Source‐based morphometry reveals structural brain pattern abnormalities in 22q11.2 deletion syndrome

Abstract

Abstract22q11.2 deletion syndrome (22q11DS) is the most frequently occurring microdeletion in humans. It is associated with a significant impact on brain structure, including prominent reductions in gray matter volume (GMV), and neuropsychiatric manifestations, including cognitive impairment and psychosis. It is unclear whether GMV alterations in 22q11DS occur according to distinct structural patterns. Then, 783 participants (470 with 22q11DS: 51% females, mean age [SD] 18.2 [9.2]; and 313 typically developing [TD] controls: 46% females, mean age 18.0 [8.6]) from 13 datasets were included in the present study. We segmented structural T1‐weighted brain MRI scans and extracted GMV images, which were then utilized in a novel source‐based morphometry (SBM) pipeline (SS‐Detect) to generate structural brain patterns (SBPs) that capture co‐varying GMV. We investigated the impact of the 22q11.2 deletion, deletion size, intelligence quotient, and psychosis on the SBPs. Seventeen GMV‐SBPs were derived, which provided spatial patterns of GMV covariance associated with a quantitative metric (i.e., loading score) for analysis. Patterns of topographically widespread differences in GMV covariance, including the cerebellum, discriminated individuals with 22q11DS from healthy controls. The spatial extents of the SBPs that revealed disparities between individuals with 22q11DS and controls were consistent with the findings of the univariate voxel‐based morphometry analysis. Larger deletion size was associated with significantly lower GMV in frontal and occipital SBPs; however, history of psychosis did not show a strong relationship with these covariance patterns. 22q11DS is associated with distinct structural abnormalities captured by topographical GMV covariance patterns that include the cerebellum. Findings indicate that structural anomalies in 22q11DS manifest in a nonrandom manner and in distinct covarying anatomical patterns, rather than a diffuse global process. These SBP abnormalities converge with previously reported cortical surface area abnormalities, suggesting disturbances of early neurodevelopment as the most likely underlying mechanism.

Neuroanatomical Correlates of Cognitive Dysfunction in 22q11.2 Deletion Syndrome

“…Global cerebellar volume has been widely found to be significantly impacted in 22q11.2DS, with a meta-analysis by Rogdaki et al [60] finding a large effect size (g = −1.25) in a sample of 147 subjects, and Schmitt et al [83] finding a mean 17.3% reduction in total cerebellar volume in 79 individuals with 22q11.2DS compared to TD. Similar analyses have been carried out by Ge et al [84], Tan et al [59], and Campbell et al [56], converging in their finding of global volumetric reductions in the cerebellum. Granular analyses of focal cerebellar deficits are more limited, though Schmitt et al [83] identified volumetric reductions along an anterior-posterior gradient such that regions of the superior posterior cerebellum, Crus I and II, as well as lobules VIIB and VIIIA, were disproportionately affected after controlling for total brain volumes [83].…”

Neuropsychological Profile of 25 Brazilian Patients with 22q11.2 Deletion Syndrome: Effects of Clinical and Socioeconomic Variables

“…Neuropsychological findings include deficits in a wide range of cognitive functions, such as attention, executive functioning, and visuospatial processing [11,17,[19][20][21][22][23]. Correlates of cognitive and intellectual deficits have been attributed to volumetric alterations in patients with 22q11.2DS [24][25][26][27], as well as to the emergence of psychotic symptoms [18,28,29].…”