Maternal Stress and Depressive Symptoms and Infant Development at Six Months: the Mothers and Children's Environmental Health (MOCEH) Prospective Study.

Our objective is to evaluate the relationships between prenatal maternal stress and depressive symptoms, respectively, and infant neurodevelopment at 6 months, adjusted for heavy metals and oxidative stress. This research is a part of a multi-center birth cohort study in South Korea. Information on stress and depressive symptoms was collected during the first trimester using Psychosocial Well-Being Index Short Form (PWI-SF) and Center for Epidemiological Studies Depression Scale (CES-D). The Korean Bayley Scales of Infant Development-II assessment (BSID-II), which includes the standardized mental development index (MDI) and psychomotor developmental index (PDI), and Korean Ages & Stages Questionnaires (K-ASQ) were applied to infants at six months of age. A higher index score indicates better development. Among 641 babies, 320 were female (50%). Maternal PWI ≥ 29 (vs. PWI ≤ 18) during early pregnancy was associated with a decrease in MDI scores of 5.37 points (P = 0.02) after adjusting for socioeconomic factors. Maternal CES-D ≥ 26 (vs. CES-D ≤ 10) during early pregnancy was associated with a decrease in MDI scores of 8.18 points (P = 0.01). The associations remained significant even after adjustment for lead, cadmium, and MDA levels (P < 0.05). However, no association was found between maternal PWI/CES-D and PDI score. No interaction was observed between stress and lead exposure. We found an inverse association between prenatal maternal stress and depressive symptoms, and MDI scores in 6-month-old infants after adjustment for prenatal lead exposure, which is known to affect cognitive function negatively.

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.

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.

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.

Secondhand smoke exposure during pregnancy and infantile neurodevelopment.

During prenatal development, the nervous system may be more susceptible to environmental toxicants, such as secondhand smoke. The authors assessed the effects of prenatal and postnatal secondhand smoke exposure on the neurodevelopment of 6-month infants. The subjects were 414 mother and infant pairs with no medical problems, taken from the Mothers' and Children's Environmental Health study. Prenatal and postnatal exposures to secondhand smoke were determined using maternal self-reports. Examiners, unaware of exposure history, assessed the infants at 6 months of age using the Bayley Scales of Infant Development. Bayley scores were compared for secondhand smoke exposed and unexposed groups after adjusting for potential confounders. Multiple logistic regression analysis was carried out to estimate the risk of developmental delay posed by SHS exposure. The multivariate model included residential area, maternal age, pre-pregnancy body mass index, education, income, infant sex, parity, birth weight, and type of feeding. After adjusting for covariates, secondhand smoke exposure during pregnancy was found to be related to a decrease in mental developmental index score, but not to a decrease in psychomotor developmental index score. In addition, secondhand smoke exposure during pregnancy was found to increase the risk of developmental delay (mental developmental index score ≤85) at 6 months. This study suggests that the infants of non-smoking women exposed to secondhand smoke are at risk of neurodevelopmental delay.

Pulmonary function of healthy Korean children from three independent birth cohorts: Validation of the Global Lung Function Initiative 2012 equation.

BACKGROUND AND OBJECTIVE: Global Lung Function Initiative (GLI) 2012 equations were developed to resolve the age-related disparity in interpreting spirometry results. Local validation of the equation is needed, especially in Northeast Asian children. This study evaluated the GLI equation in Korean children. METHODS: Spirometry indices (FEV1, FVC, FEV1/FVC, and FEF25%-75%) and clinical information were gathered from three population-based birth cohorts. Predicted GLI reference values and z scores of spirometry results were calculated for 1239 healthy children. The mean, standard deviation of z scores were compared with the expected 0 and 1. Probabilities of falling below the lower limit of normal (LLN) (z score: -1.64) were compared with the expected value 5%. GLI z scores were assessed according to low (<-2), normal (≥-2 and ≤2), and high (>2) BMI z score groups. RESULTS: Mean z scores significantly differed from 0 for FEV1/FVC in males (mean [95% confidence interval]: 0.18 [0.08, 0.27]) and forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) in females (-0.23 [-0.31, -0.15] and -0.26 [-0.36, -0.16], respectively). The standard deviation was larger than 1 for all variables in males and FVC and FEV1/FVC in females. The probability of falling below the LLN was significantly larger than 5% for FEV1 (12.13% [9.64, 14.77]), FVC (15.86% [13.06, 18.81]), and forced expiratory flow at 25%-75% of forced vital capacity (FEF25%-75%) (7.31% [5.29, 9.49]) in males and FVC (11.91% [9.40, 14.60]) in females. FEV1 and FVC z scores increased across low to high body mass index (BMI) groups, and FEV1/FVC decreased from low to high BMI groups. CONCLUSION: GLI equations marginally differ from real-world values, which should be considered by pulmonologists in practice or research.

Possible association of norepinephrine transporter -3081(A/T) polymorphism with methylphenidate response in attention deficit hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a heritable disorder characterized by symptoms of inattention and/or hyperactivity/impulsivity. Methylphenidate (MPH) has been shown to block the norepinephrine transporter (NET), and genetic investigations 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 -3081(A/T) and G1287A polymorphisms with MPH response in ADHD. METHODS: This study enrolled 112 children and adolescents with ADHD. A response criterion was defined based on the Clinical Global Impression-Improvement (CGI-I) score, and the ADHD Rating Scale-IV (ARS) score was also assessed at baseline and 8 weeks after MPH treatment. RESULTS: We found that the subjects who had the T allele as one of the alleles (A/T or T/T genotypes) at the -3081(A/T) polymorphism showed a better response to MPH treatment than those with the A/A genotype as measured by the CGI-I. We also found a trend towards a difference in the change of the total ARS scores and hyperactivity/impulsivity subscores between subjects with and without the T allele. No significant association was found between the genotypes of the SLC6A2 G1287A polymorphism and response to ADHD treatment. CONCLUSION: Our findings provide evidence for the involvement of the -3081(A/T) polymorphism of SLC6A2 in the modulation of the effectiveness of MPH treatment in ADHD.

Effect of environmental exposure to lead and tobacco smoke on inattentive and hyperactive symptoms and neurocognitive performance in children.

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.

Regional differences in cerebral perfusion associated with the alpha-2A-adrenergic receptor genotypes in attention deficit hyperactivity disorder.

BACKGROUND: Neurobiologic studies have suggested that dysregulation of central noradrenergic systems may be involved in the pathophysiology of attention deficit hyperactivity disorder (ADHD), and it has been hypothesized that genetic changes in the norepinephrine pathways might contribute to dysfunction of the prefrontal cortex circuits in ADHD. We previously reported decreased cerebral blood flow in the right lateral prefrontal cortex and both orbitofrontal cortices in children with ADHD. Genetic investigations have shown that the alpha-2A-adrenergic receptor gene (ADRA2A) is associated with ADHD. Our aim was to examine whether the presence of a risk allele of the ADRA2A MspI polymorphism is associated with differences in regional cerebral blood flow in boys with ADHD. METHODS: We recruited 21 Korean boys with ADHD (mean age 9.9, standard deviation [SD] 2.7 yr) and 11 age- and sex-matched controls (mean age 10.6 [SD 2.1] yr). Each participant underwent technetium-99m-hexamethylpropylene amine oxime ((99m)Tc-HMPAO) single-photon emission computed tomography. We performed image analyses with voxe-wise t statistics using SPM2. RESULTS: We found regional hypoperfusion in the prefrontal regions, including the right orbitofrontal and right medial gyri, and the bilateral putamen and cerebellum in boys with ADHD relative to controls (p < 0.0005, uncorrected for multiple comparisons). Boys with ADHD who carried the C allele (n = 13) at the ADRA2A MspI polymorphism had reduced perfusion in the bilateral orbitofrontal regions compared with those without the C allele (n = 8) (p < 0.0005, uncorrected for multiple comparisons). LIMITATIONS: This study was limited by the small sample size, and we did not obtain genetic data from the controls. CONCLUSION: Our findings suggest that regional differences in cerebral perfusion in the orbitofrontal cortex represent an intermediate neuroimaging phenotype associated with the ADRA2A MspI polymorphism; these data support the validity of the noradrenergic hypothesis regarding the pathophysiology of ADHD.

Does oppositional defiant disorder have temperament and psychopathological profiles independent of attention deficit/hyperactivity disorder?

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.

Neurocognitive effects of switching from methylphenidate-IR to OROS-methylphenidate in children with ADHD.

OBJECTIVES: This study evaluated neurocognitive changes after switching from immediate release forms of methylphenidate (MPH-IR) to osmotic release oral system methylphenidate (OROS-MPH). METHODS: 102 children with attention-deficit/hyperactivity disorder (ADHD) participated in an open label, 28 day trial, performing neurocognitive test at baseline and at 28 days after the switch from MPH-IR to OROS-MPH. RESULTS: There were significant improvements in the commission error and the reaction time of both visual and auditory continuous performance tests (CPTs) at 28 days after switching from MPH-IR to OROS-MPH. A positive correlation was observed between the improvement in parent/caregiver-rated IOWA Conners total score (Delta IOWA) and the reduction in commission error (r = 0.3, p = 0.001) and reduction in reaction time variability (r = 0.3, p = 0.006) of visual CPT. In a linear regression model, the change in parent/caregiver-rated IOWA Conners scale total scores were significant predictors of change in commission error (beta = 0.3, p = 0.005, CI = 0.4-2.3, adjusted R(2) = 0.12) and RT variability (beta = 0.3, p = 0.004, CI = 0.5-2.4, adjusted R(2) = 0.09) of visual CPT. CONCLUSIONS: These data suggest that MPH-IR may be successfully switched to OROS-MPH treatment with associated improvements in neurocognitive performance. Large-scale controlled trials are needed to replicate these findings.

Temperament and character among Korean children and adolescents with anxiety disorders.

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.

Full syndrome and subthreshold attention-deficit/hyperactivity disorder in a Korean community sample: comorbidity and temperament findings.

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.

Aripiprazole in the treatment of early-onset schizophrenia spectrum disorder: A case series in Korean children and adolescents.

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.

Association between the alpha-2C-adrenergic receptor gene and attention deficit hyperactivity disorder in a Korean sample.

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 (chi2 = 19.07, p = 0.025). We found a trend for preferential transmission of the 183-bp allele (chi2 = 3.72, p = 0.054), and a significantly lower-than-expected rate of transmission of the 187-bp allele (chi2 = 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.

Associations between symptoms of attention deficit hyperactivity disorder, depression, and suicide in Korean female adolescents.

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.

No evidence of an association between norepinephrine transporter gene polymorphisms and attention deficit hyperactivity disorder: a family-based and case-control association study in a Korean sample.

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.