Structural brain abnormalities associated with deletion at chromosome 22q11

BackgroundVelo-cardio-facial syndrome (VCFS) is associated with deletions in the q11 band of chromosome 22, learning disability and psychosis, but the neurobiological basis is poorly understood.AimsTo investigate brain anatomy in adults with VCFS.MethodMagnetic resonance imaging was used to study 10 patients with VCFS and 13 matched controls. We carried out three analyses: qualitative; traced regional brain volume; and measurement of grey and white matter volume.ResultsThe subjects with VCFS had: a high prevalence of white matter hyperintensities and abnormalities of the septum pellucidum; a significantly smaller volume of cerebellum; and widespread differences in white matter bilaterally and regional specific differences in grey matter in the left cerebellum, insula, and frontal and right temporal lobes.ConclusionsDeletion at chromosome 22q11 is associated with brain abnormalities that are most likely neurodevelopmental and may partially explain the high prevalence of learning disability and psychiatric disorder in VCFS.

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Effects of a functional COMT polymorphism on brain anatomy and cognitive function in adults with velo-cardio-facial syndrome

Psychological Medicine ◽

10.1017/s0033291707000700 ◽

2007 ◽

Vol 38 (1) ◽

pp. 89-100 ◽

Cited By ~ 31

Author(s):

T. van Amelsvoort ◽

J. Zinkstok ◽

M. Figee ◽

E. Daly ◽

R. Morris ◽

...

Keyword(s):

White Matter ◽

Brain Development ◽

Matter Density ◽

Parahippocampal Gyrus ◽

Brain Anatomy ◽

Neurocognitive Performance ◽

Comt Genotype ◽

Brain Volumes ◽

Velo Cardio Facial Syndrome ◽

And Function

BackgroundVelo-cardio-facial syndrome (VCFS) is associated with deletions at chromosome 22q11, abnormalities in brain anatomy and function, and schizophrenia-like psychosis. Thus it is assumed that one or more genes within the deleted region are crucial to brain development. However, relatively little is known about how genetic variation at 22q11 affects brain structure and function. One gene on 22q11 is catechol-O-methyltransferase (COMT): an enzyme that degrades dopamine and contains a functional polymorphism (Val158Met) affecting enzyme activity. Here, we investigated the effect of COMT Val158Met polymorphism on brain anatomy and cognition in adults with VCFS.MethodThe COMT Val158Met polymorphism was genotyped for 26 adults with VCFS on whom DNA was available. We explored its effects on regional brain volumes using hand tracing approaches; on regional grey- and white-matter density using computerized voxel-based analyses; and measures of attention, IQ, memory, executive and visuospatial function using a comprehensive neuropsychological test battery.ResultsAfter corrections for multiple comparisons Val-hemizygous subjects, compared with Met-hemizygotes, had a significantly larger volume of frontal lobes. Also, Val-hemizygotes had significantly increased grey matter density in cerebellum, brainstem, and parahippocampal gyrus, and decreased white matter density in the cerebellum. No significant effects of COMT genotype on neurocognitive performance were found.ConclusionsCOMT genotype effects on brain anatomy in VCFS are not limited to frontal regions but also involve other structures previously implicated in VCFS. This suggests variation in COMT activity is implicated in brain development in VCFS.

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Cerebral MR Morphometry and Neurodevelopmental Outcome in Children before Fontan Procedure at 2 Years of Age: White Matter Volume Is Smaller after Norwood Procedure

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0036-1571859 ◽

2016 ◽

Vol 64 (S 02) ◽

Author(s):

B. Reich ◽

W. Knirsch ◽

K. Mayer ◽

R. Tuura ◽

I. Scheer ◽

...

Keyword(s):

White Matter ◽

Fontan Procedure ◽

Neurodevelopmental Outcome ◽

Norwood Procedure ◽

White Matter Volume ◽

Matter Volume

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Preliminary Evidence for a Relationship between Elevated Plasma TNFα and Smaller Subcortical White Matter Volume in HCV Infection Irrespective of HIV or AUD Comorbidity

International Journal of Molecular Sciences ◽

10.3390/ijms22094953 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4953

Author(s):

Natalie M. Zahr ◽

Kilian M. Pohl ◽

Allison J. Kwong ◽

Edith V. Sullivan ◽

Adolf Pfefferbaum

Keyword(s):

White Matter ◽

Proinflammatory Cytokines ◽

Soluble Protein ◽

Subcortical White Matter ◽

Control Group ◽

White Matter Volume ◽

Brain Volumes ◽

Protein Levels ◽

Matter Volume ◽

Patient Groups

Classical inflammation in response to bacterial, parasitic, or viral infections such as HIV includes local recruitment of neutrophils and macrophages and the production of proinflammatory cytokines and chemokines. Proposed biomarkers of organ integrity in Alcohol Use Disorders (AUD) include elevations in peripheral plasma levels of proinflammatory proteins. In testing this proposal, previous work included a group of human immunodeficiency virus (HIV)-infected individuals as positive controls and identified elevations in the soluble proteins TNFα and IP10; these cytokines were only elevated in AUD individuals seropositive for hepatitis C infection (HCV). The current observational, cross-sectional study evaluated whether higher levels of these proinflammatory cytokines would be associated with compromised brain integrity. Soluble protein levels were quantified in 86 healthy controls, 132 individuals with AUD, 54 individuals seropositive for HIV, and 49 individuals with AUD and HIV. Among the patient groups, HCV was present in 24 of the individuals with AUD, 13 individuals with HIV, and 20 of the individuals in the comorbid AUD and HIV group. Soluble protein levels were correlated to regional brain volumes as quantified with structural magnetic resonance imaging (MRI). In addition to higher levels of TNFα and IP10 in the 2 HIV groups and the HCV-seropositive AUD group, this study identified lower levels of IL1β in the 3 patient groups relative to the control group. Only TNFα, however, showed a relationship with brain integrity: in HCV or HIV infection, higher peripheral levels of TNFα correlated with smaller subcortical white matter volume. These preliminary results highlight the privileged status of TNFα on brain integrity in the context of infection.

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Reduced Relationship to Cortical White Matter Volume Revealed by Tractography-Based Segmentation of the Corpus Callosum in Young Children With Developmental Delay

American Journal of Psychiatry ◽

10.1176/ajp.2006.163.12.2157 ◽

2006 ◽

Vol 163 (12) ◽

pp. 2157-2163 ◽

Cited By ~ 13

Author(s):

Carissa Cascio ◽

Martin Styner ◽

Rachel G. Smith ◽

Michele D. Poe ◽

Guido Gerig ◽

...

Keyword(s):

White Matter ◽

Young Children ◽

Corpus Callosum ◽

Developmental Delay ◽

White Matter Volume ◽

Matter Volume

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White Matter Integrity Predicts Delay Discounting Behavior in 9- to 23-Year-Olds: A Diffusion Tensor Imaging Study

Journal of Cognitive Neuroscience ◽

10.1162/jocn.2009.21107 ◽

2009 ◽

Vol 21 (7) ◽

pp. 1406-1421 ◽

Cited By ~ 119

Author(s):

Elizabeth A. Olson ◽

Paul F. Collins ◽

Catalina J. Hooper ◽

Ryan Muetzel ◽

Kelvin O. Lim ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Delay Discounting ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Imaging Study ◽

Temporal Lobes ◽

Brain White Matter ◽

Independent Effects ◽

Age Range

Healthy participants (n = 79), ages 9–23, completed a delay discounting task assessing the extent to which the value of a monetary reward declines as the delay to its receipt increases. Diffusion tensor imaging (DTI) was used to evaluate how individual differences in delay discounting relate to variation in fractional anisotropy (FA) and mean diffusivity (MD) within whole-brain white matter using voxel-based regressions. Given that rapid prefrontal lobe development is occurring during this age range and that functional imaging studies have implicated the prefrontal cortex in discounting behavior, we hypothesized that differences in FA and MD would be associated with alterations in the discounting rate. The analyses revealed a number of clusters where less impulsive performance on the delay discounting task was associated with higher FA and lower MD. The clusters were located primarily in bilateral frontal and temporal lobes and were localized within white matter tracts, including portions of the inferior and superior longitudinal fasciculi, anterior thalamic radiation, uncinate fasciculus, inferior fronto-occipital fasciculus, corticospinal tract, and splenium of the corpus callosum. FA increased and MD decreased with age in the majority of these regions. Some, but not all, of the discounting/DTI associations remained significant after controlling for age. Findings are discussed in terms of both developmental and age-independent effects of white matter organization on discounting behavior.

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