Genetic contributions to changes of fiber tracts of ventral visual stream in 22q11.2 deletion syndrome

Abstract

Patients with 22q11.2 deletion syndrome (22q11.2DS) represent a population at high risk for developing schizophrenia, as well as learning disabilities. Deficits in visuo-spatial memory are thought to underlie some of the cognitive disabilities. Neuronal substrates of visuo-spatial memory include the inferior fronto-occipital fasciculus (IFOF) and the inferior longitudinal fasciculus (ILF), two tracts that comprise the ventral visual stream. Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) is an established method to evaluate white matter (WM) connections in vivo. DT-MRI scans of nine 22q11.2DS young adults and nine matched healthy subjects were acquired. Tractography of the IFOF and the ILF was performed. DT-MRI indices, including Fractional anisotropy (FA) (measure of WM changes), axial diffusivity (AD, measure of axonal changes) and radial diffusivity (RD, measure of myelin changes) of each of the tracts and each group were measured and compared. The 22q11.2DS group showed statistically significant reductions of FA in IFOF in the left hemisphere. Additionally, reductions of AD were found in the IFOF and the ILF in both hemispheres. These findings might be the consequence of axonal changes, which is possibly due to fewer, thinner, or less organized fibers. No changes in RD were detected in any of the tracts delineated, which is in contrast to findings in schizophrenia patients where increases in RD are believed to be indicative of demyelination. We conclude that reduced axonal changes may be key to understanding the underlying pathology of WM leading to the visuo-spatial phenotype in 22q11.2DS.

White Matter Abnormalities and Cognitive Impairment in Early-Onset Schizophrenia-Spectrum Disorders

“…50 Patients with 22q.11.2 deletion syndrome, who are at genetic high risk for developing schizophrenia, also showed lower FA values in left IFOF. 51 Together, these data suggest that the observed WM tract alterations may represent a risk factor for development of psychosis.…”

White matter microstructural abnormalities of the cingulum bundle in youths with 22q11.2 deletion syndrome: Associations with medication, neuropsychological function, and prodromal symptoms of psychosis

“…However, it has also been shown that AD (and FA) increase during adolescence in typical youth (Kubicki et al, 2013; Kumar et al, 2013; Wu et al, 2014) suggesting that axonal coherence continues to improve during adolescence. Interestingly, in the case of 22q11.2DS improvement to normal levels might not be reached, as a DTI study of adults with 22q11.2DS found that FA and AD remain reduced (Kikinis et al, 2013; Kikinis et al, 2012). This implies that white matter pathology in 22q11.2DS may involve both early aberrant developmental and ongoing deleterious processes.…”

“…These areas also show aberrant connectivity in individuals with schizophrenia. Other significant DTI findings in 22q11.2DS include abnormalities within fibers of the visual ventral stream and a significant correlation between FA values in left parietal areas and arithmetic subtest scores (Barnea-Goraly et al, 2005; Kikinis et al, 2013). In addition, children with 22q11.2DS have higher parietal FA values that are related to poorer performance on an attentional counting task, thereby suggesting a different developmental trajectory related to disruption in parietal connectivity via the superior longitudinal fasciculus (SLF; Simon et al, 2008).…”

Impact of second-generation antipsychotics on white matter microstructure in adolescent-onset psychosis

“…Already in 1996, Aloia and colleagues proposed that the disruption of semantic networks have potential implications for the origin of “thought disorder” in schizophrenia 24 . Adding to this hypothesis, patients with 22q11.2 deletion syndrome, who are genetically at high risk for developing schizophrenia, showed lower FA values in left IFOF 25 . Furthermore, DeRosse and colleagues found that lower FA proximal to the SLF and corticospinal tract bilaterally, and left IFOF and left inferior longitudinal fasciculus (ILF), were associated with higher levels of psychotic-like experiences in otherwise healthy volunteers 26 .…”