Atypical development of white matter microstructure of the corpus callosum in males with autism: a longitudinal investigation

Abstract

BackgroundThe corpus callosum is the largest white matter structure in the brain, and it is the most consistently reported to be atypical in diffusion tensor imaging studies of autism spectrum disorder. In individuals with typical development, the corpus callosum is known to undergo a protracted development from childhood through young adulthood. However, no study has longitudinally examined the developmental trajectory of corpus callosum in autism past early childhood.MethodsThe present study used a cohort sequential design over 9 years to examine age-related changes of the corpus callosum in 100 males with autism and 56 age-matched males with typical development from early childhood (when autism can first be reliably diagnosed) to mid-adulthood (after development of the corpus callosum has been completed) (3 to 41 years of age).ResultsThe group with autism demonstrated a different developmental trajectory of white matter microstructure in the anterior corpus callosum’s (genu and body) fractional anisotropy, which suggests atypical brain maturation in these regions in autism. When analyses were broken down by age group, atypical developmental trajectories were present only in the youngest participants (10 years of age and younger). Significant main effects for group were found in terms of decreased fractional anisotropy across all three subregions of the corpus callosum (genu, body, and splenium) and increased mean diffusivity, radial diffusivity, and axial diffusivity in the posterior corpus callosum.ConclusionsThese longitudinal results suggest atypical early childhood development of the corpus callosum microstructure in autism that transitions into sustained group differences in adolescence and adulthood. This pattern of results provides longitudinal evidence consistent with a growing number of published studies and hypotheses regarding abnormal brain connectivity across the life span in autism.Electronic supplementary materialThe online version of this article (doi:10.1186/s13229-015-0001-8) contains supplementary material, which is available to authorized users.

Toddlers later diagnosed with autism exhibit multiple structural abnormalities in temporal corpus callosum fibers

“…First, anatomical studies have reported that one or more subregions of the corpus callosum (CC) are smaller in older children, adolescents, and adults with autism (Egaas et al 1995; Frazier and Hardan 2009; Travers et al 2015, but also see Haar et al 2014). Second, fMRI studies have reported that toddlers, children, adolescents, and adults with autism exhibit decreased inter-hemispheric functional connectivity during rest/sleep in comparison to controls (e.g., Anderson et al, 2011; Dinstein et al, 2011; Di Martino et al, 2014).…”

“…Since autism is a disorder of early neural development (Courchesne et al, 2011; Willsey et al, 2013; Stoner et al, 2014), it is particularly important to examine inter-hemispheric connectivity at very young ages when the behavioral symptoms of autism first emerge (Courchesne et al 2007; Pierce et al 2011). Only a few DTI studies have done so and all have reported that the CC at young ages in autism exhibits abnormally increased FA values (Ben Bashat et al 2007; Weinstein et al 2011; Xiao et al 2014; Travers et al 2015; Solso et al 2016). This finding stands in sharp contrast to findings in mature children, adolescents and adults where nearly every study has reported reduced CC FA values in autism (Barnea-Goraly et al 2004; Alexander et al 2007; Jou et al 2011; Travers et al 2012; Vogan et al 2016).…”

7,8-Dihydroxyflavone as a pro-neurotrophic treatment for neurodevelopmental disorders

“…These symptoms usually become apparent between 12 and 24 months of age (Rogers, 2009). Neuroanatomical studies reveal abnormal development of grey and white matter in the corpus callosum and frontal cortex (Itahashi et al, 2015;Lange et al, 2015;Travers et al, 2015) and neuropathology such as reduced pyramidal cell numbers and sizes in the cingulate cortex (Uppal et al, 2014), Brodmann areas 44 and 45 (Jacot-Descombes et al, 2012) and many other brain regions (D. G. Amaral et al, 2008).…”

Brain imaging research in autism spectrum disorders

“…Results of studies examining longitudinal growth trajectories of white matter microstructure during this period in ASD are pending [55]. Elevated levels of brain lactate may develop in localized areas of the brain in some ASD adults [56].…”