Callosal thickness reductions relate to facial dysmorphology in fetal alcohol spectrum disorders

Abstract

Background: Structural abnormalities of the corpus callosum (CC), such as reduced size and increased shape variability, have been documented in individuals with fetal alcohol spectrum disorders (FASD). However, the regional specificity of altered CC structure, which may point to the timing of neurodevelopmental disturbances and/or relate to specific functional impairments, remains unclear. Furthermore, associations between facial dysmorphology and callosal structure remain undetermined.

Methods: One hundred and fifty-three participants (age range 8 to 16) including 82 subjects with FASD and 71 nonexposed controls were included in this study. The structural magnetic resonance imaging data of these subjects was collected at 3 sites (Los Angeles and San Diego, California, and Cape Town, South Africa) and analyzed using classical parcellation schemes, as well as more refined surface-based geometrical modeling methods, to identify callosal morphological alterations in FASD at high spatial resolution.

Results: Reductions in callosal thickness and area, specifically in the anterior third and the splenium, were observed in FASD compared with nonexposed controls. In addition, reduced CC thickness and area significantly correlated with reduced palpebral fissure length.

Conclusions: Consistent with previous reports, findings suggest an adverse effect of prenatal alcohol exposure on callosal growth and further indicate that fiber pathways connecting frontal and parieto-occipital regions in each hemisphere may be particularly affected. Significant associations between callosal and facial dysmorphology provide evidence for a concurrent insult to midline facial and brain structural development in FASD.

Figure 1

FASD effects on callosal thickness across three sites controlling for sex, age, and site as well as within Los Angeles (LA), South Africa (SA), and San Diego (SD) site controlling for sex and age. The color bar encodes the p value with hot-color indicating increased thickness and cold-color indicating decreased thickness in controls compared to FASD subjects.

Figure 2

Average callosal area measurements of the total area, area 1 (anterior third including rostrum, genu and rostral body), area 2 (anterior midbody), area 3 (posterior midbody), area 4 (isthmus), and area 5 (splenium) of the FASD and non-exposed (NC) control subjects within each site, corrected for age, gender, and total white matter. The vertical lines represent the standard error bars. The p values indicate significant group difference in callosal areas while controlling for age and gender, while those remained significant after controlling for total white matter were marked with a “*”.

Figure 3

Relationships between regional callosal thickness and palpebral fissure length (PFL) within the FASD group, controlling for sex, age, total white matter, and site. The color bar encodes the p value with hot-color indicating positive correlation and cold-color indicating negative correlation.