scholarly journals Abnormalities in brain white matter in adolescents with 22q11.2 deletion syndrome and psychotic symptoms

2016 ◽  
Vol 11 (5) ◽  
pp. 1353-1364 ◽  
Author(s):  
Zora Kikinis ◽  
Kang Ik K. Cho ◽  
Ioana L. Coman ◽  
Petya D. Radoeva ◽  
Sylvain Bouix ◽  
...  
Keyword(s):  
White Matter ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
Psychotic Symptoms ◽  
22Q11.2 Deletion ◽  
Brain White Matter

scholarly journals M162. FRONTO-STRIATAL-THALAMIC CIRCUITRY ABNORMALITIES IN WHITE MATTER TRACTS IN INDIVIDUALS WITH 22Q11.2 DELETION SYNDROME

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S197-S198
Author(s):  
Carina Heller ◽  
Saskia Steinmann ◽  
Nikos Makris ◽  
Lily Charron ◽  
Kevin M Antshel ◽  
...  
Keyword(s):  
Young Adults ◽  
White Matter ◽  
Cognitive Decline ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
Psychotic Symptoms ◽  
Healthy Controls ◽  
22Q11.2 Deletion ◽  
Prodromal Symptoms ◽  
The Right

Abstract Background Cognitive decline is considered a fundamental component in schizophrenia. Abnormalities in fronto-striatal-thalamic (FST) sub-circuits are present in schizophrenia and are associated with cognitive impairments. However, it remains unknown whether abnormalities in FST sub-circuits are present before psychosis onset. This may be elucidated by investigating young adults with 22q11.2 deletion syndrome (22q11DS), of whom 30% will develop schizophrenia in adulthood. In 22q11DS, cognitive decline, most pronounced in Verbal IQ (VIQ), precedes the onset of psychosis and those who develop psychosis diverge more strongly from a typical cognitive trajectory. Based on these findings, studies of young adults with 22q11DS without overt psychosis but with prodromal symptoms may increase our understanding of cognitive manifestations and early pathology in FST sub-circuits in schizophrenia. Here we examined white matter (WM) tracts in FST sub-circuits, especially those involving dorsolateral (DLPFC) and ventrolateral prefrontal cortex (VLPFC), and their associations with VIQ in young adults with 22q11DS with and without prodromal symptoms. Methods We compared Fractional Anisotropy (FA), Axial Diffusivity (AD), and Radial Diffusivity (RD) in tracts of the FST sub-circuits in 21 individuals with 22q11DS with prodromal symptoms (age: M=21.43) and 30 individuals without prodromal symptoms (age: M=20.73) to 30 healthy controls (age: M=20.89). Two-tensor tractography was applied to reconstruct WM fiber tracts of the whole brain, followed by applying the White Matter Query Language (WMQL) method to select tracts between striatum and thalamus, with the rostral middle frontal gyrus (rMFG) and inferior frontal gyrus (IFG), representing DLPFC and VLPFC. This yielded four tracts of interest: thalamus-rMFG, thalamus-IFG, striatum-rMFG, and striatum-IFG tracts. Additionally, correlations between the dMRI measures and scores on VIQ were performed. Results FA was significantly increased, while RD was significantly decreased in most WM tracts in both 22q11DS groups when compared to healthy controls. In the whole 22q11DS group, VIQ correlated negatively with FA in the right thalamus-IFG tract (r=-0.336, p=.018), while RD correlated positively with VIQ in the right thalamus-IFG tract (r=0.290, p=.043) in individuals with 22q11DS, such that increased FA and decreased RD were associated with a lower VIQ. We followed up on the results in individuals with 22q11DS with prodromal symptoms to determine whether the presence of prodromal symptoms drove the correlations. VIQ correlated significantly with FA (r=-0.491, p=0.024, FDR-adjusted=0.048) and significantly at trend level with RD (r=0.487, p=0.025, FDR-adjusted=0.050) in the right thalamus-IFG tract in individuals with 22q11DS with prodromal symptoms. Discussion Microstructural abnormalities in brain WM tracts connecting the thalamus and the striatum with prefrontal cortices are present in young adults with 22q11DS with and without prodromal symptoms compared to healthy controls. These abnormalities are associated with the individuals’ cognitive performance in VIQ in individuals with 22q11DS with prodromal symptoms and therefore emphasize the potential involvement of the FST sub-circuits in schizophrenia. While changes in FST circuitry have been reported in patients with schizophrenia, we observed that changes in FST circuitry are also present in young adults with 22q11DS at risk for but without psychotic symptoms. Our results suggest that psychosis onset in 22q11DS may be associated with a complex pattern of WM alterations. Furthermore, cognitive abnormalities, especially in VIQ, present an important preclinical risk factor for psychosis in 22q11DS.

scholarly journals M155. RECIPROCAL CHANGES IN WHITE MATTER MICROSTRUCTURE IN 22Q11.2 DELETION AND DUPLICATION SYNDROME

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S194-S195
Author(s):  
Johanna Seitz ◽  
Monica Lyons ◽  
Leila Kushan ◽  
Kang Ik Kevin Cho ◽  
Tashrif Billah ◽  
...  
Keyword(s):  
White Matter ◽  
Symptom Score ◽  
Negative Symptom ◽  
Free Water ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
Psychotic Symptoms ◽  
22Q11.2 Deletion ◽  
White Matter Microstructure ◽  
Human Connectome Project

Abstract Background The 22q11.2 deletion syndrome is a neurogenetic disorder that is associated with both physical anomalies and neurocognitive impairments. Deletion carriers have a greatly elevated risk of developing schizophrenia (SCZ); as such, it offers a compelling ‘high-penetrance’ model to explore the neuropathology of SCZ risk. Indeed, widespread structural alterations of both gray and white matter have been reported for 22q11.2 deletion carriers. Interestingly, there are also cases of duplications at the same gene locus. While less is known about the phenotype associated with 22q11.2 duplication, carriers also present physical and neurodevelopmental abnormalities, although they may have reduced risk of developing SCZ compared to the general population. The only study to date which looked at brain structure in duplication carriers found reciprocal effects of 22q11.2 deletion and duplication on cortical thickness and surface measurements. In the present study, we apply diffusion magnetic resonance imaging (MRI) to examine the white matter microstructure in both 22q11.2 deletion and duplication carriers. Methods Multi-shell diffusion-weighted images were acquired on a 3 Tesla MRI scanner from 13 healthy control individuals (HC), 25 deletion carriers, and 18 22q11.2 duplication carriers. Images were preprocessed utilizing the Human Connectome Project (HCP) Minimal Preprocessing Pipeline v4.0.0. Free Water imaging was applied, which differentiates the diffusion signal into a free-water compartment and a tissue compartment. The output parameters are the free-water fractional volume (FW) and a free-water corrected diffusion tensor from which fractional anisotropy of the tissue (FAT) is calculated. We compared FAT and FW maps between 1) HC and 22q11.2 deletion carriers and 2) HC and 22q11.2 duplication carriers using Tract-Based Spatial Statistics (TBSS) and voxel-wise, non-parametric statistics (5000 permutations, threshold-free cluster enhancement, corrected for age and sex). Lastly, white matter clusters that displayed significant differences between 22q11.2 deletion or duplication and HC were extracted. We averaged FAT and FW values over these significant clusters for each individual and correlated with the scores of the Structured Interview for Prodromal Syndromes (SIPS). Results 22q11.2 deletion carriers showed significant (p<0.05) FW reductions (72% of white matter skeleton) and FAT increase (8%) when compared to HC. In contrast, 22q11.2 duplication carriers displayed the opposite effect, with significant (p<0.05) widespread FW increase (51%) and FAT decrease (50%) when compared to HC. Both 22q11.2 deletion and duplication carriers scored higher on the SIPS than HC, with negative symptom score differences being the most pronounced (mean for HC= 1.36, mean for 22q11.2 duplication = 7.0, mean for 22q11.2 deletion =9.96, F=6.68, df=2, p<.003). FAT and FW were not associated with SIPS scores in 22q11.2 deletion syndrome. However, FAT was negatively correlated with the negative symptom score in 22q11.2 duplication carriers (Spearman rho=-.61, p<.009). Discussion We observed opposing effects of gene-dosage on FAT and FW. While we did not see an association between WM measurements and psychotic symptoms in 22q11.2 deletion, there was an association of WM structure with negative symptoms in 22q11.2 duplication carriers. These findings highlight the importance of studying the influence of reciprocal chromosomal imbalance on white matter architecture. Ongoing longitudinal studies may help advance understanding of the role of microstructural white matter abnormalities in the emergence of neuropsychiatric symptoms.

scholarly journals In vivo evidence of microstructural hypo-connectivity of brain white matter in 22q11.2 deletion syndrome

2020 ◽  
Author(s):  
Erika Raven ◽  
Jelle Veraart ◽  
Rogier Kievit ◽  
Sila Genc ◽  
Isobel Ward ◽  
...  
Keyword(s):  
White Matter ◽  
Large Scale ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
Typically Developing ◽  
22Q11.2 Deletion ◽  
Genetic Syndrome ◽  
Brain White Matter ◽  
Axonal Morphology

Abstract 22q11.2 Deletion Syndrome, or 22q11.2DS, is a genetic syndrome associated with high rates of schizophrenia, autism, and attention deficit hyperactivity disorder, in addition to widespread structural and functional abnormalities throughout the brain. Experimental animal models have identified neuronal connectivity deficits, e.g., decreased axonal length and complexity of axonal branching, as a primary mechanism underlying atypical brain development in 22q11.2DS. However, it is still unclear whether deficits in axonal morphology can also be observed in people with 22q11.2DS. Here, we provide an unparalleled in vivo characterisation of white matter microstructure in both typically-developing children and children with 22q11.2DS using a dedicated magnetic resonance imaging scanner which is sensitive to axonal morphology. By extracting a rich array of diffusion metrics, we present microstructural profiles of typical and atypical white matter development, and provide new evidence of connectivity differences between typically-developing and 22q11.2DS children. A recent, large-scale consortium study identified higher diffusion anisotropy and reduced overall mobility of water as hallmark microstructural alterations of white matter in 22q11.2DS, in particular for commissural fibers. We observed similar findings across all white matter tracts in this study, in addition to identifying deficits in axonal morphology. This, in combination with reduced tract volume measurements, supports the hypothesis that microstructural connectivity in 22q11.2DS is mediated by densely packed axons with disproportionately small diameters. Our findings provide insight into the in vivo mechanistic features of 22q11.2DS, and promote further investigation of shared features in neurodevelopmental and psychiatric disorders.

Psychotic symptoms in children and adolescents with 22q11.2 deletion syndrome: Neuropsychological and behavioral implications

2006 ◽  
Vol 84 (2-3) ◽  
pp. 187-193 ◽  
Author(s):  
Martin Debbané ◽  
Bronwyn Glaser ◽  
Melissa K. David ◽  
Carl Feinstein ◽  
Stephan Eliez
Keyword(s):  
Children And Adolescents ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
Psychotic Symptoms ◽  
22Q11.2 Deletion

The interaction between neurocognitive functioning, subthreshold psychotic symptoms and pharmacotherapy in 22q11.2 deletion syndrome: A longitudinal comparative study

2018 ◽  
Vol 48 (1) ◽  
pp. 20-26 ◽  
Author(s):  
R. Weinberger ◽  
O. Weisman ◽  
Y. Guri ◽  
T. Harel ◽  
A. Weizman ◽  
...  
Keyword(s):  
Psychotic Disorders ◽  
22Q11.2 Deletion Syndrome ◽  
Structured Interview ◽  
Neurocognitive Functioning ◽  
Deletion Syndrome ◽  
Psychotic Symptoms ◽  
Psychiatric Evaluation ◽  
Neurocognitive Performance ◽  
22Q11.2 Deletion ◽  
Genetic Syndrome

AbstractBackgroundThe 22q11.2 deletion syndrome (22q11DS) is the most common genetic syndrome associated with schizophrenia. The goal of this study was to evaluate longitudinally the interaction between neurocognitive functioning, the presence of subthreshold psychotic symptoms (SPS) and conversion to psychosis in individuals with 22q11DS. In addition, we attempted to identify the specific neurocognitive domains that predict the longitudinal evolution of positive and negative SPS, as well as the effect of psychiatric medications on 22q11DS psychiatric and cognitive developmental trajectories.MethodsForty-four participants with 22q11DS, 19 with Williams syndrome (WS) and 30 typically developing (TD) controls, age range 12–35 years, were assessed at two time points (15.2 ± 2.1 months apart). Evaluation included the Structured Interview for Prodromal Symptoms (SIPS), structured psychiatric evaluation and the Penn Computerized Neurocognitive Battery (CNB).Results22q11DS individuals with SPS had a yearly conversion rate to psychotic disorders of 8.8%, compared to none in both WS and TD controls. Baseline levels of negative SPS were associated with global neurocognitive performance (GNP), executive function and social cognition deficits, in individuals with 22q11DS, but not in WS. Deficits in GNP predicted negative SPS in 22q11DS and the emergence or persistence of negative SPS. 22q11DS individuals treated with psychiatric medications showed significant improvement in GNP score between baseline and follow-up assessments, an improvement that was not seen in untreated 22q11DS.ConclusionsOur results highlight the time-dependent interplay among positive and negative SPS symptoms, neurocognition and pharmacotherapy in the prediction of the evolution of psychosis in 22q11DS.

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