• Biomolecules & Therapeutics
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• v.30 no.4
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• pp.320-327
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• 2022

Neurodevelopmental disorders are complex conditions that pose difficulty in the modulation of proper motor, sensory and cognitive function due to dysregulated neuronal development. Previous studies have reported that an imbalance in the excitation/inhibition (E/I) in the brain regulated by glutamatergic and/or GABAergic neurotransmission can cause neurodevelopmental and neuropsychiatric behavioral deficits such as autism spectrum disorder (ASD). NMDA acts as an agonist at the NMDA receptor and imitates the action of the glutamate on that receptor. NMDA however, unlike glutamate, only binds to and regulates the NMDA receptor subtypes and not the other glutamate receptors. This study seeks to determine whether NMDA administration in mice i.e., over-activation of the NMDA system would result in long-lasting behavioral deficits in the adolescent mice. Both gender mice were treated with NMDA or saline at early postnatal developmental period with significant synaptogenesis and synaptic maturation. On postnatal day 28, various behavioral experiments were conducted to assess and identify behavioral characteristics. NMDA-treated mice show social deficits, and repetitive behavior in both gender mice at adolescent periods. However, only the male mice but not female mice showed increased locomotor activity. This study implies that neonatal exposure to NMDA may illicit behavioral features similar to ASD. This study also confirms the validity of the E/I imbalance theory of ASD and that NMDA injection can be used as a pharmacologic model for ASD. Future studies may explore the mechanism behind the gender difference in locomotor activity as well as the human relevance and therapeutic significance of the present findings.

• Journal of Korean Neurosurgical Society
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• v.59 no.3
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• pp.242-246
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• 2016

Craniosynostosis is the premature fusion of calvarial sutures, resulting in deformed craniofacial appearance. Hence, for a long time, it has been considered an aesthetic disorder. Fused sutures restrict growth adjacent to the suture, but compensatory skull growth occurs to accommodate the growing brain. The primary goal for the management of this craniofacial deformity has been to release the constricted skull and reform the distorted shape of the skull vault. However, the intellectual and behavioral prognosis of affected children has also been taken into consideration since the beginning of the modern era of surgical management of craniosynostosis. A growing body of literature indicates that extensive surgery, such as the whole-vault cranioplasty approach, would result in better outcomes. In addition, the age at treatment is becoming a major concern for optimal outcome in terms of cosmetic results as well as neurodevelopment. This review will discuss major concerns regarding neurodevelopmental issues and related factors.

• BMB Reports
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• v.52 no.7
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• pp.424-433
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• 2019

Autism spectrum disorder (ASD) is a complex neurodevelopmental monogenic disorder with a strong genetic influence. Idiopathic autism could be defined as a type of autism that does not have a specific causative agent. Among signalling cascades, mTOR signalling pathway plays a pivotal role not only in cell cycle, but also in protein synthesis and regulation of brain homeostasis in ASD patients. The present review highlights, underlying mechanism of mTOR and its role in altered signalling cascades as a triggering factor in the onset of idiopathic autism. Further, this review discusses how distorted mTOR signalling pathway stimulates truncated translation in neuronal cells and leads to downregulation of protein synthesis at dendritic spines of the brain. This review concludes by suggesting downstream regulators such as p70S6K, eIF4B, eIF4E of mTOR signalling pathway as promising therapeutic targets for idiopathic autistic individuals.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.29 no.1
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• pp.7-13
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• 2018

Objectives: Problem behaviors pose a great obstacle to daily functioning in children with neurodevelopmental deficits and are an important target for treatment. In this study, we translated the Behavior Problems Inventory (BPI)-01 into Korean language and tested its psychometric properties. Methods: We attained the approval of the BPI author and performed standard translation-back translation. Then, professional caregivers examined appropriateness according to cultural and situational contexts in order to make necessary modifications of the Korean version of the BPI. Results: The BPI-01, Korea-Scales of Independent Behavior-Revised (K-SIB-R), and Child Behavior Checklist were completed for 98 autistic spectrum disorder or intellectual development disorder participants (mean age=28.3, standard deviation=7.3, range=10.1-51.7). The inter-rater reliability of the BPI-01 was found to be high (r=0.992-1.000). As for the results for concurrent validity for subscale items of BPI-01 and scales of SIB, correlations between SIB and BPI-01 subscales were statistically significant (r=0.357-0.672). Discussion: The Korean version of the BPI-01 showed good psychometric properties with high reliability and sufficient convergent validity. Further examination of the validity of BPI-01 should be carried out with inclusion of younger aged children and a closer look at less frequently occurring symptoms.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.32 no.1
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• pp.35-40
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• 2021

Objectives: Among the many intervention programs for children with autism spectrum disorder (ASD), the Early Start Denver Model (ESDM) is one of the few approaches that has succeeded in demonstrating clinical efficacy in randomized control trials. Here, we investigate the clinical efficacy of ESDM intervention in young children with ASD in a community setting within Japan. Methods: All subjects were children with ASD who received ESDM intervention during the study period. Each ESDM session lasted 75 min and occurred once per week for at least 12 weeks. The outcome measures consisted of the Kyoto Scale of Psychological Development (K-test), Aberrant Behavior Checklist-Japanese version (ABC-J), and the Clinical Global Impression-Severity scale (CGI-S). Results: Twenty-seven subjects (29.4±6.4 months old) received ESDM intervention that lasted for 8.0±2.6 months on average. The score on Language and Social developmental quotient on the K-test increased significantly after the intervention. The total scores on the ABC-J and CGI-S significantly decreased after completion of the ESDM intervention. Conclusion: Our results suggest that ESDM intervention could reduce the severity of distinct clinical features of ASD, such as impairments in social interaction and communication assessed by the K-test, and maladaptive behavior rated by the ABC-J and CGI-S. We believe that the ESDM adapted to each institution might become one of the standard options for children with ASD in Japan.

• Journal of Korean Neuropsychiatric Association
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• v.57 no.2
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• pp.190-208
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• 2018

Objectives To initiate and develop a treatment guideline in multidisciplinary approaches for related professions who are either working and/or living with children and adolescents with neurodevelopmental disorders who show behavioral problems. Methods To collect and reflect opinions from multiple professions who assumedly have different interventions or mediations on behavioral problems, a self-report survey and Focus Group Interview (FGI) were conducted for a group of child and adolescent psychiatrists, behavioral therapists, special education teachers, social welfare workers, and caregivers. Results According to a self-report survey and FGI results from multiple professional groups, aggressive behavior is the mostly common behavioral problem necessitating urgent interventions. However, both mainly used intervention strategies and effective treatment methods were different depending on professional backgrounds, such as pharmacological treatment, parent training, and behavior therapy, even though they shared an importance of improving communication skills. In addition, there was a common understanding of necessity to include parent training in a guideline. Lastly the data suggested lack of proper treatment facilities, qualified behavior therapists, and lack of standardized treatment guideline in the field needed to be improved for a quality of current therapeutic services. Conclusion It is supported that several subjects should be included in the guidelines, such as how to deal with aggressive behavior, parent training, and biological aspects of neurodevelopmental disorders. Also, it is expected that publishing the guideline would be helpful to above multiple professions as it is investigated that there are lack of treatment facility and qualified behavioral therapists compared to need at the moment.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.26 no.2
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• pp.86-93
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• 2015

Autism spectrum disorder (ASD) is a neurodevelopmental disorder marked by impaired social communication and repetitive, restricted behaviors and activities. The prevalence of ASD has been increasing for the past 2 decades, but evidence-based therapeutic approaches are lacking for patients with ASD. To date, there is no cure for the core symptoms of ASD, and the existing treatments focus on improving the patient's function and adaptation by using behavioral intervention methods. Behavioral interventions have been proven to show the greatest effect when applied before the age of 2 years, for at least 40-60 hours per week. Many clinicians and ASD families are unfamiliar with the treatment methods, and consequently, may seek unproven and potentially hazardous methods. The purpose of this article was to present an extensive and updated review on evidence-based ASD behavioral interventions that are commonly used in clinical settings.

• Clinical Psychopharmacology and Neuroscience
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• v.16 no.4
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• pp.415-421
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• 2018

Objective: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in social skills and communication with repetitive behaviors. Etiology is still unclear although it is thought to develop with interaction of genes and environmental factors. Oxytocin has extensive effects on intrauterine brain development. Vitamin D, affects neural development and differentiation and contributes to the regulation of around 900 genes including oxytocin receptor gene. In the present study, the contribution of D vitamin receptor and oxytocin receptor gene polymorphisms in the development of ASD in Turkish community was investigated. To our knowledge, this is the first study examining these two associated genes together in the literature. Methods: Eighty-five patients diagnosed with ASD according to DSM-5 who were referred to outpatient clinics of Child and Adolescent Psychiatry of Başkent University and Mersin University and 52 healthy, age and gender-matched controls were included in the present study. Vitamin D receptor gene rs731236 (Taq1), rs2228570 (Fok1), rs1544410 (Bsm1), rs7975232 (Apa1) polymorphisms and oxytocin receptor gene rs1042778 and rs2268493 polymorphisms were investigated using real time polymerase chain reaction method. Results: No significant difference between groups in terms of distribution of genotype and alleles in each of polymorphisms for these genes could be found. Conclusion: Knowledge of genes and polymorphisms associated with the development of ASD may be beneficial for early diagnosis and future treatment. Further studies with larger populations are required to demonstrate molecular pathways which may play part in the development of ASD in Turkey.

• Clinical and Experimental Pediatrics
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• v.57 no.9
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• pp.384-395
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• 2014

Febrile seizure (FS) is the most common seizure disorder of childhood, and occurs in an age-related manner. FS are classified into simple and complex. FS has a multifactorial inheritance, suggesting that both genetic and environmental factors are causative. Various animal models have elucidated the pathophysiological mechanisms of FS. Risk factors for a first FS are a family history of the disorder and a developmental delay. Risk factors for recurrent FS are a family history, age below 18 months at seizure onset, maximum temperature, and duration of fever. Risk factors for subsequent development of epilepsy are neurodevelopmental abnormality and complex FS. Clinicians evaluating children after a simple FS should concentrate on identifying the cause of the child's fever. Meningitis should be considered in the differential diagnosis for any febrile child. A simple FS does not usually require further evaluation such as ordering electroencephalography, neuroimaging, or other studies. Treatment is acute rescue therapy for prolonged FS. Antipyretics are not proven to reduce the recurrence risk for FS. Some evidence shows that both intermittent therapy with oral/rectal diazepam and continuous prophylaxis with oral phenobarbital or valproate are effective in reducing the risk of recurrence, but there is no evidence that these medications reduce the risk of subsequent epilepsy. Vaccine-induced FS is a rare event that does not lead to deleterious outcomes, but could affect patient and physician attitudes toward the safety of vaccination.

• The Journal of Korea Assosiation for Disability and Oral Health
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• v.11 no.1
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• pp.17-20
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• 2015

Autism is a life-long neurodevelopmental disorder characterized by qualitative abnormalities in reciprocal social interactions and patterns of communication. Patients with autism are difficult to manage during dental treatment. Thus they need special consideration like physical restraint, conscious sedation or general anesthesia. A 5-year-old male dental patient with autism was reffered to dental treatment under conscious sedation using intramuscular midazolam that creats anterograde amnesia. Dental procedure using midazolm which cause anterograde amnesia can be effective treatment strategy in autism patient.