Effects of Antidepressant Treatment on Symptom Measures of Attention in Adolescents with Depression: A Preliminary Open-Label Study.

Objective: The effects of selective serotonin reuptake inhibitor (SSRI) on deficits in attention and executive function in adolescents with major depressive disorder (MDD) are relatively unknown. We aimed to investigate changes in symptom measures of attention in adolescents with MDD treated with escitalopram. Methods: The study included 82 MDD adolescents and 54 healthy controls aged from 12 to 17 years. Symptom measures of attention were assessed using the Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS) and Child Behavior Checklist attention problems scale at baseline and during week 8. Adolescents who showed at least 40% improvement in the Children's Depression Rating Scale-Revised (CDRS-R) scores from baseline to week 8 were referred to as "responders." Results: No baseline differences were found between the responders (n = 47) and nonresponders (n = 35) in their age, sex, intelligence quotient, CDRS-R score, and attention measures. Linear mixed models showed significant group-by-time interaction effect in the ADHD-RS inattention subscale score, but not in the other attention measures. Conclusion: Our results suggest that treating depressive symptoms with SSRI may lead to improvements in attention in MDD adolescents. Monitoring changes in symptom measures of attention can be useful when treating adolescents with MDD. ClinicalTrials.gov identifier: NCT03547219.

The indirect effect of peer problems on adolescent depression through nucleus accumbens volume alteration.

Literature suggests that neurobiological factors such as brain structure play an important role in linking social stress with depression in adolescence. We aimed to examine the role of subcortical volumetric alteration in the association between peer problems as one type of social stress and adolescent depression. We hypothesized that there would be indirect effects of peer problems on adolescent depression through subcortical volumetric alteration. Seventy eight adolescents with major depressive disorder (MDD) (age mean [SD] = 14.9 ± 1.5, 56 girls) and 47 healthy controls [14.3 ± 1.4, 26 girls]) participated in this study. High-resolution structural T1 images were collected using the Siemens 3T MR scanner. Subcortical volumes were segmented using the Freesurfer 6.0 package. Peer problems were assessed using the Peer-Victimization Scale and the Bullying-Behavior Scale. There was a significant indirect effect of peer problems on adolescent depression through nucleus accumbens (NAcc) volume alteration, but not through the amygdala and hippocampal volumes. This result supported our model, which stated that peer problems have indirect effects through subcortical volumetric alteration (i.e., increased NAcc volume) on adolescent depression. Our finding suggests that altered NAcc volume may serve as a pathway, through which peer problems as one type of social stressor contribute to adolescent depression.

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.

Early changes of serum BDNF and SSRI response in adolescents with major depressive disorder.

BACKGROUND: Recent evidence suggests that brain-derived neurotrophic factor (BDNF) levels and their early changes may predict antidepressant response in adults with major depressive disorder (MDD). However, in adolescents, BDNF levels in depression and their changes during antidepressant treatment are relatively unknown. We aimed to investigate whether pre-treatment BDNF levels and their early changes predict antidepressant response in depressed adolescents. METHODS: The study included 83 MDD adolescents and 52 healthy controls aged 12 to 17 years. All depressed adolescents were treated with escitalopram in an 8 week, open-label trial. Depression severity and serum BDNF level at baseline, and weeks 2 and 8 were measured with the Children's Depression Rating Scale-Revised (CDRS-R) and ELISA, respectively. RESULTS: Responders showed a significant decrease in BDNF levels at week 2 but non-responders and healthy controls had no changes in BDNF levels at week 2. The early decrease (baseline - week 2) of BDNF levels predicted SSRI response with moderate sensitivity and specificity. Logistic regression analysis revealed that early BDNF decrease predicted SSRI response at week 8 after controlling for other demographic and clinical variables. LIMITATIONS: The follow-up duration of the study was limited in 8 weeks. It remains possible that serum BDNF levels would have changed with longer treatment. CONCLUSIONS: This is the first longitudinal study to investigate the effect of antidepressants on BDNF levels in adolescents with MDD. Our findings suggest that a decrease of serum BDNF levels in early phase of SSRI treatment may be associated later SSRI response in adolescents with MDD.

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.

Breastfeeding is associated with enhanced learning abilities in school-aged children.

OBJECTIVE: The majority of studies on the associations between breastfeeding and cognitive functioning have focused on IQ, with only a few investigating learning skills, and none of the latter adjusting for maternal IQ. We examined the association between breastfeeding and learning abilities in school-aged children using a cross-sectional design. METHODS: We recruited 868 children, aged 8-11 years and parents completed the Learning Disability Evaluation Scale (LDES). Multivariable linear regression models were used and age, gender, area of residence, annual family income, maternal education, and maternal age at delivery, were included as covariates. Maternal IQ was added to further adjust for the effects of maternal cognitive ability. Path analysis was conducted to investigate the mediation effect of maternal IQ between breastfeeding and learning skills. RESULTS: Children who were ever-breastfed had higher learning quotient scores on the LDES (p = 0.001) as well as higher scores on subscales related to speaking (p = 0.001), reading (p = 0.005), writing (p = 0.004), spelling (p = 0.003), and mathematical calculation (p = 0.003) than the never-breastfed participants. All of these variables remained significant after adjusting for gestational and socioeconomic factors and for maternal IQ as covariates. The path analysis showed that breastfeeding had both indirect and direct effects on the learning quotient. CONCLUSIONS: The results suggest that breastfeeding is positively associated with learning skills in school-aged children.

Interactions Between Early Trauma and Catechol-O-Methyltransferase Genes on Inhibitory Deficits in Children With ADHD.

OBJECTIVE: To investigate the interaction between childhood trauma exposure with the catechol-O-methyltransferase (COMT) and dopamine receptor D4 (DRD4) polymorphisms in relation to neuropsychological measures in children with ADHD. METHOD: A cross-sectional examination of early traumatic experiences and the continuous performance test (CPT) were performed in 55 children with ADHD. Participants were also genotyped for the DRD4 exon III 48-bp variable number of tandem repeats (VNTR) polymorphism and the COMT Val158-Met (rs4680) polymorphism. RESULTS: There was significant interaction between the effects of the COMT genotype and trauma in commission errors. In participants with ADHD carrying the COMT Val/Val genotype, the group exposed to trauma showed significantly higher commission errors than the non-traumatized group. However, for the participants with other genotypes, no significant differences were found. CONCLUSION: This study suggests that there exists a genetic influence on the association between childhood trauma and the severity of inhibitory deficits in children with ADHD.

Genetic association analyses of neuregulin 1 gene polymorphism with endopheontype for sociality of Korean autism spectrum disorders family.

To determine the genetic association between qualitative and quantitative traits of autism spectrum disorder (ASD) and neuregulin 1 (NRG1)-a schizophrenia candidate gene-we examined six single nucleotide polymorphisms (SNPs) in NRG1 using a family-based association test (FBAT) in Korean families with ASD. rs35753505 and rs6994992 SNPs in NRG1 revealed a statistically significant family-based association with three quantitative traits for sociality.

Clinical characteristics and precipitating factors of adolescent suicide attempters admitted for psychiatric inpatient care in South Korea.

OBJECTIVE: We aimed to examine the rates, correlates, methods, and precipitating factors of suicide attempts among adolescent patients admitted for psychiatric inpatient care from 1999 to 2010 in a university hospital in Korea. METHODS: The subjects consisted of 728 patients who were admitted for psychiatric inpatient care in a university hospital over a 12-year period and who were aged 10-19 years at the time of admission. We retrospectively investigated the information on suicidal behaviors and other clinical information by reviewing the subjects' electronic medical records. Whether these patients had completed their suicide on 31 December 2010 was determined by a link to the database of the National Statistical Office. RESULTS: Among 728 subjects, 21.7% had suicidal ideation at admission, and 10.7% admitted for suicidal attempts. Female gender, divorced/widowed parents, and the presence of mood disorders were associated with a significantly increased likelihood of suicide attempts. Most common method of suicide attempts was cutting, and most common reason for suicide attempts was relationship problems within the primary support group. A diagnosis of schizophrenia was associated with increased risk of death by suicide after discharge. CONCLUSION: These results highlight the role of specific psychosocial factor (e.g., relational problems) and psychiatric disorders (e.g., mood disorders) in the suicide attempts of Korean adolescents, and the need for effective prevention strategies for adolescents at risk for suicide.

Family-based association study of the arsenite methyltransferase gene (AS3MT, rs11191454) in Korean children with attention-deficit hyperactivity disorder.

We examined the association between the selected polymorphisms in two candidate genes, the arsenite methyltransferase gene (AS3MT, rs11191454) and the inter-α-trypsin inhibitors heavy chain-3 gene (ITIH3, rs2535629), and attention-deficit hyperactivity disorder (ADHD) in a Korean population. A total of 238 patients with ADHD, along with both of their biological parents, were recruited. The children were administered intelligence quotient tests, whereas their parents completed the Child Behavior Checklist. In the transmission disequilibrium test on 181 trios, we found overtransmission of the A allele at the AS3MT rs11191454 polymorphism in children with ADHD (χ²=8.81, P=0.003). However, there was no preferential transmission at the ITIH3 rs52535629 polymorphism (χ²=0.14, P=0.707). Our results provide preliminary evidence for the overtransmission of the A allele at the AS3MT rs11191454 polymorphism in ADHD.

Prevalence, correlates, and comorbidities of DSM-IV psychiatric disorders in children in Seoul, Korea.

The present study reports past-year prevalence of and comorbidities associated with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) disorders in 1645 children aged 6 to 12 years in Seoul, Korea. The diagnosis was based on the parental version of the Diagnostic Interview Schedule for Children (DISC-IV). Our participants completed the Children's Depression Inventory (CDI). The estimated prevalence of any full-syndrome and subthreshold DSM-IV disorders were 16.2% and 28.1%, respectively. The most prevalent disorders were specific phobia (9.6%), attention-deficit hyperactivity disorder (ADHD; 5.9%), and oppositional defiant disorder (ODD; 4.9%). The estimated prevalence of depressive disorder was 0.1% according to the DISC-IV and1.9% according to the CDI. ADHD, ODD, and anxiety disorders were highly comorbid. Our study highlights the importance of obtaining children's self-report data in addition to the parents' interview, particularly for depression, and the importance of early detection of subthreshold conditions and considering comorbid diagnoses.

Di-(2-ethylhexyl) phthalate exposure is negatively correlated with trait anxiety in girls but not with trait anxiety in boys or anxiety-like behavior in male mice.

The authors aimed to study the effects of postnatal exposure to phthalate on anxiety-like behavior in mice and anxiety proneness in children. Male Imprinting Control Region (ICR) mice aged 4 weeks were administered 20 to 540 mg/kg of di-(2-ethylhexyl) phthalate (DEHP) or vehicle and assessed in the Open Field Test. A group of 277 children aged 8-11 years (150 males) was recruited from South Korea. A cross-sectional examination of urinary DEHP and dibutylphthalate metabolite concentrations was conducted, and the children were scored on the Trait Anxiety Inventory for Children (TAIC). DEHP metabolite concentrations in the urine were significantly and negatively correlated with TAIC scores in the female population but not in the male population. There were no significant group differences in the percentage of distance moved or time spent in the central area in male mice treated with DEHP or vehicle. Our results suggest a sex-dependent effect of DEHP on anxiety proneness in childhood.

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.

Environmental lead exposure and attention deficit/hyperactivity disorder symptom domains in a community sample of South Korean school-age children.

BACKGROUND: Low-level environmental exposure to lead has been associated with both reduced intelligence and symptoms of attention deficit/hyperactivity disorder (ADHD). However, few studies have estimated the association of lead and intelligence independent of ADHD, and it is not clear from previous studies whether lead is associated with both inattention and impulsivity ADHD symptoms. OBJECTIVES: We estimated mutually adjusted associations of environmental lead exposure with both intelligence and ADHD symptoms, and associations between lead and specific ADHD-related domains. METHODS: Blood lead concentrations were measured in a general population of 1,001 children 8-11 years of age. We used multivariable linear regression models to estimate associations of blood lead concentrations with IQ scores, teacher and parent ratings of ADHD symptoms, and measures of inattention and impulsivity. Models were adjusted for demographic variables and other environmental exposures (blood levels of mercury and manganese, urinary concentrations of cotinine, phthalate metabolites, and bisphenol A). RESULTS: Associations of blood lead with lower IQ and higher impulsivity were robust to adjustment for a variety of covariates. When adjusted for demographic characteristics, other environmental exposures, and ADHD symptoms or IQ, a 10-fold increase in blood lead concentration was associated with lower Full-Scale IQ (-7.23; 95% CI: -13.39, -1.07) and higher parent- and teacher-rated hyperactivity/impulsivity scores (ADHD Rating Scale, 1.99; 95% CI: 0.17, 3.81 and 3.66; 95% CI: 1.18, 6.13, respectively) and commission errors (Continuous Performance Test, 12.27; 95% CI: -0.08, 24.62). Blood lead was not significantly associated with inattention in adjusted models. CONCLUSIONS: Low-level lead exposure was adversely associated with intelligence in school-age children independent of ADHD, and environmental lead exposure was selectively associated with impulsivity among the clinical features of ADHD.

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.

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.

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.

Blood manganese levels in relation to comorbid behavioral and emotional problems in children with attention-deficit/hyperactivity disorder.

Patients with attention-deficit/hyperactivity disorder (ADHD) appear to be more vulnerable to the development of other psychiatric disorders than the general population. The proposed neurotoxic mechanisms of manganese involve striatal dopamine neurotransmission, implicated in the pathophysiology of ADHD. We investigated whether the adverse impact of manganese is particularly pronounced in children with ADHD. Blood manganese concentration and diagnosis of ADHD were assessed in a general population of 890 children, aged 8-11 years. The main outcome measure was the Child Behavior Checklist (CBCL). A significant interaction was found between ADHD status and blood manganese level in predicting CBCL total problems score as well as anxiety/depression, social problems, delinquent behavior, aggressive behavior, internalizing problems, and externalizing problems. The directions of the interactions indicated that blood manganese level was more positively correlated with CBCL scores in ADHD children than in the healthy population. In ADHD children, only the fifth quintile of blood manganese concentration was significantly associated with the CBCL total problems score. ADHD children may be more vulnerable than the general school-age population to the neurotoxic effects of manganese exposure, which lead to an elevated risk of developing comorbid mental conditions.

Association between urine phthalate levels and poor attentional performance in children with attention-deficit hyperactivity disorder with evidence of dopamine gene-phthalate interaction.

Although there is some evidence supporting the existence of an association between prenatal maternal or postnatal child's urine phthalate metabolite concentrations and poor attentional performances, the interaction between urine phthalate metabolite levels and genetic variation for neuropsychological deficit of attention-deficit hyperactivity disorder (ADHD) has not been examined. The aim of this study was to determine whether phthalate metabolites in urine are associated with poor neuropsychological performance in children with ADHD, and whether such association is affected by genotype-phthalate interaction. A cross-sectional examination of urine phthalate metabolite concentrations and the continuous performance test (CPT) were performed in 179 Korean children with ADHD recruited from department of psychiatry of university hospital. Correlations between urine phthalate metabolite concentrations and the CPT scores were investigated, and the interaction of phthalate metabolite levels with the selected polymorphisms at major candidate genes for ADHD, namely dopamine receptor D4 (DRD4), dopamine transporter, α-2A-adrenergic receptor, and norepinephrine transporter genes. For the subjects with the DRD4 4/4 genotype, there were significant associations of the urine phthalate metabolite concentrations with the number of omission errors, the number of commission errors, and the response time variability scores on the CPT. However, for the subjects without the DRD4 4/4 genotype, no significant associations were found. The results of this study suggest a possible association between phthalate metabolite concentrations and poor attentional performances of ADHD as well as a genetic influence on this association. Further prospective and epigenetic studies are needed to investigate causality and pathophysiological mechanisms.

Differential perinatal risk factors in children with attention-deficit/hyperactivity disorder by subtype.

We compared the attention-deficit/hyperactivity disorder(ADHD) combined subtype (ADHD-C) to the ADHD inattentive subtype (ADHD-I) in terms of genetic, perinatal, and developmental risk factors as well as clinical and neuropsychological characteristics. A total of 147 children diagnosed with ADHD between the ages of 6 and 15 years participated in this study. The parents of the children completed the structured diagnostic interview, the ADHD Rating Scale-IV, the Children's Behavior Checklist, and structured questionnaires on perinatal risk factors, and the children underwent a neuropsychological test and were genotyped. A total of 502 children without ADHD were recruited from the community as a healthy control group. The ADHD-C children showed more severe externalizing symptoms, showed more deficits in a continuous performance test, and were more likely to have comorbid disorders. Maternal stress during pregnancy, postpartum depression, and changes in the primary caretaker during first 3 years were significantly associated with both ADHD-I and ADHD-C. The ADHD-I group was less likely to have received regular prenatal check-ups and more likely to have had postnatal medical illness than the ADHD-C group. There were no significant differences in the genotype frequencies of the dopamine transporter (DAT1) and the serotonin transporter -linked polymorphic region (5-HTTLPR) polymorphisms between ADHD-I and ADHD-C groups. This study shows that the inattentive subtype of ADHD is different from the combined subtype in many parameters including severity of symptoms, comorbidity, neuropsychological characteristics, and environmental risk factors.