1. {{[Neuroanatomical basis of pervasive developmental disorders and its pathogenesis]}}. {Seishin Shinkeigaku Zasshi};2008;110(10):893-899.
Since recent literature has argued to give up a single explanation covering diverse symptom defining autism-spectrum disorder (ASD), our study focuses on deficits in social cognition as the target of phenotype in searching cause for ASD. First study revealed that the gray matter volume reductions in several regions important for social cognition were common to monozygotic twins with Asperger’s syndrome as compared with healthy matched controls. The findings suggest a contribution of shared genetic factors to underlying the structural abnormalities in ASD. Second study showed that the young healthy females showed greater cooperativeness as well as larger relative global and regional gray matter volumes than the matched males, particularly in the social-brain regions including posterior inferior frontal and anterior medial prefrontal cortices. Moreover, specifically in females, higher cooperativeness was tightly coupled with the larger relative total gray matter volume and more specifically with the regional gray matter volume in most of the regions revealing larger in female sex-dimorphism. These results suggest that sexually-dimorphic factors may affect the neurodevelopment of these « social-brain » regions, leading to higher cooperativeness in females. The findings may also have an implication for the pathophysiology of autism; characterized by severe dysfunction in social reciprocity, abnormalities in social-brain, and disproportionately low probability in females. Third study showed a gender specific relationship between a polymorphism of oxytocin-receptor gene and regional gray matter volume of inferior frontal gyrus in healthy young adults. Forth study demonstrates the correlation between smaller-than normal volume of posterior inferior frontal gyrus and worse function of social communication in the males with ASD compared with matched controls. Furthermore, we would like to discuss the possibility of future study examining the relationship between oxytocin-induced enhancement of social cognition and polymorphisms of genes encoding oxytocin-related molecules using neuroimaging as endophenotypes.
2. Ming X, Johnson WG, Stenroos ES, Mars A, Lambert GH, Buyske S. {{Genetic variant of glutathione peroxidase 1 in autism}}. {Brain Dev} (Feb);32(2):105-109.
3. Molloy CA, Murray DS, Kinsman A, Castillo H, Mitchell T, Hickey FJ, Patterson B. {{Differences in the clinical presentation of Trisomy 21 with and without autism}}. {J Intellect Disabil Res};2009 (Feb);53(2):143-151.
BACKGROUND: Autism occurs 10 times more often in children with Down syndrome than in the general population, but diagnosing co-occurring autism in Down syndrome with severe intellectual disability is challenging. The objective of this case-control study was to identify characteristics differentiating children with trisomy 21 with and without autism and to determine the extent to which severe cognitive impairment affects the measures of autism symptomatology. METHOD: Twenty children with trisomy 21 and autism (cases) were compared with children with trisomy 21 without autism (controls) matched on chronologic age, race and gender. Communication, cognitive and adaptive behaviour skills were assessed with standardized instruments. Medical history was reviewed and medical records were examined for early head growth. Scores on the diagnostic algorithm of the Autism Diagnostic Interview–Revised (ADI-R) were compared after adjusting for cognitive ability as measured by the Stanford-Binet (Fifth Edition) non-verbal change sensitive score. RESULTS: Cases performed significantly more poorly on all assessments. Mean case-control differences for matched pairs were all significant at P < 0.0001 for receptive and expressive language skills, cognitive skills and adaptive skills. Seven cases had a history of seizures compared with one control(P = 0.01). After adjusting for cognitive ability, the mean scores on the Reciprocal Social Interaction, Communication, and Restricted, Repetitive and Stereotyped Behaviours domains of the ADI-R diagnostic algorithm remained significantly higher in cases compared with controls (P < 0.0001). All participants had decreased head size consistent with Down syndrome, with no case-control differences. CONCLUSION: Children with trisomy 21 and autism have significantly more impaired brain function than children with trisomy 21 without autism. However, the deficits in the core domains of social reciprocity and communication, and the restricted and repetitive interests are not entirely explained by the more severe cognitive impairment. This autism phenotype in children with trisomy 21 which includes an increased risk for seizures may indicate a widespread loss of functional connectivity in the brain.
4. Nakashima N, Yamagata T, Mori M, Kuwajima M, Suwa K, Momoi MY. {{Expression analysis and mutation detection of DLX5 and DLX6 in autism}}. {Brain Dev} (Feb);32(2):98-104.
