• Journal of Korean Society of Neurocognitive Rehabilitation
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• v.10 no.2
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• pp.35-44
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• 2018

This study was conducted to explore the effects of semi-structured $DIRFloortime^{(R)}$ treatment on the enhancement of language comprehension and information processing of children with high-performance autistic spectrum disabilities. We measured the general characteristics of the test subjects, which are level of autism, total intelligence, language comprehension and information processing indicators. The intervention method used was a semi-structured $DIRFloortime^{(R)}$ therapy using board game intervention program after revising and supplementing the expert content validity. A pre/post-test for a group was designed as a similar experiment and the pre/post test was initiated with the t certification at .05 of significance level. After initiating the program, the post test has shown that the language comprehension indicators showed statistically significant levels of difference (p<.001) and the information processing indicator also had a statistically significant effect (p<.001). There was a statistically significant difference (p<.001) in the level of verbal comprehension index after the program implementation, and statistically significant differences in the information processing index (p<.001). The semi-structured $DIRFloortime^{(R)}$ treatment using boardgames for enhancing the language comprehension and information processing indicators of children with high performance autistic spectrum disorder had a significant effect.

• Therapeutic Science for Rehabilitation
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• v.7 no.4
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• pp.57-66
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• 2018

Objective: The purpose of this study is to investigate the effect of interactive metronome (IM) training on attention among children on the autistic spectrum. Methods: This is a single case study, using ABA design, of one child with autism spectrum disorder (ASD) who had attentional difficulties. A total of 20 sessions were conducted: 3 baseline sessions (A), 14 intervention sessions (B), and 3 follow-up baseline sessions (A'). During the intervention period (B), IM training was performed. Inattention and attention activities were measured as the dependent variables in all three phases (A, B, and A'). Results: Compared to baseline, the subject's inattention decreased in the IM training mediation period, and the performance of activities requiring attention also improved. The intervention effect was maintained even during the follow-up baseline period. Conclusion: The results of this study suggest that IM training positively influences attention among children with ASD with attention deficit symptoms. Further, it provides the clinical basis of IM training as an intervention for children with ASD.

• Biomolecules & Therapeutics
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• v.24 no.3
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• pp.207-243
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• 2016

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication impairments, as well as repetitive and restrictive behaviors. The phenotypic heterogeneity of ASD has made it overwhelmingly difficult to determine the exact etiology and pathophysiology underlying the core symptoms, which are often accompanied by comorbidities such as hyperactivity, seizures, and sensorimotor abnormalities. To our benefit, the advent of animal models has allowed us to assess and test diverse risk factors of ASD, both genetic and environmental, and measure their contribution to the manifestation of autistic symptoms. At a broader scale, rodent models have helped consolidate molecular pathways and unify the neurophysiological mechanisms underlying each one of the various etiologies. This approach will potentially enable the stratification of ASD into clinical, molecular, and neurophenotypic subgroups, further proving their translational utility. It is henceforth paramount to establish a common ground of mechanistic theories from complementing results in preclinical research. In this review, we cluster the ASD animal models into lesion and genetic models and further classify them based on the corresponding environmental, epigenetic and genetic factors. Finally, we summarize the symptoms and neuropathological highlights for each model and make critical comparisons that elucidate their clinical and neurobiological relevance.

• Biomolecules & Therapeutics
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• v.30 no.3
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• pp.232-237
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• 2022

Autism spectrum disorder (ASD) having core characteristics of social interaction problems and repetitive behaviors and interests affects individuals at varying degrees and comorbidities, making it difficult to determine the precise etiology underlying the symptoms. Given its heterogeneity, ASD is difficult to treat and the development of therapeutics is slow due to the scarcity of animal models that are easy to produce and screen with. Based on the theory of excitation/inhibition imbalance in the brain with ASD which involves glutamatergic and/or GABAergic neurotransmission, a pharmacologic agent to modulate these receptors might be a good starting point for modeling. N-methyl-D-aspartic acid (NMDA) is an amino acid derivative acting as a specific agonist at the NMDA receptor and therefore imitates the action of the neurotransmitter glutamate on that receptor. In contrast to glutamate, NMDA selectively binds to and regulates the NMDA receptor, but not other glutamate receptors such as AMPA and kainite receptors. Given this role, we aimed to determine whether NMDA administration could result in autistic-like behavior in adolescent mice. Both male and female mice were treated with saline or NMDA (50 and 75 mg/kg) and were tested on various behavior experiments. Interestingly, acute NMDA-treated mice showed social deficits and repetitive behavior similar to ASD phenotypes. These results support the excitation/inhibition imbalance theory of ASD and that NMDA injection can be used as a pharmacologic model of ASD-like behaviors.

• Therapeutic Science for Rehabilitation
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• v.8 no.3
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• pp.83-95
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• 2019

Objective: The purpose of this study was to investigate the effects of the Power Card strategy on the receptive vocabulary and expressive vocabulary in children with autism spectrum disorders. Method: Three children with autism spectrum disorder were selected for this study and the power card strategy language intervention was applied, using a multiple baseline design across individuals. The target vocabulary was selected by examining the individual preferred characters. Power cards were constructed, and intervention was applied to improve the receptive vocabulary and expressive vocabulary through the baseline stage, intervention, and maintenance. Result: The application of the power card strategy showed that the acquisition rate of receptive vocabulary in children with autism spectrum disorder was increased, and expressive vocabulary acquisition rate was also improved. Conclusion: During the intervention period using the power card strategy, the children's target receptive vocabulary and expressive vocabulary acquisition rates improved, and the acquisition rate was maintained, even after the intervention. This suggests that the power card strategy is effective in improving the vocabulary of autistic children with disabilities, of school age.

• Journal of Preventive Medicine and Public Health
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• v.52 no.3
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• pp.200-204
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• 2019

On September 12, 2018, President Jae-In Moon announced the Comprehensive Plan for Lifelong Care for People with Developmental Disabilities, with representatives from the associated government branches (Ministry of Health and Welfare, Ministry of Education, and Ministry of Employment and Labor) in attendance. The goals of this plan are to provide health, medical, rehabilitative, special education, and social welfare services according to the life-stages of the affected individuals; to reduce parental pressure; to promote social interventions; and to enhance community-level participation in order to create a 'welfare society in harmony.' However, in order for the plan to succeed, additional efforts must be made in the following areas. First, an epidemiological survey is needed to understand the scale, prevalence, and incidence of developmental disabilities and to establish an evidence base to support policy development. Second, accurate definitions of developmental disabilities must be established in order to avoid policy discrimination based on impairment type and age. Third, personal evaluations to assess disabled individuals' unmet needs and customized service designs to deliver those needs are required. Fourth, the plan must fulfill the goals of accessibility and fairness that the government intends to provide. Fifth, the government should consider an integrated financial support system and to propose a detailed plan for monetary distributions. Finally, an integrated system that links health, medical, employment, educational, and welfare services must be constructed.

• BMB Reports
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• v.55 no.5
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• pp.238-243
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• 2022

Autism or autism spectrum disorder (ASD) is a behavioral syndrome characterized by persistent deficits in social interaction, and repetitive patterns of behavior, interests, or activities. The gene encoding Methyl-CpG binding protein 2 (MeCP2) is one of a few exceptional genes of established causal effect in ASD. Although genetically engineered mice studies may shed light on how MeCP2 loss affects synaptic activity patterns across the whole brain, such studies are not considered practical in ASD patients due to the overall level of impairment, and are technically challenging in mice. For the first time, we show that hippocampal MeCP2 knockdown produces behavioral abnormalities associated with autism-like traits in rats, providing a new strategy to investigate the efficacy of therapeutics in ASD. Ketamine, an N-Methyl-D-aspartate (NMDA) blocker, has been proposed as a possible treatment for autism. Using the MeCP2 knockdown rats in conjunction with a rat model of valproic acid (VPA)-induced ASD, we examined gene expression and ASD behaviors upon ketamine treatment. We report that the core symptoms of autism in MeCP2 knockdown rats with social impairment recovered dramatically following a single treatment with ketamine.

• Journal of Environmental Health Sciences
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• v.38 no.6
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• pp.541-549
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• 2012

Objectives: This study was undertaken in order to evaluate a potential mechanism involved in gastro-intestinal problems observed in autistic subjects and uses an animal model of autism investigation. Methods: BTBR T+tf/J, a mouse strain with typical socio-behavioral characteristics of autistic subjects and FVB mice with highly social behaviors as the control strain were used. Both genders of mice aged three weeks and six months were used from four separate litters for each strain. Serum was prepared following cardiac puncture, and mesenteric lymph nodes were collected for in vitro stimulation and enumeration of major immune cell proportion. Results: The level of serum IgA was significantly enhanced in six-month-old BTBR mice compared with three-week-old BTBR, which was not observed with the FVB control mice. The serum IgE level was also higher among BTBR mice than among age-sex matched FVB mice, respectively. Considering the ratio of interleukin-4 vs interferon-gamma production from mesenteric lymph node T cells, skewedness toward type-2 reactivities was observed. In addition, the proportion of B cells in mesenteric lymph nodes was significantly higher in BTBR mice than in FVB mice. Conclusion: Upregulation of mucosal immunity related with enhanced type-2 immune reactivity observed in BTBR mice could be involved with the etiology of gastro-intestinal abnormalities in autism.

• Genomics & Informatics
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• v.8 no.1
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• pp.19-27
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• 2010

To discover genetic markers for autism spectrum disorder (ASD), we previously applied genome-wide BAC array comparative genomic hybridization (array-CGH) to 28 autistic patients and 62 normal controls in Korean population, and identified that chromosomal losses on 8p23.1 and on 17p11.2 are significantly associated with autism. In this study, we developed an 8.5K ASD-specific BAC array covering 27 previously reported ASD-associated CNV loci including ours and examined whether the associations would be replicated in 8 ASD patient cell lines of four different ethnic groups and 10 Korean normal controls. As a result, a CNV-loss on 8p23.1 was found to be significantly more frequent in patients regardless of ethnicity (p<0.0001). This CNV region contains two coding genes, DEFA1 and DEFA3, which are members of DEFENSIN gene family. Two other CNVs on 17p11.2 and Xp22.31 were also distributed differently between ASDs and controls, but not significant (p=0.069 and 0.092, respectively). All the other loci did not show significant association. When these evidences are considered, the association between ASD and CNV of DEFENSIN gene seems worthy of further exploration to elucidate the pathogenesis of ASD. Validation studies with a larger sample size will be required to verify its biological implication.

• Korean Journal of Biological Psychiatry
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• v.13 no.4
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• pp.289-298
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• 2006

Objectives : Autism is a complex neurodevelopmental spectrum disorder with a strong genetic component. Previous neurochemical and genetic studies suggested the possible involvement of glutamate N-methyl-D-aspartate(NMDA) receptor in autism. The aim of study was to investigate the association between the NMDA2B receptor gene(GRIN2B) and autism spectrum disorders(ASD) in the Korean population. Methods : The patients with ASD were diagnosed with Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule based on DSM-IV diagnostic classification. The present study was conducted with the detection of four single nucleotide polymorphisms(SNPs) in GRIK2 and family-based association analysis of the single nucleotide polymorphisms in Korean ASD trios using transmission disequilibrium test (TDT). Results : One hundred twenty six patients with ASD and their biological parents were analyzed. 86.5% were male and 85.1% were diagnosed as autistic disorder. The mean age was $71.9{\pm}31.6$ months(range : 26-185 months). We found that rs1805247 showed significantly preferential transmission(TDT ${\chi}^2$=12.8, p<0.001) in ASD. Conclusion : One SNP in GRIN2B gene was significantly associated with ASD in the Korean population. This result suggests the possible involvement of glutamate NMDA receptor gene in the development of ASD.