Altered white matter microstructure in 22q11.2 deletion syndrome: a multisite diffusion tensor imaging study

Abstract

22q11.2 deletion syndrome (22q11DS)-a neurodevelopmental condition caused by a hemizygous deletion on chromosome 22-is associated with an elevated risk of psychosis and other developmental brain disorders. Prior single-site diffusion magnetic resonance imaging (dMRI) studies have reported altered white matter (WM) microstructure in 22q11DS, but small samples and variable methods have led to contradictory results. Here we present the largest study ever conducted of dMRIderived measures of WM microstructure in 22q11DS (334 22q11.2 deletion carriers and 260 healthy age-and sex-matched controls; age range 6-52 years). Using harmonization protocols developed by the ENIGMA-DTI working group, we identified widespread reductions in mean, axial and radial diffusivities in 22q11DS, most pronounced in regions with major cortico-cortical and cortico-thalamic fibers: the corona radiata, corpus callosum, superior longitudinal fasciculus, posterior thalamic radiations, and sagittal stratum (Cohen's d's ranging from −0.9 to −1.3). Only the posterior limb of the internal capsule (IC), comprised primarily of corticofugal fibers, showed higher axial diffusivity in 22q11DS. 22q11DS patients showed higher mean fractional anisotropy (FA) in callosal and projection fibers (IC and corona radiata) relative to controls, but lower FA than controls in regions with predominantly association fibers. Psychotic illness in 22q11DS was associated with more substantial diffusivity reductions in multiple regions. Overall, these findings indicate large effects of the 22q11.2 deletion on WM microstructure, especially in major cortico-cortical connections. Taken together with findings from animal models, this pattern of abnormalities may reflect disrupted neurogenesis of projection neurons in outer cortical layers.

Deviation from normative brain development is associated with symptom severity in autism spectrum disorder

“…Within the Advanced group, ASD was associated with higher regional FA values compared with typically development, whereas, lower FA values were present in the Delayed group. Both groups had FA differences in the brain regions previously reported in ASD, such as internal capsule [93][94][95][96], external capsule [97,98], and inferior temporal gyrus [99] in the Advanced group, corpus callosum [95,97,[100][101][102][103], cerebellar peduncle [95,97,104], and inferior frontooccipital fasciculus [98,100] in the Delayed group, and cingulum [100,[105][106][107] in both groups. Notably, the regions that showed significant differences were not same for the subgroups.…”

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

“…Postema et al 97 ; Guadalupe et al 174 Average patterns of left-right anatomical asymmetry of the healthy brain were mapped, outcome. The large scale and inclusivity of these analyses -in terms of populations, sample sizes, numbers of coordinating centers, and diversity of imaging and genetic data-has been instrumental for demonstrating robust associations between clinical factors and brain alterations, and for stratifying patients with the same diagnosis according to differential treatment outcomes 10,17 . Thus, a valuable aspect of the existing ENIGMA studies is the ability to identify the most robust pattern of noninvasively measured neurobiological features involved in clinical syndromes across multiple samples that are more representative of the global population.…”

White matter abnormalities across different epilepsy syndromes in adults: an ENIGMA Epilepsy study

“…Scanner type was used as the batch effect and diagnosis (patients versus controls) and syndrome (GGE, TLE-HS, TLE-NL, and ExE) were used as the biological phenotypes of interest. This technique has been recently applied in other ENIGMA DTI investigations of brain disorders (Villalón-Reina et al, 2019;Zavaliangos-Petropulu et al, 2019).…”