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This study compared children who experience attention-deficit/hyperactivity disorder (ADHD) symptoms but do not meet criteria (i.e., subthreshold ADHD) with those with the full syndrome and healthy controls. Presence of ADHD symptoms was determined in a nationwide community sample of 921 children, aged 8-11 years. The main outcome measures comprised attentional symptoms, comorbidity profiles, academic performance, and neurocognitive ability (i.e., ADHD Rating Scale, Child Behavior Checklist, Learning Disability Evaluation Scale, and Stroop Color-Word Test, respectively). Subthreshold ADHD was equally prevalent in boys and girls, and more prevalent in low-income families. Throughout all the outcome measurements, subthreshold ADHD was both a significantly milder condition than full syndrome ADHD and a significantly more severe condition than non-ADHD status. The findings were consistent across the total as well as the subtest scores, and after correction for multiple comparisons ( p < 0.0017). Children with subthreshold ADHD were found to experience significant symptoms and functional impairments. The results of this study support the clinical relevance of subthreshold ADHD in a childhood population. Subthreshold diagnostic criteria for ADHD may be more sensitive in detecting ADHD symptoms in girls than the full syndrome criteria, and subthreshold clinical, cognitive, and behavioral symptoms of ADHD may occur in a subset of children who are possibly more sensitive to their environment. Further consideration about the diagnostic threshold for ADHD may particularly benefit girls and children in low-income families. [ABSTRACT FROM AUTHOR]

Background Bisphenol A ( BPA) has been shown to affect brain and behavior in rodents and nonhuman primates, but there are few studies focusing on its relationship to human neurobehavior. We aimed to investigate the relationship between environmental exposure to BPA and childhood neurobehavior. Methods Urinary BPA concentrations and behavioral and learning characteristics were assessed in a general population of 1,089 children, aged 8-11 years. The main outcome measures were the Child Behavior Checklist ( CBCL) and the Learning Disability Evaluation Scale ( LDES). Results Urinary levels of BPA were positively associated with the CBCL total problems score and negatively associated with the learning quotient from the LDES. The linear association with the CBCL anxiety/depression score and the quadratic association with the LDES listening score were significant after correction for multiple comparisons. Conclusions Environmental exposure to BPA might be associated with childhood behavioral and learning development. The results suggest possible nonmonotonic relationships. [ABSTRACT FROM AUTHOR]

Background: The present study assessed the association between blood lead and urinary cotinine levels and inattentive and hyperactive symptoms and neurocognitive performance in children. Methods: A total of 667 children (age range 8–11) were recruited from nine schools in five Korean cities. The teachers and parents completed the Korean version of the Attention-deficit/hyperactivity disorder Rating Scales (K-ARS), and the children performed neurocognitive tests. Blood lead and urinary cotinine levels were then measured. Results: The inattentive, hyperactive, and total scores of the teacher-rated K-ARS were positively associated with blood lead level, and the results of the continuous performance test (CPT), Stroop Color–Word Test, and Children’s Color Trails Test were inversely associated with urinary cotinine level when controlled for age, gender, father’s educational level, maternal IQ, child’s IQ, residential area, birth weight, and cotinine (for lead) or lead (for cotinine). The association between blood lead level and commission errors score on the CPT disappeared when the effect of urinary cotinine level was controlled. Conclusions: These findings indicate that environmental exposure to tobacco smoke in children is associated with poor neurocognitive performance, and low levels of lead are associated with inattention and hyperactivity symptoms. [ABSTRACT FROM AUTHOR]

Abstract: Findings from preclinical and clinical research support the involvement of central noradrenergic dysregulation in the etiology of attention deficit hyperactivity disorder (ADHD). Previous studies have suggested that the alpha-2C-adrenergic receptor gene (ADRA2C) is associated with ADHD. The aims of this study were to examine the association between the ADRA2C (GT)n repeat polymorphism (STR marker adra2c1) and ADHD in a Korean sample. In this case-control and family-based association study, we assessed 184 ADHD probands, 150 normal controls, and 98 trios. There were no significant differences in the allele frequencies of the ADRA2C polymorphism between the ADHD and control groups (p >0.05). The overall allele-wise transmission disequilibrium test (TDT) analysis showed statistical significance (χ 2 =19.07, p =0.025). We found a trend for preferential transmission of the 183-bp allele (χ 2 =3.72, p =0.054), and a significantly lower-than-expected rate of transmission of the 187-bp allele (χ 2 =6.26, p =0.012). With regard to the temperament profiles of the Junior Temperament and Character Inventory (JTCI), the ADHD subjects with the 183/183 genotype at the ADRA2C polymorphism showed a trend toward a lower score in the Novelty Seeking (p =0.020) profile than did those with the other genotypes. Our findings provide important evidence that the ADRA2C polymorphism is involved in the etiology of ADHD in Korean subjects. In addition, our results provide evidence that the temperament of Novelty Seeking and ADHD might share molecular genetic characteristics related to the noradrenergic system. [Copyright &y& Elsevier]

The objective of this study was to examine the associations between symptoms of attention-deficit/hyperactivity disorder (ADHD), depression, and suicide in Korean female adolescents. It was hypothesized that the relationship between ADHD symptoms and suicidal ideation would be mediated by the level of depressive symptoms. Seven hundred and eighty-eight high school girls completed the Conners/Wells Adolescent Self-Report Scale: Short Form, Children's Depression Inventory, and Reynolds Suicidal Ideation Questionnaire. Path analyses were conducted using the statistical program, AMOS version 4.0, to determine the best fitting model. The conduct, cognitive, and hyperactivity problems of the ADHD symptoms in each domain were associated positively with the depressive symptoms, with the depressive symptoms being associated with suicidal ideation. This initially proposed model represented an acceptable fit to the data (root mean square error of approximation, RMSEA=0.077; normed fit index, NFI=0.998; non-NFI, NNFI=0.990; comparative fit index, CFI=0.998). The inclusion of a direct path from the conduct problems of ADHD symptoms to suicidal ideation significantly improved the model fit (RMSEA=0, NFI=1, NNFI=1, CFI=1). The results of our study suggest that depressive symptoms partially mediate the relationship between ADHD symptoms and suicidal ideation, and that the conduct problems of ADHD symptoms are associated with suicidal ideation both directly and indirectly via the depressive symptoms in Korean female adolescents. Depression and Anxiety, 2008. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to examine the clinical validities and efficiencies of the Child Behavior Checklist (CBCL) and the ADHD Rating Scale-IV (ARS) in identifying children with attention-deficit hyperactivity disorder (ADHD) in Korean community-based samples.Method: A large sample of elementary school students (n = 1668) participated in this study. We used the CBCL and the ARS as the screening instruments. Diagnoses were determined by clinical psychiatric interviews and confirmed by DSM-IV-based structured interviews.Results: Of the 46 subjects who underwent clinical psychiatric interviews, 33 were diagnosed as having ADHD. A T score of 60 with regard to the Attention Problems profile of the CBCL resulted in a reasonable level of sensitivity or positive predictive value in the diagnosis of ADHD. In both the parent and teacher reports of the ARS, 90th percentile cut-off points resulted in a high level of predictive value. The highest levels of specificity and positive predictive value were obtained when we combined the CBCL (T > or = 60 in Attention Problems) and the ARS (parent-teacher total > or = 90th percentile) reports.Conclusions: These findings suggest that the combined use of the CBCL and the ARS could serve as a rapid and useful clinical method of predicting or even diagnosing children with ADHD in epidemiologic case definitions. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The association between low blood lead levels (<5μg/dL) and the inattention-hyperactivity symptoms and neurocognitive profiles of school-aged Korean children was investigated. Methods: We measured blood lead levels in 256 Korean children aged 8–10years. Teachers completed the Attention-Deficit Hyperactivity Disorder Rating Scale (T-ARS)-IV to assess inattentive and hyperactive symptoms. Parents completed the Korean version of the Learning Disability Evaluation Scale (K-LDES). Children performed neurocognitive tests [The Continuous Performance Test (CPT), the Children''s Color Trails Test, and the Stroop Color and Word Test (SCWT)]. Results: A linear regression analysis indicated that the blood lead concentrations were associated with the inattention scores [B =4.8, S.E.=1.6, 95% confidence interval (CI): 1.5–8.0], the hyperactivity subscores (3.1, 1.4, 0.3–5.9), and the total score (7.9, 2.9, 2.1–13.6) on the T-ARS; the number of omission errors on the CPT (20.6, 7.1, 6.5–34.6); the listening (−1.4, 0.7, −2.8 to −0.1), reading (−2.1, 0.7, −3.4 to −0.7), writing (−2.0, 0.7, −3.4 to −0.6), spelling (−2.2, 0.7, −3.7 to −0.7), and calculating (−1.8, 0.7, −3.1 to −0.4) scores on the K-LDES; and the color–word score on the SCWT (−6.7, 3.4, −13.3 to −0.1). A logistic regression analysis indicated that the probability of inattentive and hyperactive symptoms was increased with higher blood lead levels in boys with an odds ratio of 2.768 [B =1.018, S.E.=0.487, p =0.036, 95% CI: 1.066–7.187]. Conclusion: This study suggests that even low blood lead levels (<5μg/dL) are associated with inattentive and hyperactivity symptoms and learning difficulties in school-aged children. [Copyright &y& Elsevier]

Abstract: To determine the association between arginine vasopressin receptor 1A gene (AVPR1A) and autism spectrum disorders (ASDs), we examined 3 single nucleotide polymorphisms (SNPs), namely, rs7294536, rs3759292, and rs10877969, in the promoter region of AVPR1A by using a family-based association test (FBAT) in 151 Korean trios. Our results demonstrated a statistically significant association between autism and SNPs (additive model: rs7294536, χ 2 =9.328, df =2, P =0.002; rs10877969, χ 2 =11.529, df =2, P <0.001) as well as between autism and haplotype analysis (additive model: χ 2 =14.122, df =3, P =0.003). In addition, we found that ADI-R scores calculated by using a diagnostic algorithm for failure to develop peer relationships (A2) were higher in subjects having the AA genotype than in subjects having the AG and GG genotypes of rs7294536. Thus, our study provides evidence for a possible association between these SNPs and the phenotype of ASDs. [Copyright &y& Elsevier]

Abstract: Objective: The aim of this case series was to assess the effectiveness and tol-erability of aripiprazole in Korean children and adolescents with early-onset schizophrenia spectrum (EOSS) disorder. Methods: The medical records of aripiprazole-treated patients with EOSS were retrospectively reviewed. Changes in illness severity were measured using the Clinical Global Impression-Severity of Illness (CGI-S) and Clinical Global Impression-Improvement (CGI-I) scales. Results: Data from 22 children and adolescents were included (12 girls, 10 boys; mean [SD] age, 14.0 [2.4] years). The mean (SD) dosage of aripiprazole was 19.8 (9.4) mg/d (median, 18.7 mg/d; mode, 15, 30 mg/d), and the range of treatment duration was 21 to 838 days. Mean (SD) CGI-S score improved significantly from baseline to end point (from 5.7 [0.7] to 4.3 [1.4]; P < 0.001). Based on changes in chart-extracted CGI-I scores, significantly greater improvement was associated with negative symptoms compared with positive symptoms (U = 25.5; P = 0.028; r = −0.47). Aripiprazole was discontinued due to insufficient effect in 5 patients (22.7%) and treatment-emergent adverse events in 3 patients (13.6%). Conclusion: The results from this small study suggest that aripiprazole was moderately effective in reducing psychotic symptoms in these Korean children and adolescents with EOSS. [Copyright &y& Elsevier]

Abstract: Several studies examining the association between G72/G30 polymorphisms and schizophrenia in cohorts of various ethnic origins have recently been reported. The aim of the current study was to examine the genetic influence of the G72/G30 polymorphisms in the Korean population. Nine G72/G30 single-nucleotide polymorphisms (SNPs) were genotyped in 388 patients with schizophrenia and 367 normal controls from the Korean population. Based on statistical analyses, the positive associations of previous studies of other populations were not replicated in the present study. However, 2 of the 9 tested SNPs, rs778294 and rs947267, were found to be associated with the risk of schizophrenia after correction for multiple testing (P cor =0.03 and P cor =0.04, respectively). The rs778294 SNP, taken singly, had not been found to be associated with schizophrenia in previous studies, and the second SNP, rs947267, showed an opposite direction of genetic effect on schizophrenia risk here than in a previous study. Our association results were not consistent with those found in other populations, and, thus could be chance findings. Therefore, further studies with larger sample sizes are needed to confirm a risk allele for this gene if it exists. [Copyright &y& Elsevier]

Abstract: This study examined the association of the reticulon 4 receptor (RTN4R) gene with schizophrenia and smooth pursuit eye movement (SPEM) abnormality in a Korean population. Although we failed to provide convincing evidence that RTN4R is associated with schizophrenia development and SPEM impairment, our findings may be useful for further genetic studies. [Copyright &y& Elsevier]

Schizophrenia is a debilitating mental disorder with a high heritability rate. Located on chromosome 1p31.3, the human cAMP-specific 3',5'-cyclic phosphodiesterase 4B (PDE4B) gene has been considered as an important candidate gene for the risk of schizophrenia. Several genetic association studies reported the association between PDE4B polymorphisms and the risk of schizophrenia in Caucasian, African American, Indian, and Japanese populations. The aim of this study is to examine the association of PDE4B variations with schizophrenia and smooth pursuit eye movement (SPEM) abnormality in a Korean population. A case-control association analysis was carried out by comparing the genotype distribution of eight PDE4B polymorphisms between 457 schizophrenia patients and 386 normal healthy subjects. Differences in the frequency distribution of PDE4B single nucleotide polymorphisms (SNPs) and haplotypes were analyzed by logistic regression analyses controlling for age as a covariate. Statistical analyses revealed nominal significant associations of rs1040716, rs472952, rs1321177, and rs2144719 with the risk of schizophrenia (p = 0.02~0.05). The rs11208756 polymorphism showed a nominal significant association with SPEM abnormality (p = 0.05). In a meta-analysis with Japanese and Korean populations, three SNPs (rs472952, rs1040716, and rs2180335) revealed significant associations with schizophrenia (meta-p value = 0.0038~0.019). Our results support previously reported association of PDE4B variations with schizophrenia in other populations. The findings in this study add a new evidence for the involvement of PDE4B gene in schizophrenia etiology.

The purpose of this study was to investigate a possible association between norepinephrine genes and cardiovascular side effects of the Osmotic Controlled-Release Oral Delivery System-methylphenidate (OROS-MPH) in Korean children with attention-deficit/hyperactivity disorder (ADHD). One hundred and one children with ADHD (8.7 ± 1.7 years) were recruited from child psychiatric centers at six university hospitals in South Korea. All participants were drug-naive ADHD children treated with OROS-MPH for 12 weeks. During the treatment period the investigators titrated the OROS-MPH dosage on the basis of symptom severity and side effects. Resting heart rate (HR), diastolic blood pressure (DBP), and systolic blood pressure (SBP) were examined before and after treatment. The percentage change score (post-treatment - pretreatment/pretreatment × 100) of each parameter was calculated. Genotyping of SLC6A2 -3081(A/T) and G1287A, and alpha-2A-adrenergic receptor (ADRA2A) MspI and DraI polymorphisms was performed. Clinically significant changes were not found in cardiovascular monitoring during the course of treatment. An increase of HR after OROS-MPH treatment was found to be statistically significant (t = 3.54, p = 0.001). Changes in SBP and DBP were not significant and no specific change was found in the ECGs. However, an additive regression analysis demonstrated a significant association between SLC6A2 -3081(A/T) and percentage change in HR post-treatment (p = 0.01) after controlling for age, gender, dosage of MPH and response and baseline pulse rate. Children with ADHD having the T/T genotype of SLC6A2 showed a 12.5% increase in HR compared to baseline, whereas children with the A/T or A/A genotype showed a 3.5% and 2.5% increase after OROS-MPH treatment, respectively. There was also a significant association between the ADRA2A MspI genotype and percentage change of DBP post-treatment after controlling for age, gender, dosage of MPH and response and baseline DBP (p = 0.009). Children with ADHD having the C/C genotype of ADRA2A MspI showed an 18.5% increase in DBP compared to baseline, but children with the G/G or G/C genotype showed a 0.2% decrease after OROS-MPH treatment. The overall cardiovascular effects of OROS-MPH were modest. However, our findings show a positive association between norepinephrine-related gene polymorphisms and cardiovascular response induced by MPH in Korean children with ADHD. Consideration must be given to such children or adults with specific norepinephrine-related genotypes, especially if they show significant changes in HR or DBP after OROS-MPH administration.

The zinc finger DHHC domain-containing protein 8 (ZDHHC8) is located in the 22q11 microdeletion region and may contribute to the behavioral deficit associated with 22q11 deletion syndrome. Although polymorphisms of ZDHHC8 have been reported to be associated with the risk of schizophrenia, those associations are still controversial. This study was performed to validate the genetic association of ZDHHC8 polymorphisms with the risk of schizophrenia, and also to scrutinize the association with smooth pursuit eye movement (SPEM) abnormality in a Korean population. Five SNPs of ZDHHC8 were genotyped by TaqMan assay. Their genetic effects on the risk of schizophrenia were analyzed in 354 patients and 396 controls using allele-based chi(2) analyses. Association of ZDHHC8 polymorphisms with SPEM abnormality among 166 schizophrenic patients were analyzed using multiple regressions. No ZDHHC8 polymorphisms were found to be associated with the risk of schizophrenia. However, four SNPs and one haplotype (ht4) were strongly associated with the risk of SPEM abnormality even after multiple correction (P = 0.00005-0.0007, P(corr) = 0.0001-0.002). The results of the present study provide the first evidence that ZDHHC8 on the 22q11 locus might have influence on SPEM function of schizophrenia patients in a Korean population and may provide a new clue for understanding differential effects of candidate genes in schizophrenia., ((c) 2010 Wiley-Liss, Inc.)

Objective: The aims of this study were to investigate the prevalence, associated co-morbid psychiatric disorders and behavioral/emotional problems associated with the subtypes of specific phobia in children and adolescents., Methods: A total of 2673 randomly selected children and adolescents from Seoul, Korea were assessed using the parent version of the Diagnostic Interview Schedule for Children (DISC-IV) and Children's Behavior Checklist (CBCL). We analyzed differences in psychiatric co-morbidities and CBCL profiles among the subtypes of specific phobia., Results: The 1-year prevalence of specific phobia was 7.9% (95% CI 7.63-8.17). Animal phobia was associated with anxiety disorder (OR 8.68, 95% CI 1.91-39.51) and oppositional defiant disorder (OR 2.55, 95% CI 1.27-5.12). Nature-environment phobia was associated with anxiety disorder (OR 25.70, 95% CI 6.16-107.10). Blood-injection-injury phobia showed associations with attention-deficit/hyperactivity disorder (ADHD: OR 6.74, 95% CI 2.81-16.15). Subjects with nature-environment phobia scored higher than did controls on the anxious/depressed, social problems, attention problems, and total behavioral problem profiles of the CBCL. Subjects with blood-injection-injury phobia scored significantly higher than did controls on the attention problems, aggressive behaviors, and externalizing problem profiles., Conclusions: Contrary to animal phobias, nature-environment and blood-injection-injury phobias were associated with various behavioral and emotional problems and approximately correlated to their co-morbid psychiatric disorders. Among these subtypes, significant differences were found in demographic characteristics, co-morbid psychiatric disorders, and emotional/behavioral problems. These findings suggest that distinctive clinical characteristics might be related with different subtypes of specific phobia and clinician must consider psychiatric co-morbidities when treating children & adolescents with specific phobia., ((c) 2010 Elsevier Ltd. All rights reserved.)

Background: Most studies on temperamental and behavioral/emotional characteristics of oppositional defiant disorder (ODD) did not rule out the effect of comorbid attention-deficit/hyperactivity disorder (ADHD). The main objective of this study was to identify the temperamental and psychopathological patterns of ODD independent of comorbid ADHD. We also aimed to compare the patterns of temperament and psychopathology between ODD with and without ADHD., Method: Parents of 2673 students, randomly selected from 19 representative schools in Seoul, Korea, completed the Diagnostic Interview Schedule for Children Version IV. Among 118 children and adolescents with ODD diagnosed by the Diagnostic Interview Schedule for Children Version IV, the parents of 94 subjects (mean age, 10.4 +/- 3.0 years) and the parents of a random sample of 94 age- and gender-matched non-ODD/non-ADHD children and adolescents completed the parent's version of the Child Behavior Checklist (CBCL) and the Junior Temperament and Character Inventory., Results: Subjects with ODD showed temperament and character profiles of high Novelty Seeking, low Self-directedness, and low Cooperativeness, a distinct pattern on the CBCL, and were at increased risk for anxiety and mood disorders compared to the controls after controlling for the effect of comorbid ADHD. The children and adolescents with both ODD and ADHD showed decreased levels of Persistence and Self-directedness and higher scores on 4 subscales of the CBCL (Anxious/Depressed, Attention Problems, Delinquent Behaviors, and Aggressive Behaviors) compared to those with ODD only., Conclusions: Oppositional defiant disorder is associated with specific temperamental and behavioral/emotional characteristics, independent of ADHD. Moreover, the results of this study support that co-occurring ADHD and ODD have differentially higher levels of behavioral and emotional difficulties., (Copyright 2010 Elsevier Inc. All rights reserved.)

Schizophrenia is a multifactorial disorder characterized by the contribution of multiple susceptibility genes that may act in conjunction with epigenetic processes and environmental factors. The catechol-O-methyltransferase (COMT) gene, which is located in the 22q11 microdeletion, has been considered as a candidate gene for schizophrenia because of its ability to degrade catecholamines, including dopamine. In a genetic analysis, neurophysiological endophenotype in schizophrenia, such as smooth pursuit eye movement (SPEM) disturbance, is considered to be a good trait marker, because it may be under more direct genetic control. This study was performed to examine the genetic association of COMT polymorphisms with the risk of schizophrenia and SPEM abnormality in a Korean population. Six single-nucleotide polymorphisms of COMT were genotyped by TaqMan assay. Their genetic effects on the risk of schizophrenia were analyzed in 354 patients and 396 controls using chi(2) analyses. Among the schizophrenic patients, 166 subjects were selected for association analyses of COMT polymorphisms with SPEM abnormality. From the six COMT polymorphisms, rs6267 showed an association with the reduced risk of schizophrenia after correction (P(corr) = 0.02). In analysis of SPEM abnormality, no significant associations were detected with COMT polymorphisms. The results of the present study provide the evidence that in a Korean population, COMT on the 22q11 locus is likely involved in the development of schizophrenia, but not in the SPEM function abnormality.

Objectives: The aims of this study were to examine the symptoms of posttraumatic stress and anxiety/depression in Korean children after direct or indirect exposure to a single incident of trauma during a fire-escape drill and to assess the incidence of psychiatric disorders in this population., Method: A total of 1,394 students who attended the elementary school at which the traumatic event took place were evaluated using self-administered questionnaires (the Child Posttraumatic Stress Disorder-Reaction Index [CPTSD-RI], State Anxiety Scale of the State-Trait Anxiety Inventory for Children [STAIC], and Children's Depression Inventory [CDI]), as well as structured diagnostic interviews (Diagnostic Interview Schedule for Children, Version-IV [DISC-IV]) at 2 days (time point 1), 2 months (time point 2), and 6 months (time point 3) after the incident. The 335 students who witnessed the accident were defined as the direct-exposure group, and the remaining students (n = 1,059) were defined as the indirect-exposure group. The study was conducted from May to November 2007., Results: At time point 1, the prevalence of severe posttraumatic stress disorder (PTSD), anxiety, and depressive symptoms was 18.2%, 5.5%, and 3.4%, respectively. The prevalence of severe PTSD symptoms, as measured by the CPTSD-RI, was significantly higher in the direct-exposure group than in the indirect-exposure group (36.6% vs 12.7%, respectively; P < .001). At time point 2, the prevalence of severe PTSD symptoms was 7.4% (14.0% in the direct-exposure group and 4.9% in the indirect-exposure group, P < .001). The mean total CPTSD-RI score was significantly higher (P < .001) in the direct-exposure group than in the indirect-exposure group. At time point 3, thirty-eight of the 58 subjects (65.5%) evaluated with the DISC-IV in the direct-exposure group had 1 or more of the 7 anxiety/depressive disorders assessed, including subthreshold diagnoses. Among the diagnoses meeting full DSM-IV criteria for each disorder, agoraphobia was the most prevalent (22.4%), followed by generalized anxiety disorder (13.8%), separation anxiety disorder (6.9%), PTSD (5.2%), and social phobia (5.2%). When the subthreshold diagnoses were considered along with the full syndrome diagnoses, separation anxiety disorder was the most common diagnosis (41.4%), followed by agoraphobia (34.5%), obsessive-compulsive disorder (22.4%), PTSD (20.7%), and social phobia (20.7%)., Conclusions: The results of this study provide important evidence that various anxiety/depressive disorders, in addition to PTSD, might follow after direct or indirect exposure to trauma. Our findings highlight the importance of comprehensive screening for psychiatric problems in children exposed to trauma of any scale., (©Copyright 2009 Physicians Postgraduate Press, Inc.)

Objective: The main objective of this study was to investigate the comorbid disorders and temperamental profiles of full syndrome and subthreshold attention-deficit/hyperactivity disorder (ADHD)., Method: A sample of 2,493 students was randomly selected from six representative elementary schools in Seoul, Korea. Among 245 children with full syndrome and subthreshold ADHD diagnosed by the diagnostic interview schedule for children-4th version, parents of 185 subjects (mean age 9.0 +/- 1.7 years) and of a random sample of 185 age- and gender-matched non-ADHD children have completed the parent's version of the children behavior checklist (CBCL) and the juvenile temperament and character inventory (JTCI)., Results: The prevalence rates of full syndrome and subthreshold ADHD were, respectively, 5.90% (95% confidence interval = 4.74-7.06) and 9.00% (95% confidence interval = 7.58-10.41). Subthreshold ADHD cases did not differ from full syndrome ADHD in any JTCI profile, showing high novelty seeking/low persistence/low self-directedness than controls. Subthreshold ADHD also showed increased risk for externalizing disorders and higher scores in eight CBCL scales (somatic complaints, anxious/depressed, social problems, attention problems, delinquent behaviors, aggressive behaviors, externalizing problems and total behavioral problems) compared to the controls., Conclusions: These results support the clinical relevance of subthreshold ADHD in Asian culture. Increased clinical awareness for children with subthreshold ADHD is needed.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a strong genetic component and environmental risk factors. Nitric oxide (NO), which is produced by nitric oxide synthase (NOS), may play a role in the development of ASD. We genotyped nine single nucleotide polymorphisms (SNPs) in the NOS-I gene and nine SNPs in the NOS-IIA gene and carried out the transmission disequilibrium test (TDT) and haplotype analysis in 151 Korean ASD trios. We found preferential transmission of the A allele of rs8068149 (P = 0.039) and G allele of rs1060826 (P = 0.035) of NOS-IIA in ASD and the haplotype analysis revealed that the two haplotypes had significant associations (P = 0.014 and 0.031, respectively). The behavioral subdomain score of failure to use nonverbal behaviors to regulate social interaction in Autism Diagnostic Interview-Revised (ADI-R) was significantly higher in subjects with the GG or AG allele in rs1060826 of NOS-IIA compared to those who had the AA allele (P = 0.027). These results provide significant but weak evidence for an association between NOS-IIA and ASD in the Korean population., (2008 Wiley-Liss, Inc.)

The purpose of this study was to evaluate the temperament and character of children and adolescents with anxiety disorders in samples from Korean community. The study subjects were children and adolescents diagnosed with social phobia (n = 66), separation anxiety disorder (n = 47), specific phobia (n = 415), and obsessive-compulsive disorder (n = 42) with the diagnostic interview schedule for children, version IV (DISC-IV) in representative community samples. Among these, we excluded other psychiatric disorder comorbid samples, with the exception of externalizing disorders. We assessed the subjects of each anxiety group using the junior temperament and character inventory (JTCI). Social phobias were significantly associated with high harm avoidance and low self-directedness on the JTCI. The association of specific phobias with high harm avoidance, and obsessive-compulsive disorder with low self-directedness was also significant. Separation anxiety disorder was not associated with any temperament and character on the JTCI. Children and adolescents with anxiety disorders have different temperaments and character profiles in accordance with diagnostic groups, which implies the specific pathophysiological mechanism of each anxiety disorder.

Objective: Treatment resistance in early onset schizophrenia (EOS) is one of the most challenging problems in child and adolescent psychiatry. We retrospectively examined the therapeutic dosage, clinical response, and side effect profiles of long-term clozapine treatment in Korean children and adolescents with refractory EOS or very early onset schizophrenia (VEOS)., Method: 26 refractory patients treated with clozapine for more than 1 year were analyzed. Efficacy was determined by comparing hospitalization rate and duration, before and after clozapine treatment. Tolerability was assessed through review of documented adverse events., Results: A significant reduction in hospital days per year was observed in 25 (96.2%) patients after clozapine treatment compared to before clozapine. Long-term benefit of the treatment was supported by a further reduction of the hospitalization rate in 14 patients treated with clozapine for more than 3 years. Neutropenia developed in 26.9% patients at 1 year and there was no agranulocytosis. Overall, eight male patients (8/12, 66.7%) and one female patient (1/14, 7%) developed neutropenia and out of the nine patients, seven patients were maintained and two patients were successfully rechallenged on clozapine., Conclusion: These findings suggest that long-term clozapine treatment may effectively reduce the amount of time Asian patients with refractory EOS or VEOS spend in the hospital. However careful monitoring of adverse events is required.

Previous studies have demonstrated that the MspI and DraI polymorphisms at the alpha-2A-adrenergic receptor gene (ADRA2A) are associated with ADHD. However, few studies have been designed to ascertain the association between the ADRA2A genotypes and the performance on neurocognitive measures in ADHD. The aims of this study were to examine the association of the ADRA2A MspI and DraI polymorphisms with ADHD in Korean subjects, and to determine the relationship between the genotypes of these two polymorphisms and the candidate endophenotypes, as measured by the continuous performance test (CPT). In a case-control study, we assessed 186 ADHD probands and 150 normal controls. One hundred eight trios were studied in a family based association analysis. The transmission disequilibrium test (TDT) analysis showed preferential transmission of the C allele of the DraI polymorphism (chi(2) = 5.88, P = 0.015). In the haplotype analyses, a trend of over-transmission of haplotype C/C was observed (chi(2) = 3.80, P = 0.051). The homozygous subjects for the C allele (C/C genotype) at the DraI polymorphism showed a trend toward a higher mean T-score with respect to the response time variability profiles of the CPT than did those with the other genotypes (C/T + T/T genotypes; P = 0.042). The homozygous subjects for the G allele (G/G genotype) at the MspI polymorphism showed a tendency to have a lower mean T-score with respect to the response time variability profiles of the CPT (P = 0.068). The results of this study provide important evidence for the involvement of the ADRA2A MspI and DraI polymorphisms in the etiology of ADHD in Korean subjects. In addition, our results provide evidence for the possible role of these two polymorphisms in ADHD symptom expression, such as increased response time variability., (2008 Wiley-Liss, Inc.)

Cyclooxygenase-2 (Cox-2) is an inducible enzyme involved in neuroplasticity and the neuropathology of the central nervous system. This study evaluated the relationship between autism spectrum disorders (ASDs) and polymorphisms of PTGS2 (the gene encoding Cox-2) with 151 Korean family trios including children with ASDs. We found that the A allele of rs2745557 was preferentially transmitted in ASDs (p < 0.01) and that the GAAA haplotype was significantly associated with ASDs (p < 0.01). We also observed statistically significant associations between each genotype and the specific symptom domain scores of ADOS and ADI-R, including communication, qualitative abnormalities in reciprocal social interaction, and overactivity/agitation.

Aims: The purpose of the present study was to assess patterns of temperament and character in a clinical sample of Korean children with attention-deficit hyperactivity disorder (ADHD) and to investigate the relationship between patterns of temperament and character and the severity of ADHD symptoms., Methods: Fifty-one children who met DSM-IV criteria for ADHD and 51 age- and sex-matched healthy comparison subjects completed the Junior Temperament and Character Inventory (JTCI) and the DuPaul's ADHD Rating Scale (ARS-IV)., Results: Children with ADHD had significantly higher scores of Novelty Seeking and lower scores of Self-directedness in both parents' rating and children's self-rating. In addition, low Self-directedness scores predicted higher total scores of ARS-IV., Conclusions: In a clinical sample of Korean children with ADHD, a distinct pattern of temperament and character was found. The current findings suggest that low Self-directedness may be related to the severity of ADHD symptoms.

Neurobiological and pharmacological research has suggested that dysregulation of the central noradrenergic systems might be involved in the pathophysiology of attention deficit hyperactivity disorder (ADHD). Previous studies have demonstrated that the norepinephrine transporter gene (SLC6A2) is associated with ADHD. The aims of this study were to examine the association of the SLC6A2 G1287A and -3081(A/T) polymorphisms with ADHD in Korean children and adolescents, and to determine the relationships of the genotypes of these two polymorphisms with continuous performance test results and the Junior Temperament and Character Inventory profiles of ADHD. In a case-control study, we assessed 186 ADHD probands and 150 normal controls; 109 trios were studied in a family-based association analysis. There were no significant differences in the genotype or allele frequencies of the SLC6A2 G1287A and -3081(A/T) polymorphisms between the ADHD and control groups (p > 0.05). In the transmission disequilibrium test analyses, there was no evidence for biased transmission of any of the alleles of the SLC6A2 G1287A and -3081(A/T) polymorphisms. In the haplotype analyses of these two polymorphisms, the global and individual chi(2) tests showed no significant associations between any of the haplotypes and ADHD. There were no significant differences with respect to the continuous performance test results and the Junior Temperament and Character Inventory profiles in the ADHD probands according to the genotypes of the SLC6A2 G1287A and -3081(A/T) polymorphisms. Our findings do not support SLC6A2 as a major genetic susceptibility factor in ADHD., (Copyright 2008 S. Karger AG, Basel.)

Objective: The aim of this study was to examine whether there is a difference in the behavioural characteristics of community- and clinic-based children with attention-deficit hyperactivity disorder (ADHD) in Korea., Method: The study included 75 community-based and 72 clinic-based subjects with ADHD. The parents of all the children completed the parent versions of the Child Behavior Checklist (CBCL)., Results: The community-based ADHD subjects scored significantly higher (P < 0.01) than clinic-based subjects in the Somatic Complaints and Delinquent Behaviour profiles of the CBCL. The community-based subjects with ADHD, combined subtype, showed significantly higher mean scores in the Somatic Complaints (P < 0.01) and Thought Problems (P < 0.05) profiles than the clinic-based subjects with ADHD, combined subtype., Conclusion: These findings suggest the possibility of an increased incidence of behavioural or emotional problems in community-based ADHD subjects when compared with clinic-based subjects in Korea.

The dopamine transporter gene (DAT1) has been extensively studied as one of the candidate genes in attention-deficit/hyperactivity disorder (ADHD). Several studies have reported on the association between the DAT1 10-repeat allele and cognitive variables in ADHD. However, few studies have been designed to ascertain the association between DAT1 genotypes other than the 10-repeat allele and cognitive endophenotypes in ADHD. The aim of this study was to examine the relationship between the DAT1 genotypes and the candidate endophenotypes, inattention and impulsivity symptoms, as measured by the continuous performance test (CPT), in a Korean sample of 85 children diagnosed with DSM-IV ADHD. Compared to the normal control group, the frequencies of the 9/10 genotype were significantly higher in the ADHD probands (chi(2)=13.45, p=0.02, OR=4.12, 95% CI: 2.21-12.34) and parents of probands (chi(2)=11.60, p=0.03). The 9-repeat allele frequencies were significantly higher in the ADHD probands (chi(2)=11.55, p=0.03, OR=4.43, 95% CI: 1.55-11.78) and parents of probands (chi(2)=12.70,p=0.03) than the normal control group. Compared to the ADHD probands without the 9-repeat allele (n=74), the mean T-score, with regard to the commission errors of the CPT, was significantly higher (p<0.05) in the ADHD probands with the 9-repeat allele (n=11). Compared to the ADHD probands with other DAT1 genotypes, the mean T-score, with respect to the commission errors of the CPT, was significantly higher in the ADHD probands with the 9/10 genotype (p<0.05). The results of this study suggest the possibility of an association between the DAT1 9-repeat allele and the impulsivity phenotype of ADHD.

The purpose of this study is to examine the behavioral and developmental characteristics of children with inv(9). This case control study included 12 inv(9) subjects and 45 normal students. All of the subjects, together with their parents, underwent a psychiatric interview and parent questionnaire consisting of a Child Behavior Checklist (CBCL). The mean scores with regard to the social problems and total problems profiles of the CBCL were significantly higher in the inv(9) group than in the normal control group. The inv(9) group exhibited language and motor developmental delay. These findings suggest that there is a possibility of inv(9) being associated with child developmental or behavioral problems.

The purpose of this study was to examine the psychiatric characteristics of children with Prader-Willi syndrome in Korea, focusing particularly on their behavioral problems and obsessive-compulsive spectrum symptoms. Fourteen patients with Prader-Willi syndrome, together with their parents, underwent a psychiatric interview and parent questionnaire consisting of a Child Behavior Checklist. Twenty-four patients with mental retardation and 45 normal students were selected as control groups. Compared with the normal control group, the rates of inclusion in the clinical range and the mean scores with regard to social problems, thought problems, attention problems, delinquent behavior, aggressive behavior, externalizing problems, and total problems profiles were significantly higher (P < .01) in the Prader-Willi syndrome group according to the results of the Child Behavior Checklist. Compared with the mental retardation group, there was a statistically significant (P < .05) difference in the delinquent behavior profile. Comparing selected Child Behavior Checklist items related to obsessive-compulsive spectrum symptoms, the Prader-Willi syndrome group showed significantly more (P < .05) compulsion, skin picking, and stealing than the mental retardation or normal control groups. These findings suggest that children with Prader-Willi syndrome in Korea have many behavioral problems, including obsessive-compulsive spectrum symptoms, needing proper psychiatric attention and treatment. This is the first study in Korea to evaluate the psychiatric and behavioral characteristics of children with Prader-Willi syndrome.

In order to develop a structured and objective diagnostic instrument, authors completed: (1) the translation and back translation of the Korean version of the Kiddie-Schedule for Affective Disorders and Schizophrenia - Present and Lifetime Version (K-SADS-PL) and (2) the examination of its validity and reliability of the K-SADS-PL-Korean version (K-SADS- PL) when used with Korean children. A total of 91 study subjects were recruited from child and adolescent psychiatry outpatient clinics. Clinical diagnoses were used as a gold standard for the examination of validity of K-SADS-PL-K. Consensual validity of threshold and sub-threshold diagnoses were good to excellent for attention-deficit/hyperactivity disorder (ADHD), fair for tic and oppositional defiant disorders, and poor to fair for anxiety and depressive disorders. Inter-rater and test-retest reliabilities were fair to excellent for ADHD and tic disorder. The significant correlations between the K-SADS-PL-K and Korean Child Behavior Checklist (K-CBCL) were found, which provided additional support for the concurrent validity of the K-SADS-PL-K. Sensitivities varied according to the diagnostic categories, but specificities remained high over all diagnoses, suggesting that the K-SADS-PL-K is a desirable confirmatory diagnostic tool. The results of this study suggest that the K-SADS-PL-K is an effective instrument for diagnosing major child psychiatric disorders, including ADHD, behavioral disorders and tic disorders in Korean children. Future studies will examine the validity and reliability of the K-SADS-PL-K in larger samples, including adolescents and community samples on a variety of child and adolescent psychiatric disorders.

Tardive dyskinesia (TD) is usually regarded as one of the most serious side-effects of the long-term usage of neuroleptics due to its high prevalence and potentially irreversible nature. Previously, several genetic polymorphisms were investigated for an association with TD in various ethnic populations. Among them, the Ser9Gly variant in the MscI restriction site of the dopamine D3 receptor gene was reported to be associated with TD. We have investigated the association of Ser9Gly polymorphism of the dopamine D3 receptor gene with TD in Korean schizophrenics. The frequencies of the genotypes of Ser/Ser, Ser/Gly and Gly/Gly in 54 schizophrenic patients without TD were 21 (38.9%), 33 (61.1%) and 0 (0%), while the corresponding frequencies in 59 schizophrenic patients with TD were 25 (42.4%), 28 (47.5%) and 6 (10.1%). We have found a significant genotypic association of the Gly/Gly genotype with TD in Korean schizophrenics (P = 0.028, two-tailed Fisher's exact test). However, there was no significant allelic association of the Ser9Gly allele with TD (chi2 = 0.288, d.f. = 1, P = 0.591) and there was no significant difference in the Abnormal Involuntary Movement Scale score between the three genotypic groups (P = 0.071, anova). In conclusion, we suggest that Gly/Gly homozygotes in the MscI polymorphic site of the dopamine D3 receptor gene may cause some change in the function of the dopamine D3 receptor and may be involved the pathogenesis of TD.