TD boys vs. TD girls: Enlarged frontal GM & parietal WM volumes. Autistic boys over age: No relationship between age & any brain structure. TD boys over age: Correlations with age on almost all brain structures assessed. Autistic girls over age: Cerebral WM, parietal WM, frontal WM, and occipital WM volumes increased with age. TD girls over age: Correlations with age on only the frontal WM and parietal WM volumes. |
| *ICD-10 *ADI-R *ADOS |
ASD women: 37.9 ± 11.4 Typical women: 35.0 ± 14 |
ASD vs. typical women – GM. Reduced bilateral OFC, basal ganglia, & temporal lobes. Smaller R medial occipital lobe & L frontal lobe. ASD vs. typical women – WM: Reduced density in bilateral brain stem and anterior temporal lobes. Increased density in the projection & association fibers of parietal, frontal, posterior temporal, & occipital lobes, in the cerebellum, & the commissural fibers of the CC. |
| *ICD-10 *ASQ *Clinical interviews |
Autistic subjects: 20.9 – 53.3 Typical subjects: 20.3 – 55.2 |
Both high functioning autistic and typical women had significantly larger ratio of CC / TBV than the men – but this was explained by brain size. |
| *ADI *ADOS-G *MSEL *VABS |
Autistic boys: 22–67 months Autistic girls: 26–58 months TD boys: 12–63 months TD girls: 12–61 months |
Autistic vs. TD boys: Enlarged temporal & frontal GM. Cingulate GM increased at a nonlinear rate, compared to controls. Autistic vs. TD girls: Enlarged temporal & cingulate GM. Total cerebrum, cerebral GM, cerebral WM, temporal GM, and frontal GM increased at an abnormal rate, compared to controls. |
| *DSM-IV-TR *ADOS *CARS |
2–7 |
ASD vs. TD girls: 5% enlargement of total intracranial volume. Increased GM in bilateral SFG and R TPJ. |
| *DSM-IV *AAA *DISCD |
Autistic women: 32 ± 7 Autistic men: 32 ± 10 Typical women: 32 ± 8 Typical men: 28 ± 8 |
Typical men vs. typical women: Enlarged GM volumes in the rolandic operculum & R inferior parietal lobe Autistic men vs. autistic women: No such enlargement. Autistic men vs. typical men: No such enlargement. Typical men vs. typical women: Higher FA in the CC, R & L cingulum (i.e. the anterior portion), & corona radiata Autistic men vs. autistic women: No sex differences in FA. |
| *ICD-10 *DSM-IV *ADI-R *ADOS *ASQ *AAA |
18–49 |
Autistic and typical men vs. women – WM: Larger in 6 clusters in occipital, frontal, & TPOJ regions. Autistic and typical women vs. men – WM: Larger in 3 clusters in cerebellum / brain stem, internal capsule, and fibers from CC. Autistic vs. typical women – WM: Larger in 2 clusters in TPOJ regions (posterior cingulum, CC, inferior longitudinal fasciculus, and R arcuate fasciculus). Smaller in 2 clusters in bilateral internal capsule at thalamus and basal ganglia. Autistic vs. typical men – WM: No difference in size in TPOJ regions. Larger in 2 clusters in bilateral internal capsule at thalamus and basal ganglia. Autistic and typical men vs women – GM: Larger in 6 clusters in DMPFC, frontal & occipital poles, sensory motor cortices, Heschl gyri, superior temporal gyri, lingual and calcarine gyri, lateral temporal regions, temporo-occipital regions, precuneous, superior cerebellar hemispheres, posterior cingulate cortices, & brainstem. Autistic and typical women vs. men – GM: Larger volumes in 9 clusters in supplementary motor area, L DLPFC, primary somatosensory cortex, caudate, thalamus, bilateral OFC, fusiform, parahippocampal, hippocampal gyri, & cerebellar vermis and hemispheres. For autistic females, abnormal brain regions overlapped with sexually dimorphic GM & WM regions in typical controls; however, this was not the case for autistic males. |
| *ADOS-G *ADI-R |
3–5 |
ASD boys vs. girls – smaller CC region projecting to the OFC ASD girls vs. boys – smaller CC region projecting to the anterior frontal cortex ASD girls vs. TD girls – greater MD, AD, & RD ASD boys vs. TD boys – no difference |
Sample Size
TD = typically developing, DD = developmental delay
Diagnostic Criteria
AAA = Adult Asperger Assessment, ABC = Aberrant Behavior Checklist, ADI-R = Autistic Diagnostic Interview-Revised, ADOS-G = Autism Diagnostic Observation Schedule – Generic, ASQ = Autism Spectrum Quotient, AGRE = Autism Genetic Resource Exchange, AT = Autism-Tics, CARS = Childhood Autism Rating Scale, BAPQ = Broad Autism Phenotype Questionnaire, DISCD = Diagnostic Interview for Social & Communication Disorders, DSF = Diagnosis Summary Form, DSM = Diagnostic Statistical Manual, ICD-10 = International Statistical Classification of Diseases-10, MSEL = Mullen Scales of Early Learning, RBS-R = Repetitive Behavior Scale-Revised, VABS = Vineland Adaptive Behavior Scales
Brain Regions
GM = gray matter, WM = white matter, FA = fractional anisotropy, R = right, L = left, CC = corpus callosum, DLPFC = dorsolateral prefrontal cortex, DMPFC = dorsomedial prefrontal cortices, OFC = orbitofrontal cortex, SFG = superior frontal gyrus, TBV = total brain volume, TPJ = temporal-parietal junction, TPOJ = temporal-parietal-occipital junction, MD = mean diffusivity, AD = axial diffusivity, RD = radial diffusivity.