Marcelo M. Victor

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.

Late-onset ADHD in adults: Milder, but still dysfunctional

OBJECTIVE The requirement in classificatory systems that some impairment from attention-deficit/hyperactivity disorder (ADHD) symptoms starts before 7 years of age (age of onset of impairment criteria - AOC) has been harshly criticized. Although there is evidence that late-onset ADHD is a valid diagnosis, little is known about the role of age of onset of impairment on the clinical profile of adult patients. METHODS The diagnoses of 349 adults with ADHD followed DSM-IV criteria. ADHD and oppositional defiant disorder (ODD) were evaluated with the K-SADS-E, and other comorbidities with the SCID-IV and the MINI. Subjects were divided in early and late-onset groups (age of onset of impairment between 7 and 12 years old). The effect of age of onset over clinical and demographic characteristics was tested by regression models. RESULTS Late-onset subjects were diagnosed later (P=0.04), had a lower frequency of problems with authority and discipline (P=0.004), and lower scores in SNAP-IV (P<0.001) and in Barkleys scale for problems in areas of life activities (P=0.03). On the other hand, late-onset patients presented a higher prevalence of comorbid general anxiety disorder (GAD) (P=0.01). Both groups had a similar profile in the remaining comorbidities and sociodemographic characteristics. CONCLUSIONS This study provides initial evidence that adults with late-onset ADHD have less severity, lower frequency of externalizing symptoms and increased comorbidity with GAD, but similar profile in other comorbidities. In addition, the data suggest that late-onset patients have a higher probability of delayed diagnosis despite the significant impairment of their condition.

The burdened life of adults with ADHD: impairment beyond comorbidity.

Since approximately 70% of adult patients with attention-deficit/hyperactivity disorder (ADHD) have at least one comorbid disorder, rating of impairment specifically attributable to ADHD is a hard task. Despite the evidence linking environmental adversities with negative outcomes in ADHD, life events measures have not been used to rate the disorder impairment. The present study tested for the first time the hypothesis that increased ADHD severity is associated with an increase in negative recent life events, independently of comorbidity status. The psychiatric diagnoses of 211 adult ADHD outpatients were based on DSM-IV criteria assessed through structured interviews (K-SADS-E for ADHD and ODD, MINI for ASPD and SCID-IV-R for other comorbidities). ADHD severity was evaluated with the Swanson, Nolan and Pelham rating scale (SNAP-IV) and recent life events with the Life Experience Survey. Higher SNAP-IV inattention and hyperactivity scores, female gender, lower socioeconomic status and the presence of comorbid mood disorders were associated with negative life events. Poisson regression models with adjustment for possible confounders confirmed the effect of inattention and hyperactivity severity on negative life events. Our results suggest that the negative life events experienced by these patients are associated to the severity of ADHD independently from comorbid psychiatric disorders.

Inattention and Hyperactivity Dimensions of ADHD Are Associated with Different Personality Profiles

Background: Previous studies have suggested that individuals with ADHD have high scores in novelty seeking and harm avoidance. However, it is not known whether personality is associated with specific subtypes and dimensions of the disorder. The aim of this study is to test for associations between scores in the temperament and character inventory of C.R. Cloninger with adult ADHD subtypes and severity. Sampling and Methods: The diagnostic interviews of 296 adult ADHD patients followed the DSM-IV criteria. ADHD dimensions were evaluated with the SNAP-IV scores, and personality dimensions were assessed using the Temperament and Character Inventory. Results: The combined subtype (n = 168) was associated with higher scores in novelty seeking (p < 0.001) and lower scores in cooperativeness (p = 0.006) than the inattentive subtype (n = 128). Higher inattention scores were associated with decreased self-directedness (p < 0.001) and increased harm avoidance (p = 0.02), whereas higher hyperactivity/impulsivity scores correlated positively with novelty seeking (p < 0.001) and persistence (p = 0.03). Conclusions: These findings suggest that personality dimensions are strongly correlated with ADHD subtypes and severity dimensions, pointing to the need for studies evaluating the mechanisms behind this association.

The impact of individual and methodological factors in the variability of response to methylphenidate in ADHD pharmacogenetic studies from four different continents

Several studies have evaluated the association between individual polymorphisms and response to methylphenidate (MPH) in subjects with attention‐deficit/hyperactivity disorder (ADHD). There are few replication studies for each polymorphism of interest and results are sometimes inconsistent in this field. Although data collection from multiple international sites would allow large sample sizes, this approach has been criticized for introducing sampling variability due to differences in ethnicity and methodology between studies. To examine these issues, we aggregated nine pharmacogenetic studies from four different continents and conducted a two stage analysis: (a) we evaluated the role of methodological aspects in the variability of ADHD symptom improvement between studies using meta‐regression analysis; (b) we assessed the role of individual characteristics of the subjects in the variability of ADHD symptoms improvement using multivariate regression analysis in the same data sets. At the study level, from five evaluated factors, only the design of the study (open studies vs. randomized controlled trials) was significantly associated with heterogeneity of results (P = 0.001). At the individual level, age (P < 0.001), comorbid oppositional defiant disorder (P < 0.001), and pre‐treatment scores (P < 0.001) were associated with change of ADHD scores with treatment in the final multivariate model. Our results suggest that joint analyses of pharmacogenetic studies are feasible and promising, since fixed variables, such as the site where the study was conducted, were not related to results. Nevertheless, stratified analyses according to the design of the study must be preferentially conducted and the role of individual factors such as demographic data and comorbid profile as confounders should be assessed.

Serotonin transporter gene polymorphism and the phenotypic heterogeneity of adult ADHD

SummaryThe present study investigates possible associations between the 5-HTT control region polymorphism (5-HTTLPR) with adult ADHD, including subtypes, severity, temperament profile and comorbidities. The polymorphic site was genotyped in 312 adult patients with ADHD and 236 controls, all of them Brazilians of European descent. The interviews followed the DSM-IV criteria, using the K-SADS-E for ADHD and oppositional defiant disorder, SCID-I and MINI for comorbidities and the TCI for temperament dimensions. The 5-HTTLPR polymorphism was not associated with ADHD. Carriers of the S allele presented slightly higher inattention and novelty seeking scores, and a higher frequency of drug dependence. These differences do not persist after correction for multiple comparisons. These results suggest that the 5-HTTLPR polymorphism does not have a direct role in the predisposition to adult ADHD. There is suggestive evidence for a small effect in some behavioral phenotypes related to ADHD.

Cognitive Deficits in Adults with ADHD Go beyond Comorbidity Effects.

Objective: This study addresses if deficits in cognitive, attention, and inhibitory control performance in adults with ADHD are better explained by the disorder itself or by comorbid conditions. Method Adult patients with ADHD (n = 352) and controls (n = 94) were evaluated in the ADHD program of a tertiary hospital. The diagnostic process for ADHD and comorbidities was based on Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria. Stepwise regression analyses evaluated the effect of ADHD, demographics, and comorbidities on the scores from Wechsler Adult Intelligence Scale–Revised, Continuous Performance Test, and Stroop Color and Word Test. Results: Patients with ADHD of both genders had worse performance on neuropsychological domains, even after adjustment for comorbidities. The presence of comorbid bipolar disorder and specific phobia are associated with more Stroop errors, whereas patients with generalized anxiety disorder present a longer execution time in Stroop. Conclusion: Neuropsychological deficits in adults with ADHD go beyond comorbidity. Specific comorbid disorders may influence the neuropsychological functioning in adults with ADHD.

No significant association between genetic variants in 7 candidate genes and response to methylphenidate treatment in adult patients with ADHD.

Results from pharmacogenetic investigations of methylphenidate (MPH) response in patients with ADHD are still inconsistent, especially among adults. This study investigates the role of genetic variants (SLC6A4, HTR1B, TPH2, DBH, DRD4, COMT, and SNAP25) in the response to MPH in a sample of 164 adults. Genes were chosen owing to previous evidence for an influence in ADHD susceptibility. No significant differences in allele or genotype frequencies between MPH responders and nonresponders were detected. In conclusion, our findings do not support an effect of these genes in the pharmacogenetics of MPH among adults with ADHD.

Adrenergic α2A receptor gene is not associated with methylphenidate response in adults with ADHD

Adrenergic α2A receptor gene (ADRA2A) is one of the most promising candidate genes for ADHD pharmacogenetics. Thus far, three studies have investigated the association between the ADRA2A −1291 C>G polymorphism and the therapeutic response to methylphenidate (MPH) in children with ADHD, all of them with positive results. The aim of this study is to investigate, for the first time, the association between three ADRA2A polymorphisms (−1291 C>G, −262 G>A, and 1780 C>T) and the response to MPH in adults with ADHD. The sample comprises 165 Brazilians of European descent evaluated in the adult ADHD outpatient clinic of the Hospital de Clínicas de Porto Alegre. The diagnostic procedures followed the DSM-IV criteria. Drug response was assessed by both categorical and dimensional approaches, through the scales Swanson, Nolan, and Pelham Rating scale version IV and the Clinical Global Impression-Severity Scale, applied at the beginning and after the 30th day of treatment. We found no evidence of association between the three ADRA2A polymorphisms and the therapeutic response to MPH treatment. Our findings do not support a significant role for the ADRA2A gene in ADHD pharmacogenetics, at least among adult patients.

Smoking is associated with lower performance in WAIS-R Block Design scores in adults with ADHD

Adults with attention-deficit/hyperactivity disorder (ADHD) are predisposed to smoking, but the neuropsychological correlates of this association have not been elucidated so far. The present study evaluates possible associations between cognitive performance and smoking and other comorbidities in adults with ADHD. Two hundred and sixty-four (264) patients were evaluated in the adult ADHD outpatient clinic of the Hospital de Clínicas de Porto Alegre. The diagnoses were based on the DSM-IV criteria and interviews were performed with the Portuguese version of K-SADS-E for ADHD and oppositional-defiant disorder. Axis I psychiatric comorbidities were evaluated with the SCID-IV and the cognitive performance with the Vocabulary and Block Design subtests of the Wechsler Adult Intelligence Scale-Revised (WAIS-R). The evaluation of the influence of the WAIS-R scores on each dependent variable was performed with logistic regression analyses. Lower scores in the Block Design subtest of WAIS-R were associated with smoking and the presence of anxiety disorder. These results suggest that a subgroup of ADHD patients with lower Block Design subtest scores may be at increased risk of smoking as a cognitive enhancement. Our findings also confirmed the previously suggested association between anxiety and lower Block Design scores.