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.

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 Episodic Behavioural Regression in an 8-Year-Old Female: Sequelae of 22q11.2 Duplication Syndrome

2018 ◽  
Vol 2018 ◽  
pp. 1-3
Author(s):  
A. Bahji ◽  
S. Khalid-Khan
Keyword(s):  
Case Reports ◽  
22Q11.2 Deletion Syndrome ◽  
Autism Spectrum ◽  
Deletion Syndrome ◽  
Medical Illness ◽  
22Q11.2 Deletion ◽  
Genetic Syndrome ◽  
Potential Risk Factors ◽  
22Q11.2 Duplication Syndrome ◽  
Duplication Syndrome

22q11.2 duplication syndrome is a recently discovered genetic syndrome with unclear neuropsychiatric sequelae. While its connection to 22q11.2 deletion syndrome is actively investigated, case reports on the neuropsychiatric sequelae of affected individuals have been previously described, largely focusing on comorbid autism spectrum disorder. Here, we present the case of an 8-year-old female experiencing episodes of severe behavioural regression following medical illness. We analyze the case and relate it to the available literature and identify potential risk factors.

scholarly journals Large-Scale Brain Network Dynamics Provide a Measure of Psychosis and Anxiety in 22q11.2 Deletion Syndrome

2019 ◽  
Vol 4 (10) ◽  
pp. 881-892 ◽  
Author(s):  
Daniela Zöller ◽  
Corrado Sandini ◽  
Fikret Işik Karahanoğlu ◽  
Maria Carmela Padula ◽  
Marie Schaer ◽  
...  
Keyword(s):  
Large Scale ◽  
Network Dynamics ◽  
22Q11.2 Deletion Syndrome ◽  
Brain Network ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion

scholarly journals Large-Scale Evidence for an Association Between Peripheral Inflammation and White Matter Free Water in Schizophrenia and Healthy Individuals

2020 ◽  
Author(s):  
Maria A Di Biase ◽  
Andrew Zalesky ◽  
Suheyla Cetin-Karayumak ◽  
Yogesh Rathi ◽  
Jinglei Lv ◽  
...  
Keyword(s):  
White Matter ◽  
Large Scale ◽  
Interleukin 2 ◽  
Free Water ◽  
Markers Of Inflammation ◽  
Brain White Matter ◽  
Inflammatory Processes ◽  
Weighted Magnetic Resonance Imaging

Abstract Introduction Clarifying the role of neuroinflammation in schizophrenia is subject to its detection in the living brain. Free-water (FW) imaging is an in vivo diffusion-weighted magnetic resonance imaging (dMRI) technique that measures water molecules freely diffusing in the brain and is hypothesized to detect inflammatory processes. Here, we aimed to establish a link between peripheral markers of inflammation and FW in brain white matter. Methods All data were obtained from the Australian Schizophrenia Research Bank (ASRB) across 5 Australian states and territories. We first tested for the presence of peripheral cytokine deregulation in schizophrenia, using a large sample (N = 1143) comprising the ASRB. We next determined the extent to which individual variation in 8 circulating pro-/anti-inflammatory cytokines related to FW in brain white matter, imaged in a subset (n = 308) of patients and controls. Results Patients with schizophrenia showed reduced interleukin-2 (IL-2) (t = −3.56, P = .0004) and IL-12(p70) (t = −2.84, P = .005) and increased IL-6 (t = 3.56, P = .0004), IL-8 (t = 3.8, P = .0002), and TNFα (t = 4.30, P < .0001). Higher proinflammatory signaling of IL-6 (t = 3.4, P = .0007) and TNFα (t = 2.7, P = .0007) was associated with higher FW levels in white matter. The reciprocal increases in serum cytokines and FW were spatially widespread in patients encompassing most major fibers; conversely, in controls, the relationship was confined to the anterior corpus callosum and thalamic radiations. No relationships were observed with alternative dMRI measures, including the fractional anisotropy and tissue-related FA. Conclusions We report widespread deregulation of cytokines in schizophrenia and identify inflammation as a putative mechanism underlying increases in brain FW levels.

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.

scholarly journals Aberrant early growth of individual trigeminal sensory and motor axons in a series of mouse genetic models of 22q11.2 deletion syndrome

2020 ◽  
Vol 29 (18) ◽  
pp. 3081-3093
Author(s):  
Zahra Motahari ◽  
Thomas M Maynard ◽  
Anastas Popratiloff ◽  
Sally A Moody ◽  
Anthony-S LaMantia
Keyword(s):  
Developmental Disorders ◽  
Axon Growth ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
Motor Axons ◽  
22Q11.2 Deletion ◽  
Critical Determinant ◽  
Sensory Axons ◽  
Anterior Posterior

Abstract We identified divergent modes of initial axon growth that prefigure disrupted differentiation of the trigeminal nerve (CN V), a cranial nerve essential for suckling, feeding and swallowing (S/F/S), a key innate behavior compromised in multiple genetic developmental disorders including DiGeorge/22q11.2 Deletion Syndrome (22q11.2 DS). We combined rapid in vivo labeling of single CN V axons in LgDel+/− mouse embryos, a genomically accurate 22q11.2DS model, and 3D imaging to identify and quantify phenotypes that could not be resolved using existing methods. We assessed these phenotypes in three 22q11.2-related genotypes to determine whether individual CN V motor and sensory axons wander, branch and sprout aberrantly in register with altered anterior–posterior hindbrain patterning and gross morphological disruption of CN V seen in LgDel+/−. In the additional 22q11.2-related genotypes: Tbx1+/−, Ranbp1−/−, Ranbp1+/− and LgDel+/−:Raldh2+/−; axon phenotypes are seen when hindbrain patterning and CN V gross morphology is altered, but not when it is normal or restored toward WT. This disordered growth of CN V sensory and motor axons, whose appropriate targeting is critical for optimal S/F/S, may be an early, critical determinant of imprecise innervation leading to inefficient oropharyngeal function associated with 22q11.2 deletion from birth onward.

scholarly journals The 22q11.2 Deletion Syndrome: A Gene Dosage Perspective

2006 ◽  
Vol 6 ◽  
pp. 1881-1887 ◽  
Author(s):  
Antonio Baldini
Keyword(s):  
Developmental Stages ◽  
Gene Dosage ◽  
Single Gene ◽  
22Q11.2 Deletion Syndrome ◽  
Genomic Region ◽  
Deletion Syndrome ◽  
Genomic Disorder ◽  
22Q11.2 Deletion ◽  
Developmental Context

The 22q11.2 deletion/DiGeorge syndrome is a relatively common “genomic” disorder that results from heterozygous deletion of a 3-Mbp segment of chromosome 22. Of the more than 30 genes deleted in this syndrome,TBX1is the only one that has been found to be mutated in some patients with a phenotype that is very similar to that of patients with the full deletion, suggesting thatTBX1haploinsufficiency is a major contributor to the syndrome’s phenotype. Multi- and single-gene mouse models have provided a considerable amount of information about the consequences of decreased and increased dosage of the genomic region (and in particular of theTbx1gene) on mouse embryonic development. Modified alleles ofTbx1, as well as conditional ablation strategies have been utilized to mapin vivothe tissues and developmental stages most sensitive to gene dosage. These experiments have revealed substantially different sensitivity to gene dosage in different tissues and at different times, underlying the importance of the developmental context within which gene dosage reduction occurs.

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