Mental Retardation And Developmental Disabilities Research Reviews[JOURNAL]
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200 papers
Correlates across the structural, functional, and molecular phenotypes of fragile X syndrome.
Beckel-Mitchener A, Greenough WT
Ment Retard Dev Disabil Res Rev · 2004 · PMID 14994289 · Publisher ↗
Fragile X syndrome (FXS) is characterized by a pattern of morphological, functional, and molecular characteristics with, in at least some cases, apparent relationships among phenotypic features at different levels. Gross...
Fragile X syndrome (FXS) is characterized by a pattern of morphological, functional, and molecular characteristics with, in at least some cases, apparent relationships among phenotypic features at different levels. Gross morphology differences in the sizes of some human brain regions are accompanied by fine structural alterations in the shapes and in the numbers of dendritic spines in both humans and the knockout mouse model. The excess number of spines, their immature appearance, and the impaired withdrawal of inappropriately oriented dendrites in FXS or the mouse model suggest impairment of neuronal maturation, including dendritic and spine pruning. It is not clear how these differences arise, although regionally or globally impaired translation of the mRNAs that interact with the Fmr1 protein product, FMRP, in the vicinity of the synapse, including genes involved in synapse development and plasticity and dendritic retraction, is certainly plausible. FMRP binds mRNA and may be involved in both transport and translation of the mRNAs it binds. The mRNAs it binds belong to multiple functional classes, apparently indicating that FMRP may impact multiple cellular processes. In one example, the glucocorticoid receptor, whose mRNA binds FMRP, regulates the stress-sensitive glucocorticosteroids. Both human FXS and the mouse model exhibit a protracted elevation in glucocorticosteroids after stress. Possible relationships of other genes to morphological and functional characteristics of FXS are also discussed.
The fragile X mental retardation protein, FMRP, recognizes G-quartets.
Darnell JC, Warren ST, Darnell RB
Ment Retard Dev Disabil Res Rev · 2004 · PMID 14994288 · Publisher ↗
Fragile X mental retardation is a disease caused by the loss of function of a single RNA-binding protein, FMRP. Identifying the RNA targets recognized by FMRP is likely to reveal much about its functions in controlling s...
Fragile X mental retardation is a disease caused by the loss of function of a single RNA-binding protein, FMRP. Identifying the RNA targets recognized by FMRP is likely to reveal much about its functions in controlling some aspects of memory and behavior. Recent evidence suggests that one of the predominant RNA motifs recognized by the FMRP protein is an intramolecular G-quartet and that the RGG box of FMRP mediates this interaction. Searching databases of mRNA sequence information, as well as compiled sequences of predicted FMRP targets based on biochemical identification, has revealed that many of these predicted FMRP targets contain intramolecular G-quartets. Interestingly, many of the G-quartet containing RNA targets encode proteins involved in neuronal development and synaptic function. Defects in the metabolism of this set of RNAs, presumably in the translation of their protein products, is likely to underlie the behavioral and cognitive changes seen in the disease.
Psychopharmacology in fragile X syndrome--present and future.
Berry-Kravis E, Potanos K
Ment Retard Dev Disabil Res Rev · 2004 · PMID 14994287 · Publisher ↗
In addition to cognitive disability, fragile X syndrome (FXS) is associated with behavioral problems that are often functionally limiting. There are few controlled trials to guide treatment; however, available informatio...
In addition to cognitive disability, fragile X syndrome (FXS) is associated with behavioral problems that are often functionally limiting. There are few controlled trials to guide treatment; however, available information does suggest that medications can be quite helpful for a number of categories of behavioral disturbance in FXS. Specifically, stimulants appear to be quite useful for management of distractibility, hyperactivity, and impulsive behavior; antidepressants help with anxiety, obsessive-compulsive behaviors and mood dysregulation; and antipsychotics can reduce aggression. These medications are supportive and help minimize dysfunctional behaviors and maximize functioning. As more is learned about the neural functions of FMRP, medications in the future will be expected to target specific synaptic mechanisms dysregulated in FXS brain and thus ameliorate the cognitive deficit with resultant behavioral improvements. This article summarizes knowledge about effectiveness and approaches to management of currently available psychopharmacology for behavior in FXS and discusses early leads to future treatments for cognition.
Phenotypic variation and FMRP levels in fragile X.
Loesch DZ, Huggins RM, Hagerman RJ
Ment Retard Dev Disabil Res Rev · 2004 · PMID 14994286 · Publisher ↗
Data on the relationships between cognitive and physical phenotypes, and a deficit of fragile X mental retardation 1 (FMR1) gene-specific protein product, FMRP, are presented and discussed in context with earlier finding...
Data on the relationships between cognitive and physical phenotypes, and a deficit of fragile X mental retardation 1 (FMR1) gene-specific protein product, FMRP, are presented and discussed in context with earlier findings. The previously unpublished results obtained, using standard procedures of regression and correlations, showed highly significant associations in males between FMRP levels and the Wechsler summary and subtest scores and in females between these levels and the full-scale intelligence quotient (FSIQ), verbal and performance IQ, and some Wechsler subtest scores. The published results based on data from 144 extended families with fragile X, recruited from Australia and the United States within a collaborative NIH-supported project, were obtained using robust modification of maximum likelihood in pedigrees. The results indicated that processing speed, short-term memory, and the ability to control attention, especially in the context of regulating goal-directed behavior, may be primarily affected by the FMRP depletion. The effect of this depletion on physical phenotype was also demonstrated, especially on body and head height and extensibility of finger joints. It is recommended that further studies should rely on more accurate measures of FMRP levels, and use of larger samples, to overcome extensive variability in the data.
Fragile X-associated tremor/ataxia syndrome (FXTAS).
Hagerman PJ, Hagerman RJ
Ment Retard Dev Disabil Res Rev · 2004 · PMID 14994285 · Publisher ↗
Carriers of fragile X mental retardation 1 (FMR1) premutation alleles (55 to 200 CGG repeats) are generally spared the more serious neurodevelopmental problems associated with the full-mutation carriers (>200 repeats) of...
Carriers of fragile X mental retardation 1 (FMR1) premutation alleles (55 to 200 CGG repeats) are generally spared the more serious neurodevelopmental problems associated with the full-mutation carriers (>200 repeats) of fragile X syndrome. However, some adult male premutation carriers (55-200 repeats) develop a neurological syndrome involving intention tremor, ataxia, dementia, parkinsonism, and autonomic dysfunction. In excess of one-third of male premutation carriers over 50 years of age develop the fragile X-associated tremor/ataxia syndrome (FXTAS). FXTAS also represents a new form of inclusion disease, with eosinophilic intranuclear inclusions found throughout the brain in both neurons and astrocytes. Because FXTAS appears to be relatively specific to male premutation carriers, who are known to possess elevated levels of FMR1 mRNA, the neuropathology may arise as a consequence of a toxic gain-of-function of the mRNA itself, although this proposal requires additional direct testing. One of the critical needs at present is a better estimate for the prevalence of this disorder, because FXTAS is likely to be underdiagnosed in the adult movement disorders clinics.
The neuroanatomy and neuroendocrinology of fragile X syndrome.
Hessl D, Rivera SM, Reiss AL
Ment Retard Dev Disabil Res Rev · 2004 · PMID 14994284 · Publisher ↗
Fragile X syndrome (FXS), caused by a single gene mutation on the X chromosome, offers a unique opportunity for investigation of gene-brain-behavior relationships. Recent advances in molecular genetics, human brain imagi...
Fragile X syndrome (FXS), caused by a single gene mutation on the X chromosome, offers a unique opportunity for investigation of gene-brain-behavior relationships. Recent advances in molecular genetics, human brain imaging, and behavioral studies have started to unravel the complex pathways leading to the cognitive, psychiatric, and physical features that are unique to this syndrome. In this article, we summarize studies focused on the neuroanatomy and neuroendocrinology of FXS. A review of structural imaging studies of individuals with the full mutation shows that several brain regions are enlarged, including the hippocampus, amygdala, caudate nucleus, and thalamus, even after controlling for overall brain volume. These regions mediate several cognitive and behavioral functions known to be aberrant in FXS such as memory and learning, information and sensory processing, and social and emotional behavior. Two regions, the cerebellar vermis, important for a variety of cognitive tasks and regulation of motor behavior, and the superior temporal gyrus, involved in processing complex auditory stimuli, are reported to be reduced in size relative to controls. Functional imaging, typically limited to females, has emphasized that individuals with FXS do not adequately recruit brain regions that are normally utilized by unaffected individuals to carry out various cognitive tasks, such as arithmetic processing or visual memory tasks. Finally, we review a number of neuroendocrine studies implicating hypothalamic dysfunction in FXS, including abnormal activation of the hypothalamic-pituitary-adrenal (HPA) axis. These studies may help to explain the abnormal stress responses, sleep abnormalities, and physical growth patterns commonly seen in affected individuals. In the future, innovative longitudinal studies to investigate development of neurobiologic and behavioral features over time, and ultimately empirical testing of pharmacological, behavioral, and even molecular genetic interventions using MRI are likely to yield significant positive changes in the lives of persons with FXS, as well as increase our understanding of the development of psychiatric and learning problems in the general population.
Attention and language in fragile X.
Cornish K, Sudhalter V, Turk J
Ment Retard Dev Disabil Res Rev · 2004 · PMID 14994283 · Publisher ↗
Fragile X syndrome (FXS) is a well-recognized cause of mental retardation and developmental delay in males. Alongside the well-documented clinical characteristics of the condition, recent advances in technology and metho...
Fragile X syndrome (FXS) is a well-recognized cause of mental retardation and developmental delay in males. Alongside the well-documented clinical characteristics of the condition, recent advances in technology and methodology have begun to define FXS at a number of different levels: genetic, brain structure and function, cognition, and behavior. This article suggests that the FXS phenotype is not merely a juxtaposition of spared and impaired functions but rather may be characterized by an inhibitory control deficit that interferes with the individual's ability to modulate output causing perseverative responding across various skill areas. It is further suggested that an inability to modulate arousal may be at least one cause for the inhibitory control deficit that typifies the FXS phenotype. The approach to understanding atypical development outlined here holds exciting promise for future research in FXS and other developmental disorders.
Newborn screening for fragile X syndrome.
Bailey DB
Ment Retard Dev Disabil Res Rev · 2004 · PMID 14994282 · Publisher ↗
Newborn screening for fragile X syndrome (FXS) is technically possible, and in the relatively near future accurate and inexpensive screening technologies are likely to be available. When that happens, will America's publ...
Newborn screening for fragile X syndrome (FXS) is technically possible, and in the relatively near future accurate and inexpensive screening technologies are likely to be available. When that happens, will America's public health system adopt newborn screening for fragile X syndrome? This article addresses this issue by first placing screening for FXS in the context of the history and current status of newborn screening policy and practice. Lack of a proven medical treatment may stand as a barrier to newborn screening, but strong arguments can be made that early intervention provides important services for identified newborns and their families. Furthermore, other arguments could be used to justify newborn screening, including informed reproductive risk, medically necessary information, and consumer demand. Fragile X syndrome is offered as a prototype for many of the issues that will face society as more genetic disorders are discovered and new technologies for screening are developed.
Preface: fragile X syndrome: frontiers of understanding gene-brain-behavior relationships.
Crnic LS, Hagerman R
Ment Retard Dev Disabil Res Rev · 2004 · PMID 14994281 · Publisher ↗
Abstract loading — click title to view on PubMed.
Cochlear implants in young children.
Niparko JK, Blankenhorn R
Ment Retard Dev Disabil Res Rev · 2003 · PMID 14648819 · Publisher ↗
The cochlear implant is best characterized as a device that provides access to the sound environment. The device enables the hearing pathway to respond to environmental and speech sounds, providing informational cues fro...
The cochlear implant is best characterized as a device that provides access to the sound environment. The device enables the hearing pathway to respond to environmental and speech sounds, providing informational cues from the surroundings and from others that may escape visual detection. As the developmental effects of a profound hearing loss are multiple, cochlear implants have been applied to ever younger children in an attempt to promote a more normal level of developmental learning through audition. In deafness, transducer elements of the inner ear fail to trigger auditory nerve afferent nerves in the presence of sound input. However, large reserves of afferent fibers exist even in the auditory nerve of a profoundly deaf patient. Furthermore, these nerve fibers retain the ability to respond to prosthetic activation. Through developmental learning in the early, formative years, auditory centers of the brain appear capable of processing information from the implant to provide speech comprehension and oral language development. Multichannel implants have replaced original single channel designs. multichannel devices enable larger percentages of recipients to recognize the spoken word without visual cues because they provide spectral information in addition to temporal and intensity cues. Testing under conditions of auditory (implant)-only input reveals significant open-set speech understanding capabilities in more than 75% of children after three years of device use. The benefit provided by implants may vary with a number of conditions including: hearing history, age of deafness onset, age at implantation, etiology of deafness, linguistic abilities, and the presence of a motivated system of support of oral language development. Patient variables should be given individual consideration in judging candidacy for a cochlear implant and in planning rehabilitative and education services after surgery and activation of the device.
Early intervention after universal neonatal hearing screening: impact on outcomes.
Yoshinaga-Itano C
Ment Retard Dev Disabil Res Rev · 2003 · PMID 14648818 · Publisher ↗
This article summarizes the developmental outcomes of Colorado children with significant hearing loss. Some of the research compares children born in hospitals that have implemented universal newborn hearing screening pr...
This article summarizes the developmental outcomes of Colorado children with significant hearing loss. Some of the research compares children born in hospitals that have implemented universal newborn hearing screening programs for newborns. Other research compares the developmental outcomes of children who have been early-identified with hearing loss. Early-identification is defined as identification of hearing loss within the first six months of life. Late identification in the Colorado studies is defined as age of identification of hearing loss after the age of six months. In a few of the Colorado studies, age at initiation of intervention was used. Within the Colorado system, age of identification can be interpreted as almost synonymous with age of intervention, as the vast majority of children enter intervention services with two months after the identification of the hearing loss. Children who were early-identified and had early initiation of intervention services (within the first year of life) had significantly better vocabulary, general language abilities, speech intelligibility and phoneme repertoires, syntax as measured by mean length of utterance, social-emotional development, parental bonding, and parental grief resolution. Two other studies (Nebraska and Washington state) of early- versus later-initiation of intervention services report findings similar to the Colorado studies. Direct comparisons with the historical literature are not possible because the developmental delays of what would now be termed "later-identified" were too low to report developmental ages for the birth through five-year-old population.
Communication options for children with hearing loss.
Gravel JS, O'Gara J
Ment Retard Dev Disabil Res Rev · 2003 · PMID 14648817 · Publisher ↗
This article examines the communication options that are available for use within families of infants and young children who are hard-of-hearing or deaf. The need for language development, regardless of the specific comm...
This article examines the communication options that are available for use within families of infants and young children who are hard-of-hearing or deaf. The need for language development, regardless of the specific communication mode, is stressed. The demands of the current environment of early identification and intervention often put families in a position of needing to decide among communication methods before they are fully knowledgeable and/or emotionally ready. Specific communication options are delineated and considered within a continuum of spoken and visual language. Available research related to early acquisition of language by infants and young children who are hard-of-hearing and deaf is reviewed; outcomes, when available, are presented for specific methods from reports of older children. Factors that influence families' decisions regarding the selection of a communication option are highlighted in the context of the existing literature. An ongoing evaluative process that respects the choices of families is advocated; a context in which change(s) in communication mode through childhood is viewed as a positive circumstance. The ultimate goal in the selection of any communication approach is to ensure that infants and young children who are hard of hearing or deaf and their families are language proficient and fluent communicators.
Early amplification options.
Gabbard SA, Schryer J
Ment Retard Dev Disabil Res Rev · 2003 · PMID 14648816 · Publisher ↗
Children with permanent hearing loss have been remediated with hearing amplification devices for decades. The influx of young infants identified with hearing loss through successful newborn hearing screening programs has...
Children with permanent hearing loss have been remediated with hearing amplification devices for decades. The influx of young infants identified with hearing loss through successful newborn hearing screening programs has established a need for amplification resources for infants within the first six months of life. For the approximately two of every 1000 infants born who are identified with bilateral hearing loss [Mehl and Thomson, 1998, Pediatrics 101, p. e4], the use of amplification is commonly the first step in treating the sequella of their loss. The use of hearing aids, combined with early intervention, has been shown to significantly improve the speech and language skills of young children with hearing loss [Yoshinaga-Itano, 2000, Seminars in Hearing 21, p. 309]. Speech and language delays have contributed to compromised academic performance of school aged children with hearing loss [Johnson et al., 1997, Educational Audiology Handbook, Singular Publishing, San Diego]. Most hard-of-hearing and deaf children use hearing aids and other assistive listening devices every day throughout their lifetime and the life expectancy of a hearing aid is only five to eight years. The current challenge for pediatric audiologists is selecting and evaluating the available amplification to provide the best options for children and their families. Amplification technology has seen an explosion in growth the past few years and the options continue to expand rapidly. This article examines currently available amplification technology and reviews the selection criteria that may be used for infants and young children. Issues such as style, type, amplification features, signal processing strategies, and verification and validation tools are also discussed.
Families and children with hearing loss: grief and coping.
Kurtzer-White E, Luterman D
Ment Retard Dev Disabil Res Rev · 2003 · PMID 14648815 · Publisher ↗
Parental coping with the diagnosis of their child's hearing impairment has not received a great deal of research attention, despite the evident importance of it. Parental coping has been changing with the inception of ne...
Parental coping with the diagnosis of their child's hearing impairment has not received a great deal of research attention, despite the evident importance of it. Parental coping has been changing with the inception of newborn screening as we move from a parent-initiated model of diagnosis to an institution-initiated model. Coping now begins without any preparation, and without any time for parents to "enjoy" their child as "normal." The grief models, based on the death experience, usually employed to describe parental reactions to the diagnosis may also be inappropriate. Death grief is terminable whereas parental grief is chronic. There is not sufficient research on the long-term effects of chronic grief and how that impacts on parent-child bonding. There is evidence that our screening endeavors have far outstripped our habilitation efforts, leaving parents with a diagnosis but without support. This gap must be closed.
Auditory neuropathy/dys-synchrony: diagnosis and management.
Berlin CI, Hood L, Morlet T … +2 more , Rose K, Brashears S
Ment Retard Dev Disabil Res Rev · 2003 · PMID 14648814 · Publisher ↗
Auditory brainstem responses (ABRs) and otoacoustic emissions (OAEs) are objective measures of auditory function, but are not hearing tests. Normal OAEs reflect normal cochlear outer hair cell function, and an ABR indica...
Auditory brainstem responses (ABRs) and otoacoustic emissions (OAEs) are objective measures of auditory function, but are not hearing tests. Normal OAEs reflect normal cochlear outer hair cell function, and an ABR indicates a synchronous neural response. It is quite possible for a patient to have normal OAEs but absent or grossly abnormal ABR and a behavioral audiogram that is inconsistent with either test. These patients, who may constitute as much as 10% of the diagnosed deaf population, have auditory neuropathy/dys-synchrony (AN/AD). To diagnose AN/AD accurately, ABRs are obtained in response to condensation and rarefaction clicks to distinguish cochlear microphonics (CM) from neural responses. Appropriate management is confounded by variation among patients and changes in auditory function in some patients over time. Recommendations for management include visual language exposure through methods such as American Sign Language (ASL), Cued Speech, or baby signs, and closely following patients.
Diagnostic testing for hearing loss in infants and young children.
Widen JE, Keener SK
Ment Retard Dev Disabil Res Rev · 2003 · PMID 14648813 · Publisher ↗
An early, reliable diagnosis and description of hearing loss is essential in determining appropriate treatment to minimize potential developmental delays attributed to the loss. Objective assessment of auditory function...
An early, reliable diagnosis and description of hearing loss is essential in determining appropriate treatment to minimize potential developmental delays attributed to the loss. Objective assessment of auditory function is possible shortly after birth. Both objective and subjective measures of auditory status are used in a test battery approach to determine the type, degree, and configuration of the hearing loss. This paper reviews the diagnostic test procedures used to define the hearing capability of infants and young children. For the youngest infants electrophysiologic tests, primarily auditory evoked potentials, are used to estimate hearing sensitivity. Later behavioral audiometric measures based on operant conditioning techniques become the primary component of the test battery. Diagnostic audiologic assessment is an ongoing process that requires special equipment and expertise when directed to infants and young children.
Infants and children with hearing loss--part 2: Overview.
Vohr B
Ment Retard Dev Disabil Res Rev · 2003 · PMID 14648812 · Publisher ↗
Abstract loading — click title to view on PubMed.
A systems neuroscience approach to autism: biological, cognitive, and clinical perspectives.
Eigsti IM, Shapiro T
Ment Retard Dev Disabil Res Rev · 2003 · PMID 12953300 · Publisher ↗
Autism is a behaviorally defined disorder characterized by a broad constellation of symptoms. Numerous studies directed to the biological substrate demonstrate clear effects of neurodevelopmental differences that will li...
Autism is a behaviorally defined disorder characterized by a broad constellation of symptoms. Numerous studies directed to the biological substrate demonstrate clear effects of neurodevelopmental differences that will likely point to the etiology, course, and long-term outcomes of the disorder. Consistently replicated research on the neural underpinnings of autism is reviewed. In general, results suggest several main conclusions: First, autism is a heterogeneous disorder and is likely to have multiple possible etiologies; second, structural brain studies have indicated a variety of diffuse anatomical differences, reflective of an early developmental change in the growth or pruning of neural tissue, rather than localized lesions; similarly, neurochemical studies suggest early, neuromodulatory discrepancies rather than gross or localized abnormalities; and finally, there are a number of limitations on studies of brain activity that to date preclude definitive answers to questions of how the brain functions differently in autism. The large number of active research programs investigating the cognitive neuroscience of autism spectrum disorders, in combination with the exciting development of new methodologies and tools in this area, indicates the drama and excitement of work in this area.
The development of reading impairment: a cognitive neuroscience model.
McCandliss BD, Noble KG
Ment Retard Dev Disabil Res Rev · 2003 · PMID 12953299 · Publisher ↗
This review discusses recent cognitive neuroscience investigations into the biological bases of developmental dyslexia, a common disorder impacting approximately 5 to 17 percent of the population. Our aim is to summarize...
This review discusses recent cognitive neuroscience investigations into the biological bases of developmental dyslexia, a common disorder impacting approximately 5 to 17 percent of the population. Our aim is to summarize central findings from several lines of evidence that converge on pivotal aspects of the brain bases of developmental dyslexia. We highlight ways in which the approaches and methodologies of developmental cognitive neuroscience that are addressed in this special issue-including neuroimaging, human genetics, refinement of cognitive and biological phenotypes, neural plasticity and computational model-can be employed in uncovering the biological bases of this disorder. Taking a developmental perspective on the biological bases of dyslexia, we propose a simple cascading model for the developmental progression of this disorder, in which individual differences in brain areas associated with phonological processing might influence the specialization of visual areas involved in the rapid processing of written words. We also discuss recent efforts to understand the impact of successful reading interventions in terms of changes within cortical circuits associated with reading ability.
A review of the biological bases of ADHD: what have we learned from imaging studies?
Durston S
Ment Retard Dev Disabil Res Rev · 2003 · PMID 12953298 · Publisher ↗
Attention Deficit Hyperactivity Disorder (ADHD) is a common and impairing neuropsychiatric disorder with onset at preschool age. Although a significant amount of progress has been made investigating the neurobiology of t...
Attention Deficit Hyperactivity Disorder (ADHD) is a common and impairing neuropsychiatric disorder with onset at preschool age. Although a significant amount of progress has been made investigating the neurobiology of this disorder, its precise etiology still remains unclear. Converging evidence from studies of the neuropharmacology, genetics, neuropsychology, and neuroimaging of ADHD imply the involvement of fronto-striatal circuitry in ADHD. However, while it does appear that poor inhibitory control and the deficits in fronto-striatal circuitry associated with it are central, there is evidence to suggest that more posterior cerebral areas are also implicated in this disorder. Anatomical studies suggest widespread reductions in volume throughout the cerebrum and cerebellum, while functional imaging studies suggest that affected individuals activate more diffuse areas than controls during the performance of cognitive tasks. The future impact of new MR imaging methodologies on the field is discussed.
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