GAD1 gene polymorphisms are associated with hyperactivity in Attention-Deficit/Hyperactivity Disorder.

Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders of childhood. Recent studies suggest a role for γ-aminobutyric acid (GABA) on ADHD hyperactive/impulsive symptoms due to behavioral disinhibition resulting from inappropriate modulation of both glutamatergic and GABAergic signaling. The glutamic acid decarboxylase (GAD1) gene encodes a key enzyme of GABA biosynthesis. The aim of the present study was to investigate the possible influence of GAD1 SNPs rs3749034 and rs11542313 on ADHD susceptibility. The clinical sample consisted of 547 families with ADHD probands recruited at the ADHD Outpatient Clinics from Hospital de Clínicas de Porto Alegre. Hyperactive/impulsive symptoms were evaluated based on parent reports from the Swanson, Nolan, and Pelham Scale-version IV (SNAP-IV). The C allele of rs11542313 was significantly overtransmitted from parents to ADHD probands (P = 0.02). Hyperactive/impulsive score was higher in rs3749034G allele (P = 0.005, Cohen's D = 0.19) and rs11542313C allele (P = 0.03; Cohen's D = 0.16) carriers. GAD1 haplotypes were also associated with higher hyperactive/impulsive scores in ADHD youths (global P-value = 0.01). In the specific haplotype test, the GC haplotype was the one with the highest hyperactive/impulsive scores (P = 0.03). Our results suggest that the GAD1 gene is associated with ADHD susceptibility, contributing particularly to the hyperactive/impulsive symptom domain. © 2016 Wiley Periodicals, Inc.

Cadherin-13 gene is associated with hyperactive/impulsive symptoms in attention/deficit hyperactivity disorder.

Several efforts have been made to find new genetic risk variants which explain the high heritability of ADHD. At the genome level, genes involved in neurodevelopmental pathways were pointed as candidates. CDH13 and CTNNA2 genes are within GWAS top hits in ADHD and there are emerging notions about their contribution to ADHD pathophysiology. The main goal of this study is to test the association between SNPs in CDH13 and CTNNA2 genes and ADHD across the life cycle in subjects with ADHD. This study included 1,136 unrelated ADHD cases and 946 individuals without ADHD. No significant association between CDH13 and CTNNA2 was observed between cases and controls across different samples (P ≥ 0.096 for all comparisons). No allele was significantly more transmitted than expected from parents to ADHD probands. The CDH13 rs11150556 CC genotype was associated with more hyperactive/impulsive symptoms in youths with ADHD (children/adolescents clinical sample: F = 7.666, P = 0.006, FDR P-value = 0.032; Pelotas Birth Cohort sample: F = 6.711, P = 0.011, FDR P-value = 0.032). Although there are many open questions regarding the role of neurodevelopmental genes in ADHD symptoms, the present study suggests that CDH13 is associated with hyperactive/impulsive symptoms in youths with ADHD.

Insomnia Polygenic Component on Attention Deficit-Hyperactivity Disorder: Exploring this Association Using Genomic Data from Brazilian Families.

Introduction Insomnia is highly prevalent among individuals with Attention-Deficit/Hyperactivity Disorder (ADHD). However, the biological mechanisms shared between both conditions is still elusive. We aimed to investigate whether insomnia's genomic component is able to predict ADHD in childhood and adolescence. Methods A Brazilian sample of 259 ADHD probands and their biological parents were included in the study. Their genomic DNA genotypes were used to construct the polygenic risk score for insomnia (Insomnia PRS), using the largest GWAS summary statistics as a discovery sample. The association was tested using logistic regression, under a case-pseudocontrol design. Results Insomnia PRS was nominally associated with ADHD (OR = 1.228, p = 0.022), showing that the alleles that increase the risk for insomnia also increase the risk for ADHD. Discussion Our results suggest that genetic factors associated with insomnia may play a role in the ADHD genetic etiology, with both phenotypes likely to have a shared genetic mechanism.

Assessing the role of protected areas in the land-use change dynamics of a biodiversity hotspot.

Although protected areas (PAs) are designed to safeguard natural ecosystems from anthropic modifications, many PAs worldwide are subjected to numerous human-induced impacts. We evaluated whether the establishment of PAs in the Upper Paraná River floodplain region could reduce anthropic landscape changes and whether there is a difference in protection when using different PA restriction categories. We analyzed the overall landscape dynamics using 30 years of land-use time series data and evaluated the change intensity via a partial land-use intensity analysis. Despite the increasing landscape anthropization, the PAs seemed to relieve the general change process, protecting natural areas mainly from agricultural expansion. Concerning the degree of use restriction, more restricted protection led to less human-induced changes. Finally, accessing PA effectiveness is a multidisciplinary challenge for researchers; however, this knowledge is crucial to avoid misunderstandings or poorly crafted public policies or decisions that may harm the environment.

Cathechol-O-methyltransferase Val(158)Met polymorphism is associated with disruptive behavior disorders among children and adolescents with ADHD.

COMT Val(158)Met polymorphism has been associated with both symptoms of attention-deficit/hyperactivity disorder (ADHD) and disruptive behavior disorders (DBD): that is, oppositional defiant disorder (ODD) and conduct disorder (CD) often comorbid with ADHD. The aim of this study was to test the association between COMT Val(158)Met polymorphism and the presence of DBD in children with ADHD (n = 516). Homozygous Val/Val children showed a higher prevalence of ADHD comorbid with DBD (χ(2) = 5.762; p = 0.016; OR = 1.58; CI(95%) = 1.07-2.35). Our findings replicate previous results and suggest a role for COMT in the etiology of DBD in children and adolescents with ADHD.

Stress-related genetic components in attention-deficit/hyperactivity disorder (ADHD): Effects of the SERPINA6 and SERPINA1 genetic markers in a family-based brazilian sample.

SERPINA6 and SERPINA1 were recently identified as the main genes associated with plasma cortisol concentration in humans. Although dysregulation in the Hypothalamus-Pituitary-Adrenal (HPA) axis has been observed in Attention Deficit/Hyperactivity Disorder (ADHD), the molecular mechanisms underlying this relationship are still unclear. Evaluation of the SERPINA6/SERPINA1 gene cluster in ADHD may provide relevant information to uncover them. We tested the association between the SERPINA6/SERPINA1 locus, including 95 single nucleotide polymorphisms (SNPs), and ADHD, using data from a Brazilian clinical sample of 259 ADHD probands and their parents. The single SNP association was tested using binary logistic regression, and we performed Classification and Regression Tree (CART) analysis to evaluate genotype combinations' effects on ADHD susceptibility. We assessed SNPs' regulatory effects through the Genotype-Tissue Expression (GTEx) v8 tool, and performed a complementary look-up analysis in the largest ADHD GWAS to date. There was a suggestive association between ADHD and eight variants located in the SERPINA6 region and one in the intergenic region between SERPINA6 and SERPINA1 after correction for multiple tests (p < 0.032). CART analysis showed that the combined effects of genotype GG in rs2144833 and CC in rs10129500 were associated with ADHD (OR = 1.78; CI95% = 1.24-2.55). The GTEx assigned the SNPs as eQTLs for genes in different tissues, including SERPINA6, and the look-up analysis revealed two SNPs associated with ADHD. These results suggest a shared genetic component between cortisol levels and ADHD. HPA dysregulation/altered stress response in ADHD might be mediated by upregulation of corticosteroid binding globulin (CBG, encoded by SERPINA6) expression.

Are family variables associated with ADHD, inattentive type? A case-control study in schools.

Attention-deficit/hyperactivity disorder (ADHD) seems to be associated with significant psychosocial adversity. However, few studies assessed the role of environmental, social and interpersonal factors specifically in ADHD, inattentive type (ADHD-I). Thus, this study aims to investigate whether family environment risk factors are associated with ADHD-I. In a case-control study, we assessed a non-referred sample of 100 children and adolescents with ADHD-I and 100 non-ADHD controls (6-18 years old). They were systematically evaluated through structured diagnostic interviews. The following family adversity measures were used: Rutter's family adversity index (marital discord, low social class, large family size, paternal criminality, maternal mental disorder), Family Environment Scale (FES) (subscores of cohesion, expressiveness and conflict) and Family Relationship Index (FRI) (based on the subscores above). After adjusting for confounding factors (social phobia and maternal history of ADHD), the odds ratio (OR) for ADHD-I increased as the number of Rutter's indicators increased. Families of children with lower FES cohesion subscores presented higher OR for ADHD-I (OR 1.24; 95% confidence interval 1.05-1.45). Lower levels of FRI, a general index of family relationship, were also related to higher risk of ADHD-I (OR 1.11; 95% confidence interval 1.03-1.21). Our findings suggest that family adversity (in general), low family cohesion and low FRI (in particular) are associated with an increase in the risk for ADHD-I. However, the cross-sectional nature of the study limits our ability to infer causality.

Computerized Cognitive Training for ADHD as an Add-On Treatment to Stimulants: A Randomized Clinical Trial.

Objective: Computerized cognitive training (CCT) as add-on treatment to stimulants for ADHD core symptoms is scarcely investigated. The purpose of this study is to assess the effect of CCT in a randomized controlled clinical trial for ADHD in children and adolescents treated with stimulants. Method: Fifty-three participants aged 6 to 13 years receiving stimulant treatment and presenting ADHD residual symptoms were randomized either to a CCT (n = 29) or to a controlled nonactive condition (n = 24) for four sessions/week during 12 weeks. The main outcome measure was inattentive symptoms assessed using the Swanson, Nolan, and Pelham-IV (SNAP-IV) Scale. Secondary outcomes include, among others, hyperactive/impulsive symptoms and cognitive tests. Results: There were neither significant group differences on ADHD-inattentive symptoms after the intervention nor on both ADHD-hyperactivity/impulsivity symptoms and cognitive measures. Conclusion: Our study does not provide evidence for the benefits of cognitive training over nonactive training on core ADHD symptoms in medicated ADHD children and adolescents.

Do hyperactive symptoms matter in ADHD-I restricted phenotype?

The objective of the current study was to evaluate a proposed restrictive inattentive type of Attention Deficit Hyperactivity Disorder (ADHD) by comparing clinical correlates among youths with ADHD inattentive type (ADHD-I) as a function of the number of hyperactivity symptoms presented (none vs. 3 or less) and controls (individuals without ADHD). The sample for this community-based study was comprised of youths aged 6 to 18 years from 12 public schools in Porto Alegre, Brazil. ADHD-I groups had lower levels of adaptive functioning (p < .001) and a higher occurrence of familial ADHD (p < .001) when compared with the controls. There was no significant difference between the two ADHD-I groups. Also, both ADHD-I groups had higher rates of oppositional defiant disorder than controls (p < .001) without significant difference between them. For generalized anxiety disorder and social phobia, only the ADHD-I without HI group showed significant differences compared to controls.

Food intake and serum levels of iron in children and adolescents with attention-deficit/hyperactivity disorder.

OBJECTIVE: To investigate hematologic variables related to iron deficiency and food intake in attention-deficit/hyperactivity disorder. METHOD: The sample comprised 62 children and adolescents (6-15 years old) divided into three groups: Group 1: 19 (30.6%) patients with attention-deficit/hyperactivity disorder using methylphenidate for 3 months; Group 2: 22 (35.5%) patients with attention-deficit/hyperactivity disorder who were methylphenidate naive and Group 3: 21 (33.9%) patients without attention-deficit/hyperactivity disorder. Serum iron, ferritin, transferrin, hemoglobin, mean corpuscular volume, red cell distribution width, mean corpuscular hemoglobin concentration, nutritional diagnostic parameters - Body Mass Index Coefficient, food surveys were evaluated among the groups. RESULTS: The attention-deficit/hyperactivity disorder group drug naive for methylphenidate presented the highest red cell distribution width among the three groups (p = 0.03). For all other hematologic and food survey variables, no significant differences were found among the groups. No significant correlation between dimensional measures of attention-deficit/hyperactivity disorder symptoms and ferritin levels was found in any of the three groups. CONCLUSION: Peripheral markers of iron status and food intake of iron do not seem to be modified in children with attention-deficit/hyperactivity disorder, but further studies assessing brain iron levels are needed to fully understand the role of iron in attention-deficit/hyperactivity disorder pathophysiology.

Effects of computerized cognitive training as add-on treatment to stimulants in ADHD: a pilot fMRI study.

The neurofunctional effects of Cognitive training (CT) are poorly understood. Our main objective was to assess fMRI brain activation patterns in children with ADHD who received CT as an add-on treatment to stimulant medication. We included twenty children with ADHD from a clinical trial of stimulant medication and CT (10 in medication + CT and 10 in medication + non-active training). Between-group differences were assessed in performance and in brain activation during 3 fMRI paradigms of working memory (N-back: 0-back, 1-back, 2-back, 3-back), sustained attention (Sustained Attention Task - SAT: 2 s, 5 s and 8 s delays) and inhibitory control (Go/No-Go). We found significant group x time x condition interactions in working memory (WM) and sustained attention on brain activation. In N-back, decreases were observed in the BOLD signal change from baseline to endpoint with increasing WM load in the right insula, right putamen, left thalamus and left pallidum in the CT compared to the non-active group; in SAT - increases in the BOLD signal change from baseline to endpoint with increasing delays were observed in bilateral precuneus, right insula, bilateral associative visual cortex and angular gyrus, right middle temporal, precentral, postcentral, superior frontal and middle frontal gyri in the CT compared to the non-active group. CT in ADHD was associated with changes in activation in task-relevant parietal and striato-limbic regions of sustained attention and working memory. Changes in brain activity may precede behavioral performance modifications in working memory and sustained attention, but not in inhibitory control.

Further evidence for the association between attention deficit/hyperactivity disorder and the serotonin receptor 1B gene.

Several evidences suggested that the serotonin 5-HT1B receptor gene (HRT1B) might be involved in the susceptibility to attention deficit/hyperactivity disorder (ADHD). Prior studies reported excess transmissions of the HRT1B gene 861G allele to affected ADHD children and of a haplotype block containing this variant and two functional promoter SNPs to probands with ADHD-inattentive subtype. However, some investigations did not replicate these findings. Therefore, we tested for biased transmissions of haplotypes derived from the 861G > C, -161A > T, and -261T > G SNPs from parents to 343 families with ADHD children. We also sought to replicate findings from the literature that the association between HTR1B is preferentially with ADHD-Inattentive subtype. Using a transmission disequilibrium test we found evidence for an excess transmission of haplotype. -261G/-161T/861G (P = 0.014) for affected children in the total sample. When the analysis was repeated with 143 families with ADHD-Inattentive subtype no significant associations were observed. Our results provide additional evidence that HRT1B gene may be an important risk factor for the development of ADHD, but this effect seems not to be attributable to inattentive cases.

CLOCK Polymorphisms in Attention-Deficit/Hyperactivity Disorder (ADHD): Further Evidence Linking Sleep and Circadian Disturbances and ADHD.

Circadian and sleep disorders, short sleep duration, and evening chronotype are often present in attention-deficit/hyperactivity disorder (ADHD). CLOCK, considered the master gene in the circadian rhythm, has been explored by few studies. Understanding the relationship between ADHD and CLOCK may provide additional information to understand the correlation between ADHD and sleep problems. In this study, we aimed to explore the association between ADHD and CLOCK, using several genetic markers to comprehensively cover the gene extension. A total of 259 ADHD children and their parents from a Brazilian clinical sample were genotyped for eight single nucleotide polymorphisms (SNPs) in the CLOCK locus. We tested the individual markers and the haplotype effects using binary logistic regression. Binary logistic and linear regressions considering ADHD symptoms among ADHD cases were conducted as secondary analysis. As main result, the analysis showed a risk effect of the G-A-T-G-G-C-G-A (rs534654, rs1801260, rs6855837, rs34897046, rs11931061, rs3817444, rs4864548, rs726967) haplotype on ADHD. A suggestive association between ADHD and rs534654 was observed. The results suggest that the genetic susceptibility to circadian rhythm attributed to the CLOCK gene may play an important role on ADHD.

An overview of fish stocking in Brazil

Fish stocking is a common management strategy in Brazil, yet no assessment has examined its real extent and features. The present work investigated fish stocking practices in Brazil between 2010 and 2019 to characterize propagule pressure, species composition, the use of non-native species, geographical and temporal trends, environment types, and responsible agencies. Based on information disseminated on the internet, the study detected 1,155 stocking events (ca. 115 events/year). In total, ca. 56.4 million fish were stocked, with an average of ca. 90 thousand fish/event. We found events in all Brazilian regions involving 436 municipalities and 21 states. Most events occurred in the Northeast region (66.3%), which received alone ca. 41 million fish. Reservoirs were the primary target environment, and the public sector conducted most events. Fish stocking involved 63 taxa, including 14 non-native taxa and three hybrids. Considering the events that informed composition, 62.4% released non-native species, which summed 19.7 million fish. These results provide a broad overview of fish stocking practices in Brazil, and reveal that this action is widely disseminated. Its frequent use, associated with the lack of proper criteria and the illegal stocking of non-native species, raise concerns about technical aspects, outcomes, and potential environmental impacts.

A estocagem de peixes é uma estratégia de manejo comum no Brasil, mas nenhum estudo investigou sua real extensão e características. O presente trabalho investigou práticas de estocagem de peixes realizadas no Brasil entre 2010 e 2019, para caracterizar a pressão de propágulos, composição de espécies, participação de espécies não-nativas, variação espaço-temporal, ambientes e órgãos responsáveis. Com base em informações divulgadas na internet, o estudo detectou 1155 eventos de estocagem (ca. 115 eventos/ano). No total, ca. 56,4 milhões de peixes foram liberados, com média de ca. 90 mil peixes/evento. Encontramos eventos em todas as regiões brasileiras, envolvendo 436 municípios e 21 estados. A região nordeste somou a maioria dos casos (66,3%), e sozinha recebeu cerca de 41 milhões de peixes. Os reservatórios foram o principal ambiente alvo, sendo o setor público o principal responsável pelas ações. A estocagem de peixes envolveu 63 táxons, incluindo 14 táxons não-nativos e três híbridos. Considerando os eventos que informaram a composição das espécies, 62,4% liberaram espécies não-nativas, que somaram 19,7 milhões de peixes. Estes resultados fornecem um amplo panorama das práticas de estocagem de peixes no Brasil, e revelam que essa ação de manejo é amplamente disseminada. Seu uso frequente, associado com a falta de critérios apropriados e a soltura ilegal de espécies não-nativas, suscita preocupações quanto a aspectos técnicos, resultados, e potenciais impactos ambientais.

Computerized cognitive training in children and adolescents with attention deficit/hyperactivity disorder as add-on treatment to stimulants: feasibility study and protocol description.

Background: Cognitive training has received increasing attention as a non-pharmacological approach for the treatment of attention deficit/hyperactivity disorder (ADHD) in children and adolescents. Few studies have assessed cognitive training as add-on treatment to medication in randomized placebo controlled trials. The purpose of this preliminary study was to explore the feasibility of implementing a computerized cognitive training program for ADHD in our environment, describe its main characteristics and potential efficacy in a small pilot study. Methods: Six ADHD patients aged 10-12-years old receiving stimulants and presenting residual symptoms were enrolled in a randomized clinical trial to either a standard cognitive training program or a controlled placebo condition for 12 weeks. The primary outcome was core ADHD symptoms measured using the Swanson, Nolan and Pelham Questionnaire (SNAP-IV scale). Results: We faced higher resistance than expected to patient enrollment due to logistic issues to attend face-to-face sessions in the hospital and to fill the requirement of medication status and absence of some comorbidities. Both groups showed decrease in parent reported ADHD symptoms without statistical difference between them. In addition, improvements on neuropsychological tests were observed in both groups - mainly on trained tasks. Conclusions: This protocol revealed the need for new strategies to better assess the effectiveness of cognitive training such as the need to implement the intervention in a school environment to have an assessment with more external validity. Given the small sample size of this pilot study, definitive conclusions on the effects of cognitive training as add-on treatment to stimulants would be premature.

Association between alpha-2a-adrenergic receptor gene and ADHD inattentive type.

BACKGROUND: Previous investigations have demonstrated that an MspI polymorphism at the adrenergic alpha2A receptor gene (ADRA2A) is associated with severity of attention-deficit/hyperactivity disorder (ADHD) inattentive symptoms in clinical samples composed mainly of subjects with ADHD, combined type. This study aimed to investigate the association between this ADRA2A polymorphism and attention-deficit/hyperactivity disorder-inattentive type (ADHD-I) in a nonreferred sample. METHODS: In a case-control study, we assessed a sample of 100 children and adolescents with ADHD-I and 100 non-ADHD controls. Cases and controls were matched by gender and age and were screened by using teacher reports in a revised version of the Swanson, Nolan, and Pelham rating scale at 12 schools. Psychiatric diagnoses were derived through structured diagnostic interviews. RESULTS: Homozygous subjects for the G allele at the ADRA2A had significantly higher odds ratio (OR) for ADHD-I than did those with other genotypes (CC + CG genotypes), even after adjusting for potential confounders (p = .02; OR = 3.78; 95% confidence interval = 1.23-11.62). In family-based analyses, no significant associations were detected. CONCLUSIONS: Our results suggest that the ADRA2A may be associated with ADHD-I, replicating previous findings from clinical samples that have suggested the importance of this gene for the dimension of inattention. In addition, these results support the role of the noradrenergic system in ADHD.

Smoking during pregnancy and attention-deficit/hyperactivity disorder, predominantly inattentive type: a case-control study.

OBJECTIVE: Few previous studies assessed specifically attention-deficit/hyperactivity disorder, predominantly inattentive subtype (ADHD-I) in nonreferred samples. This study investigated the association between ADHD-I and prenatal exposure to nicotine. METHOD: In a case-control study performed between September 2002 and April 2005, we assessed a nonreferred Brazilian sample of 100 children and adolescents with ADHD-I and 100 non-ADHD controls (6-18 years old). Cases and controls, matched by gender and age, were screened using teacher reports in the Swanson, Nolan, and Pelham-IV (SNAP-IV) scale. They were systematically evaluated through structured diagnostic interviews. Prenatal exposure to nicotine and potential confounding factors were evaluated by direct interview with mothers. RESULTS: Adjusting for confounding factors (maternal ADHD, oppositional defiant disorder, birth weight, and alcohol use during pregnancy), children whose mothers smoked>or=10 cigarettes per day during pregnancy presented a significantly higher odds ratio for ADHD-I than children who were not exposed to nicotine during pregnancy (odds ratio 3.44; 95% confidence interval 1.17-10.06). Dimensional analyses showed significantly higher inattentive scores in subjects whose mothers smoked>or=10 cigarettes per day than in others after adjusting for confounding factors (p=.002). CONCLUSIONS: In a nonreferred sample, the authors expanded to ADHD-I previous findings documenting the association between prenatal exposure to nicotine and broadly defined ADHD in clinical samples.

Attention-deficit/hyperactivity disorder in a diverse culture: do research and clinical findings support the notion of a cultural construct for the disorder?

There is still some debate in the literature whether Attention-Deficit Disorder/Hyperactivity (ADHD) is best conceptualized as a biological disorder or if it is best understood as a cultural construct. This review aims to contribute to disentangle this issue assessing clinical and research data on ADHD in a complete diverse culture from a developing country. We performed a systematic computerized review of the literature on ADHD in Brazil. All investigations were included if dealing with ADHD prevalence, etiology, symptomatological construct, or treatment. Findings were compared to those from studies in developed countries. The prevalence rates of ADHD (5.8% using DSM-IV criteria, 1.5% using ICD-10), the bi-dimensional factor construct extracted from factor analyses (inattention and hyperactivity/impulsivity), the pattern of ADHD comorbidity in clinical samples, the family genetic data suggesting a 39% family transmission in clinical samples and the role of some potential candidate genes in dopaminergic and noradrenergic systems, as well as data on the efficacy of methylphenidate in the disorder are all very similar to findings from developed countries. Taken together, these findings suggest that ADHD is not a cultural construct, reinforcing the importance of applying similar research methodology in different cultures to make findings comparable.

Juvenile bipolar disorder in Brazil: clinical and treatment findings.

BACKGROUND: Because few studies were conducted to evaluate bipolar disorder in children and adolescents outside North America, this investigation aims to describe clinical features, pattern of comorbidities, and response to pharmacologic treatment in a sample of youths with bipolar disorder (BD) from a pediatric psychopharmacology outpatient clinic in Brazil. METHODS: We performed a retrospective chart review of all patients under age 15 with BD diagnoses who were evaluated and treated in our clinic from 1998-2001. A comparison sample of subjects with attention-deficit/hyperactivity disorder (ADHD) without BD (n = 362) was also evaluated. RESULTS: The prevalence of juvenile BD in our sample was 7.2% (36/500) (95% confidence interval = 5.2-9.9). Irritable mood was detected in 91.7% of the bipolar patients. The main comorbidity found was ADHD (58.3%). Children with BD had significantly higher rates of abnormally elevated CBCL scores in the externalizing dimension, anxiety and depression, delinquent behavior, and aggressive behavior scales than ADHD subjects (p <.05). Most BD patients (78%) needed combination drug therapy to achieve symptomatic control. CONCLUSIONS: Our results replicate clinical and treatment findings from U.S. investigations in a different culture demonstrating that juvenile BD is not a rare disorder in clinical samples.

Further evidence for the association between attention-deficit/hyperactivity disorder and the dopamine-beta-hydroxylase gene.

Attention-deficit/hyperactivity disorder (ADHD) is a very common and heterogeneous psychiatric disorder of childhood with marked inattentive, hyperactive, and impulsive symptoms. The DBH gene, the locus that encodes the enzyme dopamine-beta-hydroxylase (DbetaH), seems to be an important candidate gene for association studies, since DbetaH catalyzes the conversion of dopamine to norepinephrine. The aim of this study was to test for association between the DBH gene and ADHD in a sample of 88 Brazilian nuclear families. Haplotype relative risk (HRR) analysis of the DBH TaqI restriction site polymorphism showed a preferential transmission of the TaqI A2 allele in our whole ADHD sample (chi(2)=3.61, one-tailed P=0.03). The significant effect of the A2 allele was stronger when only families with no ADHD parental diagnosis were considered (chi(2)=5.42, one-tailed P=0.01). Our results suggest a contribution of this gene to ADHD susceptibility, partially replicating previous findings that have demonstrated an association between the DBH TaqI A2 allele and ADHD.