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1.
Dyslexia ; 16(3): 194-212, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20680991

RESUMO

Three major 'neural systems', specialized for different types of information processing, are the sensory, declarative, and procedural systems. It has been proposed (Trends Neurosci., 30(4), 135-141) that dyslexia may be attributable to impaired function in the procedural system together with intact declarative function. We provide a brief overview of the increasing evidence relating to the hypothesis, noting that the framework involves two main claims: first that 'neural systems' provides a productive level of description avoiding the underspecificity of cognitive descriptions and the overspecificity of brain structural accounts; and second that a distinctive feature of procedural learning is its extended time course, covering from minutes to months. In this article, we focus on the second claim. Three studies-speeded single word reading, long-term response learning, and overnight skill consolidation-are reviewed which together provide clear evidence of difficulties in procedural learning for individuals with dyslexia, even when the tasks are outside the literacy domain. The educational implications of the results are then discussed, and in particular the potential difficulties that impaired overnight procedural consolidation would entail. It is proposed that response to intervention could be better predicted if diagnostic tests on the different forms of learning were first undertaken.


Assuntos
Encéfalo/fisiopatologia , Desenvolvimento Infantil , Dislexia/fisiopatologia , Desenvolvimento da Linguagem , Aprendizagem/fisiologia , Encéfalo/crescimento & desenvolvimento , Cerebelo/crescimento & desenvolvimento , Cerebelo/fisiopatologia , Criança , Pré-Escolar , Dislexia/psicologia , Humanos , Lactente , Prática Psicológica
2.
Clin Epigenetics ; 11(1): 103, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31311581

RESUMO

BACKGROUND: Autism spectrum disorder (ASD) is a common and etiologically heterogeneous neurodevelopmental disorder. Although many genetic causes have been identified (> 200 ASD-risk genes), no single gene variant accounts for > 1% of all ASD cases. A role for epigenetic mechanisms in ASD etiology is supported by the fact that many ASD-risk genes function as epigenetic regulators and evidence that epigenetic dysregulation can interrupt normal brain development. Gene-specific DNAm profiles have been shown to assist in the interpretation of variants of unknown significance. Therefore, we investigated the epigenome in patients with ASD or two of the most common genomic variants conferring increased risk for ASD. Genome-wide DNA methylation (DNAm) was assessed using the Illumina Infinium HumanMethylation450 and MethylationEPIC arrays in blood from individuals with ASD of heterogeneous, undefined etiology (n = 52), and individuals with 16p11.2 deletions (16p11.2del, n = 9) or pathogenic variants in the chromatin modifier CHD8 (CHD8+/-, n = 7). RESULTS: DNAm patterns did not clearly distinguish heterogeneous ASD cases from controls. However, the homogeneous genetically-defined 16p11.2del and CHD8+/- subgroups each exhibited unique DNAm signatures that distinguished 16p11.2del or CHD8+/- individuals from each other and from heterogeneous ASD and control groups with high sensitivity and specificity. These signatures also classified additional 16p11.2del (n = 9) and CHD8 (n = 13) variants as pathogenic or benign. Our findings that DNAm alterations in each signature target unique genes in relevant biological pathways including neural development support their functional relevance. Furthermore, genes identified in our CHD8+/- DNAm signature in blood overlapped differentially expressed genes in CHD8+/- human-induced pluripotent cell-derived neurons and cerebral organoids from independent studies. CONCLUSIONS: DNAm signatures can provide clinical utility complementary to next-generation sequencing in the interpretation of variants of unknown significance. Our study constitutes a novel approach for ASD risk-associated molecular classification that elucidates the vital cross-talk between genetics and epigenetics in the etiology of ASD.


Assuntos
Transtorno do Espectro Autista/genética , Transtorno Autístico/genética , Transtornos Cromossômicos/genética , Metilação de DNA , Proteínas de Ligação a DNA/genética , Estudo de Associação Genômica Ampla/métodos , Deficiência Intelectual/genética , Fatores de Transcrição/genética , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Deleção Cromossômica , Cromossomos Humanos Par 16/genética , Epigênese Genética , Feminino , Redes Reguladoras de Genes , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , Sensibilidade e Especificidade , Análise de Sequência de DNA
3.
Clin Neurophysiol ; 118(4): 845-55, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17317301

RESUMO

OBJECTIVE: To investigate whether attentional difficulties are a "core" feature of developmental Dyslexia. METHODS: Behavioural indices and event related potentials (ERPs) were recorded from 10 dyslexic participants (ages 15.5-17.4) and 10 control participants (ages 14.4-18.3) in the Continuous Performance Task (CPT), an established test of attentional performance. Participants were screened to ensure that none was diagnosable as attention deficit (ADHD). RESULTS: There were no significant differences in mean reaction time, error rate or sustained attention between the groups. By contrast, the P3 amplitude was significantly smaller and its latency significantly longer for the dyslexic group. This component was significantly lateralised in controls, whereas in dyslexics it was symmetrical. CONCLUSIONS: Under the relatively light workload conditions of the CPT, "pure" dyslexic participants showed no behavioural signs of attentional difficulties. The attenuated, delayed and symmetrical ERPs in our dyslexic group may reflect abnormal information processing in the right parietal lobe and abnormal interhemispheric asymmetry in Dyslexia. SIGNIFICANCE: The behavioural data suggest that abnormal attentional performance is not a "core" feature of developmental Dyslexia, and highlight the importance of distinguishing between dyslexic participants with and without ADHD symptoms. The presence of electrophysiological markers of Dyslexia in CPT revealed the atypical brain organisation that characterises "pure" Dyslexia.


Assuntos
Atenção , Comportamento/fisiologia , Dislexia/fisiopatologia , Potenciais Evocados P300/fisiologia , Testes Neuropsicológicos , Adolescente , Análise de Variância , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Desempenho Psicomotor/fisiologia , Tempo de Reação
4.
Trends Neurosci ; 24(9): 508-11, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11506881

RESUMO

Surprisingly, the problems faced by many dyslexic children are by no means confined to reading and spelling. There appears to be a general impairment in the ability to perform skills automatically, an ability thought to be dependent upon the cerebellum. Specific behavioural and neuroimaging tests reviewed here indicate that dyslexia is indeed associated with cerebellar impairment in about 80% of cases. We propose that disorders of cerebellar development can in fact cause the impairments in reading and writing characteristic of dyslexia, a view consistent with the recently appreciated role of the cerebellum in language-related skills. This proposal has implications for early remedial treatment.


Assuntos
Doenças Cerebelares/psicologia , Cerebelo/fisiopatologia , Dislexia/psicologia , Animais , Doenças Cerebelares/fisiopatologia , Dislexia/fisiopatologia , Humanos
5.
Arch Gen Psychiatry ; 56(7): 649-54, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10401513

RESUMO

BACKGROUND: Adolescence provides a window to examine regional and disease-specific late abnormal brain development in schizophrenia. Because previous data showed progressive brain ventricular enlargement for a group of adolescents with childhood-onset schizophrenia at 2-year follow-up, with no significant changes for healthy controls, we hypothesized that there would be a progressive decrease in volume in other brain tissue in these patients during adolescence. METHODS: To examine cortical change, we used anatomical brain magnetic resonance imaging scans for 15 patients with childhood-onset schizophrenia (defined as onset of psychosis by age 12 years) and 34 temporally yoked, healthy adolescents at a mean (SD) age of 13.17 (2.73) years at initial baseline scan and 17.46 (2.96) years at follow-up scan. Cortical gray and white matter volumes were obtained with an automated analysis system that classifies brain tissue into gray matter, white matter, and cerebrospinal fluid and separates the cortex into anatomically defined lobar regions. RESULTS: A significant decrease in cortical gray matter volume was seen for healthy controls in the frontal (2.6%) and parietal (4.1%) regions. For the childhood-onset schizophrenia group, there was a decrease in volume in these regions (10.9% and 8.5%, respectively) as well as a 7% decrease in volume in the temporal gray matter. Thus, the childhood-onset schizophrenia group showed a distinctive disease-specific pattern (multivariate analysis of variance for change X region X diagnosis: F, 3.68; P = .004), with the frontal and temporal regions showing the greatest between-group differences. Changes in white matter volume did not differ significantly between the 2 groups. CONCLUSIONS: Patients with very early-onset schizophrenia had both a 4-fold greater decrease in cortical gray matter volume during adolescence and a disease-specific pattern of change. Etiologic models for these patients' illness, which seem clinically and neurobiologically continuous with later-onset schizophrenia, must take into account both early and late disruptions of brain development.


Assuntos
Córtex Cerebral/anatomia & histologia , Imageamento por Ressonância Magnética , Esquizofrenia Infantil/diagnóstico , Adolescente , Idade de Início , Córtex Cerebral/crescimento & desenvolvimento , Ventrículos Cerebrais/anatomia & histologia , Ventrículos Cerebrais/crescimento & desenvolvimento , Criança , Feminino , Humanos , Estudos Longitudinais , Masculino
6.
J Neural Transm Suppl ; (69): 19-36, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16355601

RESUMO

Theoretical frameworks for dyslexia must explain how the well-established phonological deficits and the literacy deficits arise. Our longstanding research programme has led to a distinctive 'twin level' framework that proposes, first, that the core deficits are well described in terms of poor skill automaticity. Second, these 'cognitive level' symptoms are attributed to abnormal cerebellar function--a 'brain-level' analysis. The evidence includes data from behavioural, imaging, neuroanatomical and learning studies. The frame-work leads to an 'ontogenetic' analysis that links cerebellar deficit at birth, via problems in articulation and working memory, to the known phonological, speed and literacy difficulties. Differences in locus of cerebellar impairment, experience and/or links to other brain regions may account for subtypes of dyslexia and possibly other developmental disorders. The automaticity/ cerebellar deficit framework provides an explicit demonstration that it is possible to explain motor, speed and phonological deficits within a unified account, integrating previously opposed approaches.


Assuntos
Cerebelo/fisiopatologia , Dislexia/fisiopatologia , Dislexia/psicologia , Aprendizagem , Doenças Cerebelares/fisiopatologia , Humanos
7.
Biol Psychiatry ; 46(10): 1418-28, 1999 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-10578456

RESUMO

Childhood-onset schizophrenia (defined by an onset of psychosis by age 12) is a rare and severe form of the disorder that is clinically and neurobiologically continuous with the adult-onset disorder. There is growing evidence for more salient risk or etiologic factors, particularly familial, in this possibly more homogeneous patient population. For the 49 patients with very early onset schizophrenia studied to date at the National Institute of Mental Health, there were more severe premorbid neuro-developmental abnormalities, a higher rate of cytogenetic anomalies, and a seemingly higher rate of familial schizophrenia and spectrum disorders than later onset cases. There was no evidence for increased obstetric complications or environmental stress. These data, while preliminary, suggest that a very early age of onset of schizophrenia may be secondary to greater familial vulnerability. Consequently, genetic studies of these patients may be particularly informative and may provide important etiologic information.


Assuntos
Esquizofrenia/diagnóstico , Fatores Etários , Encéfalo/anatomia & histologia , Criança , Pré-Escolar , Humanos , Imageamento por Ressonância Magnética , Fatores de Risco , Movimentos Sacádicos/fisiologia , Esquizofrenia/etiologia , Psicologia do Esquizofrênico
8.
Biol Psychiatry ; 46(7): 892-8, 1999 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-10509172

RESUMO

BACKGROUND: Previous NIMH childhood onset schizophrenia (COS) anatomic brain MRI studies found progression of ventricular volume and other structural brain anomalies at 2-year follow up across mean ages 14 to 16 years. However, studies in adult patients generally do not show progression of ventricular volume or correlation of ventricular volume with duration of illness. To address issues of progression of brain anomalies in schizophrenia, this report extends previous studies to include a third longitudinal scan, uses a larger sample size, and includes measures of the amygdala and hippocampus. METHODS: Volumes of the total cerebrum, lateral ventricles, hippocampus, and amygdala were quantified on 208 brain magnetic resonance imaging scans from 42 adolescents with COS (23 with one or more repeat scan) and 74 age- and gender-matched controls (36 with one or more repeat scan). A statistical technique permitting combined use of cross-sectional and longitudinal data was used to assess age-related changes, linearity, and diagnostic group differences. RESULTS: Differential nonlinear progression of brain anomalies was seen during adolescence with the total cerebrum and hippocampus decreasing and lateral ventricles increasing in the COS group. The developmental curves for these structures reached an asymptote by early adulthood for the COS group and did not significantly change with age in the control group. CONCLUSIONS: These findings reconcile less striking progression of anatomic brain images usually seen for adult schizophrenia and complement other data consistent with time-limited, diagnostic-specific decreases in brain tissue. Adolescence appears to be a unique period of differential brain development in schizophrenia.


Assuntos
Encéfalo/anormalidades , Imageamento por Ressonância Magnética , Transtornos Neurocognitivos/diagnóstico , Esquizofrenia Infantil/diagnóstico , Adolescente , Adulto , Tonsila do Cerebelo/anormalidades , Tonsila do Cerebelo/patologia , Encéfalo/patologia , Córtex Cerebral/anormalidades , Córtex Cerebral/patologia , Ventrículos Cerebrais/anormalidades , Ventrículos Cerebrais/patologia , Criança , Estudos Transversais , Progressão da Doença , Feminino , Hipocampo/anormalidades , Hipocampo/patologia , Humanos , Estudos Longitudinais , Masculino
9.
Am J Psychiatry ; 158(8): 1291-8, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11481165

RESUMO

OBJECTIVE: Although childhood-onset schizophrenia is relatively rare, a sizable group of children with severe emotional disturbances have transient psychotic symptoms that fall outside of current syndrome boundaries. The relationship of this group of children to those with childhood-onset schizophrenia and other childhood psychiatric disorders is unclear. In this study, the authors compared smooth pursuit eye tracking, a biological trait marker associated with schizophrenia, of children and adolescents with psychotic disorder not otherwise specified to that of children with childhood-onset schizophrenia and healthy comparison subjects. METHOD: By means of infrared oculography, smooth pursuit eye movements during a 17 degrees /second visual pursuit task were quantitatively and qualitatively compared in 55 young adolescents (29 with childhood-onset schizophrenia and 26 with psychotic disorder not otherwise specified) and their respective independent healthy comparison groups (a total of 38 healthy subjects). RESULTS: Subjects with childhood-onset schizophrenia had qualitatively poorer eye tracking, higher root mean square error, lower gain, and a greater frequency of catch-up saccades than healthy children. Subjects with psychotic disorder not otherwise specified also had qualitatively poorer eye tracking, higher root mean square error, and lower gain than healthy children, but saccade frequency did not differ significantly. CONCLUSIONS: Children with childhood-onset schizophrenia exhibit a pattern of eye-tracking dysfunction similar to that reported for adult patients. Similar abnormalities were seen in the subjects with psychotic disorder not otherwise specified except that they did not exhibit a greater frequency of catch-up saccades. Prospective longitudinal neurobiological and clinical follow-up studies of both groups are currently underway to further validate the distinction between these two disorders. Also, family studies are planned to establish whether eye-tracking dysfunction represents a trait- or state-related phenomenon in subjects with psychotic disorder not otherwise specified.


Assuntos
Transtornos da Motilidade Ocular/diagnóstico , Transtornos Psicóticos/diagnóstico , Acompanhamento Ocular Uniforme/fisiologia , Adolescente , Fatores Etários , Idade de Início , Criança , Feminino , Humanos , Masculino , Transtornos da Motilidade Ocular/fisiopatologia , Transtornos Psicóticos/genética , Transtornos Psicóticos/fisiopatologia , Acompanhamento Ocular Uniforme/genética , Movimentos Sacádicos/fisiologia , Esquizofrenia/diagnóstico , Esquizofrenia/genética , Esquizofrenia/fisiopatologia , Esquizofrenia Infantil/diagnóstico , Esquizofrenia Infantil/genética , Esquizofrenia Infantil/fisiopatologia , Escalas de Wechsler/estatística & dados numéricos
10.
Am J Psychiatry ; 156(10): 1575-9, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10518169

RESUMO

OBJECTIVE: Cytogenetic abnormalities are increased in schizophrenia, suggesting a possible etiologic contribution. However, their clinical and pathophysiologic roles in the disorder are unknown. To investigate this, a group of children and adolescents participating in a comprehensive study of childhood-onset schizophrenia were screened for chromosomal abnormalities, and their clinical and neurobiological correlates were examined. METHOD: Cytogenetic screening with the use of high-resolution banding, fluorescent in situ hybridization for chromosome 22q11 deletions, and molecular fragile X testing was undertaken in a group of 47 children and adolescents with very early onset of schizophrenia. Clinical, neurobiological (including brain morphometry), and risk factor measures of the subjects with cytogenetic abnormalities were compared with those of the remaining patients without cytogenetic anomalies. RESULTS: Five patients had previously undiagnosed cytogenetic abnormalities. Lower performance IQ and more pronounced premorbid developmental impairments were seen in this subgroup. Rates of obstetric complications, familial schizophrenia spectrum disorders, and familial eye tracking dysfunction were similar for the patients with and without cytogenetic abnormalities. CONCLUSIONS: Cytogenetic abnormalities appear to be increased in childhood-onset schizophrenia, suggesting an association with a very early age at onset. The data from the subgroup of patients with cytogenetic anomalies are consistent with a model in which a childhood onset of schizophrenia is due to a greater impairment of neurodevelopment secondary to the interaction of a number of factors, particularly genetic ones.


Assuntos
Aberrações Cromossômicas , Esquizofrenia/genética , Adolescente , Idade de Início , Encéfalo/anatomia & histologia , Escalas de Graduação Psiquiátrica Breve/estatística & dados numéricos , Ventrículos Cerebrais/anatomia & histologia , Criança , Deleção Cromossômica , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/epidemiologia , Família , Feminino , Hipocampo/anatomia & histologia , Humanos , Testes de Inteligência/estatística & dados numéricos , Imageamento por Ressonância Magnética , Masculino , Prevalência , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Fatores de Risco , Esquizofrenia/diagnóstico , Esquizofrenia/epidemiologia , Psicologia do Esquizofrênico
11.
Am J Psychiatry ; 156(10): 1650-2, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10518182

RESUMO

OBJECTIVE: Increased obstetrical complications have been reported in individuals with adult-onset schizophrenia, with several studies finding an association between such complications and an earlier age at onset. Consequently, obstetrical records were examined for individuals with childhood-onset schizophrenia to determine if birth complications were more prevalent. METHOD: The birth records of 36 patients with childhood-onset schizophrenia and 35 sibling comparison subjects were rated for birth complications by two psychiatrists who were unaware of group membership. RESULTS: There were no significant differences between the groups in rates of obstetrical complications. Patients with such complications did not have a relatively earlier age at onset of schizophrenia. CONCLUSIONS: A very early age at onset of schizophrenia is probably not due to birth complications.


Assuntos
Família , Complicações do Trabalho de Parto/epidemiologia , Complicações na Gravidez/epidemiologia , Esquizofrenia/epidemiologia , Idade de Início , Comorbidade , Feminino , Predisposição Genética para Doença , Humanos , Incidência , Masculino , Prontuários Médicos , Gravidez , Esquizofrenia/diagnóstico , Esquizofrenia/genética , Fatores Sexuais
12.
Am J Psychiatry ; 157(5): 794-800, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10784474

RESUMO

OBJECTIVE: As both premorbid neurodevelopmental impairments and familial risk factors for schizophrenia are prominent in childhood-onset cases (with onset of psychosis by age 12), their relationship was examined. METHOD: Premorbid language, motor, and social impairments were assessed in a cohort of 49 patients with childhood-onset schizophrenia. Familial loading for schizophrenia spectrum disorders, familial eye-tracking dysfunction, and obstetrical complications were assessed without knowledge of premorbid abnormalities and were compared in the patients with and without developmental impairments. RESULTS: Over one-half of the patients in this group had developmental dysfunction in each domain assessed. The patients with premorbid speech and language impairments had higher familial loading scores for schizophrenia spectrum disorders and more obstetrical complications, and their relatives had worse smooth-pursuit eye movements. The boys had more premorbid motor abnormalities, but early language and social impairments did not differ significantly between genders. There were no other significant relationships between premorbid social or motor abnormalities and the risk factors assessed here. CONCLUSIONS: Premorbid developmental impairments are common in childhood-onset schizophrenia. The rates of three risk factors for schizophrenia (familial loading for schizophrenia spectrum disorders, familial eye-tracking dysfunction, and obstetrical complications) were increased for the probands with premorbid speech and language impairments, suggesting that the pathophysiology of schizophrenia involves the abnormal development of language-related brain regions.


Assuntos
Deficiências do Desenvolvimento/epidemiologia , Transtornos do Desenvolvimento da Linguagem/epidemiologia , Esquizofrenia/diagnóstico , Distúrbios da Fala/epidemiologia , Adolescente , Idade de Início , Encéfalo/fisiopatologia , Criança , Pré-Escolar , Comorbidade , Deficiências do Desenvolvimento/genética , Família , Feminino , Humanos , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Masculino , Transtornos Mentais/epidemiologia , Transtornos Mentais/genética , Gravidez , Complicações na Gravidez/epidemiologia , Acompanhamento Ocular Uniforme/genética , Fatores de Risco , Esquizofrenia/epidemiologia , Esquizofrenia/genética , Psicologia do Esquizofrênico , Distúrbios da Fala/diagnóstico
13.
Neuropsychologia ; 37(7): 787-95, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10408646

RESUMO

This study investigated the possibility that the previously mixed findings relating to cognitive deficits in Parkinson's disease might be attributable to inhomogeneity within the patients sampled, with attentional deficits occurring only for those Parkinson's patients who also have additional frontal lobe impairment. Twenty-five patients with idiopathic Parkinson's disease were classified as showing frontal dysfunction, or not, on the basis of their performance on the Wisconsin Card Sorting Test and the picture arrangement subtest of the WAIS. The two groups, and a control group of normal elderly subjects matched for age and IQ, undertook tests of visual attention designed to dissociate baseline response speed from central information processing speed. Error rates did not differ between the groups. Performance of the non-frontally impaired Parkinson's group was indistinguishable from that of the controls. By contrast, the 'frontally impaired' Parkinson's group responded significantly more slowly than the controls. Further analyses indicated that for the frontally-impaired Parkinson's group, information processing and automatic functions were unimpaired but there was a generalised slowing (as reflected by increased baseline response time) which may represent a non-specific global cognitive impairment. These findings suggest that the frontal lobes may be implicated in slowed response speed in Parkinson's disease.


Assuntos
Transtornos Cognitivos/etiologia , Transtornos Cognitivos/fisiopatologia , Lobo Frontal/fisiopatologia , Doença de Parkinson/complicações , Doença de Parkinson/fisiopatologia , Tempo de Reação , Adulto , Idoso , Estudos de Casos e Controles , Transtornos Cognitivos/psicologia , Feminino , Humanos , Inteligência , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Testes Neuropsicológicos , Doença de Parkinson/psicologia
14.
Proc Biol Sci ; 259(1354): 43-7, 1995 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-7700875

RESUMO

In addition to their language-related difficulties, dyslexic children suffer problems in motor skill, balance, automatization and speeded performance. Given the recent evidence for cerebellar involvement in the acquisition of language fluency, these problems suggest cerebellar deficit. To test the hypothesis of cerebellar dysfunction in dyslexia, a time estimation task considered to be a sensitive index of cerebellar function was administered to matched groups of dyslexic and control children. The dyslexic children showed the predicted deficit on time estimation (among the most severe obtained in our research programme) but not on a control, loudness estimation, task. Cerebellar dysfunction, therefore, provides a parsimonious account of otherwise disparate data on deficits in dyslexia.


Assuntos
Cerebelo/fisiopatologia , Dislexia/fisiopatologia , Percepção do Tempo , Estimulação Acústica , Adolescente , Criança , Humanos , Percepção Sonora , Psicometria , Desempenho Psicomotor , Limiar Sensorial
15.
J Endocrinol ; 143(3): 557-64, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7836902

RESUMO

Elevation of non-esterified fatty acids (NEFA) in vivo is associated with abnormal control of TSH. To determine whether TSH secretion is directly inhibited by NEFA, as has been reported for GH, cultured rat anterior pituitary cells were exposed for 20 h to oleic acid in medium containing 7.7 x 10(-5) mol/l bovine serum albumin (BSA). In a molar ratio with albumin of 1.2 (total oleic acid 9 x 10(-5) mol/l), or greater, oleic acid inhibited basal GH secretion (maximum inhibition to 40% of control) while basal TSH was less affected, a ratio of 3 (2.3 x 10(-4) mol/l oleic acid) or greater causing a smaller degree of inhibition (maximum inhibition to 80% of control). In the presence of 10(-9) mol/l growth hormone-releasing hormone or 10(-8) mol/l TRH, inhibition was achieved at a ratio of 12 (9 x 10(-4) mol/l oleic acid) or greater. Basal TSH was less sensitive to inhibition by thyroxine (T4) in the presence of oleic acid/albumin at a ratio of 6 or greater, and inhibition by oleic acid was less than additive with T4 at a ratio of 6 or greater. Responses to tri-iodothyronine (T3) were unaffected at a ratio of 6 (4.6 x 10(-4) mol/l oleic acid), but a ratio of 12 inhibited the effects of both T3 and T4 on TSH.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Hormônio do Crescimento/metabolismo , Ácidos Oleicos/farmacologia , Adeno-Hipófise/metabolismo , Tireotropina/metabolismo , Animais , Células Cultivadas , Depressão Química , Hormônio Liberador de Hormônio do Crescimento/farmacologia , Masculino , Ácido Oleico , Adeno-Hipófise/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Hormônio Liberador de Tireotropina/farmacologia , Tiroxina/farmacologia
16.
Am J Med Genet ; 96(6): 749-53, 2000 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-11121174

RESUMO

Childhood-onset schizophrenia (COS) is defined by the development of first psychotic symptoms by age 12. While recruiting patients with COS refractory to conventional treatments for a trial of atypical antipsychotic drugs, we discovered a unique case who has a familial t(1;7)(p22;q21) reciprocal translocation and onset of psychosis at age 9. The patient also has symptoms of autistic disorder, which are usually transient before the first psychotic episode among 40-50% of the childhood schizophrenics but has persisted in him even after the remission of psychosis. Cosegregating with the translocation, among the carriers in the family available for the study, are other significant psychopathologies, including alcohol/drug abuse, severe impulsivity, and paranoid personality and language delay. This case may provide a model for understanding the genetic basis of schizophrenia or autism. Here we report the progress toward characterization of genomic organization across the translocation breakpoint at 7q21. The polymorphic markers, D7S630/D7S492 and D7S2410/D7S646, immediately flanking the breakpoint, may be useful for further confirming the genetic linkage for schizophrenia or autism in this region. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:749-753, 2000. Published 2000 Wiley-Liss, Inc.


Assuntos
Transtorno Autístico/genética , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 7/genética , Esquizofrenia/genética , Translocação Genética , Transtorno Autístico/patologia , Criança , Quebra Cromossômica/genética , Cromossomos Bacterianos , Mapeamento de Sequências Contíguas , DNA/genética , Humanos , Hibridização in Situ Fluorescente , Masculino , Esquizofrenia/patologia
17.
Cognition ; 35(2): 159-82, 1990 May.
Artigo em Inglês | MEDLINE | ID: mdl-2354611

RESUMO

The performance of a group of 23 13-year-old dyslexic children was compared with that of same-age controls on a battery of tests of motor balance. A dual-task paradigm was used--subjects performed each test twice, once as a single task, and once as a dual task concurrently with a secondary task. Two alternative secondary tasks were used, the classic counting-backwards task and an auditory choice reaction task. Both secondary tasks were calibrated for each subject to ensure that their performance on the secondary task alone fell between pre-specified performance criteria. In all single-task conditions there was no difference between the performance of the two groups. By contrast, in 19 out of the 20 tests performed under dual-task conditions, the dyslexic group were significantly impaired, whereas the controls showed no impairment, thus resulting in significantly better performance by the control group than the dyslexic group. The sole exception was that the dyslexic children were not impaired on the easiest balance condition with the choice reaction task. Under the dual-task conditions the dyslexic children also performed worse than the controls on the secondary task. It is very hard to accommodate the findings within the traditional framework of a deficit specific to lexical skills. One plausible explanation of the results is that, unlike the controls, the dyslexic children need to invest significant conscious resources for monitoring balance, and thus their performance is adversely affected by any secondary task which serves to distract attention from the primary task. This need for "conscious compensation" suggests that for dyslexic children the skill of motor balance is poorly automatized. It is possible, therefore, that many of the reading deficits of dyslexic children are merely symptoms of a more general learning deficit--the failure to fully automatize skills.


Assuntos
Atenção , Dislexia/psicologia , Memória , Retenção Psicológica , Adolescente , Conscientização , Criança , Feminino , Humanos , Masculino , Destreza Motora , Equilíbrio Postural
18.
Obstet Gynecol ; 68(5): 598-601, 1986 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-3531936

RESUMO

In a randomized double-blind placebo-controlled trial involving 71 patients, a viscous gel containing distilled water or 1 or 2 mg pure porcine relaxin was instilled in the cervical canal on the evening before the surgical induction of labor. Eleven of 48 patients receiving relaxin labored overnight, whereas only one of 23 patients went into labor. Only the 2-mg dose significantly improved the mean cervical score compared with the placebo treatment; the effect was greatest in primigravid patients with unripe cervixes. Intracervical application appeared to confer no benefit over vaginal application in effecting cervical ripening or inducing labor. Systemic absorption of the porcine relaxin after its intracervical application was confirmed by the measurement of immunoreactive relaxin in a homologous porcine relaxin radioimmunoassay. Thus, the cervical ripening effect of exogenous relaxin may be mediated either systemically or by direct action at the site of local application. This trial confirms the responsiveness of the human term cervix to exogenous relaxin and supports the suggestion that endogenous relaxin may play a similar role at term in facilitating cervical ripening and parturition.


Assuntos
Colo do Útero/efeitos dos fármacos , Trabalho de Parto Induzido , Relaxina , Administração Intravaginal , Adulto , Colo do Útero/fisiologia , Ensaios Clínicos como Assunto , Método Duplo-Cego , Feminino , Humanos , Gravidez , Distribuição Aleatória , Relaxina/administração & dosagem , Relaxina/sangue
19.
J Am Acad Child Adolesc Psychiatry ; 37(4): 372-6, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9549957

RESUMO

OBJECTIVE: To assess the benefits and side effects of risperidone in young autistic children. METHOD: In this open, prospective trial, subjects were treated with risperidone for 12 weeks. All subjects were started at 0.5 mg daily with individual titration to a maximum of 6 mg or 0.1 mg/kg daily. Behavioral ratings, completed by the investigators and the children's parents, included the Clinical Global Impressions (CGI), Children's Psychiatric Rating Scale, Conners Parent-Teacher Questionnaire, Childhood Autism Rating Scale, and Abnormal Involuntary Movement Scale. RESULTS: Ten boys, aged 4.5 to 10.8 years, were enrolled in the study and all completed the 12-week protocol. The mean final dose was 1.3 mg/day (range = 1 to 2.5 mg/day). On the basis of CGI-rated improvement, 8 of the 10 children were considered to be responders. Improvement was also demonstrated on the other scales. Transient sedation was common, and the children gained an average of 3.5 kg over the 12 weeks of the study. There was no evidence of either extrapyramidal symptoms or tardive dyskinesia. CONCLUSIONS: These results suggest that risperidone may be safe and leads to improvements in several behavioral symptoms in young children with autism. Controlled studies of risperidone in young autistic children are warranted.


Assuntos
Antipsicóticos/uso terapêutico , Transtorno Autístico/tratamento farmacológico , Risperidona/uso terapêutico , Criança , Pré-Escolar , Humanos , Masculino , Análise por Pareamento
20.
J Am Acad Child Adolesc Psychiatry ; 39(9): 1120-6, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10986808

RESUMO

OBJECTIVE: To determine the rates of psychiatric disorders in the first-degree relatives of children with infection-triggered obsessive-compulsive disorder (OCD) and/or tics (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections; PANDAS). METHOD: The probands of this study were 54 children with PANDAS (n = 24 with a primary diagnosis of OCD; n = 30 with a primary diagnosis of a tic disorder). One hundred fifty-seven first-degree relatives (100 parents [93%] and 57 siblings [100%]) were evaluated for the presence of a tic disorder. One hundred thirty-nine first-degree relatives (100 parents [93%] and 39 of 41 siblings over the age of 6 [95%]) were evaluated with clinical and structured psychiatric interviews to determine the presence of subclinical OCD, OCD, and other DSM-IV Axis I disorders. RESULTS: Twenty-one probands (39%) had at least one first-degree relative with a history of a motor or vocal tic; 6 mothers (11%), 9 fathers (19%), and 8 siblings (16%) received this diagnosis. Fourteen probands (26%) had at least one first-degree relative with OCD; 10 mothers (19%), 5 fathers (11%), and 2 siblings (5%), received this diagnosis. An additional 8 parents (8%) and 3 siblings (8%) met criteria for subclinical OCD. Eleven parents (11%) had obsessive-compulsive personality disorder. CONCLUSIONS: The rates of tic disorders and OCD in first-degree relatives of pediatric probands with PANDAS are higher than those reported in the general population and are similar to those reported previously for tic disorders and OCD. Further study is warranted to determine the nature of the relationship between genetic and environmental factors in PANDAS.


Assuntos
Doenças Autoimunes do Sistema Nervoso/genética , Núcleo Familiar/psicologia , Transtorno Obsessivo-Compulsivo/epidemiologia , Transtorno Obsessivo-Compulsivo/genética , Infecções Estreptocócicas/complicações , Transtornos de Tique/epidemiologia , Transtornos de Tique/genética , Adolescente , Adulto , Idade de Início , Doenças Autoimunes do Sistema Nervoso/imunologia , Doenças Autoimunes do Sistema Nervoso/microbiologia , Criança , Pré-Escolar , Comorbidade , Fatores de Confusão Epidemiológicos , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Masculino , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/imunologia , Prevalência , Estudos de Amostragem , Infecções Estreptocócicas/genética , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes , Transtornos de Tique/imunologia , Estados Unidos/epidemiologia
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