RESUMO
In 29 adults with attention deficit hyperactivity disorder (ADHD) striatal dopamine transporter (DAT) availability was assessed by [(99m)Tc]TRODAT-1 SPECT and correlated with 3' VNTR polymorphism of the DAT gene on chromosome 5p15.3. Seventeen patients showed homozygosity for the 10-repeat allele, two homozygosity of the 9 allele and 10 were heterozygous (9-10). No statistically significant difference in DAT availability was found between patients with 10-10 carriers (DAT 1.28 +/- 0.34) and with at least one 9 allele (DAT 1.31 +/- 0.27); when smokers were excluded, DAT availability was 1.38 +/- 0.28 in the 10-10 carriers (n = 12) and 1.42 +/- 0.19 in the 9-10 and 9-9 carriers (n = 7). In conclusion, no higher striatal DAT was found in patients with homozygosity of the 10 allele of the DAT gene in this study. These results differ from a study in 11 Korean children with ADHD, in which 10-10 carriers showed higher DAT availability in [(123)I]IPT SPECT. Discrepancies may be explained by differences in patient's age, ethnical differences, different imaging techniques or the limited number of patients included in both studies.
Assuntos
Alelos , Transtorno do Deficit de Atenção com Hiperatividade/genética , Corpo Estriado/fisiopatologia , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Homozigoto , Repetições Minissatélites , Polimorfismo Genético/genética , Adulto , Fatores Etários , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Cromossomos Humanos Par 5 , Corpo Estriado/diagnóstico por imagem , Comparação Transcultural , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Éxons , Feminino , Triagem de Portadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Repetições Minissatélites/genética , Compostos de Organotecnécio , Tomografia Computadorizada de Emissão de Fóton Único , TropanosRESUMO
The persistence of attention deficit hyperactivity disorder (ADHD) into adolescence and adulthood has now been accepted as a clinical entity. The rate of prevalence among adults is assumed to be from 2% to 4%. With increasing age, a symptom change has to be considered; disturbance of attention becomes more prominent, whereas hyperactivity often diminishes or changes to inactivity. Neuroimaging studies show a high striatal dopamine transporter (DAT) availability in most adults with ADHD; this can be reduced by stimulants. Nicotine seems to have a stimulant-like action on the DAT. In most adults with ADHD, therapy has to be multimodal, combining psychotherapy and medication. Methylphenidate is the first-line drug in adult ADHD; further options are amphetamine and noradrenaline reuptake inhibitors. Nonresponders to methylphenidate seem to have no elevated DAT availability prior to therapy. Combination with other psychiatric disorders occurs frequently in adults with ADHD; in these patients additional pharmacological treatment with special regard to the comorbid disease is recommended.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Nicotina/uso terapêutico , Adolescente , Adulto , Fatores Etários , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/patologia , Corpo Estriado/patologia , Diagnóstico por Imagem/métodos , Quimioterapia Combinada , Humanos , Metilfenidato/uso terapêutico , Neurobiologia/métodosRESUMO
In this study, we investigated whether availability of striatal dopamine transporter (DAT) may have an influence on the response of adult patients with attention deficit hyperactivity disorder (ADHD) on methylphenidate (MPH). In 18 non-smoking and non-medicated adult patients with ADHD, availability of DAT was measured with [(99m)Tc] TRODAT-1 SPECT. Then, the patients received methylphenidate (MPH), individually titrated up to 60 mg per day. Ten weeks later, clinical improvement was rated by Clinical Global Impressions scale. In all, 6 patients were classified as non-responders, and 12 responded to MPH. From the non-responders, 5 presented with a DAT availability below that of normal controls of the same age, whereas in the group of responders all patients had elevated DAT availability. There was a significant negative correlation between values for global clinical improvement and striatal DAT availability. In conclusion, ADHD patients with low DAT availability seem not to respond to therapy with MPH.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Inibidores da Captação de Dopamina/uso terapêutico , Metilfenidato/uso terapêutico , Neostriado/metabolismo , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neostriado/diagnóstico por imagem , Compostos de Organotecnécio , Escalas de Graduação Psiquiátrica , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão de Fóton Único , TropanosRESUMO
There is evidence that abnormalities within the dopamine system in the brain play a major role in the pathophysiology of attention deficit hyperactivity disorder (ADHD). For instance, dopaminergic psychostimulants, the drugs of first choice in ADHD, interact directly with the dopamine transporter (DAT). Molecular genetic studies suggest involvement of a polymorphism of the DAT gene in ADHD. More recent imaging studies show abnormalities in various brain structures, but particularly in striatal regions. In the current paper we review recent studies in this area. First in vivo measurements of DAT with single photon emission computed tomography (SPECT) in ADHD patients revealed an elevation of striatal DAT density. No differences in DAT density between the left and right side and between putamen and caudate nucleus have been found in [99mTc]TRODAT-1 SPECT of ADHD patients. Patients with ADHD and with a history of nicotine abuse both displayed lower values of DAT density in [99mTc]TRODAT-1 SPECT than non-smokers with ADHD. DAT seem to be elevated in non-smoking ADHD patients suffering from the purely inattentive subtype of ADHD as well as in those with the combined or purely hyperactive/impulsive subtype.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Mapeamento Encefálico , Glicoproteínas de Membrana , Proteínas de Membrana Transportadoras/fisiologia , Neostriado/fisiopatologia , Proteínas do Tecido Nervoso , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Proteínas da Membrana Plasmática de Transporte de Dopamina , Humanos , Proteínas de Membrana Transportadoras/efeitos dos fármacos , Proteínas de Membrana Transportadoras/genética , Neostriado/diagnóstico por imagem , Neostriado/efeitos dos fármacos , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologia , Tabagismo/fisiopatologia , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Eleven adult patients with attention deficit hyperactivity disorder (ADHD) without medication, consuming 7-40 cigarettes per day, showed statistically significant lower values for striatal dopamine transporter (DAT) measured by [99mTc]TRODAT-1 SPECT compared to 11 non-smoking drug-naive patients with ADHD, matched for sex and age, despite higher ADHD scores for the smokers. Because stimulants have been shown to reduce primarily elevated DAT density in adults with ADHD, it can be suggested that nicotine acts in a similar way on striatal DAT as do stimulants.