Biomedical subjects

Carolyn B Mervis

Publications and source records attributed to Carolyn B Mervis.

At least 19 recordsLinked to original sources

PubMed2006

Prevalence of psychiatric disorders in 4 to 16-year-olds with Williams syndrome.

The prevalence of a range of DSM-IV psychiatric disorders in a sample of 119 4-16-year-old children with Williams syndrome (WS) was assessed using a structured diagnostic interview with their parents. Most children (80.7%) met criteria for at least one DSM-IV diagnosis. The most prevalent diagnoses were Attention Deficit/Hyperactivity Disorder (ADHD; 64.7%) and Specific Phobia (53.8%). There was a significant shift in Predominant Type of ADHD as a function of CA, from Combined for the youngest group (ages 4-6 years) to Inattentive for the oldest group (ages 11-16 years). The prevalence of Generalized Anxiety Disorder (GAD) increased significantly with age. These findings are another step toward defining the behavioral phenotype of WS.

Adolescent↗

PubMed2006

Neural mechanisms in Williams syndrome: a unique window to genetic influences on cognition and behaviour.

Williams syndrome, a rare disorder caused by hemizygous microdeletion of about 28 genes on chromosome 7q11.23, has long intrigued neuroscientists with its unique combination of striking behavioural abnormalities, such as hypersociability, and characteristic neurocognitive profile. Williams syndrome, therefore, raises fundamental questions about the neural mechanisms of social behaviour, the modularity of mind and brain development, and provides a privileged setting to understand genetic influences on complex brain functions in a 'bottom-up' way. We review recent advances in uncovering the functional and structural neural substrates of Williams syndrome that provide an emerging understanding of how these are related to dissociable genetic contributions characterized both in special participant populations and animal models.

Animals↗

PubMed2006

Correlates of sleep and pediatric bipolar disorder.

STUDY OBJECTIVE: To determine, based on a large community sample, the prevalence and associated sleep characteristics of children with a bipolar mood disturbance behavioral profile. METHODS: Participants who fit the pediatric bipolar disorder profile as derived from the Child Behavior Checklist were matched to control participants for age, sex, ethnicity, parentally reported attention-deficit/hyperactivity disorder, psychotropic medication usage, and apnea-hypopnea indexes. Paired comparisons were made between the groups to examine differences on polysomnographic data and parentally reported sleep characteristics. RESULTS: Thirteen (approximately 3%) of 438 participants fit the pediatric bipolar disorder profile. These children demonstrated significant sleep-continuity disturbances with poorer sleep efficiency and more awakenings after sleep onset, less rapid eye movement sleep, and longer periods of slow-wave sleep than their matched counterparts during overnight polysomnography. In addition, responses to a parental-report questionnaire about child sleep behavior suggest these children have significant sleep problems, including more difficulty initiating sleep, restless sleep, nightmares, and morning headaches relative to the control group. CONCLUSIONS: Children with a pediatric bipolar disorder profile display consistent quantitative differences in sleep relative to matched controls. Prevalence rates of pediatric bipolar disorder, as assessed by the Child Behavior Checklist, are consistent with those found in the adult bipolar population.

Aggression↗

PubMed2005

Severe expressive-language delay related to duplication of the Williams-Beuren locus.

The Williams-Beuren syndrome (WBS) locus, at 7q11.23, is prone to recurrent chromosomal rearrangements, including the microdeletion that causes WBS, a multisystem condition with characteristic cardiovascular, cognitive, and behavioral features. It is hypothesized that reciprocal duplications of the WBS interval should also occur, and here we present such a case description. The most striking phenotype was a severe delay in expressive speech, in contrast to the normal articulation and fluent expressive language observed in persons with WBS. Our results suggest that specific genes at 7q11.23 are exquisitely sensitive to dosage alterations that can influence human language and visuospatial capabilities.

Attention Deficit Disorder with Hyperactivity↗

PubMed2005

Genetic contributions to human gyrification: sulcal morphometry in Williams syndrome.

Although gyral and sulcal patterns are highly heritable, and emerge in a tightly controlled sequence during development, very little is known about specific genetic contributions to abnormal gyrification or the resulting functional consequences. Williams syndrome (WS), a genetic disorder caused by hemizygous microdeletion on chromosome 7q11.23 and characterized by abnormal brain structure and striking cognitive (impairment in visuospatial construction) and behavioral (hypersocial/anxious) phenotypes, offers a unique opportunity to study these issues. We performed a detailed analysis of sulcal depth based on geometric cortical surface representations constructed from high-resolution magnetic resonance imaging scans acquired from participants with WS and from healthy controls who were matched for age, sex, and intelligence quotient, and compared between-group differences with those obtained from a voxel-based morphometry analysis. We found bilateral reductions in sulcal depth in the intraparietal/occipitoparietal sulcus (PS) in the brains of participants with WS, as well as in the collateral sulcus and the orbitofrontal region in the left hemisphere. The left-hemisphere PS in the WS group averaged 8.5 mm shallower than in controls. Sulcal depth findings in the PS corresponded closely to measures of reduced gray matter volume in the same area, providing evidence that the gray matter volume loss and abnormal sulcal geometry may be related. In the context of previous functional neuroimaging findings demonstrating functional alterations in the same cortical regions, our results further define the neural endophenotype underlying visuoconstructive deficits in WS, set the stage for defining the effects of specific genes, and offer insight into genetic mechanisms of cortical gyrification.

Adolescent↗

PubMed2005

Neural correlates of genetically abnormal social cognition in Williams syndrome.

Williams-Beuren syndrome (WBS), caused by a microdeletion of approximately 21 genes on chromosome 7q11.23, is characterized by unique hypersociability combined with increased non-social anxiety. Using functional neuroimaging, we found reduced amygdala activation in individuals with WBS for threatening faces but increased activation for threatening scenes, relative to matched normal controls. Activation and interactions of prefrontal regions linked to amygdala, especially orbitofrontal cortex, were abnormal, suggesting a genetically controlled neural circuitry for regulating human social behavior.

Amygdala↗

PubMed2005

Functional, structural, and metabolic abnormalities of the hippocampal formation in Williams syndrome.

Williams syndrome (WS), caused by microdeletion of some 21 genes on chromosome 7q11.23, is characterized by dysmorphic features, mental retardation or learning difficulties, elastin arteriopathy, and striking neurocognitive and social-behavioral abnormalities. Recent studies of murine knockouts of key genes in the microdeleted region, LIM kinase 1 (LIMK1) and cytoplasmatic linker protein 2 (CYLN2), demonstrated significant functional and metabolic abnormalities, but grossly normal structure, in the hippocampal formation (HF). Furthermore, deficits in spatial navigation and long-term memory, major cognitive domains dependent on hippocampal function, have been described in WS. We used multimodal neuroimaging to characterize hippocampal structure, function, and metabolic integrity in 12 participants with WS and 12 age-, sex-, and IQ-matched healthy controls. PET and functional MRI studies showed profound reduction in resting blood flow and absent differential response to visual stimuli in the anterior HF in WS. Spectroscopic measures of N-acetyl aspartate, considered a marker of synaptic activity, were reduced. Hippocampal size was preserved, but subtle alterations in shape were present. These data demonstrate abnormalities in HF in WS in agreement with murine models, implicate LIMK1 and CYLN2 in human hippocampal function, and suggest that hippocampal dysfunction may contribute to neurocognitive abnormalities in WS.

Adult↗

PubMed2005

Intellectual abilities and adaptive behavior of children and adolescents with Kabuki syndrome: a preliminary study.

Very little is known about the intellectual abilities and adaptive behavior of individuals who have Kabuki syndrome, beyond the fact that most individuals with this syndrome have mental retardation. To fill this gap, we have completed psychological assessments of 11 children and adolescents with Kabuki syndrome. Results indicated that most of the participants functioned in the range of mild mental retardation, with both intellectual and adaptive behavior in the mildly deficient range and problem behaviors, if any, limited to mild difficulties with inattention and/or hyperactivity-impulsivity and mild problems with obsession/anxiety. At the lower extreme, one child evidenced severe mental retardation and profound adaptive behavior impairment accompanied by serious externalizing and internalizing problem behaviors. At the upper extreme, one adolescent had average intelligence and adaptive behavior, with problem behaviors well within the normal range for his chronological age. Most participants evidenced relative intellectual strengths in verbal and reasoning abilities and a relative weakness in visuospatial construction abilities. This pattern affected adaptive behavior as well, yielding a relative strength in Social Interaction and Communicative Skills and considerable weakness in Motor Skills and Personal Living Skills.

Abnormalities, Multiple↗

PubMed2004

Neural basis of genetically determined visuospatial construction deficit in Williams syndrome.

A unique opportunity to understand genetic determinants of cognition is offered by Williams syndrome (WS), a well-characterized hemideletion on chromosome 7q11.23 that causes extreme, specific weakness in visuospatial construction (the ability to visualize an object as a set of parts or construct a replica). Using multimodal neuroimaging, we identified a neural mechanism underlying the WS visuoconstructive deficit. Hierarchical assessment of visual processing with fMRI showed isolated hypoactivation in WS in the parietal portion of the dorsal stream. In the immediately adjacent parietooccipital/intraparietal sulcus, structural neuroimaging showed a gray matter volume reduction in participants with WS. Path analysis demonstrated that the functional abnormalities could be attributed to impaired input from this structurally altered region. Our observations confirm a longstanding hypothesis about dorsal stream dysfunction in WS, demonstrate effects of a localized abnormality on visual information processing in humans, and define a systems-level phenotype for mapping genetic determinants of visuoconstructive function.

Adult↗

PubMed2004

What are theories for? Concept use throughout the continuum of dinosaur expertise.

Although it is now well established that object concepts are situated within broader systems of theoretical knowledge, it is less clear how theories influence the use of object concepts at various points throughout the continuum of expertise. Two studies were conducted to investigate the impact of specific theories (concerning dinosaurs) and overarching framework theories (of biology) on children's and adults' performance on categorization tasks involving familiar and less familiar concepts. Although expertise increased the quantity of deep feature knowledge possessed by children and increased their understanding of biologically adaptive relations among features, few aspects of children's performance generalized beyond highly familiar dinosaurs. Children's specific theories related to dinosaurs were empirically constrained and relatively dissociated from other types of biological knowledge. The interaction of specific concept knowledge with broader framework theories of biology throughout the continuum of expertise is considered.

Animals↗

PubMed2004

Methodological issues in group-matching designs: alpha levels for control variable comparisons and measurement characteristics of control and target variables.

Group-matching designs are commonly used to identify the diagnosis-specific characteristics of children with developmental disabilities. In this paper, we address three issues central to the use of this design. The first concerns the alpha level to be used for considering groups to be matched on the control variable(s). The second involves the measurement characteristics of the control and target variables. We discuss the properties of standard scores, raw scores, and age equivalents and argue against the use of age equivalents. In addition, we consider the appropriateness of the commonly made prediction that groups that are matched for a control variable such as language ability or nonverbal reasoning ability but are not matched for chronological age should perform at equivalent levels on the target variable. Finally, we discuss issues related to the interpretation of significant between-group differences on the target variable, assuming groups are well-matched on the control variables, and describe the benefits of a method that focuses on characterizing a disorder on a case-by-case basis and then aggregating the cases, using the measures of sensitivity and specificity from signal detection theory.

Age Factors↗

PubMed2004

Neurobehavioral correlates of sleep-disordered breathing in children.

The effects of sleep-disordered breathing (SDB) on neurobehavioral function were examined in two matched groups of children from the general population. Thirty-five children with polysomnographically confirmed SDB were matched for ethnicity, age, gender, maternal educational attainment, and maternal smoking, to healthy children with no evidence of SDB. Children with SDB had significantly lower mean scores on the Differential Ability Scales for General Conceptual Ability (similar to IQ) and for the Non-verbal Cluster. On the neuropsychology assessment battery (NEPSY), children with SDB scored significantly lower than the control group on the attention/executive function domain and two subtests within that domain, one measuring visual attention and the other executive function. In addition, children with SDB scored significantly lower than the controls on one subtest from the NEPSY language domain: Phonological Processing. This subtest measures phonological awareness, a skill that is critical for learning to read. No differences in behavior, as measured by the Child Behavior Checklist (CBCL) or the Conners' Parent Rating Scale, were found between the two groups. Using a novel algorithm to assess sleep pressure, we found that children with SDB were significantly sleepier than controls. Furthermore, total arousal index was negatively correlated with neurocognitive abilities, suggesting a role for sleep fragmentation in pediatric SDB-induced cognitive dysfunction.

Aptitude↗

PubMed2004

Neurobehavioral implications of habitual snoring in children.

OBJECTIVE: Current guidelines for the treatment of children with obstructive sleep apnea (OSA) suggest that primary snoring (PS) in children is benign. However, PS has not been well evaluated, and it is unknown whether PS is associated with serious morbidity. This study investigated whether PS is associated with neurobehavioral deficits in children. METHODS: Parents of 5- to 7-year-old snoring children in public schools were surveyed about their child's sleeping habits. Children with a history of snoring and nonsnoring children were invited for overnight polysomnographic assessment and a battery of neurobehavioral tests. Only children who did not have a history of attention-deficit/hyperactivity disorder and were not considered hyperactive by parental report were tested. RESULTS: Children with a history of snoring, an obstructive apnea index of <1/hour of total sleep time (hrTST), an apnea/hypopnea index <5/hrTST, and no gas exchange abnormalities were classified as PS (n = 87). Control subjects were defined as children without a history of snoring, an obstructive apnea index <1/hrTST, an apnea/hypopnea index <5/hrTST, and no gas exchange abnormalities (n = 31). Although means for both groups were in the normal range, the PS children were found to perform worse on measures related to attention, social problems, and anxious/depressive symptoms. In addition, although within the normal range, both overall cognitive abilities and certain language and visuospatial functions were significantly lower for the PS group than for the control subjects. CONCLUSIONS: PS seems to be associated with significant neurobehavioral deficits in a subset of children, possibly related to increased susceptibility to sleep fragmentation. Larger studies are urgently required because current guidelines for treatment of snoring in children may require reevaluation.

Attention Deficit and Disruptive Behavior Disorder↗

PubMed2003

GTF2I hemizygosity implicated in mental retardation in Williams syndrome: genotype-phenotype analysis of five families with deletions in the Williams syndrome region.

Most individuals with Williams syndrome (WS) have a 1.6 Mb deletion in chromosome 7q11.23 that encompasses the elastin (ELN) gene, while most families with autosomal dominant supravalvar aortic stenosis (SVAS) have point mutations in ELN. The overlap of the clinical phenotypes of the two conditions (cardiovascular disease and connective tissue abnormalities such as hernias) is due to the effect of haploinsufficiency of ELN. SVAS families often have affected individuals with some WS facial features, most commonly in infancy, suggesting that ELN plays a role in WS facial gestalt as well. To find other genes contributing to the WS phenotype, we studied five families with SVAS who have small deletions in the WS region. None of the families had mental retardation, but affected family members had the Williams Syndrome Cognitive Profile (WSCP). All families shared a deletion of LIMK1, which encodes a protein strongly expressed in the brain, supporting the hypothesis that LIMK1 hemizygosity contributes to impairment in visuospatial constructive cognition. While the deletions from the families nearly spanned the WS region, none had a deletion of FKBP6 or GTF2I, suggesting that the mental retardation seen in WS is associated with deletion of either the centromeric and/or telomeric portions of the region. Comparison of these five families with reports of other individuals with partial deletions of the WS region most strongly implicates GTF2I in the mental retardation of WS.

Adolescent↗

PubMed2003

Heat shock protein 27 gene: chromosomal and molecular location and relationship to Williams syndrome.

Heat shock protein 27 (HSP27) is one of a number of actin-binding proteins that regulate actin polymerization. Three related HSP27 sequences had previously been mapped to chromosomes 3, 9, and X. We have used fluorescent in-situ hybridization (FISH) to correct and refine the map position of the transcribed HSP27 gene (locus HSPB1) to chromosome 7q11.23. This band also contains the site of the deletion associated with Williams syndrome (WS). To define the relationship between HSP27 and the WS deletion, we used two-color FISH on previously G-banded and photographed metaphase chromosomes from WS cell-lines and peripheral blood. Six WS patients with longer deletions that extend telomeric to the classical WS deletion region were analyzed for deletion length using HSP27, cosmids generated from P193O22 (cos11) and B350L10 (cos64 and 82), B350L10, B161A02, and B363M4. The BAC 363M4 was selected from the Washington University database and contains HSP27. Our results indicated that HSP27 was deleted in three patients and that HSP27 is telomeric to cos11, cos64, cos82, and B350L10. B363M4 was demonstrated to overlap the telomeric end of B161A02 and HSP27 may be contained partially within the telomeric end of B161A02. The possible role of HSP27 in the cognitive features of WS is discussed.

Chromosome Mapping↗

PubMed2003

Williams syndrome: 15 years of psychological research.

Williams syndrome is a rare genetic disorder caused by a microdeletion of about 20 genes on chromosome 7q11.23. The importance of this syndrome for theories and models of cognition became apparent about 15 years ago, when Bellugi, Sabo, and Vaid (1988) argued that Williams syndrome was a paradigm case of the independence of language from cognition. In particular, it was argued that individuals with Williams syndrome have "intact" language despite severe mental retardation. More recent findings indicate a more complex relation between language and characteristics associated with this syndrome. The articles in this special issue form 3 overlapping clusters: articles concerned with language development relative to cognitive development, articles concerned with other aspects of cognition, and articles concerned with interpersonal relations and personality. Together, these articles provide strong evidence of the importance of the study of neurodevelopmental genetic disorders for enhancing understanding of the complex manner in which initial genetic differences impact both behavior and processing strategies from infancy through adulthood. Our hope is that this issue will motivate further studies, informed by the genetic-developmental approach, on both Williams syndrome and other neurodevelopmental genetic disorders.

Cognition Disorders↗

PubMed2003

The roles of verbal short-term memory and working memory in the acquisition of grammar by children with Williams syndrome.

The roles of verbal short-term and working memory were examined in a sample of children with Williams syndrome (mean chronological age 10 years, 2 months) and a sample of grammar-matched children who are developing normally. Forward digit span, nonword repetition, and backward span were all found to be correlated with receptive grammatical ability in the sample of children with Williams syndrome, but not in the sample of children who are developing normally. The relation between working memory, as measured by backward digit span, and grammatical ability was found to be significantly stronger in children with Williams syndrome than in the control group. This finding highlights the possibility that children with Williams syndrome may rely on their working memory to a greater extent than children who are developing normally to learn grammar. Hierarchical regression analyses indicated receptive vocabulary may mediate the relations among forward digit span, backward digit span, and grammatical ability for the children with Williams syndrome. Phonological short-term memory, however, contributed independently to grammatical ability even after receptive vocabulary was taken into account.

Adolescent↗

PubMed2003

Attentional characteristics of infants and toddlers with Williams syndrome during triadic interactions.

Two studies were conducted to consider the looking behavior of infants and toddlers with Williams syndrome (WS). In Study 1,the looking behavior of a 10-month-old girl with WS during play sessions with her mother and with a stranger was compared to that of 2 groups of infants who were developing normally (ND),1 matched for chronological age and the other for developmental age. The infant with WS spent more than twice as much time looking at her mother as the infants in either contrast group did. She also spent twice as much time looking at the stranger. In addition, during 78%of this time, her gaze at the stranger was coded as extremely intense. Looks of this intensity were virtually never made by the ND infants. In Study 2,the looking behavior of 31 individuals with WS ages 8 to 43 months during a genetics evaluation was compared to that of 319 control children in the same age range (242 with developmental delay due to causes other than WS).Twenty-three of the 25 participants with WS aged 33 months or younger demonstrated extended and intense looking at the geneticist. In contrast, none of the control participants looked extensively or intently at the geneticist. Findings are discussed in the context of previous research on arousal and focused attention during normal development and on temperament and personality of older children and adults with WS. It is argued that the unusual looking patterns evidenced by infants and toddlers with WS presage the unusual temperament and personality of older individuals with WS, and the possibility of a genetic basis for these behaviors is addressed.

Attention↗