Review of Early Intervention for Children with Autism Spectrum Disorder: Focused on Randomized Controlled Trials

Early identification and intervention for autism spectrum disorder (ASD) were reported to be important for outcomes or clinical courses. However, there have been a few robust evidences for effectiveness of early intervention until now. This review aims to identify the effectiveness of early intervention by investigating the randomized controlled trial (RCT) of early intervention for autism. There are some RCT studies using behavioral program. Although there are some significant findings, the outcome measurements and small sample size are the limitations. Further studies are needed.

Validation Study of Behavior Problems Inventory-01 among Korean Children and Adolescents

OBJECTIVES: The purpose of this study was to examine the reliability and validity of the Korean version of the Behavior Problems Inventory (BPI-01) among children and adolescents aged between 3 and 18. METHODS: The control group consisting of one hundred children and adolescents was recruited from schools and the patient group consisting of forty one children and adolescents with autism spectrum disorder were recruited from a hospital. We compared the measurements of both groups. To assess the concurrent validity of the BPI-01, we compared the problem behavior index of the Korean Scale of Independent Behavior-Revised (K-SIB-R) and, to assess the discriminant validity, we compared the Korean version of the Child Behavior Checklist (K-CBCL). The Cronbach's alpha of the BPI-01 was measured to assess its reliability. Correlation analyses between the BPI-01 and the other scale were carried out to examine the former's concurrent and discriminant validity. RESULTS: The patient group showed a significantly higher score for all three subscales of the BPI than the control group. The Cronbach's alpha was 0.92 for the total severity score of the BPI and ranged between 0.67–0.89 for each subscale in the patient group. All subscales of the BPI-01's, i.e., self injurious behavior, stereotyped behavior and aggressive/destructive behavior, were significantly correlated with the corresponding subscales of the K-SIB-R. The BPI-01 generally did not demonstrate any significant correlation with emotional items such as anxiety/depression in the K-CBCL. Especially, the BPI-01's stereotyped behavior subscale showed little correlation with externalizing behaviors such as social problems and aggressive behaviors. CONCLUSION: This study found that the Korean version of BPI-01 is a reliable and valid behavior rating instrument for problem behavior in developmental disabilities among children and adolescents.

Clinical Characteristics of Aggressive Behavior Problems in Children with Autism Spectrum Disorder: Preliminary Study

OBJECTIVES: The aim of this study was to investigate the clinical characteristics of aggressive behavior problems in children and adolescents with autism spectrum disorder (ASD). METHODS: Children and adolescents with ASD, aged 6–18 years, were included in this study. We divided them into two groups according to the presence or absence of aggressive behavior. They were assessed using three scales, the Korean-Child Behavior Checklist (K-CBCL), Behavior Problem Inventory, and Social Communication Questionnaire, which were completed by their parents, who conducted a continuous performance test to evaluate their attention function. The statistical analysis was done using the Mann-Whitney U-test between the two groups at a p-value of 0.05. RESULTS: A total of 17 children participated in this study. Ten children (7 boys, 12.4±4.27 years) were included in the group with aggressive behavior problems and 7 children (6 boys, 13.8±3.53 years) in the group without aggressive behavior problems. There were no significant differences in the age, gender or intelligence quotient of the two groups. The children with aggressive behavior problems showed a trend of higher T-scores in the attention problems and anxiety/depressed subscale of the CBLC (p<0.1). CONCLUSION: The results suggest that aggressive behavior problems in children with ASD may be related to their attention problems, anxiety and depression.

A Survey for Mental Health of Children Whose Parents Have Psychiatric Disorders: A Preliminary Study for Mental Health Screening of High Risk Children

OBJECTIVES: This study aimed to evaluate the mental health status of the children of psychiatric patients in order to plan for the resources that may be necessary to help these children achieve their full potential. METHODS: Forty-eight children (age 9–18) whose parents were registered in 5 community mental health centers located in Seoul were recruited. Tests assessing 3 psychological domains were conducted: 1) cognition: Korean version of Learning Disability Evaluation Scale, Comprehensive Attention Test, 2) parent reported emotion and behavior: Korean Child Behavior Checklist, Korean attention-deficit hyperactivity disorder Rating Scale, and 3) self-reported emotion and behavior: Korean Beck's Depression Inventory-II/Children's Depression Inventory-II, Korean Youth Self Report). We defined the children as having a high risk of developing mental health problems if their test scores were over the cut-off levels in 2 or more of the 3 domains assessed. RESULTS: Twelve (25%) children were classified as having a high risk of developing mental health issues. 20 (41.6%) children scored above the cut-off in only one of the domains. CONCLUSION: Our results suggest that the children of psychiatric patients might be vulnerable to mental illness and need early prevention or interven-tions for the sake of their mental health.

A Study about Effects of Osmotic-Controlled Release Oral Delivery System Methylphenidate on Regional Cerebral Blood Flow in Korean Children with Attention-Deficit Hyperactivity Disorder

OBJECTIVES: The objective of this study was to examine the effects of osmotic-controlled release oral delivery system methylphenidate on changes in regional cerebral blood flow (rCBF) in children with attention-deficit hyperactivity disorder (ADHD) using single photon emission computed tomography (SPECT). METHODS: A total of 26 children with ADHD (21 boys, mean age: 9.2±2.05 years old) were recruited. Each ADHD participant was examined for changes in rCBF using technetium-99m-hexamethylpropylene amine oxime brain SPECT before and after 8 weeks methylphenidate medication. Brain SPECT images of pediatric normal controls were selected retrospectively. SPECT images of ADHD children taken before medication were compared with those of pediatric normal controls and those taken after medication using statistical parametric mapping analysis on a voxel-wise basis. RESULTS: Before methylphenidate medication, significantly decreased rCBF in the cerebellum and increased rCBF in the right precuneus, left anterior cingulate, right postcentral gyrus, right inferior parietal lobule and right precentral gyrus were observed in ADHD children compared to pediatric normal controls (p-value<.0005, uncorrected). After medication, we observed significant hypoperfusion in the left thalamus and left cerebellum compared to pediatric normal controls (p-value<.0005, uncorrected). In the comparison between before medication and after medication, there was significant hyperperfusion in the superior frontal gyrus and middle frontal gyrus and significant hypoperfusion in the right insula, right caudate, right middle frontal gyrus, left subcallosal gyrus, left claustrum, and left superior temporal gyrus after methylphenidate medication (p-value<.0005, uncorrected). CONCLUSION: This study supports dysfunctions of fronto-striatal structures and cerebellum in ADHD. We suggest that methylphenidate may have some effects on the frontal lobe, parietal lobe, and cerebellum in children with ADHD.

The Code of Medical Ethics for the Korean Academy of Child and Adolescent Psychiatry: Why Is It Important?

This article provides an overview of the developmental history and rationale of medical ethics to establish the code of ethics and professional conduct of the Korean Academy of Child and Adolescent Psychiatry (KACAP). Most medical professional organizations have their own codes of ethics and conduct because they have continuous responsibility to regulate professional activities and conducts for their members. The Ethics and Award Committee of the KACAP appointed a Task-Force to establish the code of ethics and conduct in 2012. Because bioethics has become global, the Ethics Task Force examined global standards. Global standards in medical ethics and professional conduct adopted by the World Medical Association and the World Psychiatric Association have provided the basic framework for our KACAP's code of ethics and professional conduct. The Code of Ethics of the Americal Academy of Child and Adolescent Psychiatry has provided us additional specific clarifications required for child and adolescent patients. The code of ethics and professional conduct of the KACAP will be helpful to us in ethical clinical practice and will ensure our competence in recognizing ethical violations.

Clinical Characteristics of Children with Autism Spectrum Disorder According to the Presence of Motor Stereotypes

OBJECTIVES: Repetitive and stereotyped behaviors are core symptoms in children with autism spectrum disorders (ASD). The purpose of our study was to investigate the frequency of motor stereotypes in ASD children and their clinical features. METHODS: Among 171 ASD children (age range, 3-15), the ASD group with motor stereotypes was defined according to two items in the Korean version of Autism Diagnostic Interview-Revised (K-ADI-R). We compared the clinical features, behavior problems and severity of other domains in the K-ADI-R and executive functions between the ASD group with motor stereotypes and the ASD group without motor stereotypes. RESULTS: Ninety (52.6%) of 171 ASD children had motor stereotypes. The ASD group with motor stereotypes had a lower intelligence quotient score (62.23 vs. 84.94, p<.001) compared to the ASD group without motor stereotypes. The ASD group with motor stereotypes had more impairments in the social interaction domain [adjusted odds ratio (AOR) 1.11, p=.001] and communication domain (AOR 1.15, p=.008). Thought problems and lethargy were more frequent in the ASD group with motor stereotypes than the ASD group without motor stereotypes (AOR 2.059, p=.034 ; adjusted OR 1.045, p=.046). However, no significant differences in executive function were observed between the ASD group with motor stereotypes and the ASD group without motor stereotypes. CONCLUSION: The ASD group with motor stereotypes showed more impairment in social interaction and communication domains, which are core symptoms of autism. Motor stereotypes may indicate greater severity of ASD.

Neuropsychological and Behavioral Profiles in Attention-Deficit Hyperactivity Disorder Children of Parents with a History of Mood Disorders: A Pilot Study

OBJECTIVE: We aimed to investigate the neurocognitive and behavioral endophenotypes of premorbid mood disorder. We compared intelligence, neuropsychological functioning, and behavioral problems among three groups: 1) a high-risk group [attention-deficit hyperactivity disorder (ADHD) children of parents with a history of a mood disorder], 2) a low-risk group (ADHD children of parents without a history of a mood disorder), and 3) normal comparison subjects. METHODS: We used the Korean Educational Development Institute Wechsler Intelligence Scale for Children-Revised (KEDI-WISC-R), the Stroop Color Word Interference Test (Stroop), the Wisconsin Card Sorting Test (WCST), and the Rey-Osterrieth Complex Figure Test (RCFT) as neurocognitive measures, and we used the Child Behavior Checklist (CBCL) as a behavioral measure. Performance on these neuropsychological tests and score on the CBCL of 18 high-risk children were compared to those of 20 low-risk children and 24 healthy children. We also assessed the children's current mood state and familial functioning to control for the confounding effects of these variables. RESULTS: Compared to low-risk and healthy children, high-risk children were impaired on the Picture Completion and Stroop Word subtest and showed higher scores on the CBCL subscales representing internalizing symptoms. These significant group differences persisted even after adjustment for the children's current mood state and familial functioning. CONCLUSION: Neuropsychological deficits in the offspring of parents with a mood disorder may be associated with the current mood state rather than with innate characteristics, while their internalizing symptoms may partially stem from innate characteristics that are endophenotypes of a premorbid mood disorder.

Difference of the Naltrexone's Effects in Social Drinkers by Spicy Food Preference

The purpose of this study was to investigate the differences in subjective acute effects of alcohol and naltrexone among those who prefer spicy food to varying degrees. Acute biphasic alcohol effects scale (BAES), visual analogue scale for craving (VAS-C), blood alcohol concentration (BAC) and food preference scale were measured in 26 men. Repeated measures ANOVA (2 preference groupsx4 time blocks) on the stimulative subscale of BAES revealed a significant group by block interaction in naltrexone condition (N+) (P<0.001), but not in non-naltrexone condition (N-). Furthermore, repeated measures ANOVA (2 drug groupsx4 time blocks) on the stimulative subscale of BAES revealed a significant group by block interaction in strong preference for spicy food (SP) (P<0.001), but not in lesser preference for spicy food (LP). The paired t-test revealed that significant suppression of the stimulative subscale of BAES was observed at 15 min (P<0.001) and 30 min (P<0.001) after drinking when N+ compared with N- in SP. For those who prefer spicy food, the stimulative effect of acute alcohol administration was suppressed by naltrexone. This result suggests that the effect of naltrexone may vary according to spicy food preference.

Sleep Problems in Autism Spectrum Disorder / 수면정신생리

Autism Spectrum Disorder (ASD) is characterized by persistent deficits in social communication and restricted, repetitive patterns of behavior and interest. Sleep problems are not uncommon in children with autism spectrum disorders. Symptoms of insomnia are the most frequent sleep problems in individuals with ASD. Sleep problems can cause significant difficulties in the daily life of children with ASD and their families. Genetic factor, deregulations of melatonin synthesis, extraneous environmental stimuli and psychiatric and medical conditions may cause sleep problems. The first line treatment of sleep problems in ASD includes managements for potential contributing factors and parent education about sleep hygiene care for child and behavioral therapy. Supplementation with melatonin may be effective before considering other medications, such as risperidone, clonidine, and mirtazapine.

Sleep and Alcohol / 수면정신생리

Alcohol has been used as sedatives historically. The effect of alcohol on sleep is different according to its dose, timing of ingestion, and drinking frequency. Sleep problems may play a role in the development and course of alcohol-related disorders. Insomnia in alcohol-dependent patients is common and early treatment of insomnia may reduce the rate of relapse. Sleep apnea, restless legs syndrome, periodic limbs movement disorder, and altered circadian rhythm may be more frequent in this patients. Management of sleep and alcohol problems is important in treating alcohol-related disorder and sleep disorders, respectively.

Sleep and Psychological Problems in Medical Students / 수면정신생리

INTRODUCTION: Although it is well known that medical students are not getting an adequate amount of sleep, there have been only a few studies on the sleep patterns of medical students and the related factors. Therefore, the present study aimed to investigate the medical students' sleep patterns and the related factors. METHODS: A questionnaire package was administered to the 1st to 4th year medical students at one medical school. It consisted of questions asking about their lifestyles as well as Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), global assessment of recent stress scale (GASS), the center for epidemiologic studies-depression scale (CES-D), and Moudsley obsessive-compulsive inventory (MOCI). A total of 352 students (206 males and 146 females) responded to the survey and the result was analyzed using the independent t-test, the chi-square test, the paired t-test, Pearson's correlation and ANOVA. p-values of less than 0.05 were considered statistically significant in analyses. RESULTS: The weekend bedtime was significantly delayed (0 : 49 on weekday ; 1 : 34 on weekend ; t=-5.23, p<0.001), the weekend rise time was delayed (6 : 58 on weekday ; 9 : 30 on weekend ; t=-24.48, p<0.001) and the total sleep time was increased on weekends (5 : 36 on weekday ; 7 : 39 on weekend ; t=15.94, p<0.001). The PSQI score of all subjects was 6.43+/-2.64. PSQI was positively correlated with ESS (r=0.383, p<0.001), GASS (r=0.326, p<0.001), CES-D (r=0.393, p<0.001), and MOCI (r=0.247, p<0.001), but not with GPA (r=0.072, p=0.228. The more senior students had lower PSQI, GASS, CES-D, and MOCI score (p<0.05). CONCLUSION: Medical students were experiencing a lack of sleep during weekdays as they have a later bedtime and earlier rise time, and consequently had more hours of sleep on weekends. Overall, the medical students were experiencing poor sleep quality and sleep deprivation. Poor sleep quality is associated with psychological problems (daytime sleepiness, stress, depression, and obsessive tendency).

Regional Brain Perfusion before and after Treatment with Methylphenidate According to the MspI Polymorphism of the Alpha-2A Adrenergic Receptor Gene in Children with Attention-Deficit Hyperactivity Disorder

OBJECTIVES: Dysregulation of the central noradrenergic system may be involved in the pathophysiology of attention-deficit hyperactivity disorder (ADHD). The aim of this study was to examine the differences in pre- and post-treatment cerebral perfusion according to the MspI polymorphisms of the alpha-2A-adrenergic receptor gene (ADRA2A) in children with ADHD. METHODS: Thirty seven drug-naive ADHD children (8.9+1.8 years old, M=32, F=5) were genotyped. Baseline single-photon emission computed tomography (SPECT) and clinical assessments were performed for ADHD children. After treatment with methylphenidate for eight weeks, SPECT and clinical assessment were repeated. RESULTS: No differences in baseline clinical assessments or cerebral perfusion were observed according to the MspI genotype. However, after treatment, ADHD children with the G/G genotype at the MspI polymorphism showed hyperperfusion in the right cerebellar declive (p=.001, uncorrected) and hypoperfusion in the left lentiform nucleus and left cingulate gyrus (p<.001 and p=.001, uncorrected), compared to children without the G/G genotype. CONCLUSION: Although the results of this study should be interpreted cautiously, they suggest a possible role of the MspI polymorphisms of the ADRA2A gene in methylphenidate-induced changes in cerebral perfusion.

Genome-Wide Association Scan of Korean Autism Spectrum Disorders with Language Delay: A Preliminary Study

OBJECTIVE: Communication problems are a prevalent symptom of autism spectrum disorders (ASDs), which have a genetic background. Although several genome-wide studies on ASD have suggested a number of candidate genes, few studies have reported the association or linkage of specific endophenotypes to ASDs. METHODS: Forty-two Korean ASD patients who showed a language delay were enrolled in this study with their parents. We performed a genome-wide scan by using the Affymetrix SNP Array 5.0 platform to identify candidate genes responsible for language delay in ASDs. RESULTS: We detected candidate single-nucleotide polymorphisms (SNPs) in chromosome 11, rs11212733 (p-value=9.76x10(-6)) and rs7125479 (p-value=1.48x10(-4)), as a marker of language delay in ASD using the transmission disequilibrium test and multifactor dimensionality reduction test. CONCLUSION: Although our results suggest that several SNPs are associated with language delay in ASD, rs11212733 we were not able to observe any significant results after correction of multiple comparisons. This may imply that more samples may be required to identify genes associated with language delay in ASD.

Clinical Characteristics of Developmental Regression in Autism Spectrum Disorders

OBJECTIVE: A significant proportion of children with autism spectrum disorders (ASD) have regression characterized by loss of previously acquired skills. The purpose of this study was to compare demographic, clinical characteristics and autism-related symptomatology of the children who have regression with children who don't have regression. METHODS: The subjects with ASD and their unaffected siblings (SIB) were recruited from the Korean Autism Genetic Study Consortium. Typically developing children (TC) were volunteered from community. The subjects were administered the Korean version of Autism Diagnostic Interview-Revised (K-ADI-R) and the Korean version of Autism Diagnostic Observation Schedule (K-ADOS) to diagnose or exclude ASD. Regression was defined on the basis of K-ADI-R data. The Korean version of Vineland Adaptive Behavior Scale (K-VABS), Aberrant Behavior Checklist (K-ABC) and Social Responsiveness Scale (K-SRS) were obtained from their parents. RESULTS: Regression occurred in 8.33% (n=14) of children with ASD (n=168). Any SIB (n=166) and TC (n=53) did not experience regression. Regression was associated with lower IQ and lower score of K-VABS. There was no difference in autism symptom severity and K-ABC, K-SRS scores, between children with ASD who experienced regression and who did not. CONCLUSION: Regression seems to be a distinctive feature of ASD. Regression is associated with cognitive and more general functions, rather than symptoms specific to autism.

Prenatal, Perinatal and Infancy History of Autism Spectrum Disorder

OBJECTIVES: The purpose of this study was to evaluate the prenatal, perinatal, and infancy history of children with autism spectrum disorder (ASD) as compared to unaffected siblings (SIB) and typically developing children (TC). METHODS: Subjects with ASD, their SIB, and TC were recruited. All subjects were assessed using both the Korean version of Autism Diagnostic Interview-Revised (K-ADI-R) and the Korean version of Autism Diagnostic Observation Schedule (K-ADOS) and were subsequently identified as affected or unaffected. Prenatal, perinatal, and infancy history was obtained from the primary caregivers and each facet was compared in those with ASD, the SIB, and the TC groups using SPSS ver. 17.0 (p<.05). RESULTS: 70 individuals with ASD (63 males, 87.94+/-37.8months), 53 SIB (27 males, 85.40+/-48.06 months), and 32 TC (19 males, 104.19+/-23.409 months) were analyzed. The ASD group showed significantly higher rates of insufficient vaccination as they aged age (chi2=15.54, p=.000). Among the scheduled vaccinations, the DPT vaccination (chi2=10.08, p=.006) was insufficient in ASD groups. The ASD group also showed higher rates of sleep disturbances from infancy. Differences in maternal/paternal age at conception, gestational age, and growth parameters at birth were not significantly difference among the three groups. CONCLUSION: These results do not support the previous controversies regarding the relationship between prenatal/perinatal complications and ASD. However, these results indicate that perinatal and prenatal factors may contribute to the development of ASD.

Stimulants Medication of Attention-Deficit Hyperactivity Disorder

Attention-deficit hyperactivity disorder (ADHD) is characterized by inattention, hyperactivity, impulsiveness and problems in other higher cognitive processes such as executive function deficits. Currently, there are many treatment modalities, of which pharmacotherapy is the most strongly supported by scientific and clinical evidence. Stimulants, which are first choice in the pharmacological treatment of ADHD, block dopamine reuptake by binding the dopamine transporter and so increasing the concentration of dopamine in synaptic clefts. Stimulants are effective in improving core ADHD symptoms, as well as the nonspecific symptoms, such as aggressiveness and oppositional behavior. Frequently reported short-term adverse effects are decreased appetite, sleep disturbance, headache, dizziness and irritability. Although questions have been raised about the long-term side effects of stimulants, including growth suppression, cardiovascular events, and abuse potential, there is no clear evidence to support these concerns.

Screening for Attention Deficit/Hyperactivity Disorder for Children in Seoul / 신경정신의학

OBJECTIVES: The purpose of this study is to investigate a cut-off value for screening children with ADHD in community based sample using the Korean Child Behavior Checklist (K-CBCL) and the Korean ADHD Rating Scale (K-ARS). METHODS: Children aged 6 to 8 (n=661) participated in this study. The K-CBCL and the K-ARS were used as the screening instruments. Diagnoses were confirmed through the Diagnostic Interview Schedule for Children Version IV (DISC-IV). RESULTS: Of the 189 subjects who underwent the DISC-IV, 26 subjects were diagnosed as ADHD. In the K-CBCL, scores in the attention problems, externalizing problems and total behavioral problems were positively correlated with the total score of the K-ARS. The K-ARS-Parent version (K-ARS-P) and above three scales in the K-CBCL showed significant screening validity in the ROC curve analysis. The reasonable level of sensitivity, specificity, and negative predictive value were obtained in the total scores > or =90th percentile in the K-ARS-Parent and > or =60T scores in the K-CBCL attention problems. The optimal level of specificity, positive predictive value and negative predictive value were obtained when combined the K-CBCL (> or =60T scores in the attention problems and > or =63T scores in the total problems) and the total scores > or =90th percentile in the K-ARS-P. CONCLUSION: The combined use of the K-CBCL and the K-ARS-P may serve as useful screening methods for ADHD children.

The Reliability and Validity of Diagnostic Interview Schedule for Children Version IV-Korean Version (DISC-IV)

OBJECTIVES: The aim of this study was to evaluate the reliability and validity of the Korean Version of the Diagnostic Interview Schedule for Children Version IV(DISC-IV), a highly structured diagnostic interview used to assess more than 30 psychiatric disorders in children and adolescents. METHODS: A total of 91 study subjects, including 67 subjects who visited the child and adolescent psychiatry outpatient clinic at our institution and 24 community-based subjects, were assessed using the Korean Version of the DISCIV. Clinical diagnosis was used as a gold standard for the examination of the validity of the DISC-IV. Forty-four of the study subjects were randomly selected for test-retest reliability measurement. RESULTS: The validity of the Korean Version of the DISC-IV showed kappa values ranging from 0.25 to 0.40 in the clinical sample and 0.65 to 1.00 in the community sample. The sensitivities varied according to the diagnostic categories, but the specificities were excellent for all diagnostic entities. CONCLUSION: The Korean Version of the DISC-IV showed good reliability and validity in Korean children and adolescents. The Korean Version of the DISC-IV might be a useful tool for assessing psychiatric disorders in children and adolescents.