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

2007 ◽  
Vol 38 (1) ◽  
pp. 89-100 ◽  
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.

scholarly journals Structural brain abnormalities associated with deletion at chromosome 22q11

2001 ◽  
Vol 178 (5) ◽  
pp. 412-419 ◽  
Author(s):  
Therese Van Amelsvoort ◽  
Eileen Daly ◽  
Dene Robertson ◽  
John Suckling ◽  
Virginia Ng ◽  
...  
Keyword(s):  
White Matter ◽  
Learning Disability ◽  
Brain Anatomy ◽  
White Matter Volume ◽  
Brain Abnormalities ◽  
Temporal Lobes ◽  
Chromosome 22Q11 ◽  
High Prevalence ◽  
Velo Cardio Facial Syndrome ◽  
Regional Brain Volume

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.

scholarly journals Women with autistic-spectrum disorder: magnetic resonance imaging study of brain anatomy

2007 ◽  
Vol 191 (3) ◽  
pp. 224-228 ◽  
Author(s):  
Michaelc. Craig ◽  
Shahid H. Zaman ◽  
Eileen M. Daly ◽  
William J. Cutter ◽  
Dene M. W. Robertson ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
White Matter ◽  
Magnetic Resonance ◽  
Autistic Spectrum Disorder ◽  
Grey Matter ◽  
Matter Density ◽  
Spectrum Disorder ◽  
Brain Anatomy ◽  
Resonance Imaging ◽  
Autistic Spectrum

BackgroundOur understanding of anatomical differences in people with autistic-spectrum disorder, is based on mixed-gender or male samples.AimsTo study regional grey-matter and white-matter differences in the brains of women with autistic-spectrum disorder.MethodWe compared the brain anatomy of 14 adult women with autistic-spectrum disorder with 19 controls using volumetric magnetic resonance imaging and voxel-based morphometry Results Women with autistic-spectrum disorder had a smaller density bilaterally of grey matter in the frontotemporal cortices and limbic system, and of white matter in the temporal lobes (anterior) and pons. In contrast, they had a larger white-matter density bilaterally in regions of the association and projection fibres of the frontal, parietal, posterior temporal and occipital lobes, in the commissural fibres of the corpus callosum (splenium) and cerebellum (anterior lobe). Further, we found a negative relationship between reduced grey-matter density in right limbic regions and social communication ability.ConclusionsWomen with autistic-spectrum disorder have significant differences in brain anatomy from controls, in brain regions previously reported as abnormal in adult men with the disorder. Some anatomical differences may be related to clinical symptoms.

Abstract 025: Cross-sectional Relations of Serum Cortisol and Cognitive and Structural Brain Measures in Young Adults: The Framingham Heart Study

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Justin B Echouffo Tcheugui ◽  
Sarah Conner ◽  
Jayandra J Himali ◽  
Pauline Maillard Maillard ◽  
Charles S DeCarli ◽  
...  
Keyword(s):  
Young Adults ◽  
White Matter ◽  
Visual Perception ◽  
Gray Matter ◽  
Brain Volume ◽  
Brain Mri ◽  
Serum Cortisol ◽  
Matter Density ◽  
Brain Volumes ◽  
Gray Matter Density

Introduction: Chronic stress and related changes in serum cortisol have adverse effects on brain structure and cognition in animal models. However, evidence from population-based studies is scant. We assessed the association of early morning serum cortisol with cognition and brain structural integrity in middle-aged adults without dementia. Hypotheses: High or low levels of serum cortisol are associated with lower cognitive performance and brain volumes. Methods: We evaluated dementia-free Framingham Study (Generation 3) participants (mean age 48.5 years; 46.8% men), who underwent cognitive testing of memory, abstract reasoning, visual perception, attention, and executive function (n= 2231), and brain MRI (n=2018) to assess total white matter, lobar gray matter, and white matter hyperintensity volumes and fractional anisotropy (FA) measures. We used linear or logistic (cortisol categorized in tertiles, middle tertile as the reference) regression to assess the relations of cortisol with cognition, MRI volumes and voxel-based microstructural white matter integrity and gray matter density, adjusting for age, sex, APOE and vascular risk factors. Results: Higher cortisol (highest tertile vs. middle tertile) was associated with worse memory and visual perception, as well as lower total cerebral brain, occipital and frontal lobar gray matter volumes (Table ) . Higher cortisol was associated with multiple areas of microstructural changes on voxel-based analyses (gray matter density and FA). The association of cortisol with total cerebral brain volume varied by sex ( Pinteraction =0.048 , highest cortisol tertile inversely associated with cerebral brain volume in women [ P= 0.001] but not in men [ P =0.717]). There was no effect modification by the apoE4 genotype of the relations of cortisol and cognition or imaging traits. Conclusions: Higher serum cortisol was associated with lower brain volumes and impaired memory in asymptomatic young adults in their forties; women may be particularly susceptible to this influence.

scholarly journals Implication of Contactins in Demyelinating Pathologies

Life ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 51
Author(s):  
Ilias Kalafatakis ◽  
Maria Savvaki ◽  
Theodora Velona ◽  
Domna Karagogeos
Keyword(s):  
Nervous System ◽  
White Matter ◽  
Cell Adhesion Molecules ◽  
White Matter Lesions ◽  
Myelinated Axon ◽  
Immunoglobulin Superfamily ◽  
Proper Function ◽  
Myelinated Axons ◽  
And Function

Demyelinating pathologies comprise of a variety of conditions where either central or peripheral myelin is attacked, resulting in white matter lesions and neurodegeneration. Myelinated axons are organized into molecularly distinct domains, and this segregation is crucial for their proper function. These defined domains are differentially affected at the different stages of demyelination as well as at the lesion and perilesion sites. Among the main players in myelinated axon organization are proteins of the contactin (CNTN) group of the immunoglobulin superfamily (IgSF) of cell adhesion molecules, namely Contactin-1 and Contactin-2 (CNTN1, CNTN2). The two contactins perform their functions through intermolecular interactions, which are crucial for myelinated axon integrity and functionality. In this review, we focus on the implication of these two molecules as well as their interactors in demyelinating pathologies in humans. At first, we describe the organization and function of myelinated axons in the central (CNS) and the peripheral (PNS) nervous system, further analyzing the role of CNTN1 and CNTN2 as well as their interactors in myelination. In the last section, studies showing the correlation of the two contactins with demyelinating pathologies are reviewed, highlighting the importance of these recognition molecules in shaping the function of the nervous system in multiple ways.

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

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.

scholarly journals Neuroplacentology in congenital heart disease: placental connections to neurodevelopmental outcomes

2021 ◽  
Author(s):  
Rachel L. Leon ◽  
Imran N. Mir ◽  
Christina L. Herrera ◽  
Kavita Sharma ◽  
Catherine Y. Spong ◽  
...  
Keyword(s):  
Brain Development ◽  
Congenital Heart ◽  
Fetal Brain ◽  
In Utero ◽  
Structure And Function ◽  
Brain Growth ◽  
Neurodevelopmental Outcomes ◽  
Fetal Brain Development ◽  
And Function

Abstract Children with congenital heart disease (CHD) are living longer due to effective medical and surgical management. However, the majority have neurodevelopmental delays or disorders. The role of the placenta in fetal brain development is unclear and is the focus of an emerging field known as neuroplacentology. In this review, we summarize neurodevelopmental outcomes in CHD and their brain imaging correlates both in utero and postnatally. We review differences in the structure and function of the placenta in pregnancies complicated by fetal CHD and introduce the concept of a placental inefficiency phenotype that occurs in severe forms of fetal CHD, characterized by a myriad of pathologies. We propose that in CHD placental dysfunction contributes to decreased fetal cerebral oxygen delivery resulting in poor brain growth, brain abnormalities, and impaired neurodevelopment. We conclude the review with key areas for future research in neuroplacentology in the fetal CHD population, including (1) differences in structure and function of the CHD placenta, (2) modifiable and nonmodifiable factors that impact the hemodynamic balance between placental and cerebral circulations, (3) interventions to improve placental function and protect brain development in utero, and (4) the role of genetic and epigenetic influences on the placenta–heart–brain connection. Impact Neuroplacentology seeks to understand placental connections to fetal brain development. In fetuses with CHD, brain growth abnormalities begin in utero. Placental microstructure as well as perfusion and function are abnormal in fetal CHD.

scholarly journals Involvement of Thyroid Hormones in Brain Development and Cancer

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2693
Author(s):  
Gabriella Schiera ◽  
Carlo Maria Di Liegro ◽  
Italia Di Liegro
Keyword(s):  
Nervous System ◽  
Thyroid Hormones ◽  
Brain Development ◽  
Placental Transfer ◽  
Regulation Of Gene Expression ◽  
Mammalian Brain ◽  
Cancer Proliferation ◽  
Fetal Thyroid ◽  
Genomic Effects ◽  
And Function

The development and maturation of the mammalian brain are regulated by thyroid hormones (THs). Both hypothyroidism and hyperthyroidism cause serious anomalies in the organization and function of the nervous system. Most importantly, brain development is sensitive to TH supply well before the onset of the fetal thyroid function, and thus depends on the trans-placental transfer of maternal THs during pregnancy. Although the mechanism of action of THs mainly involves direct regulation of gene expression (genomic effects), mediated by nuclear receptors (THRs), it is now clear that THs can elicit cell responses also by binding to plasma membrane sites (non-genomic effects). Genomic and non-genomic effects of THs cooperate in modeling chromatin organization and function, thus controlling proliferation, maturation, and metabolism of the nervous system. However, the complex interplay of THs with their targets has also been suggested to impact cancer proliferation as well as metastatic processes. Herein, after discussing the general mechanisms of action of THs and their physiological effects on the nervous system, we will summarize a collection of data showing that thyroid hormone levels might influence cancer proliferation and invasion.

scholarly journals In utero MRI identifies consequences of early-gestation alcohol drinking on fetal brain development in rhesus macaques

2020 ◽  
Vol 117 (18) ◽  
pp. 10035-10044
Author(s):  
Xiaojie Wang ◽  
Verginia C. Cuzon Carlson ◽  
Colin Studholme ◽  
Natali Newman ◽  
Matthew M. Ford ◽  
...  
Keyword(s):  
White Matter ◽  
Brain Development ◽  
Ex Vivo ◽  
Early Recognition ◽  
Brain Mri ◽  
Fetal Brain ◽  
Fetal Mri ◽  
Diffusion Anisotropy ◽  
Self Administration ◽  
White Matter Tracts

One factor that contributes to the high prevalence of fetal alcohol spectrum disorder (FASD) is binge-like consumption of alcohol before pregnancy awareness. It is known that treatments are more effective with early recognition of FASD. Recent advances in retrospective motion correction for the reconstruction of three-dimensional (3D) fetal brain MRI have led to significant improvements in the quality and resolution of anatomical and diffusion MRI of the fetal brain. Here, a rhesus macaque model of FASD, involving oral self-administration of 1.5 g/kg ethanol per day beginning prior to pregnancy and extending through the first 60 d of a 168-d gestational term, was utilized to determine whether fetal MRI could detect alcohol-induced abnormalities in brain development. This approach revealed differences between ethanol-exposed and control fetuses at gestation day 135 (G135), but not G110 or G85. At G135, ethanol-exposed fetuses had reduced brainstem and cerebellum volume and water diffusion anisotropy in several white matter tracts, compared to controls. Ex vivo electrophysiological recordings performed on fetal brain tissue obtained immediately following MRI demonstrated that the structural abnormalities observed at G135 are of functional significance. Specifically, spontaneous excitatory postsynaptic current amplitudes measured from individual neurons in the primary somatosensory cortex and putamen strongly correlated with diffusion anisotropy in the white matter tracts that connect these structures. These findings demonstrate that exposure to ethanol early in gestation perturbs development of brain regions associated with motor control in a manner that is detectable with fetal MRI.

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