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We present an ancient Greek description written by the philosopher Theophrastus in his classic book 'Characters' comparable with modern attention-deficit hyperactivity disorder. The arguments are based in one chapter of this book--The Obtuse Man--presenting features of a character closely resembling the modern description of attentiondeficit hyperactivity disorder. In a free comparative exercise, we compared Theophrastus descriptions with modern Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) attention-deficit hyperactivity disorder symptoms. The sentences describing The Obtuse Man written by Theophrastus are similar to several symptoms of attention-deficit hyperactivity disorder and he would probably be currently diagnosed with this disorder as an adult. To our knowledge, this is the oldest description compatible with the current conception of attention-deficit hyperactivity disorder in adults in the Western literature. Differently than the moralistic view of ancient Greece regarding those symptoms, the medical attention-deficit hyperactivity disorder conception may be advantageous to patients since it might reduce prejudice and allow individuals to seek treatment. [ABSTRACT FROM AUTHOR]

Several lines of evidence suggest a relevant role for the dopamine transporter (DAT1) gene not only as a susceptibility factor for attention-deficit hyperactivity disorder (ADHD), but also as a predictor of individual methylphenidate (MPH) response. Pharmacogenetic studies of MPH response in ADHD have mainly focused on the 40-bp variable number of tandem repeats (VNTR) in the 3′ untranslated region (3′-UTR) of DAT1. Most studies were performed in samples of children and conflicting findings were obtained. Only two studies have assessed 3′-VNTR in samples of adults—one with positive and the other with negative findings. In the present study, we investigate three potentially relevant polymorphisms in DAT1 gene (−839 C > T; Int8 VNTR and 3′-VNTR), and their possible role in therapeutic response to MPH treatment in a sample of 171 Brazilian adults with ADHD. The diagnostic procedures followed the DSM-IV criteria and the outcome measures were 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. Drug response was assessed by both categorical and dimensional approaches. There was no effect of any DAT1 polymorphisms or haplotypes on MPH response. This is the second report demonstrating absence of differences in MPH response according to DAT1 genotypes in adults with ADHD. Although DAT protein is crucial for the effect of MPH, genetic variations in DAT1 gene probably do not have a significant clinical role in this sample of adults with ADHD. [ABSTRACT FROM AUTHOR]

Introduction and objective: The evaluation of methylphenidate (MPH) response in patients with ADHD has rarely evaluated the effect of comorbidities [1]. The aim of this study is to evaluate response to MPH in patients with ADHD and comorbid disorders. Methods: Sociodemographic variables, comorbidity status and response to MPH were evaluated in 164 patients with ADHD. The analyses were restricted to subjects whose comorbidities did not demand specific treatment before the use of MPH. Results: The diagnosis of current oppositional defiant disorder (ODD) was associated to a larger decrease in inattention (p = 0.05), hyperactivity (p = 0.006) and ODD SNAP scores (p\0.001) following MPH. After adjustment for basal scores, the only dimension that remained significant was SNAP ODD (p = 0.05). Other comorbidities did not present significant effects. Discussion: Overall, the presence of comorbidities does not have a major influence in response to MPH. However, patients with current ODD have a larger decrease in SNAP scores, especially in ODD scores. This effect is mainly explained by pre-treatment severity. Conclusions: These results reinforce the evidence suggesting that MPH may be effective in ODD treatment. [ABSTRACT FROM AUTHOR]

Abstract: Methylphenidate (MPH) is a first line option in the psychopharmacologic treatment of adults with Attention-Deficit/Hyperactivity Disorder (ADHD). However, there is a considerable proportion of adult patients who do not respond to treatment with MPH or discontinue drug therapy. Since effects of genetic variants in the response to MPH treatment might explain these negative outcomes, we conducted an electronic systematic search of MEDLINE-indexed literature looking for articles containing information about pharmacogenetics of ADHD in adults published until January, 2012. The keywords used were ‘ADHD’, ‘Attention-Deficit/Hyperactivity Disorder’ and ‘gene’ in combination with methylphenidate, amphetamine or atomoxetine. Only 5 pharmacogenetic studies on adult ADHD met inclusion criteria. The results evidenced that most findings obtained so far are negative, and all studies focused on MPH response. There is only one positive result, for a polymorphism at the dopamine transporter gene (DAT1) gene. The current state of the art in adult ADHD implies that pharmacogenetic tests are far from routine clinical practice. However, the integration of these studies with neuroimaging and neuropsychological tests may help to understand mechanisms of drug action and the pathophysiology of ADHD. [Copyright &y& Elsevier]

Objective: Our aim was to explore the feasibility, and efficacy of a Dialectical Behavior Therapy Skill Training Group (DBT‐ST) as an add‐on treatment for adult attention‐deficit/hyperactivity disorder (ADHD) in Latin America. Method: Adults with ADHD (n = 31) with stable medication treatment for ADHD and residual symptoms (ASRS > 20) were randomly assigned to DBT‐ST (n = 16) or treatment as usual (TaU; n = 15) for 12 weeks. Feasibility was accessed by attendance and completion rates at 12 weeks. Efficacy outcomes were measured with the ASRS, and performed at 0, 6, 12, and 16 weeks. Results: The DBT‐ST protocol had 81.25% completion rate, with a mean attendance of 87.25% of the sessions. No significant interactions between group and time were detected for outcome measures. Discussion: The DBT‐ST was feasible as add‐on treatment for adult patients with ADHD in Latin America. Replicating previous findings, DBT‐ST has shown no significantly higher improvement in ADHD symptoms in comparison with TaU. Registered at the Clinical Trials database (NCT03326427). [ABSTRACT FROM AUTHOR]

Objective The frequent comorbidity between attention-deficit hyperactivity disorder ( ADHD) and bipolar disorder ( BD) represents a challenge for disentangling specific impairments of each disorder in adulthood. Their functional impairments seem to be mediated by executive function deficits. However, little is known about the extent to which each executive function deficit might be disorder specific or explained by the comorbidity. The aim of the present study was to determine if comorbid BD could account for a significant share of executive function deficits when measured by the Wisconsin Card Sorting Test ( WCST) in adults with ADHD. Methods Adult patients with ADHD and healthy subjects were evaluated in the ADHD outpatient Program at the Hospital de Clínicas de Porto Alegre. Psychiatric diagnoses were based on DSM- IV criteria. WCST scores were compared by multivariate analysis of covariance among three groups: ADHD with BD (n = 51), ADHD without BD (n = 278), and healthy subjects (n = 91). Results When compared to patients without BD and healthy subjects, patients with ADHD and comorbid BD showed lower scores in total correct answers (p = 0.003); higher scores in total errors (p = 0.004) and non-perseverative errors (p = 0.002); and completed fewer categories (p = 0.009). Patients with ADHD without BD did not differ from healthy subjects. Conclusions WCST impairments among patients with ADHD seem to be to a large extent attributable to comorbid BD. Although other executive function deficits (e.g., in the inhibitory control domain) have been demonstrated to accompany ADHD, the present findings suggest that set-shifting deficits are strongly related to comorbid BD. [ABSTRACT FROM AUTHOR]

Abstract: The consideration of age of onset of impairment as part of the ADHD diagnosis is controversial and has been a revisited issue with the emergence of the new classifications in Psychiatry. The aim of this study is to compare patients with early and late onset of ADHD impairment in terms of neuropsychological and personality characteristics. Adult patients with ADHD (n = 415) were evaluated in the ADHD outpatient program at Hospital de Clínicas de Porto Alegre, Brazil. The diagnostic process for ADHD and comorbidities was based on DSM-IV criteria. The comparison between the two ages of onset groups (before 7; n = 209 or from 7 to 12 years; n = 206) was performed with ANOVA, followed by Stepwise forward regression analyses to restrict the number of comparisons and access the possible effect of multiple confounders. Patients with early onset ADHD present higher scores in novelty seeking in both analyses (respectively P = 0.016 and P = 0.002), but similar cognitive and attention features as compared with the late onset group. These data add to previous evidence that despite a more externalizing profile of early onset ADHD, the overall performance is similar reinforcing the need for awareness and inclusion of the late onset group in DSM-V diagnostic criteria. [Copyright &y& Elsevier]

Abstract: Objective: The prevalence of smoking is significantly increased among adults with Attention-Deficit/Hyperactivity Disorder (ADHD), and this association has a significant impact in both disorders, ascribed to either self-medication or behavioral disinhibition hypotheses. However, little is known about clinical variables associated with cigarette smoking among patients with ADHD. The present study evaluates comorbidity, demographic and personality profiles of patients with ADHD in relation to smoking status. Methods: Patients (n 422) were evaluated in the adult ADHD outpatient clinic of Hospital de Clínicas de Porto Alegre. Diagnoses were based on DSM-IV criteria and interviews were performed with Portuguese version of K-SADS-E for ADHD and Oppositional-Defiant Disorder. Axis I psychiatric comorbidities were evaluated with the SCID-I and smoking behavior with Fagerström Test for Nicotine Dependence (FTND). Personality was evaluated with Cloninger’s Temperament and Character Inventory (TCI). Results: The presence of smoking was strongly associated with externalizing characteristics as antisocial personality disorder (OR4.2) and substance dependence (OR6.5), but not with internalizing disorders. Moreover, smoking was associated with higher novelty seeking and lower harm avoidance scores. Conclusions: Smoking initiation among patients with ADHD is consistent with a behavioral disinhibition profile beyond the possible role of self-medication in smoking persistence. Smoking in these patients is strongly associated with externalizing comorbid disorders. [Copyright &y& Elsevier]

Abstract: Objective: The requirement in classificatory systems that some impairment from attention-deficit/hyperactivity disorder (ADHD) symptoms starts before 7years 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 12years 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 Barkley’s 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. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Abstract: Most adults with attention-deficit/hyperactivity disorder (ADHD) are not recognized and remain untreated, although a large fraction of these individuals are diagnosed and treated for other comorbid mental disorders, such as major depressive disorder (MDD). The fact that MDD is one of the most commonly occurring mental disorders with high comorbidity with adult ADHD raises the question whether such comorbidity is associated with differences in the clinical picture of ADHD. Three hundred and twenty adult ADHD outpatients were evaluated. Diagnoses followed DSM-IV criteria. Interviews to evaluate ADHD and oppositional defiant disorder (ODD) were performed based on the Portuguese version of K-SADS-E. Psychiatric comorbidities were investigated using SCID-IV and MINI. Regression models were applied to test MDD association with clinical and demographic outcomes. Subjects presenting ADHD and MDD had a higher frequency of generalized anxiety disorder and social phobia and a lower frequency of substance dependence, grade repetition and school suspensions, when compared to subjects with ADHD without MDD. Furthermore, adults presenting ADHD and MDD reported higher demand for psychotherapy and pharmacological treatment prior to enrollment in the study when compared to ADHD subjects free of MDD. However, contrary to what could be expected based on these data, the presence of MDD was not associated with an earlier ADHD diagnosis. These results point to the need for research and medical education into an earlier and more efficient ADHD diagnosis in patients who search for mental health care. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Substantial interindividual variability is observed in treatment response to Methylphenidate (MPH), which is considered the first-line pharmacological treatment for adults with ADHD. In addition to its main known mechanism of action involving the blockade of the dopamine transporter, experimental studies have also indicated an ability of MPH to affect vesicle synaptic transmission. Consistently with this hypothesis, genes involved in calcium-triggered vesicle exocytosis have been implicated on pharmacogenetics of MPH. In genomic approaches, pathways involved in the neurotransmitter release are therefore promising to be investigated in MPH response. The aim of this study was to assess the influence of exocytosis-related gene-sets on response to MPH. The sample with genome-wide data and immediate-release MPH response comprised 189 adults with ADHD. The outcome measure was the change (∆) in severity scores of ADHD symptoms of SNAP-IV from baseline to endpoint (at least 30 days of treatment). Subsets of inattention and hyperactivity/impulsivity symptoms was also evaluated separately. Samples were genotyped on PsychChip array and imputed using the Ricopili pipeline. The resulting dataset consisted of 5,842,472 SNPs after quality control. For SNP annotation to genes, gene locations for build 37 (hg19) and a 2 kb upstream/1 kb downstream window were used. Competitive gene-set analyses were performed in MAGMA v1.06 using the principal components regression as the gene-based model. Concomitant use of psychiatric medication and baseline scores of symptoms were included as covariates, as well as the 10 first principal components. Eight annotated gene-sets related to function and regulation of calcium-triggered vesicle exocytosis derived from Gene Ontology (biological process) and collected from Molecular Signatures Database were analyzed. Bonferroni was applied for multiple testing correction. Gene-set analysis for the change in severity scores of ADHD resulted in nominal associations for calcium ion regulated exocytosis (GO:0017156; p=0.0189), presynaptic process involved in synaptic transmission (GO:0099531; p=0.0153) and neurotransmitter transport (GO:0006836; p=0.0231) gene-sets. Analyzing specific ADHD dimensions, the same gene-sets were associated to change of inattention symptoms only, where GO:0099531 remained significant after Bonferroni correction (p=0.0012). There was considerable overlap of genes within the tested gene-sets, therefore the gene analysis revealed a shared group of nominally associated genes among the significant sets for both inattention and ADHD, including STX11, STX19, PSEN1, CACNA1A and NRXN1. Our results suggest an involvement of neurotransmitter release genes in MPH treatment response. The lack of association for hyperactivity/impulsivity symptoms might point out different treatment underlying mechanisms between ADHD dimensions. Despite the evaluation of combined effects of multiple genetic variants grouped into predefined gene-sets is an alternative strategy to GWAS to reach increased statistical power, our small sample size should be considered in the interpretation of the results. Moreover, as the selected gene-sets are not independent, an increased precision in pathway definition would be benefic to these analyses. Notwithstanding, pathways involved in neurotransmitter release emerge as important candidates to be explored in further pharmacogenetic studies of ADHD. [ABSTRACT FROM AUTHOR]