Sexual dimorphism of volume reduction but not cognitive deficit in fetal alcohol spectrum disorders: A combined diffusion tensor imaging, cortical thickness and brain volume study

Abstract

Quantitative magnetic resonance imaging (MRI) has revealed abnormalities in brain volumes, cortical thickness and white matter microstructure in fetal alcohol spectrum disorders (FASD); however, no study has reported all three measures within the same cohort to assess the relative magnitude of deficits, and few studies have examined sex differences. Participants with FASD (n = 70; 30 females; 5–32 years) and healthy controls (n = 74; 35 females; 5–32 years) underwent cognitive testing and MRI to assess cortical thickness, regional brain volumes and fractional anisotropy (FA)/mean diffusivity (MD) of white matter tracts. A significant effect of group, age-by-group, or sex-by-group was found for 9/9 volumes, 7/39 cortical thickness regions, 3/9 white matter tracts, and 9/10 cognitive tests, indicating group differences that in some cases differ by age or sex. Volume reductions for several structures were larger in males than females, despite similar deficits of cognition in both sexes. Correlations between brain structure and cognitive scores were found in females of both groups, but were notably absent in males. Correlations within a given MRI modality (e.g. total brain volume and caudate volume) were prevalent in both the control and FASD groups, and were more numerous than correlations between measurement types (e.g. volumes and diffusion tensor imaging) in either cohort. This multi-modal MRI study finds widespread differences of brain structure in participants with prenatal alcohol exposure, and to a greater extent in males than females which may suggest attenuation of the expected process of sexual dimorphism of brain structure during typical development.

White matter microstructure in fetal alcohol spectrum disorders: A systematic review of diffusion tensor imaging studies

“…This is also reinforced by the fact that more severe forms of FASD had more steeper decreases in MD than less severe forms of FASD than controls. However, in a recent cross‐sectional study on 70 patients with FASD over 5–32 years old and with the same methodology, Treit et al () did not find any differences between DTI metrics in any of the surveyed white matter tracts between PAE and TD. Moreover, age by group interactions showed steeper increases in white matter volume and FA of the genu with age in TD and of the SLF and ILF in FASD.…”

“…However, two studies in the neonatal period have emphasized on the reduced AD in FASD compared with TD newborns. Furthermore, two studies have not found any significant neural differences between 19 FASD and 27 TD with a mean age of about 10 years old (Colby et al, ), or between 70 FASD and 74 TD between ages 5 and 32 years old (Treit et al, ). In addition, there are few reports of higher FA (in structures such as globus pallidus; Lebel, Rasmussen, et al, ), right cingulum and right posterior limb of the internal capsule; Fryer et al, ) or lower MD (in genu; Lebel, Rasmussen, et al, , right anterior corona radiata and right forceps major; Fryer et al, ) comparing PAE with TD; or in relation to cognitive tasks, such as higher FA in bilateral brainstem cluster containing anterior and posterior limbs of the internal capsule in association with decreased math ability (Lebel et al, ), and higher FA in right CC and right ILF correlated with higher prosaccade and antisaccade reaction times (Green et al, ).…”

“…As a result, evaluation of CC in microstate domains deemed necessary. Furthermore, a multimodal imaging study on individuals with PAE has revealed a few correlations between different structural domains such as volumetric measures and white matter integrity (Treit et al, ).…”

Multivariate models of brain volume for identification of children and adolescents with fetal alcohol spectrum disorder

“…Participants with brain MRI included 67 participants with FASD (12.1 ± 3.3 years, 38 males) and 74 controls (11.5 ± 3.5 years, 42 males). Notably, 57 FASD and 66 control participants were included in our previous study on volumes/DTI/cortical thickness (Treit et al, ). The other 10 FASD participants were included in a much earlier diffusion MRI study (Lebel et al, ), and were the participants that did not overlap the FASD participants from (Treit et al, ).…”

“…These brain volume reductions have also been reported in infants and neonates with PAE for the corpus callosum (Jacobson et al, ) and gray matter (Donald et al, ). In addition, larger volume reductions have been observed in males with FASD suggesting sex differences (Chen, Coles, Lynch, & Hu, ; Dudek, Skocic, Sheard, & Rovet, ; Treit et al, ). However, most of these studies analyze each brain region separately (i.e., univariate analysis) and volumes have considerable overlap between groups making them unsuitable for individual FASD diagnosis.…”