Neuropathophysiological Indicators in ASD May Dissipate With Age

Madeleine Haase

April 11, 2022

The study covered in this summary was published on as a preprint and has not yet been peer reviewed.

Key Takeaways

  • White matter aberration appears greatest among younger ASD cohorts. 

  • In older adolescents and young adults, less of the corpus callosum seems affected.

  • The findings of this study support the suggestion that some early neuropathophysiological indicators in ASD may dissipate with age.

Why This Matters

  • There is strong evidence for structural and functional neuropathophysiology underlying autism spectrum disorder (ASD) symptomatology.

  • The corpus callosum is the largest commissural tract in the brain and is one of the most commonly implicated white matter tracts in research investigating the structural neuropathophysiology of ASD.

  • While the developmental profile of white matter aberration in ASD is yet to be fully elucidated, there is evidence that this effect alters as a function of age.

Study Design

  • Data for participants with (n = 54) and without (n = 50) ASD, aged 5-34 years, were obtained from the Autism Brain Imaging Data Exchange-II (ABIDE-II). 

  • Within each site, indices of fiber density (FD), fiber cross-section (FC), and combined fiber density and cross-section (FDC) were compared between those groups.

  • FC estimates specifically were log-transformed (logFC) before statistical analysis.

  • A P value of < .01 was considered statistically significant to account for multiple comparisons, based on a simple Bonferroni correction.

Key Results

  • Young adolescents with ASD (mean age, 11.19 ± 7.54) showed reduced macroscopic FC and FDC compared with age-matched neurotypical controls (mean age, 10.04 ± 4.40)

  • Reduced FD and FDC were noted in a marginally older ASD (mean age, 13.87 ± 3.15) cohort compared with matched controls (mean age, 13.85 ± 2.90). 

  • Among the oldest cohorts, a nonsignificant trend indicated reduced FD in older adolescents/young adults with ASD (mean age, 17.07 ± 3.56) compared with controls (mean age, 16.55 ± 2.95). 

  • There was a positive correlation between age and callosal mean FC and FDC in the youngest cohort. When stratified by diagnosis, this finding remained only for the ASD sample.


  • Combining diffusion MRI data across different acquisition protocols and/or sites to drive more statistically powerful analyses is not straightforward. Even with efforts to harmonize data, this risks introducing biases in the analysis. 

  • The samples available from each site in our dataset are independently small, particularly for demanding neuroimaging analyses such as FBA.

  • The age range of the youngest sample did overlap with the two older sites.

  • The research was limited to the available data obtained from the ABIDE-II database and did not allow for biological sex to be explored.


  • The authors have declared no competing interest.

  • This research was funded by an Alfred Deakin post-doctoral research fellowship held by lead author Melissa Kirkovski. Co-author Mervyn Singh is supported by the Deakin University postgraduate research scholarship. Co-author Peter G. Enticott was supported by a Future Fellowship from the Australian Research Council.

This is a summary of a preprint research study, "An investigation of age-related neuropathophysiology in autism spectrum disorder using fixel-based analysis of corpus callosum white matter micro- and macrostructure," written by Melissa Kirkovski, PhD, Cognitive Neuroscience Unit, School of Psychology, Deakin University, Geelong, Australia and colleagues on, provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on

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