Biomedical subjects

Luis A Rohde

Publications and source records attributed to Luis A Rohde.

13 recordsLinked to original sources

PubMed2007

A promoter polymorphism (-839 C > T) at the dopamine transporter gene is associated with attention deficit/hyperactivity disorder in Brazilian children.

The dopamine transporter (DAT) plays a key role in the regulation of dopaminergic neurotransmission and is also the major site of action for methylphenidate which is one of the main drugs used to treat attention deficit hyperactivity disorder (ADHD). Most association studies with ADHD have concentrated on the 3'-untranslated region of the gene (3'-UTR) mainly in a variable number of tandem repeat (VNTR) polymorphism, but these investigations have reported discordant results. In this study, we tested this VNTR polymorphism and an additional promoter polymorphism -839 C>T (Rs: 2652511) using family-based association analyses in a sample of 243 Brazilian ADHD children and adolescents and their parents. No significant linkage disequilibrium between the two polymorphisms was detected in this sample (D' = 0.56; P = 0.22). No evidence of association with the VNTR polymorphism was found. A significant association (P = 0.03) for biased transmission of the C allele at the -839 C>T polymorphism to ADHD children in the total sample was observed, which was strengthened when the analyses were restricted to the ADHD combined type (P = 0.004). Our results suggest a role for the promoter region of DAT1 gene in ADHD susceptibility in this Brazilian sample.

Attention Deficit Disorder with Hyperactivity↗

PubMed2007

Serotonin genes and attention deficit/hyperactivity disorder in a Brazilian sample: preferential transmission of the HTR2A 452His allele to affected boys.

Attention-deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders of childhood. The role of genetic factors in its etiology is strongly supported by family, adoption, and twin studies. Low serotonin activity has been associated in both animal and human studies with measures of impulsivity, aggression, and disinhibited behaviors, which make genes from the serotonin system reasonable candidates for ADHD susceptibility. In the present study, we investigated a polymorphism in the promoter region of the serotonin transporter (SLC6A4) and two polymorphisms (-1438 A > G and His452Tyr) in the serotonin 5-HTR2A receptor gene using family based association analyses in a sample of 243 Brazilian ADHD children and adolescents and their parents. No linkage disequilibrium between the two HTR2A polymorphisms was detected in this sample (P = 0.76). Considering several evidences from animal models for sexual dimorphism in serotonin genes expression, analyses were performed separately for the whole sample and for male probands. No evidences for biased transmissions of both HTR2A -1438 A > G and SLC6A4 polymorphisms to ADHD youths were observed. Preferential transmission of the HTR2A His452 allele was observed only in families with affected boys (P = 0.04). Our results suggest that findings from ADHD association studies for serotonin genes might be understood in the context of a gender effect, which may help to explain conflicting results in these association studies.

Adolescent↗

PubMed2006

Lack of gender effects on subtype outcomes in adults with attention-deficit/hyperactivity disorder: support for the validity of subtypes.

The aim of the present study is to verify if gender modifies the clinical, adaptative and psychological outcomes of adult attention-deficit/hyperactivity disorder (ADHD) subtypes. We evaluated 219 clinically referred adult patients. The interviews followed the DSM-IV criteria,using the K-SADS-E for ADHD and oppositional defiant disorder and SCID-IV for comorbidities. Regression models were used to analyze gender and subtype main effects and interactions in psychiatric outcomes. In the initial sample, 117 patients (53.5%) were of the combined subtype, 88 (40%) were inattentives and 14 (6.5%) hyperactives. There were no significant interactions between gender and subtype in any variable assessed. Men and women did not differ in the relative frequency of each subtype. Patients of the combined subtype in both genders presented a higher severity and increased rates of conduct and ODD disorders than inattentives. The main effects of gender and subtype in this sample are similar to those previously reported in other countries, suggesting the cross-cultural equivalence of the phenotype. The absence of significant interactions between gender and subtype suggests that, at least in clinical-based samples, DSM-IV adult ADHD subtypes present cross-gender validity.

Adult↗

PubMed2004

Joint analysis of the DRD5 marker concludes association with attention-deficit/hyperactivity disorder confined to the predominantly inattentive and combined subtypes.

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable, heterogeneous disorder of early onset, consisting of a triad of symptoms: inattention, hyperactivity, and impulsivity. The disorder has a significant genetic component, and theories of etiology include abnormalities in the dopaminergic system, with DRD4, DAT1, SNAP25, and DRD5 being implicated as major susceptibility genes. An initial report of association between ADHD and the common 148-bp allele of a microsatellite marker located 18.5 kb from the DRD5 gene has been followed by several studies showing nonsignificant trends toward association with the same allele. To establish the postulated association of the (CA)(n) repeat with ADHD, we collected genotypic information from 14 independent samples of probands and their parents, analyzed them individually and, in the absence of heterogeneity, analyzed them as a joint sample. The joint analysis showed association with the DRD5 locus (P=.00005; odds ratio 1.24; 95% confidence interval 1.12-1.38). This association appears to be confined to the predominantly inattentive and combined clinical subtypes.

Attention Deficit Disorder with Hyperactivity↗

PubMed2004

Weekend holidays during methylphenidate use in ADHD children: a randomized clinical trial.

OBJECTIVE: The aim of this study was to assess whether weekend drug holidays during methylphenidate (MPH) administration would change the efficacy and tolerability to the medication in male children with Attention-Deficit Hyperactivity Disorder (ADHD). METHODS: In a 28-day, double-blind study, children with diagnoses of ADHD were randomized to receive BID MPH for 7 days a week (n = 21) or to receive BID MPH on weekdays and a placebo on weekends (n = 19). Parents completed the Conners' Abbreviated Rating Scale (ABRS) to assess ADHD symptoms and the Barkley's Side Effect Rating Scale (SERS) to assess side effects on weekends. Teachers completed the ABRS on each Monday after weekends. RESULTS: Both groups showed a significant reduction on the ABRS over time as the dose was increased. However, the group difference in the ABRS scores was not statistically significant, either on weekend parent ratings (at the endpoint, p = 0.41; effect size = 0.26) or on teachers' ratings (at the endpoint, p = 0.99; effect size = 0.002). The omission of MPH on weekends was associated with significantly less severity of insomnia (F = 3.96, d.f. = 1, p = 0.05) and a trend for less interference on appetite (F = 3.18, d. f. = 1, p = 0.08). CONCLUSION: Our findings suggest that weekend holidays during MPH administration reduce the side effects of insomnia and appetite suppression without a significant increase in symptoms, either on weekends or in the first school day after them. Possible explanations for these findings (rate-dependent response or impact of demands of the environment) are discussed in this paper.

Adolescent↗

PubMed2004

[Recent advances on attention deficit/hyperactivity disorder].

OBJECTIVES: To describe the main aspects of attention deficit/hyperactivity disorder, including history, epidemiology, etiology, neurobiology, clinical features, comorbidities, diagnosis, outcome and treatment. SOURCES OF DATA: Comprehensive, non-systematic review of the literature on attention deficit/hyperactivity disorder. SUMMARY OF THE FINDINGS: Attention deficit/hyperactivity disorder has a neurobiological basis, and is highly prevalent in children and adolescents. Treatment is very efficacious, including the use of medication in most the cases. CONCLUSIONS: Pediatricians are in a privileged position to detect this disorder early and to start the initial management of less severe cases and of those not complicated by extensive comorbidities.

Adolescent↗

PubMed2003

Is the alpha-2A adrenergic receptor gene (ADRA2A) associated with attention-deficit/hyperactivity disorder?

Attention-Deficit/Hyperactivity Disorder (ADHD) is a complex childhood-onset psychiatric disorder characterized by marked symptoms of inattention, hyperactivity, and impulsivity. The role of genetic factors in its etiology is strongly supported by family, adoption, and twin studies. Although most of the molecular studies have investigated the dopamine D4 receptor gene (DRD4) and the dopamine transporter gene (DAT1) genes in its etiology, pharmacological and brain imaging evidences seem to indicate that genes of the adrenergic system could also be attractive for association studies. We investigated a sample of 96 Brazilian ADHD children and adolescents and their parents for the ADRA2A MspI polymorphism. Although no association with either MspI allele was observed through the haplotype relative risk (HRR) analysis, effects of the ADRA2A gene on inattention and combined (inattention + hyperactivity/impulsivity) symptom scores were detected (U = 222.5, z = 2.19, P = 0.03; and U = 208.5, z = 2.32, P = 0.02, respectively). Our results suggest that the ADRA2A gene might have a small effect on ADHD susceptibility or that this gene might modulate the severity of the disorder. They are also consistent with the noradrenergic theories of ADHD, suggesting a role for the alpha2A adrenergic receptors in the disorder.

Adolescent↗

PubMed2003

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.

Adolescent↗

PubMed2003

Dopamine transporter gene, response to methylphenidate and cerebral blood flow in attention-deficit/hyperactivity disorder: a pilot study.

The homozygosity of the 10-repeat allele at dopamine transporter gene (DAT1) seems to be associated with a poor response to methylphenidate (MPH) in children with attention-deficit/hyperactivity disorder (ADHD). This pilot study aimed to simultaneously assess polymorphisms at DAT1, response to MPH, and neuroimaging. Only ADHD children with at least a moderate response to MPH were included. Significantly higher regional cerebral blood flows assessed by single photon emission computerized tomography (SPECT) were detected in medial frontal and left basal ganglia areas in children with homozygosity for the 10-repeat allele at DAT1 gene (n = 4) than in children without this genotype (n = 4) (P < 0.05). These findings provide a preliminary connection between pharmacogenetics and neurobiological investigations on stimulant treatment of ADHD.

Attention Deficit Disorder with Hyperactivity↗

PubMed2002

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.

Alleles↗

PubMed2002

Dopamine transporter gene and response to methylphenidate in attention-deficit/hyperactivity disorder.

This study aims to evaluate whether a previously reported association between homozygosity for the 10-repeat allele of the dopamine transporter gene (10/10) and poor response to methylphenidate (MPH) would be replicated in a sample of Brazilian attention deficit/hyperactivity disorder (ADHD) boys. In a blind naturalistic study, 50 male ADHD youths were treated with MPH. Efficacy of the medication was measured by means of the 10-item Conners Abbreviated Rating Scale (ABRS), and the Children's Global Assessment Scale (CGAS). While 75% (15/20) of the youths without 10/10 genotype demonstrated an improvement higher than 50% in the ABRS scores with MPH, only 47% (14/30) of the subjects with 10/10 genotype achieved the same level of improvement with medication (one-tailed P = 0.04). In addition, the group without this genotype had significantly higher increase in the CGAS scores than the other group (one-tailed P < 0.01). Our findings support an association between homozygosity for the 10-repeat allele at dopamine transporter gene locus and poor response to MPH.

Adolescent↗

PubMed2002

Comparison of male adolescent-report of attention-deficit/hyperactivity disorder (ADHD) symptoms across two cultures using latent class and principal components analysis.

BACKGROUND: The goal of this study is to gauge the consistency of Attention Deficit/Hyperactivity Disorder (ADHD) latent class models that are generated by different informants such as adolescents and parents. The consistency of adolescent-derived latent classes from two different samples was assessed and these results were then compared to the class structure generated by parent-report ADHD information. METHODS: Self-reported DSM-IV Criterion A ADHD symptoms of 497 adolescent males from a population-based twin study in the state of Missouri (USA) were subjected to principal components and latent class analysis, and findings were compared to previous results obtained from identical analyses using an adolescent sample from Porto Alegre, Brazil (N = 483). RESULTS: The bi-dimensional structure of self-reported ADHD symptoms was similar for both male adolescent groups, but explained less than 40% of the symptom variance in either sample. Two factors, one with loadings on inattention symptoms only and the other with loadings on hyperactive-impulsive symptoms only, were identified in the Missouri sample. Specific ADHD latent classes did not replicate well across the Missouri and Brazilian samples, and both groups were characterized by the presence of several combined symptom classes but few inattentive or hyperactive-impulsive classes. CONCLUSIONS: While adolescent-report information across two different cultures can at least in part reproduce the two-factor structure of ADHD, results from latent class analysis suggest that adolescent reporting on their own symptoms is markedly different from the type of information parents provide about ADHD symptoms in their offspring. The current findings indicate that if male adolescents endorse any ADHD symptoms there is a tendency for them to report combined type problems.

Adolescent↗

PubMed2002

Neuropsychological performance in DSM-IV ADHD subtypes: an exploratory study with untreated adolescents.

OBJECTIVE: To explore neuropsychological performance in untreated Brazilian adolescents suffering from attention-deficit hyperactivity disorder (ADHD). METHOD: We assessed 30 untreated adolescents with ADHD and 60 healthy control subjects, aged 12 to 16 years, using a neuropsychological battery including the Wisconsin Card-Sorting Test (WCST), the Stroop Test (ST), the Digit Span, and the Word Span. RESULTS: We found neuropsychological differences among the DSM-IV ADHD subtypes. Adolescents with the predominantly inattentive subtype (ADHD-I) performed more poorly than did control subjects on both the Digit Span and the ST. On both the Digit Span and the WCST, adolescents with the combined subtype (ADHD-C) presented significantly more impairments than did control subjects. Adolescents with the predominantly hyperactive-impulsive type (ADHD-HI) did not differ significantly from the control subjects in any measure assessed, but had a better performance than did those with ADHD-C on both the Digit Span and the WCST. In addition, adolescents with ADHD-HI performed better on the ST than did adolescents with ADHD-I. CONCLUSIONS: These findings suggest cognitive differences among ADHD subtypes, supporting the diagnostic distinction among them. Adolescents with ADHD-HI do not seem to have significant cognitive deficits.

Adolescent↗