RESUMO
Polymorphisms in the CHRNA5-CHRNA3-CHRNB4 gene cluster (Chr15q25) have been robustly associated with nicotine dependence, including genome-wide studies, as well as with cognitive and neuropsychological measures. In addition, cognitive processes can be influenced by nicotine use through nicotinic acetylcholine receptors (nAChRs). Here, we evaluated the effect of polymorphisms in CHRNA5-CHRNA3-CHRNB4 gene cluster and their interaction with tobacco smoking status on cognition in patients with Attention Deficit/Hyperactivity Disorder (ADHD). Eight SNPs from the CHRNA5-CHRNA3-CHRNB4 gene cluster were evaluated on a clinical sample of 403 adults with ADHD. Cognitive performance was assessed using the Wechsler Adult Intelligence Scale-Revised (WAIS-R). Analyses of covariance were used to assess the influence of single markers and their interaction with smoking status in the Vocabulary and Block Design subtests of WAIS-R. Correction for multiple comparisons was applied. Lifetime smoking was associated to Vocabulary subtest. The TT genotypes of CHRNA5 SNPs rs588765 and rs514743 showed a trend towards association with, respectively, higher and lower scores on the Vocabulary subtest. There was a significant interaction between intergenic SNP rs8023462 and smoking on Vocabulary scores. Our results are consistent with an influence of variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster on cognitive measures. The overall scenario suggests a pleiotropic role of Chr15q25 nicotinic gene cluster with complex influences in ADHD, tobacco smoking and cognitive performance, characteristics that can be partially interdependent and may share underlying genetic factors.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Cromossomos Humanos Par 15/genética , Transtornos Cognitivos/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Receptores Nicotínicos/genética , Tabagismo/genética , Adulto , Análise de Variância , Feminino , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Família Multigênica/genética , Testes Neuropsicológicos , Escalas de Graduação PsiquiátricaRESUMO
Although the identification of reliable predictors of methylphenidate response in adults with attention-deficit/hyperactivity disorder (ADHD) is necessary to guide treatment decisions, very few data exist on this issue. Here, we assessed the predictors of clinical response to immediate-release methylphenidate hydrochloride (IR-MPH) in a naturalistic setting by analyzing the influence of demographic factors, severity, and a wide range of comorbid psychiatric disorders. Two hundred fifty adult patients with ADHD were evaluated and completed a short-term treatment with IR-MPH. Mental health diagnoses were based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria through the use of standard structured interviews. The Swanson, Nolan, and Pelham Rating Scale, version 4, adapted to adults was used to assess the severity of ADHD. In the linear regression model, only higher severity of ADHD was associated to a better IR-MPH response (b = 0.770; P < 0.001). Treatment of comorbidities in a subsample (n = 62) did not modify this pattern. Our findings suggest that in clinical settings, patients with more severe ADHD symptoms have a good response to treatment independently from the presence of mild or stabilized comorbidities and their treatments. For adults with ADHD, differently from other common psychiatric disorders such as depression and anxiety, higher severity is associated with better treatment response.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Transtornos Mentais/epidemiologia , Metilfenidato/uso terapêutico , Adulto , Comorbidade , Feminino , Humanos , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/tratamento farmacológico , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
Polymorphisms in the CHRNA5-CHRNA3-CHRNB4 gene cluster have been shown to be involved in tobacco smoking susceptibility. Considering that attention deficit/hyperactivity disorder (ADHD) not only increases the risk but may also influence the molecular mechanisms of tobacco smoking, we analyzed the association between polymorphisms in the nicotinic acetylcholine receptor genes and tobacco smoking among individuals with or without ADHD. The sample included 1,118 subjects divided into four groups according to smoking status and ADHD diagnosis. Our results demonstrate that the minor alleles of two polymorphisms (rs578776 and rs3743078) in the CHRNA3 gene are associated with an increased risk of tobacco smoking only among patients with ADHD. These alleles have been shown in previous studies to be protective factors for smoking in subjects without ADHD. These findings add to existing evidence that ADHD may exert an important modifying effect on the genetic risk of smoking and should be considered in tobacco smoking association studies.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Polimorfismo de Nucleotídeo Único , Receptores Nicotínicos/genética , Fumar/genética , Adulto , Alelos , Brasil/epidemiologia , Estudos de Casos e Controles , Análise Mutacional de DNA , Europa (Continente)/etnologia , Feminino , Predisposição Genética para Doença , Haplótipos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Risco , Fumar/epidemiologia , Adulto JovemRESUMO
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.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno Bipolar/complicações , Transtornos Cognitivos/etiologia , Função Executiva/fisiologia , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno Bipolar/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Adulto JovemRESUMO
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.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtornos Cognitivos/diagnóstico , Adulto , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/epidemiologia , Atenção/fisiologia , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/epidemiologia , Transtornos Cognitivos/epidemiologia , Comorbidade , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Inibição Psicológica , Masculino , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Teste de Stroop , Centros de Atenção Terciária , Escalas de Wechsler , Adulto JovemRESUMO
INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) are frequently co-occurring disorders in children and adolescents. However, their clinical status among adults is still under discussion. This study analyzes how the current clinical presentation of adult ADHD might be influenced by a lifetime history of CD and ODD. METHODS: We compared three groups of patients: ADHD without history of CD/ODD (n = 178), ADHD + history of ODD (n = 184), and ADHD + history of CD (n = 96). RESULTS: A history of CD (and to a lower extent ODD) is associated with a more severe and externalizing profile. CONCLUSION: Past CD and ODD entail a significant negative mental health impact on persistent ADHD, reinforcing the importance of actively assessing the developmental history of adult ADHD patients.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/epidemiologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/psicologia , Transtorno da Conduta/psicologia , Acontecimentos que Mudam a Vida , Adulto , Análise de Variância , Brasil , Transtorno da Conduta/epidemiologia , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Índice de Gravidade de Doença , População BrancaRESUMO
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.