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Biomedical subjects

S Eliez

Publications and source records attributed to S Eliez.

At least 19 recordsLinked to original sources

A multiple case study of verbal short-term memory in velo-cardio-facial syndrome.

BACKGROUND: Velo-cardio-facial syndrome (VCFS, 22q11.2 deletion) is characterized by severely delayed language development. The current study explored the integrity of verbal short-term memory (STM), a cognitive function critically involved in language development, in eight children with VCFS. METHODS: Using a multiple case study design, we presented a series of STM tasks exploring immediate serial recall for word and non-word lists to eight children with VCFS (aged 8-12 years) and to chronological-age-matched control groups. A first task assessed the integrity of phonological coding in verbal STM by comparing recall for phonologically similar and dissimilar words. Subsequently, the interaction between verbal knowledge and STM capacity was investigated by comparing recall for high- and low-imageability words, for high- and low-frequency words, and for words and non-words. A final task assessed short-term serial order recognition for digit sequences. RESULTS: When computing the number of items recalled in the word recall tasks, independently of their serial position, only one child presented consistent difficulties. Short-term recall of non-words was normal in each child. Phonological similarity and verbal knowledge influenced STM performance to a similar extent in children with VCFS and controls. On the other hand, when applying a strict serial recall criterion, difficulties with the word and non-word recall tasks were observed in most children. Half of the patients were also impaired in the serial order recognition task. CONCLUSIONS: Despite mild intellectual disability, it is possible for short-term retention capacities for verbal item information to be at an age-appropriate level in VCFS. However, STM for serial order information could be impaired more specifically.

Child↗

[Psychiatry].

The main innovation of the year 2004 was the introduction of a new, second-generation antipsychotic drug with a new mechanism of action (partial dopamine agonist), encouraging first clinical results, and an advantageous clinical tolerance profile. Additionally, three new galenic forms are presented: an oral, extended-release form of methylphenidate that could be useful in the treatment of attention-deficit/hyperactivity disorders; an intramuscular depot form of a second-generation antipsychotic drug (risperidone) with the advantage of improving adherence; and an intramuscular form of a second generation antipsychotic (olanzapine) that is valuable in emergency situations. Finally, we will briefly give an update on the advantages of lamotrigine in bipolar depression.

Antidepressive Agents↗

Evidence for superior parietal impairment in Williams syndrome.

Parietal lobe impairment is hypothesized to contribute to the dramatic visual-spatial deficits in Williams syndrome (WS). The authors examined the superior and inferior parietal lobule in 17 patients with WS and 17 control female adults (CNLs). The right and left superior parietal lobule gray matter volumes were significantly smaller in patients with WS than in CNLs, even after controlling for total cerebral gray matter. Impaired superior parietal function could explain WS visual-spatial and visual-motor problems.

Adult↗

Gray matter alteration in dyslexia: converging evidence from volumetric and voxel-by-voxel MRI analyses.

Affecting up to 4-10% of the population, dyslexia is a highly prevalent, childhood onset developmental disorder adversely influencing multiple domains of adaptive functioning throughout the lifespan. The present brain imaging study was conducted in order to investigate the neuroanatomical correlates of developmental dyslexia. The MRI brain scans of 10 males with dyslexia and 14 matched controls were analyzed with (1) a classical volumetric method measuring gray and white matter lobar volumes and (2) a voxel-by-voxel method. The voxel-by-voxel method identifies changes in tissue density and localizes morphologic alterations without limiting the analyses to predefined regions. Subsequent correlations between gray matter density and neuropsychological performance on specific phonological processing tasks (rhyme judgment) were conducted. Volumetric analyses revealed significantly reduced gray matter volumes in both temporal lobes in dyslexic individuals. The voxel-by-voxel analyses further localized changes to the left temporal lobe, revealing reduced gray matter density in the middle and inferior temporal gyri. Conversely, increased gray matter density was found in the precentral gyri bilaterally. As a combined group, the dyslexic and control subjects demonstrated positive correlations between performance on the rhyme judgment tasks and gray matter density in the middle and inferior frontal gyri, and the middle temporal gyri bilaterally. The current study indicates that dyslexia is associated with a structural gray matter deficit involving a complex fronto-temporal network implicated in phonological processing.

Adolescent↗

Attenuation of frontal asymmetry in pediatric posttraumatic stress disorder.

BACKGROUND: Volumetric imaging research has shown abnormal brain morphology in adults with posttraumatic stress disorder (PTSD) when compared with matched control subjects. In this article, we present brain imaging findings from a study of children with PTSD symptoms. METHODS: Twenty-four children between the ages of 7 and 14 with a history of trauma and PTSD symptoms were assessed with the Clinician-Administered PTSD Scale for Children and Adolescents (CAPS-CA). The sample underwent magnetic resonance imaging in a 1.5 T scanner. Brain images were analyzed by raters blind to diagnostic status using well-standardized methods, and images were compared with age- and gender-matched healthy control subjects. RESULTS: The clinical group demonstrated attenuation of frontal lobe asymmetry and smaller total brain and cerebral volumes when compared with the control group. There were no statistically significant differences in hippocampal volume between clinical and control subjects. CONCLUSIONS: Frontal lobe abnormalities may occur as a result of PTSD in children or, alternatively, be a risk factor for the development of the syndrome in this age group. The implications of the findings and their consistency with previous research are discussed.

Adolescent↗

Neurobehavioral phenotype in carriers of the fragile X premutation.

There have been contradictory findings in the fragile X (fraX) literature about possible neurocognitive and psychological symptoms due to the fraX premutation (pM). The purpose of the present study was to investigate the relationship between CGG repeat length and neurobehavioral functioning in carriers of the fraX pM. Eighty-five female carriers of the pM with allele sizes ranging from 59-166 were administered a comprehensive IQ test (WAIS-III) and completed a questionnaire designed to measure psychopathology (Symptom Checklist (SCL)-90-R). No relationship between allele size and cognition was identified. A significant negative relationship between allele size and age was found, as well as a positive relationship between allele size and depression. Follow-up analyses separating small and large allele sizes (below and above 100 CGG repeats) indicated that individuals with larger allele sizes scored significantly higher on the Interpersonal Sensitivity and Depression subscales of the SCL-90-R. Despite the limitation of few individuals with high CGG repeat lengths, our findings suggest that females with larger premutated alleles (> or = 100 repeats) display some clinical manifestations of fraX syndrome.

Adult↗

Amygdala and hippocampal volumes in children with Down syndrome: a high-resolution MRI study.

The objective of this study was to use high-resolution MRI techniques to determine whether children with Down syndrome exhibit decreases in hippocampal and amygdala volumes similar to those demonstrated in recent studies of adults with this condition. When corrected for overall brain volumes, amygdala volumes did not differ between groups but hippocampal volumes were significantly smaller in the Down syndrome group. These findings suggest that the hippocampal volume reduction seen in adults with Down syndrome may be primarily due to early developmental differences rather than neurodegenerative changes.

Amygdala↗

Preliminary evidence of widespread morphological variations of the brain in dyslexia.

The MR images of 16 men with dyslexia and 14 control subjects were compared using a voxel-based analysis. Evidence of decreases in gray matter in dyslexic subjects, most notably in the left temporal lobe and bilaterally in the temporoparietooccipital juncture, but also in the frontal lobe, caudate, thalamus, and cerebellum, was found. Widely distributed morphologic differences affecting several brain regions may contribute to the deficits associated with dyslexia.

Adolescent↗

A quantitative MRI study of posterior fossa development in velocardiofacial syndrome.

BACKGROUND: Velocardiofacial syndrome (VCFS) has been identified as a risk factor for developing schizophrenia. Qualitative neuroimaging studies indicated that VCFS was frequently associated with abnormal development of structures in the posterior fossa of the brain. The objective of this investigation was to identify the specific structures affected in the posterior fossa and investigate the association of these neuroanatomic variations with behaviors potentially related to later-onset psychiatric disorders. METHODS: Twenty-four children and adolescents with VCFS individually matched for age and gender with 24 control subjects received magnetic resonance imaging scans. Analysis of covariance models were used to investigate regional brain differences. Association between brain areas and behaviors measured on the Child Behavior Checklist (CBCL) were assessed using simple regression models. RESULTS: Children with VCFS had significantly smaller size of vermal lobules VI--VII and the pons after adjusting for overall brain size. There were no significant associations between scores on the CBCL and measures of neuroanatomic variation within the VCFS group. CONCLUSIONS: Structural alterations of the posterior fossa in VCFS are specifically limited to cerebellar vermis lobules VI--VII and pons. Previous literature has suggested that the vermis is involved in social cognition, and alteration of lobules VI--VII could therefore partially explain the neurobehavioral profile associated with VCFS.

Abnormalities, Multiple↗

Dorsal forebrain anomaly in Williams syndrome.

BACKGROUND: Williams syndrome (WMS) is a rare neurogenetic condition with a behavioral phenotype that suggests a dorsal and/or ventral developmental dissociation, with deficits in dorsal but not the ventral hemispheric visual stream. A shortened extent of the dorsal central sulcus has been observed in autopsy specimens. OBJECTIVE: To compare gross anatomical features between the dorsal and ventral portions of the cerebral hemispheres by examining the dorsal extent of the central sulcus in brain magnetic resonance images from a sample of subjects with WMS and age- and sex-matched control subjects. SUBJECTS: Twenty-one subjects having clinically and genetically diagnosed WMS (mean +/- SD age, 28.9 +/- 7.9 years) were compared with 21 age- and sex-matched typically developing controls (mean +/- SD age, 28.8 +/- 7.9 years). DESIGN: High-resolution structural magnetic resonance images were acquired. The extent of the central sulcus was qualitatively assessed via surface projections of the cerebral cortex. RESULTS: The dorsal central sulcus is less likely to reach the interhemispheric fissure in subjects with WMS than in controls for both left (P< .001, chi(2) = 15.79) and right (P< .001, chi(2) = 12.95) hemispheres. No differences between the groups were found in the ventral extent of the central sulcus. CONCLUSIONS: Anomalies in the dorsal region in patients with WMS are indicative of early neurodevelopmental problems affecting the development of the dorsal forebrain and are most likely related to the deficits in visuospatial ability and behavioral timing often observed in this condition.

Adult↗

Analysis of cerebral shape in Williams syndrome.

BACKGROUND: As a neurobehavioral disorder with a specific neurocognitive profile and a well-defined genetic etiology, Williams syndrome (WMS) provides an exceptional opportunity to examine associations among measures of behavior, neuroanatomy, and genetics. This study was designed to determine how cerebral shape differs between the brains of subjects with WMS and those of normal controls. SUBJECTS: Twenty adults with clinically and genetically diagnosed WMS (mean +/- SD age, 28.5 +/- 8.3 years) and 20 healthy, age- and sex-matched controls (mean +/- SD age, 28.5 +/- 8.2 years). DESIGN: High-resolution structural magnetic resonance imaging data were used for shape-based morphological analysis of the right and left cerebral hemispheres and the corpus callosum. Statistical analyses were performed to examine group differences. RESULTS: Both right and left cerebral hemispheres of subjects with WMS bend to a lesser degree in the sagittal plane than normal controls (P<.001). The corpus callosum also bends less in subjects with WMS (P =.05). In addition, subjects with WMS have decreased cerebral (P<.001) and corpus callosum (P<.001) midline lengths. CONCLUSIONS: Subjects with WMS have significantly different cerebral shape from normal controls, perhaps due to decreased parieto-occipital lobe volumes relative to frontal regions. The similar observation in the corpus callosum may be associated with a decreased size of the splenium in WMS. These findings may provide important clues to the effect of genes in the WMS-deleted region on brain development.

Adult↗

Parental origin of the deletion 22q11.2 and brain development in velocardiofacial syndrome: a preliminary study.

BACKGROUND: As children with velocardiofacial syndrome (VCFS) develop, they are at increased risk for psychopathology; one third will eventually develop schizophrenia. Because VCFS and the concomitant symptomatology result from a known genetic origin, the biological and behavioral characteristics of the syndrome provide an optimal framework for conceptualizing the associations among genes, brain development, and behavior. The purpose of this study was to investigate the effect of the parental origin of the 22q11.2 microdeletion on the brain development of children and adolescents with VCFS. METHODS: Eighteen persons with VCFS and 18 normal control subjects were matched individually for age and sex. Results of DNA polymorphism analyses determined the parental origin of the deletion. Nine persons with VCFS had a deletion on the maternally derived chromosome 22; 9 persons, on the paternally derived chromosome 22. High-resolution magnetic resonance imaging scans were analyzed to provide quantitative measures of gray and white matter brain tissue. RESULTS: Total brain volume was approximately 11% smaller in the VCFS group than in controls. Comparisons between VCFS subgroups (maternal vs paternal microdeletion 22q11.2) indicated a significant 9% volumetric difference in total volume of cerebral gray matter (volume was greater in patients with paternal microdeletion) but not cerebral white matter. Significant age-related changes in gray matter were detected for subjects whose 22q11.2 deletion was on the maternal chromosome. CONCLUSIONS: Children and adolescents with VCFS experience major alterations in brain volumes. Significant reduction in gray matter development is attributable to presence of 22q11.2 microdeletion on the maternal chromosome.

Abnormalities, Multiple↗

Brain anatomy, gender and IQ in children and adolescents with fragile X syndrome.

This study utilized MRI data to describe neuroanatomical morphology in children and adolescents with fragile X syndrome, the most common inherited cause of developmental disability. The syndrome provides a model for understanding how specific genetic factors can influence both neuroanatomy and cognitive capacity. Thirty-seven children and adolescents with fragile X syndrome received an MRI scan and cognitive testing. Scanning procedures and analytical strategies were identical to those reported in an earlier study of 85 typically developing children, permitting a comparison with a previously published template of normal brain development. Regression analyses indicated that there was a normative age-related decrease in grey matter and an increase in white matter. However, caudate and ventricular CSF volumes were significantly enlarged, and caudate volumes decreased with age. Rates of reduction of cortical grey matter were different for males and females. IQ scores were not significantly correlated with volumes of cortical and subcortical grey matter, and these relationships were statistically different from the correlational patterns observed in typically developing children. Children with fragile X syndrome exhibited several typical neurodevelopmental patterns. Aberrations in volumes of subcortical nuclei, gender differences in rates of cortical grey matter reduction and an absence of correlation between grey matter and cognitive performance provided indices of the deleterious effects of the fragile X mutation on the brain's structural organization.

Adolescent↗

Neuroanatomy of Down's syndrome: a high-resolution MRI study.

OBJECTIVE: Down's syndrome, the most common genetic cause of mental retardation, results in characteristic physical and neuropsychological findings, including mental retardation and deficits in language and memory. This study was undertaken to confirm previously reported abnormalities of regional brain volumes in Down's syndrome by using high-resolution magnetic resonance imaging (MRI), determine whether these volumetric abnormalities are present from childhood, and consider the relationship between neuroanatomic abnormalities and the cognitive profile of Down's syndrome. METHOD: Sixteen children and young adults with Down's syndrome (age range=5-23 years) were matched for age and gender with 15 normal comparison subjects. High-resolution MRI scans were quantitatively analyzed for measures of overall and regional brain volumes and by tissue composition. RESULTS: Consistent with prior imaging studies, subjects with Down's syndrome had smaller overall brain volumes, with disproportionately smaller cerebellar volumes and relatively larger subcortical gray matter volumes. Also noted was relative preservation of parietal lobe gray and temporal lobe white matter in subjects with Down's syndrome versus comparison subjects. No abnormalities in pattern of brain asymmetry were noted in Down's syndrome subjects. CONCLUSIONS: The results largely confirm findings of previous studies with respect to overall patterns of brain volumes in Down's syndrome and also provide new evidence for abnormal volumes of specific regional tissue components. The presence of these abnormalities from an early age suggests that fetal or early postnatal developmental differences may underlie the observed pattern of neuroanatomic abnormalities and contribute to the specific cognitive and developmental deficits seen in individuals with Down's syndrome.

Adolescent↗

Velocardiofacial syndrome: are structural changes in the temporal and mesial temporal regions related to schizophrenia?

OBJECTIVE: Velocardiofacial syndrome results from a microdeletion on chromosome 22 (22q11.2). Clinical studies indicate that more than 30% of children with the syndrome will develop schizophrenia. The authors sought to determine whether neuroanatomical features in velocardiofacial syndrome are similar to those reported in the literature on schizophrenia by measuring the volumes of the temporal lobe, superior temporal gyrus, and mesial temporal structures in children and adolescents with velocardiofacial syndrome. METHOD: Twenty-three children and adolescents with velocardiofacial syndrome and 23 comparison subjects, individually matched for age and gender, received brain magnetic resonance imaging (MRI) scans. Analysis of covariance models were used to compare regional brain volumes. Correlations between residualized brain volumes and age were standardized and compared with the Fisher r-to-z transformation. RESULTS: Children with velocardiofacial syndrome had significantly smaller average temporal lobe, superior temporal gyrus, and hippocampal volumes than normal comparison children, although these differences were commensurate with a lower overall brain size in the affected children. In a cross-sectional analysis, children with velocardiofacial syndrome exhibited aberrant volumetric reductions with age that were localized to the temporal lobe and left hippocampal regions. CONCLUSIONS: Abnormal temporal lobe and hippocampal development in velocardiofacial syndrome is potentially concordant with MRI findings in the schizophrenia literature. Temporal lobe and mesial temporal structures may represent a shared substrate for the effects of the 22q11.2 deletion and for the complex etiological pathways that lead to schizophrenia. Longitudinal research may help determine which children with velocardiofacial syndrome are at risk for serious psychiatric illness in adulthood.

Abnormalities, Multiple↗

Functional neuroanatomy of visuospatial working memory in fragile X syndrome: relation to behavioral and molecular measures.

OBJECTIVE: Fragile X syndrome is a neurogenetic disorder that is the most common known heritable cause of neurodevelopmental disability. This study examined the neural substrates of working memory in female subjects with fragile X syndrome. Possible correlations among behavioral measures, brain activation, and the FMR1 gene product (FMRP expression), as well as between IQ and behavioral measures, were investigated. METHOD: Functional magnetic resonance imaging was used to examine visuospatial working memory in 10 female subjects with fragile X syndrome and 15 typically developing female subjects (ages 10-23 years). Subjects performed standard 1-back and 2-back visuospatial working memory tasks. Brain activation was examined in four regions of the cortex known to play a critical role in visuospatial working memory. Correlations between behavioral, neuroimaging, and molecular measures were examined. RESULTS: Relative to the comparison group, subjects with fragile X syndrome performed significantly worse on the 2-back task but not on the 1-back task. In a region-of-interest analysis focused on the inferior frontal gyrus, middle frontal gyrus, superior parietal lobule, and supramarginal gyrus, comparison subjects showed significantly increased brain activation between the 1-back and 2-back tasks, but subjects with fragile X syndrome showed no change in activation between the two tasks. Significant correlations were found in comparison subjects between activation in the frontal and parietal regions and the rate of correct responses on the 2-back task, but not on the 1-back task. In subjects with fragile X syndrome, significant correlations were found during the 2-back task between FMRP expression and activation in the right inferior and bilateral middle frontal gyri and the bilateral supramarginal gyri. CONCLUSIONS: Subjects with fragile X syndrome are unable to modulate activation in the prefrontal and parietal cortex in response to an increasing working memory load, and these deficits are related to a lower level of FMRP expression in fragile X syndrome subjects than in normal comparison subjects. The observed correlations between biological markers and brain activation provide new evidence for links between gene expression and cognition.

Adolescent↗

Corpus callosum morphology of Williams syndrome: relation to genetics and behavior.

As the largest interhemispheric commissure in the brain, the corpus callosum is of particular interest in disorders that may preferentially affect white matter development such as Williams syndrome (WS). Individuals with WS possess a remarkable array of neurobehavioral peaks and valleys, including deficits in visuospatial ability, mathematics, and attention, but with relative preservation of language and affect. Our study measured the corpus callosum and its primary subdivisions using high-resolution MRI in 20 individuals with WS (13 females and seven males; mean age 28.5, SD 8.3 years; range 19 to 44 years) and 20 age- and sex-matched control participants (mean age 28.5, SD 8.2 years; range 19 to 48 years). Total midsagittal corpus callosum area was reduced (F=4.5, p=0.04, df=36) in the WS population. The area of the splenium (F=12.4, p=0.001, df=36) and isthmus (F=9.4, p=0.004, df=36) were disproportionately reduced in WS beyond the absolute reduction of the entire corpus callosum. These reductions are in concordance with other neuroanatomical findings of decreased parietooccipital volumes as well as the observed visuospatial problems associated with WS.

Adult↗