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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent evidence has implicated the orbitofrontal cortex (OFC) in the pathophysiology of social deficits in autism. An MRI-based morphometric study of the OFC was conducted involving 11 children with autism (age range 8.1-12.7 years) and 18 healthy, age-matched controls (age range 8.9-12.8 years). Decreased grey matter volume in the right lateral OFC in the patient group was found, and correlations were observed between social deficits and white, but not grey, matter structures of the OFC. These findings support the role of OFC in autism and warrant further investigations of this structure using structural and functional methodologies.
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PMID:Volumetric alterations of the orbitofrontal cortex in autism. 1686 74

This study was conducted to examine the volume of the thalamus in autism and to investigate the effect of brain size on this structure in an attempt to replicate, in a larger sample, findings from a previous study reporting the existence of a relationship between brain volume and thalamus in healthy controls but not in individuals with autism. Additionally, the relationships between thalamic volumes and clinical features were examined. Volumetric measurements of the right and left thalamic nuclei were performed on MRI scans obtained from 40 high-functioning individuals with autism (age range: 8-45 years) and 41 healthy controls (age range: 9-43 years). No differences were observed between the two groups for unadjusted thalamic volumes. However, the expected linear relationship between TBV and thalamic volume was not observed in individuals with autism. Furthermore, no correlations were observed between thalamic volumes and clinical features. Findings from this larger study are consistent with the previous report of an abnormal brain size effect on the thalamus in autism and support the possibility of abnormal connections between cortical and subcortical structures in this disorder.
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PMID:Abnormal brain size effect on the thalamus in autism. 1694 9

The article considers behavioral disturbances in children with anomalies of the cerebellum found by MRI studies. Presented are literature data on the relations between pathology of the cerebellum and early autism in children. The cerebellum is involved not only in movement coordination but also in social adaptation and speech communication. Cerebellum-specific genes expressed in early age are similar to those of hippocampus. Our own study of children with agenesis of the vermis cerebelli detected by MRI and behavioral disturbances included 20 children aged 3-15 years (mean age 7,05 years, 12 male, 8 female). Some autistic features have been found.
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PMID:[Clinical and psychological features of children with agenesis of the vermis cerebelli]. 1697 92

Deficiency of dihydropyrimidine dehydrogenase (DPD) is a rare inborn error of pyrimidine metabolism. To date, only about 50 patients are known worldwide. The clinical picture is varied and is not yet fully described. Most patients are diagnosed at the age of 1-3 years. We present a patient diagnosed 8 weeks postpartum. The female patient presented in the first 3 days after birth with agitation, choking, and vomiting. Six weeks later, the patient presented again with vomiting and insufficient weight gain. Metabolic screening of urine showed a strongly increased excretion of uracil and thymine, with no other abnormalities. This suggested a deficiency of DPD which was confirmed by enzyme analysis in peripheral blood mononucleair (PBM) cells (patient: activity <0.01 nmol/mg/h; controls: 9.9 +/- 2.8 nmol/mg/h). The patient was homozygous for the IVS14+1G>A mutation.MRI of the brain showed some cerebral atrophy; myelinization appeared normal. Many patients with DPD-deficiency suffer from convulsions and mental retardation, some show microcephaly, feeding difficulties, autism, and hypertonia. Our patient showed feeding difficulties and in the second half-year she developed slight motor retardation and generalized hypotonia. Further observation of the development of the patient may shed more light on the relationship between clinical symptoms and DPD deficiency. DPD deficiency may present in newborns with vomiting and hypotonia as the main symptoms.
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PMID:A neonate with recurrent vomiting and generalized hypotonia diagnosed with a deficiency of dihydropyrimidine dehydrogenase. 1706 71

Premutation alleles (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene are associated with autism spectrum disorder in childhood, premature ovarian failure, and the neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS). FXTAS, and perhaps the other clinical presentations among carriers, are thought to be due to toxic gain-of-function of elevated levels of the expanded-repeat FMR1 mRNA. Previous structural MRI studies have implicated the amygdala as a potential site of dysfunction underlying social deficits and/or risk for FXTAS. As a preliminary investigation of this possible association, adult males with the premutation, and male controls matched for IQ, age and education, completed three protocols that probe amygdala and sympathetic function: (i) a functional MRI paradigm that measures brain response to fearful faces; (ii) a fear-potentiated startle paradigm that differentiates responses to fearful faces and fearful non-social images and (iii) measurement of skin conductance level during a brief social encounter. Compared with controls, men with the FMR1 premutation demonstrated diminished brain activation in the amygdala and several brain areas that mediate social cognition while viewing fearful faces. The reduced amygdala activation in the premutation group was significantly associated with self-report of psychological symptoms on the Symptom Checklist-90--Revised. These men also displayed a lack of startle potentiation while viewing fearful faces and showed reduced skin conductance response when greeting an unfamiliar experimenter in comparison with the control group. The current findings may be related to social cognition deficits reported previously in children and adults with the premutation. The aetiology for this dysfunction may be elevated FMR1 mRNA or reduced FMR1 protein that occurs in carriers with higher premutation CGG repeat alleles.
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PMID:Amygdala dysfunction in men with the fragile X premutation. 1716 60

Past autism research has often been dedicated to tracing the causes of the disorder to a localized neurological abnormality, a single functional network, or a single cognitive-behavioral domain. In this review, I argue that autism is a "distributed disorder" on various levels of study (genetic, neuroanatomical, neurofunctional, behavioral). "Localizing" models are therefore not promising. The large array of potential genetic risk factors suggests that multiple (or all) emerging functional brain networks are affected during early development. This is supported by widespread growth abnormalities throughout the brain. Interactions during development between affected functional networks and atypical experiential effects (associated with atypical behavior) in children with autism further complicate the neurological bases of the disorder, resulting in an "exponentially distributed" profile. Promising approaches to a better characterization of neural endophenotypes in autism are provided by techniques investigating white matter and connectivity, such as MR spectroscopy, diffusion-tensor imaging (DTI), and functional connectivity MRI. According to a recent hypothesis, the autistic brain is generally characterized by "underconnectivity." However, not all findings are consistent with this view. The concepts and methodology of functional connectivity need to be refined and results need to be corroborated by anatomical studies (such as DTI tractography) before definitive conclusions can be drawn.
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PMID:The study of autism as a distributed disorder. 1732 18

Language delay and impairment are salient features of autism. More specifically, there is evidence of atypical semantic organization in autism, but the functional brain correlates are not well understood. The current study used functional MRI to examine activation associated with semantic category decision. Ten high-functioning men with autism spectrum disorder and 10 healthy control subjects matched for gender, handedness, age, and nonverbal IQ were studied. Participants indicated via button press response whether visually presented words belonged to a target category (tools, colors, feelings). The control condition required target letter detection in unpronounceable letter strings. Significant activation for semantic decision in the left inferior frontal gyrus (Brodmann areas 44 and 45) was found in the control group. Corresponding activation in the autism group was more limited, with smaller clusters in left inferior frontal areas 45 and 47. Autistic participants, however, showed significantly greater activation compared to controls in extrastriate visual cortex bilaterally (areas 18 and 19), which correlated with greater number of errors on the semantic task. Our findings suggest an important role of perceptual components (possibly visual imagery) during semantic decision, consistent with previous evidence of atypical lexicosemantic performance in autism. In the context of similar findings from younger typically developing children, our results suggest an immature pattern associated with inefficient processing, presumably due to atypical experiential embedding of word acquisition in autism.
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PMID:Atypical [corrected] participation of visual cortex during word processing in autism: an fMRI study of semantic decision. 1733 46

Agenesis of the corpus callosum (AgCC), a failure to develop the large bundle of fibres that connect the cerebral hemispheres, occurs in 1:4000 individuals. Genetics, animal models and detailed structural neuroimaging are now providing insights into the developmental and molecular bases of AgCC. Studies using neuropsychological, electroencephalogram and functional MRI approaches are examining the resulting impairments in emotional and social functioning, and have begun to explore the functional neuroanatomy underlying impaired higher-order cognition. The study of AgCC could provide insight into the integrated cerebral functioning of healthy brains, and may offer a model for understanding certain psychiatric illnesses, such as schizophrenia and autism.
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PMID:Agenesis of the corpus callosum: genetic, developmental and functional aspects of connectivity. 1737 41

In January 2005, J.R. Hughes and M. Melyn published an electroencephalographic study on autistic children and found 46% with seizures and also a relatively high prevalence of 20% with epileptiform discharges but without any clinical seizures (Clin EEG Neurosci 2005;36:15-20). Because the discharges have always been viewed as focal events and the clinical seizures as requiring spread, the conclusion from these data was that children with autism may have a deficiency of corticocortical fibers. Since that time many MRI and functional MRI studies have been published confirming that one of the first findings in this devastating condition is underconnectivity. Specific findings are the thinning of the corpus callosum and the reduced connectivity, especially with the frontal areas and also the fusiform face area. Other studies involving positron emission tomography scans, magnetoencephalography, and perception have added to the evidence of underconnectivity. One final point is the initial overgrowth of white matter in the first 2 years of life in autistic children, followed later by arrested growth, resulting in aberrant connectivity; myelination of white matter will likely be significant in the etiology of autism.
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PMID:Autism: the first firm finding = underconnectivity? 1753 41

Careful consideration of motor impairments, such as those documented in autism, can afford valuable insights into the neurological basis of developmental disorders. Motor signs are highly quantifiable and reproducible and can serve as markers for deficits in parallel systems important for socialization and communication. Correlations of motor signs with anatomic MRI (aMRI) measures therefore offer an important means of investigating brain abnormalities contributing to autism. Prior aMRI studies have revealed increased cerebral volume in young children with autism, particularly in 'outer zone' radiate white matter; however functional correlates of these findings have not been reported. In this study, we examined whether radiate white matter within the primary motor cortex would predict impaired motor performance in children with autism. Subjects included children ages 8-12 years: 20 with autism, 36 typically developing (TD) controls and 20 clinical controls with attention-deficit/hyperactivity disorder (ADHD). Regional tissue volumes were measured using an automated tissue classification algorithm followed by a semi-automated parcellation method. Motor performance was assessed using the Physical and Neurologic Examination of Subtle Signs (PANESS), with higher scores indicating poorer performance. Independent linear regression analyses revealed that for TD controls there was a significant negative correlation between total PANESS score and primary motor cortex white matter volume in both the right and left hemispheres, such that increased white matter volume predicted improved motor skill. In contrast, children with autism showed a robust positive correlation between total PANESS score and left hemisphere primary motor and premotor white matter volumes, such that increased white matter volume predicted poorer motor skill. No significant correlations were found for ADHD. Multivariate regression analyses revealed that the correlation between PANESS score and left motor cortex white matter volume in children with autism significantly differed from those in both ADHD and TD children. The correlation in ADHD did not significantly differ from that in TD children. The findings for the first time demonstrate an association between increasing radiate white matter volume and functional impairment in children with autism, in this case basic motor skill impairment. The observed association, which appears specific to autism, may be representative of global patterns of brain abnormality that not only contribute to motor dysfunction in autism, but also deficits in socialization and communication that define the disorder.
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PMID:Increased motor cortex white matter volume predicts motor impairment in autism. 1757 80


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