RESUMO
Objective: To compare intraocular pressure (IOP) and macular, retinal nerve fiber layer (RNFL), and ganglion cell layer (GCL) thicknesses in treatment-naive children with attention-deficit/hyperactivity disorder (ADHD), children with ADHD on regular methylphenidate (MPH) treatment for at least 3 months, and healthy controls. Methods: A total of 58 treatment-naive children with ADHD, 45 children with ADHD on regular MPH treatment, and 44 healthy controls were enrolled in this study. All participants underwent a comprehensive eye examination. Optical coherence tomography (OCT) was used to assess global RNFL thickness, central macular thickness, and GCL thickness in both eyes. Results: Separate univariate analysis of covariance (ANCOVA) on the outcome variables revealed a significant difference among the research groups with respect to IOP in the left eye. Post-hoc univariate analyses indicated that left IOP was significantly higher in children with ADHD under MPH treatment than among healthy controls. However, global RNFL thickness, central macular thickness, and GCL thickness of both eyes, as well as IOP in the right eye, were not significantly different across groups. Conclusion: Further longitudinal follow-up studies are needed to determine whether MPH treatment has any effect on IOP or OCT findings.
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Células Ganglionares da Retina/patologia , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/patologia , Pressão Intraocular/fisiologia , Macula Lutea/patologia , Fibras Nervosas/patologia , Valores de Referência , Retina/patologia , Estudos de Casos e Controles , Análise de Variância , Tomografia de Coerência ÓpticaRESUMO
OBJECTIVE: To compare intraocular pressure (IOP) and macular, retinal nerve fiber layer (RNFL), and ganglion cell layer (GCL) thicknesses in treatment-naive children with attention-deficit/hyperactivity disorder (ADHD), children with ADHD on regular methylphenidate (MPH) treatment for at least 3 months, and healthy controls. METHODS: A total of 58 treatment-naive children with ADHD, 45 children with ADHD on regular MPH treatment, and 44 healthy controls were enrolled in this study. All participants underwent a comprehensive eye examination. Optical coherence tomography (OCT) was used to assess global RNFL thickness, central macular thickness, and GCL thickness in both eyes. RESULTS: Separate univariate analysis of covariance (ANCOVA) on the outcome variables revealed a significant difference among the research groups with respect to IOP in the left eye. Post-hoc univariate analyses indicated that left IOP was significantly higher in children with ADHD under MPH treatment than among healthy controls. However, global RNFL thickness, central macular thickness, and GCL thickness of both eyes, as well as IOP in the right eye, were not significantly different across groups. CONCLUSION: Further longitudinal follow-up studies are needed to determine whether MPH treatment has any effect on IOP or OCT findings.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/patologia , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Pressão Intraocular/fisiologia , Macula Lutea/patologia , Fibras Nervosas/patologia , Células Ganglionares da Retina/patologia , Adolescente , Análise de Variância , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Valores de Referência , Retina/patologia , Tomografia de Coerência ÓpticaRESUMO
Epidemiological studies suggest sex differences in attention deficit and hyperactivity disorder (ADHD) symptomatology. The potential benefits of caffeine have been reported in the management of ADHD, but its effects were not properly addressed with respect to sex differences. The present study examined the effects of caffeine (0.3 g/L) administered since childhood in the behavior and brain-derived neurotrophic factor (BDNF) and its related proteins in both sexes of a rat model of ADHD (spontaneously hypertensive rats-SHR). Hyperlocomotion, recognition, and spatial memory disturbances were observed in adolescent SHR rats from both sexes. However, females showed lack of habituation and worsened spatial memory. Although caffeine was effective against recognition memory impairment in both sexes, spatial memory was recovered only in female SHR rats. Besides, female SHR rats showed exacerbated hyperlocomotion after caffeine treatment. SHR rats from both sexes presented increases in the BDNF, truncated and phospho-TrkB receptors and also phospho-CREB levels in the hippocampus. Caffeine normalized BDNF in males and truncated TrkB receptor at both sexes. These findings provide insight into the potential of caffeine against fully cognitive impairment displayed by females in the ADHD model. Besides, our data revealed that caffeine intake since childhood attenuated behavioral alterations in the ADHD model associated with changes in BDNF and TrkB receptors in the hippocampus.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/patologia , Comportamento Animal , Cafeína/farmacologia , Modelos Biológicos , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Feminino , Habituação Psicofisiológica/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Memória/efeitos dos fármacos , Ratos Endogâmicos SHR , Ratos Wistar , Receptor trkB/metabolismo , Reprodutibilidade dos TestesRESUMO
The aim of this study is to gather evidence of head-to-head double-blind randomized-controlled trials on the efficacy and safety of available treatments for attention deficit hyperactivity disorder (ADHD) in children and adolescents. A systematic review was conducted by two independent reviewers in ten electronic databases (PROSPERO register CRD42016043239). Methodological quality of included studies was evaluated according to the Jadad scale. Network meta-analyses were performed including double-blinded head-to-head trials comparing active allopathic drugs in patients (0-18 years old) diagnosed with ADHD. The results of efficacy and safety of atomoxetine (ATX), bupropion, buspirone (BSP), dexamphetamine, edivoxetine (EDX), guanfacine (GXR), lisdexamfetamine (LDX), methylphenidate (MPH), mixed amphetamine salts, modafinil, pindolol (PDL), reboxetine (RBX), selegiline, and venlafaxine were analyzed using ADDIS software v.1.16.5. Forty-eight trials were identified (n = 4169 participants), of which 12 were used for efficacy analysis and 33 for safety analysis. On the CGI-I scale, the analysis revealed that MPH was more effective than ATX and GXR. For the safety outcomes, according to drug ranks, LDX was more likely to cause sleep disorders (39%) as well as loss of appetite (65%) and behavior problems such as irritability (60%). BSP (71%) and EDX (44%) caused less appetite decrease. For behavioral effects, PDL was considered safest (50%). For any adverse events, RBX (89%) was the safest alternative. The lack of head-to-head trials properly reporting outcomes of interest limited some comparisons. Network meta-analysis offered a broader overview on the available treatments for ADHD, especially for safety issues, and contributes towards evidence gathering and clinical practice decisions. A core outcome set for ADHD should be designed to guide the conduction and report of clinical trials.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/patologia , Criança , Feminino , Humanos , Masculino , Resultado do TratamentoRESUMO
PURPOSE: Currently, the diagnosis of attention deficit hyperactivity disorder (ADHD) rests on clinical criteria. Nonetheless, neuroimaging studies have demonstrated that children with ADHD have different cortical thickness and volume measures to typically developing children (TDC). In general, studies do not evaluate the influence of clinical presentation in the brain morphometry of ADHD children. Our objective was to perform a pilot study in order to evaluate cortical thickness and brain volume in a sample of Brazilian ADHD children and compare these to those of TDC, taking into account the influence of clinical presentation. METHODS: We performed an analytic study comparing 17 drug-naïve ADHD children of both genders, aged between 7 and 10, and 16 TDC. ADHD subjects were first considered as one group and further separated based on clinical presentation. RESULTS: The brain volume did not differ between patients and TDC. Smaller cortical thicknesses were identified on the left superior, medium and inferior temporal cortex, as well as in the left inferior parietal cortex. When compared to TDC, combined and inattentive ADHD presentations depicted smaller cortical thickness with high significance and power. The same magnitude of results was not observed when comparing inattentive ADHD and TDC. CONCLUSIONS: In this pilot study, ADHD is associated with abnormalities involving the cortical thickness of the posterior attentional system. The cortical thickness in the left superior, medium and inferior temporal cortex, as well as in the left inferior parietal cortex may differ according to ADHD presentations.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/patologia , Mapeamento Encefálico , Córtex Cerebral/anormalidades , Encéfalo , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Projetos PilotoRESUMO
Abnormalities in the white matter microstructure of the attentional system have been implicated in the aetiology of attention deficit hyperactivity disorder (ADHD). Diffusion tensor imaging (DTI) is a promising magnetic resonance imaging (MRI) technology that has increasingly been used in studies of white matter microstructure in the brain. The main objective of this work was to perform an exploratory analysis of white matter tracts in a sample of children with ADHD versus typically developing children (TDC). For this purpose, 13 drug-naive children with ADHD of both genders underwent MRI using DTI acquisition methodology and tract-based spatial statistics. The results were compared to those of a sample of 14 age- and gender-matched TDC. Lower fractional anisotropy was observed in the splenium of the corpus callosum, right superior longitudinal fasciculus, bilateral retrolenticular part of the internal capsule, bilateral inferior fronto-occipital fasciculus, left external capsule and posterior thalamic radiation (including right optic radiation). We conclude that white matter tracts in attentional and motor control systems exhibited signs of abnormal microstructure in this sample of drug-naive children with ADHD.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/patologia , Imagem de Tensor de Difusão , Substância Branca/patologia , Anisotropia , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/complicações , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/patologia , Estudos de Casos e Controles , Criança , Transtorno da Conduta/complicações , Transtorno da Conduta/patologia , Feminino , Humanos , Masculino , NeuroimagemRESUMO
Williams-Beuren syndrome (WBS) is caused by a hemizygous contiguous gene microdeletion of 1.55-1.84 Mb at 7q11.23 region. Approximately, 28 genes have been shown to contribute to classical phenotype of SWB with presence of dysmorphic facial features, supravalvular aortic stenosis (SVAS), intellectual disability, and overfriendliness. With the use of Microarray-based comparative genomic hybridization and other molecular cytogenetic techniques, is possible define with more accuracy partial or atypical deletion and refine the genotype-phenotype correlation. Here, we report on a rare genomic structural rearrangement in a boy with atypical deletion in 7q11.23 and XYY syndrome with characteristic clinical signs, but not sufficient for the diagnosis of WBS. Cytogenetic analysis of G-banding showed a karyotype 47,XYY. Analysis of DNA with the technique of MLPA (Multiplex Ligation-dependent Probe Amplification) using kits a combination of kits (P064, P036, P070, and P029) identified an atypical deletion on 7q11.23. In addition, high resolution SNP Oligonucleotide Microarray Analysis (SNP-array) confirmed the alterations found by MLPA and revealed others pathogenic CNVs, in the chromosomes 7 and X. The present report demonstrates an association not yet described in literature, between Williams-Beuren syndrome and 47,XYY. The identification of atypical deletion in 7q11.23 concomitant to additional pathogenic CNVs in others genomic regions allows a better comprehension of clinical consequences of atypical genomic rearrangements.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Deleção Cromossômica , Cromossomos Humanos Par 7/genética , Rearranjo Gênico , Transtornos dos Cromossomos Sexuais/genética , Síndrome de Williams/genética , Cariótipo XYY/genética , Transtorno do Deficit de Atenção com Hiperatividade/patologia , Pré-Escolar , Hibridização Genômica Comparativa , Variações do Número de Cópias de DNA , Humanos , Hibridização in Situ Fluorescente , Masculino , Reação em Cadeia da Polimerase Multiplex , Fenótipo , Prognóstico , Síndrome de Williams/patologiaRESUMO
A considerable proportion of adults with attention-deficit/hyperactivity disorder (ADHD) do not respond to the treatment with methylphenidate. This scenario could be due to inherited interindividual differences that may alter pharmacologic treatment response. In this sense, in 2012 we conducted a systematic search on PUBMED-indexed literature for articles containing information about pharmacogenomics of ADHD in adults. Five studies were found on methylphenidate pharmacogenomics and the only significant association was reported by one particular study. However, this single association with the SLC6A3 gene was not replicated in two subsequent reports. In the present review, although we could not find additional pharmacogenomics studies, we discuss these up-to-date findings and suggest new approaches for this field. Additionally, using systeomic-oriented databases, we provide a broad picture of new possible candidate genes as well as potential gene-gene interactions to be investigated in pharmacogenomics of persistent ADHD.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/genética , Metilfenidato/efeitos adversos , Farmacogenética , Transtorno do Deficit de Atenção com Hiperatividade/patologia , Bases de Dados Genéticas , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Estudos de Associação Genética , Humanos , Metilfenidato/uso terapêutico , Mapas de Interação de Proteínas/efeitos dos fármacosRESUMO
BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a common comorbidity of childhood epilepsy, but the neuroanatomical correlates of ADHD in epilepsy have yet to be comprehensively characterized. METHODS: Children with new and recent-onset epilepsy with (nâ=â18) and without (nâ=â36) ADHD, and healthy controls (nâ=â46) underwent high resolution MRI. Measures of cortical morphology (thickness, area, volume, curvature) and subcortical and cerebellar volumes were compared between the groups using the program FreeSurfer 5.1. RESULTS: Compared to the control group, children with epilepsy and ADHD exhibited diffuse bilateral thinning in the frontal, parietal and temporal lobes, with volume reductions in the brainstem and subcortical structures (bilateral caudate, left thalamus, right hippocampus). There were very few group differences across measures of cortical volume, area or curvature. CONCLUSIONS: Children with epilepsy and comorbid ADHD exhibited a pattern of bilateral and widespread decreased cortical thickness as well as decreased volume of subcortical structures and brainstem. These anatomic abnormalities were evident early in the course of epilepsy suggesting the presence of antecedent neurodevelopmental changes, the course of which remains to be determined.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/patologia , Encéfalo/patologia , Epilepsia/patologia , Adolescente , Criança , Feminino , Lobo Frontal/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Lobo Temporal/patologiaRESUMO
OBJECTIVE: To characterize white matter alterations in children with isolated or concurrent developmental coordination disorder and/or attention-deficit/hyperactivity disorder (ADHD) compared with typically-developing controls, and to determine whether group differences on motor and attention tasks could be explained by differences in diffusion tensor imaging (DTI) measures. STUDY DESIGN: In a cohort of children (n = 85) with developmental coordination disorder, ADHD, or combined developmental coordination disorder+ADHD, we examined 3 major white matter tracts involved in attention and motor processes. Using DTI, the corpus callosum, superior longitudinal fasciculus, and cingulum were analyzed with respect to measures of white matter integrity. Differences in fractional anisotropy (FA), mean diffusivity, radial diffusivity, and axial diffusivity were analyzed using ANOVA. Motor and attentional functioning was assessed using standardized tests, and correlated to DTI measures. RESULTS: FA reductions were noted in the frontal regions of the corpus callosum for children with ADHD (P = .039), whereas children with developmental coordination disorder displayed similar reductions in regions of the corpus callosum underlying parietal brain regions (P = .040), as well as the left superior longitudinal fasciculus (P = .026). White matter integrity was impacted in both frontal and parietal regions for children with comorbid developmental coordination disorder+ADHD (P = .029; .046). FA was positively correlated with scores on both motor and attentional assessments in a region-specific manner. CONCLUSION: Our findings suggest that alterations in the corpus callosum underlie difficulties in motor and attention functioning. These changes are functionally and regionally distinct and could reflect a neurobiological basis for motor and attention disorders in children.