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1.
Psychiatr Genet ; 27(3): 105-109, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28230711

RESUMO

Methyl-CpG-binding protein 2 (MECP2) deleterious variants, which are responsible for Rett syndrome in girls, are involved in a wide spectrum of developmental disabilities in males. A neuropsychiatric phenotype without intellectual disability is uncommon in patients with MECP2 deleterious variants. We report on two dizygotic twins with an MECP2-related psychiatric disorder without intellectual disability. Neuropsychological and psychiatric phenotype assessments were performed, and a genetic analysis was carried out. Both patients fulfilled the Pervasive Developmental Disorder criteria on Autism Diagnostic Observation Schedule and Asperger syndrome criteria on Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV). One patient developed early-onset schizophrenia (DSM-IV criteria) with two acute psychotic episodes, the latest one following corticosteroids and sodium valproate intake, with major hyperammonemia. A novel MECP2 gene transversion c.491 G>T [p.(Ser164Ile)] was found in both twins. Pathogenicity of this variant was considered on the basis of strong clinical and molecular data. The underlying molecular basis of neuropsychiatric disorders may have important consequences on genetic counseling and therapeutic strategies.


Assuntos
Síndrome de Asperger/genética , Proteína 2 de Ligação a Metil-CpG/genética , Esquizofrenia Infantil/genética , Síndrome de Asperger/metabolismo , Transtorno Autístico/genética , Criança , Predisposição Genética para Doença/genética , Humanos , Deficiência Intelectual/genética , Masculino , Proteína 2 de Ligação a Metil-CpG/metabolismo , Mutação , Mutação de Sentido Incorreto/genética , Esquizofrenia/genética
2.
Transl Psychiatry ; 3: e279, 2013 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-23838890

RESUMO

Dysfunctional glutamatergic neurotransmission has been implicated in autism spectrum disorder (ASD). However, relatively few studies have directly measured brain glutamate in ASD adults, or related variation in glutamate to clinical phenotype. We therefore set out to investigate brain glutamate levels in adults with an ASD, comparing these to healthy controls and also comparing results between individuals at different points on the spectrum of symptom severity. We recruited 28 adults with ASD and 14 matched healthy controls. Of those with ASD, 15 fulfilled the 'narrowly' defined criteria for typical autism, whereas 13 met the 'broader phenotype'. We measured the concentration of the combined glutamate and glutamine signal (Glx), and other important metabolites, using proton magnetic resonance spectroscopy in two brain regions implicated in ASD--the basal ganglia (including the head of caudate and the anterior putamen) and the dorsolateral prefrontal cortex--as well as in a parietal cortex 'control' region. Individuals with ASD had a significant decrease (P<0.001) in concentration of Glx in the basal ganglia, and this was true in both the 'narrow' and 'broader' phenotype. Also, within the ASD sample, reduced basal ganglia Glx was significantly correlated with increased impairment in social communication (P=0.013). In addition, there was a significant reduction in the concentration of other metabolites such as choline, creatine (Cr) and N-acetylaspartate (NAA) in the basal ganglia. In the dorsolateral prefrontal cortex, Cr and NAA were reduced (P<0.05), although Glx was not. There were no detectable differences in Glx, or any other metabolite, in the parietal lobe control region. There were no significant between-group differences in age, gender, IQ, voxel composition or data quality. In conclusion, individuals across the spectrum of ASD have regionally specific abnormalities in subcortical glutamatergic neurotransmission that are associated with variation in social development.


Assuntos
Química Encefálica , Transtornos Globais do Desenvolvimento Infantil/metabolismo , Ácido Glutâmico/análise , Glutamina/análise , Adulto , Síndrome de Asperger/metabolismo , Transtorno Autístico , Gânglios da Base/química , Estudos de Casos e Controles , Criança , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Córtex Pré-Frontal/química , Índice de Gravidade de Doença
3.
Neuropharmacology ; 68: 202-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-22727823

RESUMO

Mounting evidence suggests a possible role for γ-aminobutyric acid (GABA) in the neuropathophysiology of autism spectrum disorders (ASD), but the extent of this impairment is unclear. A non-invasive, in vivo measure of GABA involves transcranial magnetic stimulation (TMS) of the primary motor cortex to probe cortical inhibition. Individuals diagnosed with ASD (high-functioning autism or Asperger's disorder) (n = 36 [28 male]; mean age: 26.00 years) and a group of healthy individuals (n = 34 [23 male]; mean age: 26.21 years) (matched for age, gender, and cognitive function) were administered motor cortical TMS paradigms putatively measuring activity at GABAA and GABAB receptors (i.e., short and long interval paired pulse TMS, cortical silent period). All cortical inhibition paradigms yielded no difference between ASD and control groups. There was, however, evidence for short interval cortical inhibition (SICI) deficits among those ASD participants who had experienced early language delay, suggesting that GABA may be implicated in an ASD subtype. The current findings do not support a broad role for GABA in the neuropathophysiology of ASD, but provide further indication that GABAA could be involved in ASD where there is a delay in language acquisition. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'.


Assuntos
Síndrome de Asperger/fisiopatologia , Transtorno Autístico/fisiopatologia , Córtex Motor/fisiopatologia , Inibição Neural/fisiologia , Ácido gama-Aminobutírico/metabolismo , Adolescente , Adulto , Síndrome de Asperger/metabolismo , Transtorno Autístico/metabolismo , Eletromiografia , Potencial Evocado Motor/fisiologia , Feminino , Humanos , Masculino , Córtex Motor/metabolismo , Estimulação Magnética Transcraniana
4.
Transl Psychiatry ; 2: e178, 2012 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-23092982

RESUMO

Atypical trajectory of brain growth in autism spectrum disorders (ASDs) has been recognized as a potential etiology of an atypical course of behavioral development. Numerous neuroimaging studies have focused on childhood to investigate atypical age-related change of brain structure and function, because it is a period of neuron and synapse maturation. Recent studies, however, have shown that the atypical age-related structural change of autistic brain expands beyond childhood and constitutes neural underpinnings for lifelong difficulty to behavioral adaptation. Thus, we examined effects of aging on neurochemical aspects of brain maturation using 3-T proton magnetic resonance spectroscopy ((1)H-MRS) with single voxel in the medial prefrontal cortex (PFC) in 24 adult men with non-medicated high-functioning ASDs and 25 age-, IQ- and parental-socioeconomic-background-matched men with typical development (TD). Multivariate analyses of covariance demonstrated significantly high N-acetylaspartate (NAA) level in the ASD subjects compared with the TD subjects (F=4.83, P=0.033). The low NAA level showed a significant positive correlation with advanced age in the TD group (r=-0.618, P=0.001), but was not evident among the ASD individuals (r=0.258, P=0.223). Fisher's r-to-z transformation showed a significant difference in the correlations between the ASD and TD groups (Z=-3.23, P=0.001), which indicated that the age-NAA relationship was significantly specific to people with TD. The current (1)H-MRS study provided new evidence that atypical age-related change of neurochemical aspects of brain maturation in ASD individuals expands beyond childhood and persists during adulthood.


Assuntos
Envelhecimento/metabolismo , Ácido Aspártico/análogos & derivados , Síndrome de Asperger/metabolismo , Transtorno Autístico/metabolismo , Córtex Pré-Frontal/metabolismo , Adulto , Fatores Etários , Ácido Aspártico/metabolismo , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Análise Multivariada
5.
J Psychiatr Res ; 46(3): 394-401, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22225920

RESUMO

Recent evidence suggests that children with autism have impaired detoxification capacity and may suffer from chronic oxidative stress. To our knowledge, there has been no study focusing on oxidative metabolism specifically in Asperger syndrome (a milder form of autism) or comparing this metabolism with other psychiatric disorders. In this study, total antioxidant status (TAOS), non-enzymatic (glutathione and homocysteine) and enzymatic (catalase, superoxide dismutase, and glutathione peroxidase) antioxidants, and lipid peroxidation were measured in plasma or erythrocyte lysates in a group of adolescent patients with Asperger syndrome, a group of adolescents with a first episode of psychosis, and a group of healthy controls at baseline and at 8-12 weeks. TAOS was also analyzed at 1 year. TAOS was reduced in Asperger individuals compared with healthy controls and psychosis patients, after covarying by age and antipsychotic treatment. This reduced antioxidant capacity did not depend on any of the individual antioxidant variables measured. Psychosis patients had increased homocysteine levels in plasma and decreased copper and ceruloplasmin at baseline. In conclusion, Asperger patients seem to have chronic low detoxifying capacity. No impaired detoxifying capacity was found in the first-episode psychosis group in the first year of illness.


Assuntos
Síndrome de Asperger , Peroxidação de Lipídeos/fisiologia , Desintoxicação Metabólica Fase I/fisiologia , Estresse Oxidativo/fisiologia , Transtornos Psicóticos , Adolescente , Síndrome de Asperger/diagnóstico , Síndrome de Asperger/metabolismo , Catalase/sangue , Ceruloplasmina/metabolismo , Criança , Cobre/sangue , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Glutationa/sangue , Glutationa Peroxidase/sangue , Homocisteína/sangue , Humanos , Masculino , Anamnese/métodos , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/metabolismo , Superóxido Dismutase/sangue
6.
Psychiatry Res ; 194(3): 230-234, 2011 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-22079057

RESUMO

Evidence from biochemical, imaging, and treatment studies suggest abnormalities of the serotonin system in autism spectrum disorders, in particular in frontolimbic areas of the brain. We used the radiotracers [(11)C]MDL 100907 and [(11)C]DASB to characterize the 5-HT(2A) receptor and serotonin transporter in Asperger's Disorder. Seventeen individuals with Asperger's Disorder (age=34.3 ± 11.1 years) and 17 healthy controls (age=33.0 ± 9.6 years) were scanned with [(11)C]MDL 100907. Of the 17 patients, eight (age=29.7 ± 7.0 years) were also scanned with [¹¹C]DASB, as were eight healthy controls (age=28.7 ± 7.0 years). Patients with Asperger's Disorder and healthy control subjects were matched for age, gender, and ethnicity, and all had normal intelligence. Metabolite-corrected arterial plasma inputs were collected and data analyzed by two-tissue compartment modeling. The primary outcome measure was regional binding potential BP(ND). Neither regional [¹¹C]MDL 100907 BP(ND) nor [¹¹C]DASB BP(ND) was statistically different between the Asperger's and healthy subjects. This study failed to find significant alterations in binding parameters of 5-HT(2A) receptors and serotonin transporters in adult subjects with Asperger's disorder.


Assuntos
Síndrome de Asperger , Benzilaminas/farmacocinética , Fluorbenzenos/farmacocinética , Piperidinas/farmacocinética , Receptor 5-HT2A de Serotonina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Adolescente , Adulto , Síndrome de Asperger/diagnóstico por imagem , Síndrome de Asperger/metabolismo , Síndrome de Asperger/patologia , Mapeamento Encefálico , Radioisótopos de Carbono , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Antagonistas da Serotonina , Adulto Jovem
7.
Med Hypotheses ; 76(5): 653-60, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21388746

RESUMO

Human alpha-fetoprotein is a pregnancy-associated protein with an undetermined physiological role. As human alpha-fetoprotein binds retinoids and inhibits estrogen-dependent cancer cell proliferation, and because retinoic acid (a retinol metabolite) and estradiol (an estrogen) can both initiate cellular gene transcription, it is hypothesized here that alpha-fetoprotein functions during critical gestational periods to prevent retinoic acid and maternal estradiol from inappropriately stimulating gene expression in developing brain regions which are sensitive to these chemicals. Prenatal/maternal factors linked to increased autism risk include valproic acid, thalidomide, alcohol, rubella, cytomegalovirus, depression, schizophrenia, obsessive-compulsive disorder, autoimmune disease, stress, allergic reaction, and hypothyroidism. It will be shown how each of these risk factors may initiate expression of genes which are sensitive to retinoic acid and/or estradiol - whether by direct promotion or by reducing production of alpha-fetoprotein. It is thus hypothesized here that autism is not a genetic disorder, but is rather an epigenetic disruption in brain development caused by gestational exposure to chemicals and/or conditions which either inhibit alpha-fetoprotein production or directly promote retinoic acid-sensitive or estradiol-sensitive gene expression. This causation model leads to potential chemical explanations for autistic brain morphology, the distinct symptomatology of Asperger's syndrome, and the differences between high-functioning and low-functioning autism with regard to mental retardation, physical malformation, and sex ratio. It will be discussed how folic acid may cause autism under the retinoic acid/estradiol model, and the history of prenatal folic acid supplementation will be shown to coincide with the history of what is popularly known as the autism epidemic. It is thus hypothesized here that prenatal folic acid supplementation has contributed to the post-1980 increase in US autism diagnoses. In addition to explaining the epidemic within the wider retinoic acid/estradiol model of causation, this theory leads to potential explanations for certain genetic findings in autism, autistic regression, and changing trends in autism symptomatology with regard to mental retardation, wheat allergy, and gastrointestinal problems.


Assuntos
Transtorno Autístico/etiologia , Regulação da Expressão Gênica no Desenvolvimento , Transcrição Gênica , Animais , Síndrome de Asperger/metabolismo , Transtorno Autístico/genética , Proliferação de Células , Epigênese Genética , Estradiol/metabolismo , Gastroenteropatias/metabolismo , Humanos , Deficiência Intelectual/patologia , Ratos , Análise de Regressão , Risco , Fatores de Risco , Resultado do Tratamento , Tretinoína/metabolismo , alfa-Fetoproteínas/metabolismo
8.
Biomed Khim ; 57(5): 562-70, 2011.
Artigo em Russo | MEDLINE | ID: mdl-22629607

RESUMO

Children with Asperger and Kanner syndromes in the stable state demonstrate similar decrease in plasma norepinephrine. In the aggravated state, these changes become more expressed and are characterized by a decrease in plasma tyrosine, norepinephrine, normetanephrine and by an increase in dopamine and homovanylic acid and a decrease in excretion of norepinephrine and an increase in excretion of homovanylic acid, epinephrine and MHPG. Only in children with Kanner syndrome in the aggravated state plasma MHPG increases, excretion of tyrosine decreases and excretion of normetanephrine increases. The observed imbalance in dopamine and epinephrine/norepinephrine systems justifies combined analysis of changes in catecholamines and their metabolites levels as the most informative approach in the study of the effect of autistic disorders.


Assuntos
Síndrome de Asperger/metabolismo , Transtorno Autístico/metabolismo , Catecolaminas/sangue , Catecolaminas/urina , Síndrome de Asperger/sangue , Síndrome de Asperger/urina , Transtorno Autístico/sangue , Transtorno Autístico/urina , Catecolaminas/metabolismo , Criança , Pré-Escolar , Dopamina/sangue , Dopamina/metabolismo , Dopamina/urina , Epinefrina/sangue , Epinefrina/metabolismo , Epinefrina/urina , Ácido Homovanílico/sangue , Ácido Homovanílico/metabolismo , Ácido Homovanílico/urina , Humanos , Metoxi-Hidroxifenilglicol/sangue , Metoxi-Hidroxifenilglicol/metabolismo , Metoxi-Hidroxifenilglicol/urina , Norepinefrina/sangue , Norepinefrina/metabolismo , Norepinefrina/urina , Tirosina/sangue , Tirosina/metabolismo , Tirosina/urina
9.
Prog Brain Res ; 186: 167-75, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21094892

RESUMO

Females in the general population on average have a stronger drive to empathize, and males in the general population on average have a stronger drive to systemize. Evidence related to these claims is reviewed. People with autism spectrum conditions have below average empathy alongside intact or even above average interest in systems. As such, they can be conceptualized as an extreme of the typical male brain.


Assuntos
Síndrome de Asperger/psicologia , Transtorno Autístico/psicologia , Encéfalo , Inteligência Emocional/fisiologia , Síndrome de Asperger/metabolismo , Transtorno Autístico/metabolismo , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Feminino , Humanos , Masculino , Fatores Sexuais
10.
Psychiatry Res ; 184(2): 77-85, 2010 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-20952166

RESUMO

People with autistic spectrum disorders (ASD, including Asperger syndrome) may have developmental abnormalities in the amygdala-hippocampal complex (AHC). However, in vivo, age-related comparisons of both volume and neuronal integrity of the AHC have not yet been carried out in people with Asperger syndrome (AS) versus controls. We compared structure and metabolic activity of the right AHC of 22 individuals with AS and 22 healthy controls aged 10-50 years and examined the effects of age between groups. We used structural magnetic resonance imaging (sMRI) to measure the volume of the AHC, and magnetic resonance spectroscopy ((1)H-MRS) to measure concentrations of N-acetyl aspartate (NAA), creatine+phosphocreatine (Cr+PCr), myo-inositol (mI) and choline (Cho). The bulk volume of the amygdala and the hippocampus did not differ significantly between groups, but there was a significant difference in the effect of age on the hippocampus in controls. Compared with controls, young (but not older) people with AS had a significantly higher AHC concentration of NAA and a significantly higher NAA/Cr ratio. People with AS, but not controls, had a significant age-related reduction in NAA and the NAA/Cr ratio. Also, in people with AS, but not controls, there was a significant relationship between concentrations of choline and age so that choline concentrations reduced with age. We therefore suggest that people with AS have significant differences in neuronal and lipid membrane integrity and maturation of the AHC.


Assuntos
Envelhecimento/metabolismo , Tonsila do Cerebelo/metabolismo , Síndrome de Asperger/metabolismo , Hipocampo/metabolismo , Adolescente , Adulto , Fatores Etários , Envelhecimento/patologia , Tonsila do Cerebelo/química , Tonsila do Cerebelo/patologia , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análise , Ácido Aspártico/metabolismo , Síndrome de Asperger/patologia , Mapeamento Encefálico , Criança , Colina/análise , Colina/metabolismo , Creatina/análise , Creatina/metabolismo , Feminino , Hipocampo/química , Hipocampo/patologia , Humanos , Processamento de Imagem Assistida por Computador , Inositol/análise , Inositol/metabolismo , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Fosfocreatina/análise , Fosfocreatina/metabolismo
11.
Psychoneuroendocrinology ; 35(10): 1578-82, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20409644

RESUMO

Individuals with high-functioning autism spectrum disorders (HFA) show difficulties in the ability to react to change. A recent study suggested that variations in the functioning of the hypothalamus-pituitary-adrenal axis, especially in one of its markers--the cortisol awakening response (CAR)--may be related to those difficulties in adolescents with Asperger's syndrome. The current study investigated the CAR in a younger sample with diagnoses from the whole autism spectrum: A group of children with HFA (N=15) was compared to a group of typically developing children (N=25). Findings suggest that the frequency of a CAR as well as the increase in cortisol levels from awakening to 30 min later were similar between groups, indicating that variations in the CAR in HFA may not be present early in life but only develop later in adolescence or may only occur in some diagnoses from the autism spectrum.


Assuntos
Transtorno Autístico/metabolismo , Hidrocortisona/metabolismo , Síndrome de Asperger/metabolismo , Criança , Interpretação Estatística de Dados , Feminino , Humanos , Masculino , Saliva/metabolismo , Vigília/fisiologia
12.
Dev Med Child Neurol ; 52(3): 289-92, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19549197

RESUMO

AIM: To study the sex ratio (proportion of males) in siblings of individuals diagnosed with autism spectrum disorders (ASDs) as children. METHOD: In the current study, we extended previous studies dealing with the androgen theory of autism and examined sex ratios in the siblings of 326 individuals with ASD (245 males, 81 females) who had been consecutively assessed at two Danish university clinics of child psychiatry during the 25-year period from 1960 to 1985. RESULTS: Among the 513 siblings, 300 were males and 213 females. This yields a sex ratio of 0.585, which is significantly higher than the Danish live-birth sex ratio over the same period (0.514, p=0.001). The sibling sex ratio was not associated with the IQ in the autistic probands. INTERPRETATION: Our findings suggest a potential indirect confirmation of the androgen theory of autism.


Assuntos
Síndrome de Asperger/epidemiologia , Transtorno Autístico/epidemiologia , Irmãos , Líquido Amniótico/química , Síndrome de Asperger/genética , Síndrome de Asperger/metabolismo , Transtorno Autístico/genética , Transtorno Autístico/metabolismo , Área Programática de Saúde , Criança , Pré-Escolar , Cromossomos Humanos X/genética , Dinamarca/epidemiologia , Feminino , Desenvolvimento Fetal , Humanos , Classificação Internacional de Doenças , Masculino , Gravidez , Diagnóstico Pré-Natal/estatística & dados numéricos , Distribuição por Sexo , Testosterona/análise , Testosterona/metabolismo
13.
Psychoneuroendocrinology ; 34(7): 1095-100, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19304400

RESUMO

In addition to abnormalities in social and communication development, a 'need for sameness' and 'resistance to change' are features of autistic spectrum disorders first identified by Kanner in 1943. Our ability to react to change is modulated by the hypothalamic-pituitary-adrenal (HPA) axis, a feature of which is a dramatic increase in cortisol upon waking, the Cortisol Awakening Response (CAR). This study examined whether the CAR was evident in 20 adolescent males with Asperger Syndrome (AS) and 18 age-matched typically developing (TD) controls (aged 11-16). Whilst a significant CAR was evidenced in the TD control group, this was not the case for those with AS. A normal diurnal decrease in cortisol, however, was evident in both groups. The implication that individuals with AS may have an impaired response to change in their environment due to a refractory HPA axis is discussed.


Assuntos
Síndrome de Asperger/metabolismo , Hidrocortisona/metabolismo , Adolescente , Estudos de Casos e Controles , Criança , Ritmo Circadiano , Humanos , Masculino , Saliva/química , Fatores de Tempo , Vigília
14.
J Autism Dev Disord ; 39(7): 1079-86, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19234776

RESUMO

Amygdala dysfunction has been proposed as a critical contributor to social impairment in autism spectrum disorders (ASD). The current study investigated biochemical abnormalities in the amygdala in 20 high functioning adults with autistic disorder or Asperger's disorder and 19 typically developing adults matched on age and IQ. Magnetic resonance spectroscopy was used to measure N-acetyl aspartate (NAA), creatine/phosphocreatine (Cre), choline/choline containing compounds (Cho), and Myoinositol (mI) in the right and left amygdala. There were no significant between-group differences in any of the metabolites. However, NAA and Cre levels were significantly correlated to clinical ratings on the Autism Diagnostic Interview-Revised. This suggests that altered metabolite levels in the amygdala may be associated with a more severe early developmental course in ASD.


Assuntos
Tonsila do Cerebelo/metabolismo , Ácido Aspártico/análogos & derivados , Síndrome de Asperger/metabolismo , Transtorno Autístico/metabolismo , Colina/metabolismo , Creatina/metabolismo , Inositol/metabolismo , Fosfocreatina/metabolismo , Adolescente , Adulto , Ácido Aspártico/metabolismo , Síndrome de Asperger/diagnóstico , Transtorno Autístico/diagnóstico , Mapeamento Encefálico/métodos , Estudos de Casos e Controles , Feminino , Lateralidade Funcional , Humanos , Processamento de Imagem Assistida por Computador , Espectroscopia de Ressonância Magnética , Masculino , Prognóstico , Índice de Gravidade de Doença , Fatores de Tempo , Adulto Jovem
15.
J Child Neurol ; 23(7): 766-74, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18487520

RESUMO

This study assessed metabolic functioning of regional brain areas to address whether there is a neurometabolic profile reflecting the underlying neuropathology in individuals with autism spectrum disorders, and if varied profiles correlate with the clinical subtypes. Thirteen children (7-16 years) with autism spectrum disorders and 8 typically developing children were compared on (1)H-magnetic resonance spectroscopy data collected from hippocampus-amygdala and cerebellar regions. The autism spectrum disorder group had significantly lower N-acetyl-aspartate/creatine ratios bilaterally in the hippocampus-amygdala but not cerebellum, whereas myo-inositol/creatine was significantly increased in all measured regions. Choline/creatine was also significantly elevated in the left hippocampus-amygdala and cerebellar regions of children with autism spectrum disorder. Comparisons within the autism spectrum disorder group when clinically subdivided by history of speech delay revealed significant metabolic ratio differences. Magnetic resonance spectroscopy can provide important information regarding abnormal brain metabolism and clinical classification in autism spectrum disorders.


Assuntos
Ácido Aspártico/análogos & derivados , Mapeamento Encefálico , Encéfalo/metabolismo , Transtornos Globais do Desenvolvimento Infantil/metabolismo , Creatina/metabolismo , Inositol/metabolismo , Adolescente , Tonsila do Cerebelo/metabolismo , Análise de Variância , Ácido Aspártico/metabolismo , Síndrome de Asperger/diagnóstico , Síndrome de Asperger/metabolismo , Transtorno Autístico/diagnóstico , Transtorno Autístico/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , Cerebelo/metabolismo , Criança , Transtornos Globais do Desenvolvimento Infantil/classificação , Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Colina/metabolismo , Cognição/fisiologia , Feminino , Lateralidade Funcional/fisiologia , Hipocampo/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Prótons , Valores de Referência , Sensibilidade e Especificidade , Estatísticas não Paramétricas
16.
J Proteome Res ; 7(12): 5327-32, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19367726

RESUMO

RP-HPLC-ESI-MS profile of naturally occurring salivary peptides of subjects with autistic spectrum disorder [ASD; N = 27:12 with diagnosis of autism, 1 with diagnosis of Asperger, 14 with diagnosis of pervasive developmental disorders not otherwise specified (PDD-NOS)] was compared to that of age-matched controls with the goal of identifying differences that could turn out to become hallmarks of at least a subgroup of ASD individuals. Phosphorylation level of four specific salivary phospho-peptides, namely statherin, histatin 1 (both, p < 0.0001) and acidic proline-rich proteins (both entire and truncated isoforms) (p < 0.005) was found significantly lower in autistic patients, with hypo-phosphorylation of at least one peptide observed in 18 ASD subjects (66%). Developmental scale assessment (Griffith or WISC-R) carried out on 14 ASD subjects highlighted a normal to borderline cognitive development in 10 of them, all included in the hypo-phosphorylated group. Phosphorylation of salivary peptides involves a Golgi casein kinase common to many organs and tissues, CNS included, whose expression seems to be synchronized during fetal development. Hypo-phosphorylation of salivary peptides suggests potential asynchronies in the phosphorylation of other secretory proteins, which could be relevant in CNS development either during embryonic development or in early infancy. These results suggest that analysis of salivary phospho-peptides might help to discriminate a considerable subgroup of ASD patients.


Assuntos
Transtorno Autístico/metabolismo , Proteínas e Peptídeos Salivares/química , Adolescente , Síndrome de Asperger/metabolismo , Síndrome de Asperger/fisiopatologia , Transtorno Autístico/fisiopatologia , Criança , Transtornos Globais do Desenvolvimento Infantil/metabolismo , Transtornos Globais do Desenvolvimento Infantil/fisiopatologia , Pré-Escolar , Feminino , Complexo de Golgi/metabolismo , Histatinas/química , Humanos , Lactente , Masculino , Peptídeos/química , Fosforilação
18.
AJNR Am J Neuroradiol ; 28(8): 1494-8, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17846198

RESUMO

BACKGROUND AND PURPOSE: One former study reported higher prefrontal N-acetylaspartate (NAA) levels in patients with Asperger syndrome (AS). The objective of the current study was to test the hypothesis that patients with AS would have higher dorsolateral prefrontal and anterior cingulate cortex NAA/creatine (Cr) and that NAA/Cr would be correlated with symptom severity. MATERIALS AND METHODS: NAA/choline (Cho), NAA/Cr, and Cho/Cr values revealed by (1)H-MR spectroscopy in 14 right-handed male patients with AS (6 medicated with risperidone), 17-38 years of age, diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria were compared with those of 21 right-handed male controls frequency-matched by age and intelligence quotient scores. RESULTS: Patients with AS had significantly higher anterior cingulate NAA/Cho levels (z = -2.18, P = .028); there was a statistical trend for higher anterior cingulate NAA/Cr (z = -1.81, P = .069) that was significant when only the unmedicated patients with AS were taken into account (z = -1.95, P = .050). There were no significant differences in dorsolateral prefrontal MR spectroscopy values. CONCLUSIONS: Our findings show that individuals with AS had higher NAA/Cho levels in the right anterior cingulate compared with healthy controls and that higher anterior cingulate NAA/Cho levels were correlated with higher Yale-Brown Obsessive Compulsive Scale total scores.


Assuntos
Ácido Aspártico/análogos & derivados , Síndrome de Asperger/diagnóstico , Síndrome de Asperger/metabolismo , Colina/metabolismo , Giro do Cíngulo/metabolismo , Espectroscopia de Ressonância Magnética , Adolescente , Adulto , Ácido Aspártico/metabolismo , Síndrome de Asperger/complicações , Manual Diagnóstico e Estatístico de Transtornos Mentais , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/complicações , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/metabolismo , Prótons
19.
Am J Psychiatry ; 163(7): 1252-63, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16816232

RESUMO

OBJECTIVE: In patients with autism, behavioral deficits as well as neuroimaging studies of the anterior cingulate cortex suggest ventral rather than dorsal striatal and thalamic abnormalities in structure and function. The authors used imaging studies to map volumetric and metabolic differences within the entire dorsoventral extent of the striatum and thalamus. METHOD: Magnetic resonance imaging (MRI) and positron emission tomography (PET) were used to measure volumes and metabolic activity in the thalamus, caudate, and putamen in 17 patients with autism or Asperger's disorder and 17 age- and sex-matched comparison subjects. Subjects performed a serial verbal learning test during the [(18)F]-fluorodeoxyglucose uptake period. The regions of interest were outlined on contiguous axial MRI slices. After PET/MRI coregistration, region-of-interest coordinates were applied to the PET scan for each individual. Between-group differences in metabolism were assessed by three-dimensional statistical probability mapping. RESULTS: The patients with autism spectrum disorders had greater volumes of the right caudate nucleus than comparison subjects as well as a reversal of the expected left-greater-than-right hemispheric asymmetry. Patients also had lower relative glucose metabolic rates bilaterally in the ventral caudate, putamen, and thalamus. Patients with autism had lower metabolic activity in the ventral thalamus than those with Asperger's disorder, but they did not differ from comparison subjects in metabolic activity in the caudate nucleus. CONCLUSIONS: These results are consistent with a deficit in the anterior cingulate-ventral striatum-anterior thalamic pathway in patients with autism spectrum disorders. The results also suggest an important role for the caudate in helping support working-memory demands.


Assuntos
Transtorno Autístico/metabolismo , Transtorno Autístico/patologia , Gânglios da Base/metabolismo , Gânglios da Base/patologia , Glucose/metabolismo , Imageamento Tridimensional/estatística & dados numéricos , Tálamo/metabolismo , Tálamo/patologia , Adolescente , Adulto , Síndrome de Asperger/diagnóstico por imagem , Síndrome de Asperger/metabolismo , Síndrome de Asperger/patologia , Transtorno Autístico/diagnóstico por imagem , Gânglios da Base/diagnóstico por imagem , Mapeamento Encefálico , Núcleo Caudado/diagnóstico por imagem , Núcleo Caudado/metabolismo , Núcleo Caudado/patologia , Feminino , Fluordesoxiglucose F18 , Lateralidade Funcional/fisiologia , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/metabolismo , Giro do Cíngulo/patologia , Humanos , Imageamento por Ressonância Magnética/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Vias Neurais/metabolismo , Vias Neurais/patologia , Tomografia por Emissão de Pósitrons/estatística & dados numéricos , Putamen/diagnóstico por imagem , Putamen/metabolismo , Putamen/patologia , Tálamo/diagnóstico por imagem
20.
Proc Natl Acad Sci U S A ; 103(21): 8275-80, 2006 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-16702548

RESUMO

Several regions of the brain (including medial prefrontal cortex, rostral anterior cingulate, posterior cingulate, and precuneus) are known to have high metabolic activity during rest, which is suppressed during cognitively demanding tasks. With functional magnetic resonance imaging (fMRI), this suppression of activity is observed as "deactivations," which are thought to be indicative of an interruption of the mental activity that persists during rest. Thus, measuring deactivation provides a means by which rest-associated functional activity can be quantitatively examined. Applying this approach to autism, we found that the autism group failed to demonstrate this deactivation effect. Furthermore, there was a strong correlation between a clinical measure of social impairment and functional activity within the ventral medial prefrontal cortex. We speculate that the lack of deactivation in the autism group is indicative of abnormal internally directed processes at rest, which may be an important contribution to the social and emotional deficits of autism.


Assuntos
Transtorno Autístico/metabolismo , Transtorno Autístico/fisiopatologia , Encéfalo/patologia , Adulto , Síndrome de Asperger/metabolismo , Síndrome de Asperger/fisiopatologia , Atenção , Mapeamento Encefálico/métodos , Humanos , Imageamento por Ressonância Magnética/métodos , Modelos Neurológicos , Atividade Motora , Vias Neurais , Estimulação Luminosa , Córtex Pré-Frontal/patologia , Desempenho Psicomotor
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