Psychometric properties and factor structure of the Korean version of the screen for child anxiety related emotional disorders (SCARED).

BACKGROUND: The aim of this study was to examine the psychometric properties of the Korean version of Screen for Child Anxiety Related Emotional Disorders (SCARED) on a sample of Korean youths and to examine the cross-cultural differences in adolescents' anxiety. METHODS: Our study included 147 adolescents (ages 12-17, 92 girls), 93 with major depressive disorder and 54 as controls. Participants were evaluated using the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL), SCARED, Child Behavior Checklist (CBCL), Disruptive Behavioral Disorder Scale (DBD) and Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS). Pearson's r and Cronbach's α values of the SCARED were calculated, and exploratory factor analysis was conducted. RESULTS: The Korean SCARED scores were correlated with the total anxiety scores of K-SADS-PL (r = 0.74) and the CBCL anxious/depressed subscale scores (r = 0.35). Results showed a five-factor structure with good internal consistency, in which some items were loaded on different factors compared to previous studies. CONCLUSIONS: The Korean SCARED demonstrated promising psychometric properties, and could be a valid scale for screening anxiety symptoms in primary care. The fact that different items comprised the factors may reflect the cultural difference between United States and Korea in experiencing anxiety.

Moderating effects of depressive symptoms on the relationship between problematic use of the Internet and sleep problems in Korean adolescents.

BACKGROUND: Adolescence is a period of marked sleep pattern changes and sleep problems, which may result from both endogenous and exogenous factors. Among the various factors affecting adolescent sleep, depression and problematic Internet use (PIU) have received considerable attention. We examined if there is a different PIU effect on sleep between depressed group and non-depressed groups. METHODS: Data for a total of 766 students' between 7th and 11th grades were analyzed. We assessed various variables related sleep to problems and depression and compared those variables between an adolescent group with problematic Internet use (PIUG) and an adolescent group with normal Internet use (NIUG). RESULTS: One hundred fifty two participants were classified as PIUG, and 614 were classified as NIUG. Compared with the NIUG, the members of the PIUG were more prone to insomnia, excessive daytime sleepiness and sleep-wake behavior problems. The PIUG also tended to include more evening types than the NIUG. Interestingly, the effect of Internet use problems on sleep problems appeared to be different according to the presence or absence of the moderating effect of depression. When we considered the moderating effect of depression, the effect of Internet use problems on sleep-wake behavior problems, insomnia and excessive daytime sleepiness increased with increasing Young's Internet Addiction Scale (IAS) scores in the non-depressed group. However, in the depressed group, the effects of Internet use problems on sleep-wake behavior problems and insomnia did not change with increasing Internet use problems, and the effect of Internet use problems on excessive daytime sleepiness was relatively decreased with increasing Internet use problems in the depressed group. CONCLUSIONS: This study demonstrated that the effect of PIU on sleep presented differently between the depressed and non-depressed groups. PIU is associated with poorer sleep in non-depressed adolescents but not in depressed adolescents. This finding might be observed because PIU may be the biggest contributor to sleep problems in the problematic Internet user without depression, but in the problematic Internet user with depression, depression might be a more important contributor to sleep problems; thus, the influence of PIU on sleep effect might be diluted.

COMT genotype affects brain white matter pathways in attention-deficit/hyperactivity disorder.

Increased dopamine availability may be associated with impaired structural maturation of brain white matter connectivity. This study aimed to derive a comprehensive, whole-brain characterization of large-scale axonal connectivity differences in attention-deficit/hyperactivity disorder (ADHD) associated with catechol-O-methyltransferase gene (COMT) Val158Met polymorphism. Using diffusion tensor imaging, whole-brain tractography, and an imaging connectomics approach, we characterized altered white matter connectivity in youth with ADHD who were COMT Val-homozygous (N = 29) compared with those who were Met-carriers (N = 29). Additionally, we examined whether dopamine transporter gene (DAT1) and dopamine D4 receptor gene (DRD4) polymorphisms were associated with white matter differences. Level of attention was assessed using the continuous performance test before and after an 8-week open-label trial of methylphenidate (MPH). A network of white matter connections linking 18 different brain regions was significantly weakened in youth with ADHD who were COMT Met-carriers compared to those who were Val-homozygous (P < 0.05, family-wise error-corrected). A measure of white matter integrity, fractional anisotropy, was correlated with impaired pretreatment performance in continuous performance test omission errors and response time variability, as well as with improvement in continuous performance test response time variability after MPH treatment. Altered white matter connectivity was exclusively based on COMT genotypes, and was not evident in DAT1 or DRD4. We demonstrated that white matter connectivity in youth with ADHD is associated with COMT Val158Met genotypes. The present findings suggest that different layers of dopamine-related genes and interindividual variability in the genetic polymorphisms should be taken into account when investigating the human connectome.

Child and adolescent psychiatry in the Far East.

AIM: Despite the general consensus on the importance of youth mental health, the scarcity of child and adolescent mental health services is prominent all over the world. Child and adolescent psychiatry (CAP) postgraduate training can play a pivotal role in increasing access to youth mental health services. In comparison to Europe and North America, however, little is reported regarding CAP training in the Far East, one of the most dynamic and rapidly developing world regions with a very young population. This paper presents an original study on the current status of academic child and adolescent psychiatry training across the Far East. METHODS: We collected data from 17 countries in the Far East using an internally distributed questionnaire to the Consortium members invited for this study, consisting of leading academic child and adolescent psychiatrists in each country. RESULTS: Based on informants' input, we found an overall underdevelopment of CAP postgraduate training systems despite CAP's recognition as a subspecialty in 12 of 17 of the nations or functionally self-governing areas in the Far East. Paucity of official guidelines for CAP training was also evident. All informants reported a need for additional child and adolescent mental health professionals. CONCLUSION: There seems to be several obstacles to the development of CAP postgraduate training in the Far East, including stigma towards mental health issues and lack of funding. International collaboration is desired to develop evidence-based and culture-tailored CAP training systems.

The role of the brain-derived neurotrophic factor genotype and parenting in early life in predicting externalizing and internalizing symptoms in children with attention-deficit hyperactivity disorder.

BACKGROUND: We aimed to determine whether early parenting is associated with externalizing and internalizing symptoms in children with attention-deficit hyperactivity disorder (ADHD) and whether such an association is affected by the brain-derived neurotrophic factor (BDNF) val66met polymorphism. METHODS: The participants included 92 patients with ADHD aged 6-15 years. Measures of parenting in early life and externalizing and internalizing symptoms and the genotype of the BDNF Val66Met polymorphism were obtained. RESULTS: The degree to which the baby's autonomy was allowed was significantly and negatively correlated with the CDI scores in ADHD children (r = -0.38, p = 0.005). After adjusting for the child's gender, the child's age, the family's gross annual income, and the maternal education level, there was a significant interaction for the BDNF genotype and mother's positive feelings about caring in relation to the development of childhood anxiety/depression in ADHD children (F = 2.51, p = 0.011). CONCLUSIONS: Our results provide evidence of an interaction between the BDNF met allele and early parenting on the development of depression/anxiety symptoms.

Increased use of lethal methods and annual increase of suicide rates in Korean adolescents: comparison with adolescents in the United States.

BACKGROUND: The lethality of the suicide method is a strong risk factor for completed suicide. We examined whether the annual change in the pattern of suicide methods was related to the annual change in suicide rates among adolescents in South Korea and the United States. METHODS: We analyzed annual data for the 2000-2009 period for South Korea and the 2000-2008 period for the United States to examine time trends in the suicide rates and suicide methods of adolescents aged 10-19 years in two countries. Data on suicide methods were obtained from the World Health Organization (WHO) mortality database. RESULTS: Suicide rates among adolescents in the United States have remained relatively steady since 2000, whereas the suicide among Korean adolescents has increased. Between 2000 and 2009, the most common suicide method among Korean adolescents was jumping for boys and girls, whereas it was hanging for girls and firearms for boys in the United States. Along with the annual increase in suicide rates in South Korea, the incidences of jumping among males and hanging (and recently jumping) among females have increased steadily, whereas suicide by self-poisoning steadily decreased. In the United States, between 2000 and 2008, the proportion of suicides committed by hanging increased, whereas those committed using firearms steadily decreased, particularly among adolescent females. CONCLUSIONS: These findings suggest that the increased use of lethal suicide methods is reflected in the increase in suicide rates in Korean adolescents. The most fruitful approach to addressing the rises in jumping suicides among Korean adolescents and hanging suicides among adolescents in the United States may be through population-based initiatives to reduce the physical availability (e.g., limiting access to or fencing off tall structures) and the social acceptability (e.g., effective and responsible regulations for reporting suicide) of these methods.

Different clinical courses of children exposed to a single incident of psychological trauma: a 30-month prospective follow-up study.

BACKGROUND: We investigated the distinct longitudinal trajectories of posttraumatic stress symptoms in a sample of 167 children, who witnessed death of two mothers of their schoolmates. METHODS: The cohort was followed-up at 2 days (T1), 2 months (T2), 6 months (T3), and 30 months (T4) after the traumatic event. The children's posttraumatic stress symptoms (T1-T4), depression (T1, T3 and T4), state anxiety (T1, T3 and T4), and quality of life (T4) were assessed, along with parental stress related to child rearing (T4). Different trajectory patterns of the children's posttraumatic stress symptoms were identified using growth mixture modeling (GMM). RESULTS: Four different patterns of symptom change were identified, which were consistent with the prototypical model, and were named Recovery (19.9%), Resilience (72.7%), Chronic Dysfunction (1.8%), and Delayed Reactions (5.6%). Significant differences were found in depression and anxiety scores, children's quality of life, and parental rearing stress according to the distinct longitudinal trajectories of posttraumatic stress symptoms. CONCLUSIONS: The present study suggests that individual differences should be taken into account in the clinical course and outcome of children exposed to psychological trauma. The two most common trajectories were the Resilience and the Recovery types, together suggesting that over 90% of children were evidenced with a favorable 30-month outcome. The latent classes were associated with significant mean differences in depression and anxiety scores, supporting the clinical validity of the distinct trajectories.

No association of the norepinephrine transporter gene (SLC6A2) and cognitive and behavioural phenotypes of patients with autism spectrum disorder.

We examined the association between the norepinephrine transporter (SLC6A2) gene and autism spectrum disorder (ASD) in a Korean population. In addition, we investigated which phenotypes of ASD are best attributed to the genotype of SLC6A2. A total of 184 subjects with ASD, their 156 unaffected siblings and both biological parents were recruited through university hospitals. We used the Autism Diagnostic Interview-Revised, the Aberrant Behaviour Checklist (ABC), the Child Behaviour Checklist (CBCL), the Stroop Colour-Word Interference Test and the Wisconsin Card Sorting Test (WCST) as quantitative measures of the ASD phenotypes. The associations between the quantitative measures and specific single-nucleotide polymorphisms (SNPs) were tested with linear regression analyses. We did not find any evidence of the over-transmission of either allele of the 10SLC6A2 SNPs in the DFAM test. At an empirical p value <0.05, findings that were consistent between the linear regression analyses and the QFAM tests were the positive associations between the A allele of rs36020 and attention problems on the CBCL and stereotypical behaviours on the ABC and between the C allele of rs1814270 and the number of trials required to complete the first WCST category. However, these associations did not remain after correction for multiple testing. The study results of this study do not support the association between the SLC6A2 and the diagnosis or phenotype of ASD. However, the study must be replicated in larger populations and with using more genetic markers.

Protective effect of breastfeeding with regard to children's behavioral and cognitive problems.

BACKGROUND: Breastfeeding has been associated with a lower risk for behavioral problems in childhood. However, it is uncertain whether these associations are mediated by the mother's or child's IQ. We examined the association between breastfeeding and attention-deficit hyperactivity disorder (ADHD) and other behavioral problems in childhood and assessed the role of the child's IQ and the mother's IQ in generating this association. FINDINGS: The current study included 874 children (8-11 years) recruited from schools in five Korean cities. Mothers were asked about nursing, and the prevalence of attention-deficit hyperactivity disorder (ADHD) and behavioral problems were compared between children who were breastfed and those who were not breastfed. After adjusting for age, gender, area of residence, and yearly family income, a lack of breastfeeding was associated with increased internalizing, externalizing, and overall behavioral problems as well as the diagnosis of ADHD. These associations weakened but mostly remained significant after adjusting for child's IQ and maternal IQ. In addition, a lack of breastfeeding was associated with low child's IQ and this association weakened, but remained significant even after adjusting for maternal IQ and the diagnosis of ADHD. CONCLUSIONS: This study suggests that there is a protective effect of breastfeeding on childhood behavioral outcomes with a partial mediation of this effect by the child's IQ, and there is a positive effect of breastfeeding on childhood intelligence with a partial mediation of this effect by the child's attention problem.

Parental quality of life and depressive mood following methylphenidate treatment of children with attention-deficit hyperactivity disorder.

AIM: This naturalistic study investigated the associations between quality of life and depressive mood in parents and symptom changes in attention-deficit hyperactivity disorder (ADHD) children. METHODS: At baseline and at weeks 4 and 8, the parents evaluated their children, who were receiving treatment with osmotic-release oral system methylphenidate (mean dosage 36.3 ± 15.5 mg/day), using the Swanson, Nolan, and Pelham - Fourth Edition (SNAP-IV-18) scale. The parents evaluated themselves using the Beck Depression Inventory (BDI) and the World Health Organization Quality of Life Assessment, Brief Version (WHOQOL-BREF). RESULTS: A significant reduction in SNAP-IV-18 scores and improvements in parental BDI scores and parental WHOQOL-BREF scores were observed. The decrease in BDI scores from baseline to 8 weeks was significantly associated with increases in WHOQOL-BREF sub-domain scores from baseline to 8 weeks, with a greater decrease at 4 weeks and after. The decrease in the SNAP-IV-18 hyperactivity-impulsivity score was significantly associated with increases in WHOQOL social sub-domain scores from baseline to 8 weeks. For those patients who showed a 25% or greater decrease in the SNAP-IV-18 total scores from baseline to 8 weeks, the decreases in the SNAP-IV-18 total score and in the inattention and hyperactivity-impulsivity scores were significantly associated with a decrease in BDI scores from baseline to 8 weeks. CONCLUSION: Methylphenidate treatment for ADHD was associated with both symptom alleviation in children with ADHD and improvement in parental depressive mood and quality of life, suggesting that the effects of treatment could go beyond symptom improvement in ADHD.

Subthreshold attention-deficit/hyperactivity disorder is associated with functional impairments across domains: a comprehensive analysis in a large-scale community study.

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.

Norepinephrine genes predict response time variability and methylphenidate-induced changes in neuropsychological function in attention deficit hyperactivity disorder.

Noradrenergic dysfunction may be associated with cognitive impairments in attention-deficit/hyperactivity disorder (ADHD), including increased response time variability, which has been proposed as a leading endophenotype for ADHD. The aim of this study was to examine the relationship between polymorphisms in the α-2A-adrenergic receptor (ADRA2A) and norepinephrine transporter (SLC6A2) genes and attentional performance in ADHD children before and after pharmacological treatment.One hundred one medication-naive ADHD children were included. All subjects were administered methylphenidate (MPH)-OROS for 12 weeks. The subjects underwent a computerized comprehensive attention test to measure the response time variability at baseline before MPH treatment and after 12 weeks. Additive regression analyses controlling for ADHD symptom severity, age, sex, IQ, and final dose of MPH examined the association between response time variability on the comprehensive attention test measures and allelic variations in single-nucleotide polymorphisms of the ADRA2A and SLC6A2 before and after MPH treatment.Increasing possession of an A allele at the G1287A polymorphism of SLC6A2 was significantly related to heightened response time variability at baseline in the sustained (P = 2.0 × 10) and auditory selective attention (P = 1.0 × 10) tasks. Response time variability at baseline increased additively with possession of the T allele at the DraI polymorphism of the ADRA2A gene in the auditory selective attention task (P = 2.0 × 10). After medication, increasing possession of a G allele at the MspI polymorphism of the ADRA2A gene was associated with increased MPH-related change in response time variability in the flanker task (P = 1.0 × 10).Our study suggested an association between norepinephrine gene variants and response time variability measured at baseline and after MPH treatment in children with ADHD. Our results add to a growing body of evidence, suggesting that response time variability is a viable endophenotype for ADHD and suggesting its utility as a surrogate end point for measuring stimulant response in pharmacogenetic studies.

Association between the GRM7 rs3792452 polymorphism and attention deficit hyperacitiveity disorder in a Korean sample.

BACKGROUND: The purpose of this study was to investigate the association between the ionotropic and glutamate receptors, N-methyl D-asparate 2A (GRIN2A) and 2B (GRIN2B), and the metabotropic glutamate receptor mGluR7 (GRM7) gene polymorphisms and attention-deficit hyperactivity disorder (ADHD) in Korean population. METHODS: We conducted a case-control analysis of 202 ADHD subjects and 159 controls, performed a transmission disequilibrium test (TDT) on 149 trios, and compared scores from the continuous performance test (CPT), the Children's Depression Inventory (CDI), and the State-Trait Anxiety Inventory for Children (STAIC) according to the genotype of the glutamate receptor genes. RESULTS: There were no significant differences in the genotype or allele frequencies of the GRIN2A rs8049651, GRIN2B rs2284411, or GRM7 rs37952452 polymorphisms between the ADHD and control groups. For 148 ADHD trios, the TDT analysis also showed no preferential transmission of the GRIN2A rs8049651 or GRIN2B rs2284411 polymorphisms. However, the TDT analysis of the GRM7 rs3792452 polymorphism showed biased transmission of the G allele (χ2 = 4.67, p = 0.031). In the ADHD probands, the subjects with GG genotype in the GRM7 rs37952452 polymorphism had higher mean T-scores for omission errors on the CPT than did those with the GA or AA genotype (t = 3.38, p = 0.001). In addition, the ADHD subjects who were homozygous for the G allele in the GRM7 rs37952452 polymorphism had higher STAIC-T (t = 5.52, p < 0.001) and STAIC-S (t = 2.74, p = 0.007) scores than did those with the GA or AA genotype. CONCLUSIONS: These results provide preliminary evidence of an association between the GRM7 rs37952452 polymorphism and selective attention deficit and anxiety found within the Korean ADHD population.

Bisphenol A in relation to behavior and learning of school-age children.

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.

White-matter connectivity and methylphenidate-induced changes in attentional performance according to α2A-adrenergic receptor gene polymorphisms in Korean children with attention-deficit hyperactivity disorder.

The authors examined the association between the MspI C/G and DraI C/T genotypes of the α2A-adrenergic receptor gene and white-matter connectivity and attentional performance before and after medication in 53 children with attention-deficit hyperactivity disorder. Subjects who carried the T allele at the DraI polymorphism showed fewer changes in the mean commission error scores after 8 weeks of medication and decreased fractional anisotropy (FA) values in the right middle frontal cortex than subjects without the T allele. Subjects with the C allele at the MspI polymorphism showed decreased FA values in the right postcentral gyrus than subjects without.

Impact of family environment on the development of tic disorders: epidemiologic evidence for an association.

BACKGROUND: Although family education generally is recommended in the treatment of tic disorders, few studies have focused on the relationship between family environment and diagnosis of tic disorders. METHODS: Presence of DSM-IV tic disorders was determined in a general population of 921 children in Korea from 2008 to 2009. Clinical risk factors were assessed, including comorbidity with attention-deficit/hyperactivity disorder; family-related factors such as the number of family members and primary caretaker of the child; and socioeconomic factors in the form of paternal education level and household yearly income. Multivariable logistic regression analyses were performed to estimate the association between a list of clinical, familial, and social variables and the odds of developing tic disorders. RESULTS: At Bonferroni corrected thresholds, a higher risk of tic disorders was significantly associated with the number of changes in primary caretaker, whereas a lower risk was associated with increasing number of children in the family. CONCLUSIONS: Family-related environmental factors may play a role in the development or exacerbation of tic disorders. The results advocate the importance of family education when treating children with tic disorders, and further research is needed on the contextual risk factors of tic disorders.

Relationship between blood manganese levels and children's attention, cognition, behavior, and academic performance--a nationwide cross-sectional study.

Manganese (Mn) is neurotoxic at high concentrations. However, Mn is an essential element that can protect against oxidative damage; thus, extremely low levels of Mn might be harmful. Our aim was to examine whether either high or low environmental Mn exposure is related to academic and attention function development among school-aged children. This cross-sectional study included 1089 children 8-11 years of age living in five representative areas in South Korea. Blood Mn, blood lead, and urine cotinine were measured. We assessed IQ with the Wechsler Abbreviated Scale of Intelligence; attention with a computerized continuous performance test called the Attention-deficit/hyperactivity disorder (ADHD) Diagnostic System (ADS), the Korean version of the Stroop Color-Word Test, the Children's Color Trails Test (CCTT), and the ADHD Rating Scale; academic functions with the Learning Disability Evaluation Scale (LDES); and emotional and behavioral problems with the Korean version of the Child Behavior Checklist (CBCL). We further assessed the presence of ADHD using a highly structured diagnostic interview, the Diagnostic Interview Schedule for Children Version IV (DISC-IV). The median blood concentration of Mn was 14.14 µg/L. We observed a nonlinear association between the CCTT2 completion time and the CPT commission error (F=3.14, p=0.03 and F=4.05, p=0.01, respectively). We divided the data into three groups: lower (<8.154 µg/L), and upper 5th percentile (>21.453 µg/L) and middle 90th percentile to determine whether a lack or overload of Mn could cause adverse effects. After adjusting for urine cotinine, blood lead, children's IQ, and other potential confounders, the high Mn group showed lower scores in thinking (B=-0.83, p=0.006), reading (B=-0.93, p=0.004), calculations (B=-0.72, p=0.005), and LQ (B=-4.06, p=0.006) in the LDES and a higher commission error in the CPT (B=8.02, p=0.048). The low Mn group showed lower color scores in the Stroop test (B=-3.24, p=0.040). We found that excess Mn in children is associated with lower scores of thinking, reading, calculation, and LQ in the LDES and higher scores of commission error in the ADS test. In contrast, lower Mn in children is associated with lower color scores in the Stroop test. The findings of this cross-sectional study suggest that excess exposure or deficiency of Mn can cause harmful effects in children.

Possible effect of norepinephrine transporter polymorphisms on methylphenidate-induced changes in neuropsychological function in attention-deficit hyperactivity disorder.

BACKGROUND: Dysregulation of noradrenergic system may play important roles in pathophysiology of attention-deficit/hyperactivity disorder (ADHD). We examined the relationship between polymorphisms in the norepinephrine transporter SLC6A2 gene and attentional performance before and after medication in children with ADHD. METHODS: Fifty-three medication-naïve children with ADHD were genotyped and evaluated using the continuous performance test (CPT). After 8-weeks of methylphenidate treatment, these children were evaluated by CPT again. We compared the baseline CPT measures and the post-treatment changes in the CPT measures based on the G1287A and the A-3081T polymorphisms of SLC6A2. RESULTS: There was no significant difference in the baseline CPT measures associated with the G1287A or A-3081T polymorphisms. After medication, however, ADHD subjects with the G/G genotype at the G1287A polymorphism showed a greater decrease in the mean omission error scores (p = 0.006) than subjects with the G/A or A/A genotypes, and subjects with the T allele at the A-3081T polymorphism (T/T or A/T) showed a greater decrease in the mean commission error scores (p = 0.003) than those with the A/A genotypes. CONCLUSIONS: Our results provide evidence for the possible role of the G1287A and A-3081T genotypes of SLC6A2 in methylphenidate-induced improvement in attentional performance and support the noradrenergic hypothesis for the pathophysiology of ADHD.

Val/Val genotype of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with a better response to OROS-MPH in Korean ADHD children.

Research on psychostimulants, analysis of animal models and genetic association studies all suggest that the brain-derived neurotrophic factor gene (BDNF) may be a good candidate for pharmacogenetic studies of attention deficit hyperactivity disorder (ADHD). Yet to date there have been no pharmacogenetic studies of BDNF in ADHD. A total of 102 drug-naive ADHD children (8.7±2.1 yr) were treated with osmotic release oral system-methylphenidate (OROS-MPH) for 12 wk, and four kinds of response criteria were applied, based first, on a combined threshold of the ADHD Rating Scale - IV (ARS) and the Clinical Global Impression - Improvement scale (CGI-I); second, on scores of 1 or 2 vs. 3-7 on the CGI - Severity scale; third, on a >50% reduction in ARS scores; and fourth, on satisfaction of all of the aforementioned criteria. The Val66Met polymorphism of BDNF and six single nucleotide polymorphisms from the SLC6A2, ADRA2A and NTF-3 genes were tested for association with each criterion. Relative to other genotypes, homozygosity for the Val allele of the BDNF Val66Met polymorphism was associated with a greater relative frequency of good response under all four response criteria (after controlling for baseline ARS score, age, gender, final dose (mg/kg) of OROS-MPH at 12 wk, and level of academic functioning). This association was significant at the uncorrected level for the first and third response criteria (p=0.013 and p=0.018, respectively) and significant at a Bonferroni-corrected level for the second and fourth response criteria (p=0.0002, p=0.0003, respectively). Our findings support an association between homozygosity for the Val allele of BDNF and better response to OROS-MPH in Korean ADHD children as assessed by four different response criteria.

Academic outcomes in Asian children aged 8-11 years with attention-deficit/hyperactivity disorder treated with atomoxetine hydrochloride.

OBJECTIVE: To investigate the relationship between changes in attention-deficit/hyperactivity disorder (ADHD) core symptoms and changes in academic outcome of Asian children treated with atomoxetine. METHODS: This open-label study enrolled patients aged 8-11 years with DSM-IV-TR-defined ADHD, who were naïve to ADHD medications and met the symptomatic severity threshold of 1.5 standard deviations above the age and gender norm for the ADHDRS-IV-Parent:Inv (ADHDRS) total score. Data collection occurred for 24 weeks and included academic outcome, measured by the school grade average (SGA). RESULTS: Of 228 patients enrolled from China (n = 82), Taiwan (n = 76), and Korea (n = 70), 77.2% completed the study. Statistically significant (P < 0.001) baseline to last observation improvements in ADHDRS and SGA scores were observed. However, no linear correlation between change in ADHDRS total score and SGA (-0.083, P = 0.293) was observed. CONCLUSIONS: Despite significant independent improvements in core ADHD symptoms and academic grades over 24 weeks, the mean improvements observed in these measures did not appear to be correlated.