Table 3.
Significant findings of investigations of sex/gender-by-diagnosis interactions and sex/gender-stratified analysis of autism-control differences in white matter connectivity (DTI/DWI/DSI).
| Study | Country of origin for study sample | Method (‘sex’ or ‘gender’ is based on the term used in the study) | Metrics/Outcome measure | Sample size (M:F) | Age range | Covariates in analysis | Notable results (‘sex’ or ‘gender’ is based on the term used in the study) |
|---|---|---|---|---|---|---|---|
| Bode et al., 2011 | Finland | DTI (whole-brain) gender stratified |
FA, MD | 27 autism (20:7) 26 TD (17:9) |
Autism11.4–17.6 yr TD 11.7–17.3 yr |
None reported | Greater FA in the area containing clusters of optic radiation and the right IFOF (significant in males only when grouped by gender) |
| Beacher et al., 2012b | United Kingdom | DTI; sMRI (ROIs: CC-genu, body, splenium; CING, CST, SLF, CR, MCP) sex*dx |
FA, MD, whole-brain volume | 28 autism (15:13) 30 TD (15:15) |
no range; autism (M) 32 ± 10 yr autism (F) 32 ± 7 yr TD (M) 28 ± 8 yr TD (F) 32 ± 8 yr |
NART score (a proxy for overall intellectual function) | significant sex*dx interaction in total white matter volume, regional gray matter volume in the right parietal operculum, and FA in the body of CC, CING, and CR |
|
Irimia et al., 2017 (GENDAAR) |
United States |
DWI; sMRI (whole-brain) sex*dx |
GM thickness, volume, cortical area, mean curvature, CD |
110 autism (55:55) 83 TD (43:40) |
autism 7–18 yr TD 8–18 yr |
none reported |
significant sex*dx interaction in white matter CD innervating, bilaterally, the lateral aspect of the temporal lobe, temporo-parieto-occipital junction and the medial parietal lobe |
|
Zeestraten et al., 2017 (MRC-AIMS) |
United Kingdom |
DTI (ROIs: frontal fiber bundles – anterior segment of AF, long segment of AF, cingulum, uncinate, IFOF and two non-frontal fiber tracts – posterior segment of AF, ILF) sex*dx + sex stratified |
FA |
98 autism (61:37) 115 TD (61:54) |
autism (M) 18–41 yr autism (F) 18–37 yr TD (M) 18–45 yr TD (F) 18–52 yr |
scanning centre, age, FSIQ |
significant sex*dx interaction in frontal tracts only; non-frontal tracts revealed no interaction lower tract mean FA in autism group compared in TD in all frontal tracts except long segment of right AF and all investigated non-frontal tracts (significant in males only) |
|
Lei et al., 2019 (GENDAAR) |
United States |
DTI (whole-brain) sex stratified |
FA |
81 autism (56:25) 39 TD (23:16) |
autism 4–21 yr TD 5–18 yr |
none reported |
significant widespread bilateral reductions in FA in association tracts (CING, IFOF, ILF, SLF, and UF), projection (ATR, CST), commissural fibers (FMAJ, FMIN) in autistic subjects (significant in females only) |
|
Andrews et al., 2019 |
United States |
DWI (whole-brain) sex*dx |
FA, MD, RD, AD |
127 autism (85:42) 54 TD (28:26) |
autism 2.2–4.1 yr TD 2.1–4.1 yr |
age, relative movement |
sex*dx interaction in measures of AD across six significant clusters incorporating areas of the body, genu, and splenium of CC; females (ASD > TD), males (ASD < TD) |
|
Kirkovski et al., 2020 |
Australia |
DWI (whole-brain) sex stratified |
FD, FC, FDC |
25 autism (12:13) 24 TD (12:12) |
autism 21–55 yr TD 19–56 yr |
framewise displacement |
FDC at the CC (posterior midbody/isthmus) was significantly reduced for females with ASD compared TD females no differences found between males with ASD and TD males |
|
Bletsch et al., 2021 (MRC-AIMS) |
United Kingdom |
DTI (whole-brain) sex*dx sex stratified |
FA, MD, GWC at GWM boundary, different sampling depths within superficial WM and into GM |
92 autism (53:39) 92 TD (51:41) |
all participants 18–52 yr |
age, FSIQ |
significant sex*dx interactions for FA and MD (most pronounced within the superficial WM) no sex*dx interaction effects for GWC sex-stratified results in males mainly showed reduction in FA (ASD < TD) and increased MD (ASD > TD) that was most pronounced effects at the GWM boundary, −1 mm and −2 mm below GWM boundary sex stratified results in females mainly showed increased FA (ASD > TD) and a reduction in MD (ASD < TD) that was most pronounced effects at GWM boundary and at 30% and 60% cortical thickness GWC was reduced (ASD < TD) in both ASD males and females compared to same-sex counterparts at 30% cortical thickness |
Abbreviations: ABIDE, Autism Brain Imaging Data Exchange; AD, axial diffusivity; AF, arcuate fasciculus; ATR, anterior thalamic radiation; CC, corpus callosum; CD, connectivity density; CING, cingulum; CR, corona radiata; CST, corticospinal tract; FA, fractional anisotropy; FC, fiber cross-section; FD, fiber density; FDC, fiber density and cross-section; FMAJ, forceps major; FMIN, forceps minor; FSIQ, full scale intelligence quotient; GENDAAR, Gender Exploration of Neurogenetics and Development to Advance Autism Research; GM, gray matter; GWC, gray-white matter tissue contrast; GWM, gray-white matter; IFOF, interior frontal occipital fasciculus; ILF, inferior longitudinal fasciculus; MCP, middle cerebellar peduncle; MD, mean diffusivity; MRC-AIMS, Medical Research Council Autism Imaging Multicentre Study; NART, National Adult Reading Test; RD, radial diffusivity; ROI, region-of-interest; SLF, superior longitudinal fasciculus; UF, uncinate fasciculus