Influence of Biogenetic Explanations of Mental Disorders on Stigma and Help-Seeking Behavior: A Systematic Review and Meta-Analysis.

BACKGROUND: Biogenetic causal explanations of mental disorders are commonly used for public education and campaigns. However, the influence of biogenetic explanations on the ideas about and attitudes toward mental illness is unclear. We examined the influence of biogenetic explanations on attitudes toward mental disorders using a meta-analytic method accompanied by subgroup analyses. METHODS: The protocol for this meta-analysis was registered in PROSPERO (CRD42020158656) in March 2020. Experimental and correlational studies were analyzed separately. Five outcome measures related to attitudes toward mental disorders were included: 'attitude toward help-seeking,' 'blame,' 'perceived dangerousness,' 'prognostic pessimism,' and 'social distance.' Subgroup analyses were performed for the type of mental disorder, population, and geographic region for which a biogenetic explanation was provided. RESULTS: A total of 44 studies were included, of which 24 were experimental and 20 were correlational. A positive attitude toward help-seeking was associated with having a biogenetic concept (d = 0.43; 95% confidence interval [CI], 0.18 to 0.67; P < 0.001) in general population and in Eastern countries in particular. Although a biogenetic explanation was associated with a decreased level of blame (d = -0.20; 95% CI, -0.38 to -0.02; P = 0.029) in the general population, it was also associated with significantly higher levels of perceived dangerousness (d = 0.13; 95% CI, 0.03 to 0.23; P = 0.008). A tendency toward a higher level of prognostic pessimism and social distance was associated with a biogenetic concept of mental disorders although there was no statistical significance. CONCLUSION: Having a biogenetic concept of the cause of mental disorders was related with a positive attitude toward help-seeking, particularly in the general population and individuals living in Eastern countries. Providing a biogenetic explanation decreased blame toward individuals with mental illness but was associated with increased perceived dangerousness and prognostic pessimism. Therefore, although a biogenetic explanation promotes public use of mental health services, it should be carefully applied to avoid an increase in negative thoughts, such as that mental illness is biologically irreversible and untreatable.

The effect of an immersive virtual reality tour of the operating theater on emergence delirium in children undergoing general anesthesia: A randomized controlled trial.

BACKGROUND AND AIMS: An immersive virtual reality tour of the operating theater could reduce preoperative anxiety. This study was designed to determine whether a preoperative immersive virtual reality tour demonstrates a reduction in emergence delirium through reducing the preoperative anxiety in children undergoing general anesthesia. METHODS: Eighty-six children were randomly allocated into either the control or virtual reality group. The control group received conventional education regarding the perioperative process. The virtual reality group watched a 4-minute virtual reality video showing the operating theater and explaining the perioperative process. Incidence and severity of emergence delirium were the main outcomes. Secondary outcomes included preoperative anxiety using modified Yale Preoperative Anxiety Scale and postoperative behavioral disturbance. RESULTS: Eighty children completed the final analysis (control group = 39, virtual reality group = 41). The incidence (risk ratio [95% CI]: 1.1 [0.5-2.8], P = 0.773) and severity of emergence delirium (mean difference [95% CI]: -0.2 [-2.7 to 2.2], P = 0.791) were similar in the two groups. After the intervention, children in the virtual reality group had a significantly lower modified Yale Preoperative Anxiety score than those in the control group (mean difference [95% CI]: 9.2 [0.3-18.2], P = 0.022). No difference was observed regarding postoperative behavioral disturbance between the two groups at postoperative 1 day (mean difference [95% CI]: -0.1 [-0.3 to 0.1], P = 0.671) and 14 day (mean difference [95% CI]: -0.0 [-0.1 to 0.0], P = 0.329). CONCLUSION: Preoperative immersive virtual reality tour of the operating theater did not reduce the incidence and severity of emergence delirium, although it was effective in alleviating preoperative anxiety in children.

Trends in Digital Media Use in Korean Preschool Children.

BACKGROUND: Children today are exposed to various media devices, and their usage of these is increasing. Prior studies have outlined forms of harm this can potentially cause. However, there has been little empirical research on the use of media devices among preschool children in Asia. The aim of this study was to examine and analyze longitudinal trends in media device use among Korean preschool children, focusing on the frequency of engagement, time spent with, and ownership of media devices, delineated by sex. METHODS: Four hundred parents of children aged 2-5 years were invited to enroll. The baseline assessment, Wave 1, was conducted between December 2015 and June 2016, and follow-up assessments, Wave 2 and Wave 3, were conducted annually for the following 2 years. Time of media use, frequency of media use, and ownership of media devices (TV, tablet PCs, and smartphones) were investigated. RESULTS: Ownership of tablet PCs increased significantly between Wave 1 and Wave 3 for boys and girls (corrected P < 0.001). Frequency of media use increased significantly between Wave 1 and Wave 3 only in boys' use of tablet PCs (mean difference 0.8 day/wk). Time of media use increased significantly between Wave 1 and Wave 3 for both sexes in all devices, measured by mean difference on weekdays and weekends (TV by 0.6 and 0.7 hr/day, tablet PCs by 0.6 and 0.8 hr/day, and smartphones by 0.4 and 0.4 hr/day). Children spent more time using media devices during weekends than on weekdays. CONCLUSION: This study observed an increase in the tendency of media device use among preschool children in Korea. The patterns of use indicate that paying attention to the types of devices children use is needed, as well as vigilance on weekends.

Maternal Depression and Children's Screen Overuse.

BACKGROUND: It is known that there are various factors associated with children's screen overuse. The aim of this study was to examine the effect of maternal depression on 2-5-year-old children's overuse of various household screen devices. METHODS: Participants were from the Internet-Cohort for Understanding of internet addiction Risk factors/Rescue in Early livelihood (I-CURE) study, an observational prospective cohort study in Korea. Screen time for six types of screen devices (smartphone, television, computer, tablet, video gaming console, and portable gaming console) were assessed by parental questionnaire. Maternal depression was measured by the Korean version of the Beck Depression Inventory II. Logistic regression models were run to determine the association between maternal depression and children's screen overuse. RESULTS: Maternal depression was associated with children's television overuse after adjusting for other factors (odds ratio, 1.954; P = 0.034). Contrary to expectation, the relationship between maternal depression and screen time was not present on other devices such as smartphones, computers and tablets. CONCLUSION: Maternal depression is related with 2-5-year-old children's television overuse. Interventions in maternal depressive symptoms and the associated changes in parent-child relationship can be useful for preventing children's television overuse.

Re-adjusting the cut-off score of the Korean version of the Childhood Autism Rating Scale for high-functioning individuals with autism spectrum disorder.

AIM: The current cut-off score of the Korean version of the Childhood Autism Rating Scale (K-CARS) does not seem to be sensitive enough to precisely diagnose high-functioning autism. The aim of this study was to identify the optimal cut-off score of K-CARS for diagnosing high-functioning individuals with autism spectrum disorders (ASD). METHODS: A total of 329 participants were assessed by the Korean versions of the Autism Diagnostic Interview - Revised (K-ADI-R), Autism Diagnostic Observation Schedule (K-ADOS), and K-CARS. IQ and Social Maturity Scale scores were also obtained. RESULTS: The true positive and false negative rates of K-CARS were 77.2% and 22.8%, respectively. Verbal IQ (VIQ) and Social Quotient (SQ) were significant predictors of misclassification. The false negative rate increased to 36.0% from 19.8% when VIQ was >69.5, and the rate increased to 44.1% for participants with VIQ > 69.5 and SQ > 75.5. In addition, if SQ was >83.5, the false negative rate increased to 46.7%, even if the participant's VIQ was ≤69.5. Optimal cut-off scores were 28.5 (for VIQ ≤ 69.5 and SQ ≤ 75.5), 24.25 (for VIQ > 69.5 and SQ > 75.5), and 24.5 (for SQ > 83.5), respectively. CONCLUSION: The likelihood of a false negative error increases when K-CARS is used to diagnose high-functioning autism and Asperger's syndrome. For subjects with ASD and substantial verbal ability, the cut-off score for K-CARS should be re-adjusted and/or supplementary diagnostic tools might be needed to enhance diagnostic accuracy for ASD.

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.

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.

Abnormal Electroencephalogram Findings and Its Correlation With Clinical Features From Pediatric Patients in Psychiatric Clinic.

Objective: We aimed to evaluate the occurrence of electroencephalogram (EEG) abnormalities in pediatric patients attending an outpatient psychiatry clinic at a tertiary center. We examined the rates of abnormalities and specific findings based on demographics, specific diagnoses, and clinical severity. Methods: This study included pediatric patients who underwent EEG at the outpatient psychiatry clinic. Patient demographics, psychiatric diagnosis, intellectual disability, intelligent quotient (IQ) score, family history of psychiatric disorders, and Clinical Global Impression-Severity (CGI-S) score were obtained through retrospective electronic health record analysis. The rate of EEG abnormalities was calculated, and specific abnormal findings were reviewed. Relationships between the rate of EEG abnormalities and diagnosis, severity, IQ, and age at EEG examination were analyzed. Results: Of 319 patients who underwent EEG, 21.3% (68 patients) of patients exhibited abnormalities, including background abnormalities (14.7%, 47 patients), interictal epileptiform discharges (IEDs) (10.3%, 33 patients), and a slow posterior dominant rhythm (3.8%, 10 patients). The frontal region was the most commonly affected area. Neurodevelopmental disorders (NDDs) had the most frequent abnormalities (29.8%), followed by anxiety (16.7%), sleep (14.3%), mood (11.7%), psychotic (5%), and conduct disorders (0%). Disease severity did not correlate with the rate of EEG abnormalities. Adjusted for age, sex, severity, and family history, patients with EEG abnormalities exhibited lower IQ scores. Conclusion: EEG abnormalities were common in pediatric patients with psychiatric disorders, with background abnormalities detected as frequently as IEDs. Disease severity was not associated with EEG abnormality, while IQ scores showed a negative correlation.

Classifying autism in a clinical population based on motion synchrony: a proof-of-concept study using real-life diagnostic interviews.

Predictive modeling strategies are increasingly studied as a means to overcome clinical bottlenecks in the diagnostic classification of autism spectrum disorder. However, while some findings are promising in the light of diagnostic marker research, many of these approaches lack the scalability for adequate and effective translation to everyday clinical practice. In this study, our aim was to explore the use of objective computer vision video analysis of real-world autism diagnostic interviews in a clinical sample of children and young individuals in the transition to adulthood to predict diagnosis. Specifically, we trained a support vector machine learning model on interpersonal synchrony data recorded in Autism Diagnostic Observation Schedule (ADOS-2) interviews of patient-clinician dyads. Our model was able to classify dyads involving an autistic patient (n = 56) with a balanced accuracy of 63.4% against dyads including a patient with other psychiatric diagnoses (n = 38). Further analyses revealed no significant associations between our classification metrics with clinical ratings. We argue that, given the above-chance performance of our classifier in a highly heterogeneous sample both in age and diagnosis, with few adjustments this highly scalable approach presents a viable route for future diagnostic marker research in autism.

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.

Methylphenidate-osmotic-controlled release oral delivery system treatment reduces parenting stress in parents of children and adolescents with attention-deficit/hyperactivity disorder.

OBJECTIVE: The aim of the current study was to investigate the effect of methylphenidate-osmotic release oral delivery system (MPH-OROS) treatment on parenting stress in parents of children and adolescents with attention-deficit/hyperactivity disorder (ADHD). METHODS: Four hundred and ninety-five children and adolescents (391 boys and 104 girls), aged 7 to 18 years who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria for ADHD, were recruited at 48 psychiatric outpatient clinics across South Korea. Children's symptoms, parenting stress, and parental depression were assessed at baseline, week 4, and week 8 of MPH-OROS treatment using the Korean version of the DuPaul's ADHD Rating Scale (ARS), the Beck's Depression Inventory (BDI), and the Parenting Stress Index, Short Form (PSI-SF). RESULTS: We found significantly decreased scores of ARS, parental BDI, and PSI-SF from baseline to week 4 and from week 4 to week 8. Also, there were positive correlations among baseline PSI-SF, ARS, and BDI scores. The changes in BDI and ARS scores were significantly associated with the PSI score changes, accounting for 20.1% and 10.0%, respectively. CONCLUSIONS: We suggest that the increased parenting stress and depression in parents of children and adolescents with ADHD can be improved following the treatment with MPH-OROS.

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.

Effects of Ephedrine-Containing Products on Weight Loss and Lipid Profiles: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Ephedrine, the main active ingredient of mahuang, may lead to weight loss; however, it can also induce cardiovascular side effects. As ephedrine use remains controversial, this study aimed to systematically review previous studies on ephedrine-containing products and perform meta-analysis of the existing evidence on weight, blood pressure (BP), heart rate, and lipid change effects of ephedrine-containing products. We searched for placebo-controlled randomized studies in PubMed, Web of Science, and EMBASE until July 2021 using the following search terms: (ephedr* OR mahuang) AND ("weight loss" OR obes* OR overweight). Mean differences (MDs) and 95% confidence intervals (CIs) were calculated to evaluate the effects of ephedrine-containing products on weight, BP, heart rate, and lipid profiles. A total of 10 articles were included. Compared with the placebo group, the ephedrine-containing product group was associated with greater weight loss, with an MD of -1.97 kg (95% CI: -2.38, -1.57). In the ephedrine-containing product group, the mean heart rate was 5.76 beats/min higher than in the placebo group (95% CI: 3.42, 8.10), whereas intergroup differences in systolic and diastolic BP were not statistically significant. The ephedrine-containing product group had a significantly higher mean high-density lipoprotein cholesterol level (MD: 2.74 mg/dL; 95% CI: 0.94, 4.55), lower mean low-density lipoprotein cholesterol level (MD: -5.98 mg/dL; 95% CI: -10.97, -0.99), and lower mean triglyceride level (MD: -11.25 mg/dL; 95% CI: -21.83, -0.68) than the placebo group. Compared with placebo, the ephedrine-containing products showed better effects on weight loss and lipid profiles, whereas they caused increased heart rate. The ephedrine-containing products may be beneficial to obese or overweight patients; however, close monitoring is needed, especially heart rate monitoring.

The Relationship between Mother's Smartphone Addiction and Children's Smartphone Usage.

OBJECTIVE: As smartphone use is becoming more common, the age of initial exposure to devices is becoming younger. Young children's screen use is influenced by various factors; it is more directly dependent on family environment than school-aged children. Our study aimed to examine the effect of mother's smartphone addition on their child's smartphone use. METHODS: Participants were from the Kids Cohort for Understanding of internet addiction Risk factors in early childhood (K-CURE) study. Adult smartphone addiction self-diagnosis scale was used to evaluate smartphone addiction degree of mother. Child's smartphone use was assessed by parental questionnaire. Using logistic regression analysis, we examine the association between mother's smartphone addiction and child's smartphone use. RESULTS: After adjusting for other factors, mother's smartphone addiction is related with early smartphone exposure of children. Highrisk group's children was exposed to smartphone earlier than low risk group (adjusted OR, 0.418; p=0.021). Contrary to expectation, there is no correlation between mother's smartphone addiction and child's smartphone use time. CONCLUSION: Our study explain that mother's smartphone addiction can affect early smartphone exposure on children. Based on our findings, further study might explore the effect of early smartphone exposure on children.

Virtual Reality vs. Tablet Video as an Experiential Education Platform for Pediatric Patients Undergoing Chest Radiography: A Randomized Clinical Trial.

Virtual reality (VR), which offers an immersive experience, has been implemented into the education of pediatric patients to reduce peri-procedural anxiety. This randomized clinical trial evaluated the effect of VR, compared with standard video, on reducing anxiety and distress in pediatric patients undergoing chest radiography. A total of 120 children aged 4 to 8 years with scheduled chest radiography appointments were randomized into either the tablet or the VR group. Children in the tablet group experienced chest radiography indirectly with a 3 min tablet video, whereas those in the VR group received the same content via a VR experience. The distress of children was measured using the Observational Scale of Behavioral Distress (OSBD) scale. Parental presence and procedural outcomes were also recorded. The number of less distressed children (OSBD score < 5) was significantly higher in the VR group than in the tablet group (49 [81.7%]) vs. 32 [53.3%]) (p = 0.001). The OSBD scores, the need for parental presence, the procedure time, and the number of repeated procedures were all lower in the VR group. The immersive VR experience appears to decrease the degree of anxiety in children and increase the efficiency of the procedures compared with the tablet video with the same content.

Derivation of iPSC lines from two idiopathic ASD patients (OFi001-A, OFi002-A).

Here we described two human induced pluripotent stem cell (hiPSC) lines from peripheral blood mononuclear cells (PBMCs) of idiopathic autism spectrum disorder (ASD) patients through forced expression of OCT4, SOX2, KLF4, and c-MYC. The hiPSC lines displayed morphology, gene expression patterns, and pluripotential differentiation potentials similar to those of human embryonic stem cells (hESCs). The hiPSC lines from idiopathic ASD patients might be useful to unveil the underlying mechanism of idiopathic ASD and finding its therapeutics.

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.

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.