RESUMO
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with working memory (WM) deficits. However, WM is a multiprocess construct that can be impaired through several pathways, leaving the source of WM impairments in ADHD unresolved. In this study, we aim to replicate, in an independent sample, previously reported deficits in component processes of WM deficits in ADHD and expand to consider their implications for neurocognitive outcomes. METHODS: In 119 children (7-14 years old, 85 with ADHD), we used electroencephalography measures to quantify component processes during performance of a spatial working memory task. We quantified stimulus encoding using alpha range (8-12 Hz) power; vigilance by the P2 event-related potential to cues; and WMmaintenance by occipital-alpha and frontal-theta (4-7 Hz) power. These measures were evaluated against metrics of executive function, ADHD symptoms, and academic achievement. RESULTS: Encoding alpha-power decreases and cue P2 amplitude were attenuated in ADHD, whereas occipital-alpha power during maintenance was significantly greater in ADHD, consistent with a compensatory response to weak encoding. Weak alpha modulation during encoding was associated with poorer reading comprehension and executive function, as well as enhanced ADHD symptoms. Previously reported effects in frontal-theta power failed to replicate. CONCLUSIONS: Stimulus encoding, a component process of WM coupled to alpha modulation, is impaired in ADHD, and, unlike WM maintenance or vigilance processes, has implications outside of the laboratory via a relationship with executive function, and, to a weaker extent, reading comprehension.
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Sucesso Acadêmico , Ritmo alfa/fisiologia , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Córtex Cerebral/fisiopatologia , Potenciais Evocados/fisiologia , Função Executiva/fisiologia , Memória de Curto Prazo/fisiologia , Memória Espacial/fisiologia , Adolescente , Criança , Compreensão/fisiologia , Feminino , Humanos , Masculino , LeituraRESUMO
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous condition for which multiple efforts to characterize brain state differences are underway. The objective of this study was to identify distinct subgroups of resting electroencephalography (EEG) profiles among children with and without ADHD and subsequently provide extensive clinical characterization of the subgroups. METHODS: Latent class analysis was used with resting state EEG recorded from a large sample of 781 children with and without ADHD (N = 620 ADHD, N = 161 Control), aged 6-18 years old. Behavioral and cognitive characteristics of the latent classes were derived from semistructured diagnostic interviews, parent completed behavior rating scales, and cognitive test performance. RESULTS: A five-class solution was the best fit for the data, of which four classes had a defining spectral power elevation. The distribution of ADHD and control subjects was similar across classes suggesting there is no one resting state EEG profile for children with or without ADHD. Specific latent classes demonstrated distinct behavioral and cognitive profiles. Those with elevated slow-wave activity (i.e. delta and theta band) had higher levels of externalizing behaviors and cognitive deficits. Latent subgroups with elevated alpha and beta power had higher levels of internalizing behaviors, emotion dysregulation, and intact cognitive functioning. CONCLUSIONS: There is population-level heterogeneity in resting state EEG subgroups, which are associated with distinct behavioral and cognitive profiles. EEG measures may be more useful biomarkers of ADHD outcome or treatment response rather than diagnosis.
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Comportamento do Adolescente/fisiologia , Transtorno do Deficit de Atenção com Hiperatividade/classificação , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Sintomas Comportamentais/fisiopatologia , Ondas Encefálicas/fisiologia , Comportamento Infantil/fisiologia , Disfunção Cognitiva/fisiopatologia , Adolescente , Sintomas Afetivos/etiologia , Sintomas Afetivos/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/genética , Sintomas Comportamentais/etiologia , Criança , Disfunção Cognitiva/etiologia , Feminino , Humanos , MasculinoRESUMO
Predictors of math achievement in attention-deficit/hyperactivity disorder (ADHD) are not well-known. To address this gap in the literature, we examined individual differences in neurocognitive functioning domains on math computation in a cross-sectional sample of youth with ADHD. Gender and anxiety symptoms were explored as potential moderators. The sample consisted of 281 youth (aged 8-15 years) diagnosed with ADHD. Neurocognitive tasks assessed auditory-verbal working memory, visuospatial working memory, and processing speed. Auditory-verbal working memory speed significantly predicted math computation. A three-way interaction revealed that at low levels of anxious perfectionism, slower processing speed predicted poorer math computation for boys compared to girls. These findings indicate the uniquely predictive values of auditory-verbal working memory and processing speed on math computation, and their differential moderation. These findings provide preliminary support that gender and anxious perfectionism may influence the relationship between neurocognitive functioning and academic achievement.
Assuntos
Ansiedade , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Matemática , Testes de Estado Mental e Demência , Perfeccionismo , Logro , Adolescente , Ansiedade/diagnóstico , Ansiedade/etiologia , Ansiedade/psicologia , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Memória de Curto Prazo , Fatores Sexuais , Adulto JovemRESUMO
In the current study we sought to dissociate the component processes of working memory (WM) (vigilance, encoding and maintenance) that may be differentially impaired in attention-deficit/ hyperactivity disorder (ADHD). We collected electroencephalographic (EEG) data from 52 children with ADHD and 47 typically developing (TD) children, ages 7-14 years, while they performed a spatial Sternberg working memory task. We used independent component analysis and time-frequency analysis to identify midoccipital alpha (8-12 Hz) to evaluate encoding processes and frontal midline theta (4-7 Hz) to evaluate maintenance processes. We tested for effects of task difficulty and cue processing to evaluate vigilance. Children with ADHD showed attenuated alpha band event-related desynchronization (ERD) during encoding. This effect was more pronounced when task difficulty was low (consistent with impaired vigilance) and was predictive of memory task performance and symptom severity. Correlated with alpha ERD during encoding were alpha power increases during the maintenance period (relative to baseline), suggesting a compensatory effort. Consistent with this interpretation, midfrontal theta power increases during maintenance were stronger in ADHD and in high-load memory conditions. Furthermore, children with ADHD exhibited a maturational lag in development of posterior alpha power whereas age-related changes in frontal theta power deviated from the TD pattern. Last, subjects with ADHD showed age-independent attenuation of evoked responses to warning cues, suggesting low vigilance. Combined, these three EEG measures predicted diagnosis with 70% accuracy. We conclude that the interplay of impaired vigilance and encoding in ADHD may compromise maintenance and lead to impaired WM performance in this group.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Memória de Curto Prazo/fisiologia , Adolescente , Nível de Alerta/fisiologia , Atenção/fisiologia , Criança , Eletroencefalografia , Feminino , Humanos , MasculinoRESUMO
Attention deficit hyperactivity disorder (ADHD) is associated with substantial functional impairment in children and in adults. Many individuals with ADHD have clear neurocognitive deficits, including problems with visual attention, processing speed, and set shifting. ADHD is etiologically complex, and although genetic factors play a role in its development, much of the genetic contribution to ADHD remains unidentified. We conducted clinical and neuropsychological assessments of 294 individuals (269 with ADHD) from 163 families (48 multigenerational families created using genealogical reconstruction, 78 affected sib pair families, and 37 trios) from the Central Valley of Costa Rica (CVCR). We used principal components analysis (PCA) to group neurocognitive and behavioral variables using the subscales of the Child Behavior Checklist (CBCL) and 15 neuropsychological measures, and created quantitative traits for heritability analyses. We identified seven cognitive and two behavioral domains. Individuals with ADHD were significantly more impaired than their unaffected siblings on most behavioral and cognitive domains. The verbal IQ domain had the highest heritability (92%), followed by auditory attention (87%), visual processing speed and problem solving (85%), and externalizing symptoms (81%). The quantitative traits identified here have high heritabilities, similar to the reported heritability of ADHD (70-90%), and may represent appropriate alternative phenotypes for genetic studies. The use of multigenerational families from a genetically isolated population may facilitate the identification of ADHD risk genes in the face of phenotypic and genetic heterogeneity.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Comportamento , Irmãos , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Criança , Cognição , Costa Rica , Análise Fatorial , Feminino , Predisposição Genética para Doença , Humanos , Padrões de Herança/genética , Masculino , Modelos Genéticos , Testes Neuropsicológicos , Linhagem , Fenótipo , Análise de Componente Principal , Adulto JovemRESUMO
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with significant impairment in multiple functional domains. This trial evaluated efficacy in ADHD symptoms and functional outcomes in young adults treated with atomoxetine. METHODS: Young adults (18-30 years old) with ADHD were randomized to 12 weeks of double-blind treatment with atomoxetine (n = 220) or placebo (n = 225). The primary efficacy measure of ADHD symptom change was Conners' Adult ADHD Rating Scale (CAARS): Investigator-Rated: Screening Version Total ADHD Symptoms score with adult prompts. Secondary outcomes scales included the Adult ADHD Quality of Life-29, Clinical Global Impression-ADHD-Severity, Patient Global Impression-Improvement, CAARS Self-Report, Behavior Rating Inventory of Executive Function-Adult Version Self-Report, and assessments of depression, anxiety, sleepiness, driving behaviors, social adaptation, and substance use. RESULTS: Atomoxetine was superior to placebo on CAARS: Investigator-Rated: Screening Version (atomoxetine [least-squares mean ± SE, -13.6 ± 0.8] vs placebo [-9.3 ± 0.8], 95% confidence interval [-6.35 to -2.37], P < 0.001), Clinical Global Impression-ADHD-Severity (atomoxetine [-1.1 ± 0.1] vs placebo [-0.7 ± 0.1], 95% confidence interval [-0.63 to -0.24], P < 0.001), and CAARS Self-Report (atomoxetine [-11.9 ± 0.8] vs placebo [-7.8 ± 0.7], 95% confidence interval [-5.94 to -2.15], P < 0.001) but not on Patient Global Impression-Improvement. In addition, atomoxetine was superior to placebo on Adult ADHD Quality of Life-29 and Behavior Rating Inventory of Executive Function-Adult Version Self-Report. Additional assessments failed to detect significant differences (P ≥ 0.05) between atomoxetine and placebo. The adverse event profile was similar to that observed in other atomoxetine studies. Nausea, decreased appetite, insomnia, dry mouth, irritability, dizziness, and dyspepsia were reported significantly more often with atomoxetine than with placebo. CONCLUSIONS: Atomoxetine reduced ADHD symptoms and improved quality of life and executive functioning deficits in young adults compared with placebo. Atomoxetine was also generally well tolerated.
Assuntos
Inibidores da Captação Adrenérgica/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Propilaminas/uso terapêutico , Adolescente , Inibidores da Captação Adrenérgica/efeitos adversos , Adulto , Análise de Variância , Cloridrato de Atomoxetina , Atenção/efeitos dos fármacos , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Método Duplo-Cego , Função Executiva/efeitos dos fármacos , Humanos , Análise dos Mínimos Quadrados , Valor Preditivo dos Testes , Propilaminas/efeitos adversos , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Porto Rico , Qualidade de Vida , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Adulto JovemRESUMO
OBJECTIVE: The combination of d-methylphenidate and guanfacine (an α-2A adrenergic agonist) may be an effective alternative to either agent as monotherapy in children with attention-deficit/hyperactivity disorder (ADHD). This study investigated the neural mechanisms underlying medication effects using cortical source analysis of electroencephalography (EEG) data. METHOD: A total of 172 children with ADHD (aged 7-14; 118 boys) completed an 8-week randomized, double-blind, comparative study with 3 treatment arms: d-methylphenidate, guanfacine, or their combination. EEG modulations of brain oscillations at baseline and end point were measured during a spatial working memory task from cortical sources localized within the anterior cingulate (midfrontal) and primary visual cortex (midoccipital), based on previously reported ADHD and control differences. Linear mixed models examined treatment effects on EEG and performance measures. RESULTS: Combined treatment decreased midoccipital EEG power across most frequency bands and task phases. Several midoccipital EEG measures also showed significantly greater changes with combined treatment than with monotherapies. D-methylphenidate significantly increased midoccipital theta during retrieval, while guanfacine produced only trend-level reductions in midoccipital alpha during maintenance and retrieval. Task accuracy improved with combined treatment, was unchanged with d-methylphenidate, and worsened with guanfacine. Treatment-related changes in midoccipital power correlated with improvement in ADHD severity. CONCLUSION: These findings show that combined treatment ameliorates midoccipital neural activity associated with treatment-related behavioral improvements and previously implicated in visuo-attentional deficits in ADHD. Both monotherapies had limited effects on EEG measures, with guanfacine further showing detrimental effects on performance. The identified midoccipital EEG profile may aid future treatment monitoring for children with ADHD. CLINICAL TRIAL REGISTRATION INFORMATION: Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder (Project1); https://clinicaltrials.gov/; NCT00429273. DIVERSITY & INCLUSION STATEMENT: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure sex and gender balance in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. We actively worked to promote sex and gender balance in our author group.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Metilfenidato , Masculino , Criança , Feminino , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Guanfacina/farmacologia , Guanfacina/uso terapêutico , Metilfenidato/uso terapêutico , Memória de Curto Prazo , Eletroencefalografia , Estimulantes do Sistema Nervoso Central/uso terapêuticoRESUMO
OBJECTIVE: The combination of d-methylphenidate and guanfacine (an α-2A agonist) has emerged as a potential alternative to either monotherapy in children with attention-deficit/hyperactivity disorder (ADHD), but it is unclear what predicts response to these treatments. This study is the first to investigate pretreatment clinical and electroencephalography (EEG) profiles as predictors of treatment outcome in children randomized to these different medications. METHOD: A total of 181 children with ADHD (aged 7-14 years; 123 boys) completed an 8-week randomized, double-blind, comparative study with d-methylphenidate, guanfacine, or combined treatments. Pretreatment assessments included ratings on ADHD, anxiety, and oppositional behavior. EEG activity from cortical sources localized within midfrontal and midoccipital regions was measured during a spatial working memory task with encoding, maintenance, and retrieval phases. Analyses tested whether pretreatment clinical and EEG measures predicted treatment-related change in ADHD severity. RESULTS: Higher pretreatment hyperactivity-impulsivity and oppositional symptoms and lower anxiety predicted greater ADHD improvements across all medication groups. Pretreatment event-related midfrontal beta power predicted treatment outcome with combined and monotherapy treatments, albeit in different directions. Weaker beta modulations predicted improvements with combined treatment, whereas stronger modulation during encoding and retrieval predicted improvements with d-methylphenidate and guanfacine, respectively. A multivariate model including EEG and clinical measures explained twice as much variance in ADHD improvement with guanfacine and combined treatment (R2= 0.34-0.41) as clinical measures alone (R2 = 0.14-.21). CONCLUSION: We identified treatment-specific and shared predictors of response to different pharmacotherapies in children with ADHD. If replicated, these findings would suggest that aggregating information from clinical and brain measures may aid personalized treatment decisions in ADHD. CLINICAL TRIAL REGISTRATION INFORMATION: Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder; https://clinicaltrials.gov; NCT00429273.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Metilfenidato , Masculino , Criança , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Guanfacina/farmacologia , Guanfacina/uso terapêutico , Metilfenidato/uso terapêutico , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Resultado do Tratamento , Estimulantes do Sistema Nervoso Central/uso terapêutico , Método Duplo-CegoRESUMO
OBJECTIVES: Attention-deficit hyperactivity disorder (ADHD) is prevalent in patients with bipolar disorder (BP), but very few studies consider this when interpreting magnetic resonance imaging findings. No studies, to our knowledge, have screened for or controlled for the presence of ADHD when examining cortical thickness in patients with BP. We used a 2 × 2 design to evaluate the joint effects of BP and ADHD on cortical thickness and uncover the importance of ADHD comorbidity in BP subjects. METHODS: The study included 85 subjects: 31 healthy controls, 17 BP-only, 19 ADHD-only, and 18 BP/ADHD. All patients with BP were subtype I, euthymic, and not taking lithium. Groups did not differ significantly in age or gender distribution. We used cortical thickness measuring tools combined with cortical pattern matching methods to align sulcal/gyral anatomy across participants. Significance maps were used to check for both main effects of BP and ADHD and their interaction. Post-hoc comparisons assessed how the effects of BP on cortical thickness varied as a function of the presence or absence of ADHD. RESULTS: Interactions of BP and ADHD diagnoses were found in the left subgenual cingulate and right orbitofrontal cortex, demonstrating that the effect of BP on cortical thickness depends on ADHD status. CONCLUSIONS: Some brain abnormalities attributed to BP may result from the presence of ADHD. Diagnostic interactions were found in regions previously implicated in the pathophysiology of BP, making it vital to control for an ADHD comorbid diagnosis when attempting to isolate neural or genetic abnormalities specific to BP.
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Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/patologia , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/patologia , Córtex Cerebral/patologia , Adulto , Mapeamento Encefálico , Distribuição de Qui-Quadrado , Comorbidade , Feminino , Humanos , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: While genetic epidemiological studies demonstrate a substantial degree of genetic predisposition for attention-deficit/hyperactivity disorder (ADHD), they also suggest that the genetics are complex and may differ between populations or ethnic groups. OBJECTIVE: This study describes the phenomenology of siblings with ADHD from the genetically isolated population of the Central Valley of Costa Rica. METHODS: Rates of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)-defined ADHD subtypes and comorbid conditions were calculated in a sample of 157 ADHD-affected children (probands and siblings) recruited for genetic studies using standardized approaches. Sib-sib comparisons and logistic regressions were conducted to identify significant patterns of concordance. RESULTS: Combined-type ADHD (69.5%) was the most common subtype among probands, followed by the inattentive (27.4%), and hyperactive-impulsive (3.2%) subtypes. Anxiety disorders were prevalent (55.9%), as were disruptive behavior disorders (30.9%) and Tourette disorder (17.0%). Probands and siblings showed high sib-sib concordance for anxiety disorders. CONCLUSIONS: ADHD in Costa Rica is similar in clinical and demographic characteristics to ADHD seen in other parts of the world, although the rates of co-occurring psychiatric disorders differ somewhat from those previously reported in Latin American samples. Comorbid anxiety is prevalent, with high rates of sib-sib concordance, and may represent a distinct, homogeneous subgroup suitable for genetic studies.
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Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtornos Mentais/epidemiologia , Adolescente , Adulto , Idade de Início , Transtorno do Deficit de Atenção com Hiperatividade/genética , Criança , Comorbidade , Costa Rica , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Transtornos Mentais/diagnóstico , Prevalência , Índice de Gravidade de Doença , IrmãosRESUMO
This research project sought to estimate the prevalence of Attention-Deficit/Hyperactivity Disorder (ADHD) and to determine if the Swanson Nolan and Pelham Rating Scale IV (SNAP-IV) Spanish version is a useful screening tool in a population of Costa Rican school children. The SNAP-IV Spanish version was given to the parents and teachers of 425 children aged 5 to 13 (mean 8.8). All subjects were also assessed with the Swanson, Kotkin, Agler, M-Flynn and Pelham Scale (SKAMP), along with diagnostic confirmation by clinical interview. The sensitivity and specificity of the SNAP-IV was assessed as a predictor of DSM-IV ADHD diagnosis. The point prevalence of Attention Deficit Hyperactivity Disorder (ADHD) in this sample was 5%. The prevalence of ADHD among girls was 7%, while that among boys was 4%. The optimal screen was the teacher-rated SNAP-IV at a 20% cutoff, which had a sensitivity of 96% and specificity of 82%. Parent sensitivities were lower than teacher sensitivities. SNAP-IV teacher ratings with a cutoff isolating the top 20% of scores correctly categorized 87% of children.
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Transtorno do Deficit de Atenção com Hiperatividade , Manual Diagnóstico e Estatístico de Transtornos Mentais , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Costa Rica , Humanos , Pais , PrevalênciaRESUMO
OBJECTIVE: The current study applies a precision medicine approach to trigeminal nerve simulation (TNS), a Food and Drug Administration-approved neuromodulation treatment for attention-deficit/hyperactivity disorder (ADHD), by testing secondary outcomes of cognitive and electroencephalographic [EEG] predictors of treatment response among subjects from the original randomized controlled trial. METHOD: Children aged 8 to 12 years with ADHD, were randomized to 4 weeks of active or sham TNS treatment, after which the sham group crossed over into 4 weeks of open-label treatment. TNS treatment responders (RESP) had an ADHD Rating Scale (ADHD-RS) Total score reduction of ≥25%, whereas nonresponders (NR) had <25% reduction posttreatment. Assessments included weekly behavioral ratings and pre-/posttreatment cognitive EEG measures. RESULTS: The final sample was 25 RESP and 26 NR comprising 34 male and 17 female children, with a mean (SD) age of 10.3 (1.4) years. Baseline measures that significantly differentiated RESP from NR included: lower working memory, lower spelling and mathematics achievement, deficits on behavioral ratings of executive function (BRIEF), and lower resting state EEG power in the right frontal (F4) region (all p values <.05). Compared to NRs, responders showed significantly increased right frontal EEG power with TNS treatment, which was predictive of improved executive functions and ADHD symptomatology (ß = 0.65, p < .001). When EEG findings and behavior were modeled together, the area under the curve (AUC) for BRIEF Working Memory scale was 0.83 (p = .003), indicating moderate prediction of treatment response. CONCLUSION: Children with ADHD who have executive dysfunction are more likely to be TNS responders and show modulation of right frontal brain activity, improved/normalized executive functions, and ADHD symptom reduction. CLINICAL TRIAL REGISTRATION INFORMATION: Developmental Pilot Study of External Trigeminal Nerve Stimulation for ADHD; http://clinicaltrials.gov; NCT02155608.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Criança , Cognição , Eletroencefalografia , Função Executiva , Feminino , Humanos , Masculino , Projetos Piloto , Resultado do Tratamento , Nervo TrigêmeoRESUMO
The present study investigated inhibitory control deficits in Tourette's Disorder (TD)-only, Attention Deficit/Hyperactivity Disorder (ADHD)-only, and TD+ADHD and explored the degree to which measures of inhibitory control, and tic and ADHD severity predicted objective tic suppressibility. Participants were youth ages 9 to 14 (M = 11.15) with TD-only (n = 24), TD+ADHD (n = 19), ADHD-only (n = 139), and typically-developing controls (n = 59) drawn from a larger study. Groups were compared on computer-based and paper and pencil neurocognitive inhibitory control tasks. Among youth with TD, neurocognitive measures of inhibitory control, subjective tic-suppressibility (Premonitory Urge for Tics Scale, item 10), and ADHD symptom severity were evaluated as predictors of objective tic suppressibility (i.e., laboratory-based tic suppression task), controlling for total tic severity. There were significant group differences on Color-Word inhibition/switching performance, though post-hoc comparisons yielded no significant pairwise group contrasts. Subjective tic suppressibility was the only significant predictor of objective tic suppressibility. The evident intact neurocognitive inhibitory control among youth with TD suggests that individuals with TD may use compensatory neural mechanisms to support typical speed and accuracy of response. The role of cognitive flexibility in mechanisms of tic suppression should also be further explored.
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Transtorno do Deficit de Atenção com Hiperatividade , Transtornos de Tique , Tiques , Síndrome de Tourette , Adolescente , Criança , Humanos , Inibição PsicológicaRESUMO
OBJECTIVE: This study evaluates dexmethylphenidate extended release (d-MPH-ER) in adults with ADHD. METHOD: Following a 5-week, randomized, controlled, fixed-dose study of d-MPH-ER 20 to 40 mg/d, 170 adults entered a 6-month open-label extension (OLE) to assess long-term safety, with flexible dosing of 20 to 40 mg/d. Exploratory effectiveness outcomes included change from Week 5 on ADHD Rating Scale (ADHD-RS) and proportion of responders on Clinical Global Impressions-Improvement (CGI-I) scale. RESULTS: 103 patients completed OLE, and effectiveness was evaluable in 102 patients. d-MPH-ER was well tolerated; the most common adverse events (>15%) were headache, insomnia, and decreased appetite. Mean improvements in ADHD-RS score were -10.2 for patients switched from placebo to d-MPH-ER (n = 20) and -8.4 for those maintained on d-MPH-ER (n = 82). Respective CGI-I responder rates were 95.0% and 95.1%. CONCLUSION: Once-daily d-MPH-ER 20 to 40 mg is safe and effective for long-term treatment of adult ADHD.
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Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Cloridrato de Dexmetilfenidato , Metilfenidato/uso terapêutico , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Cápsulas , Estimulantes do Sistema Nervoso Central/efeitos adversos , Preparações de Ação Retardada , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Metilfenidato/efeitos adversos , Pessoa de Meia-Idade , Determinação da Personalidade , Resultado do Tratamento , Adulto JovemRESUMO
Attention deficit hyperactivity disorder (ADHD) is a disorder characterized by attentional difficulties. Mindfulness is a receptive attention to present experience. Both ADHD and mindfulness are associated with attention and personality. This study tests whether individuals with ADHD have lower mindfulness scores than controls and, if true, whether personality contributes to these differences. One hundred and five adults (half with ADHD) were assessed for mindfulness, using the Kentucky Inventory of Mindfulness Skills, and personality, using the Tridimensional Character Inventory. Individuals with ADHD report themselves as less mindful than non-ADHD controls and more novelty-seeking, less self-directed, and more self-transcendent. Mindfulness is negatively associated with ADHD and positively associated with self-directedness and self-transcendence. Analyses of subscales of mindfulness suggest that ADHD is associated most with the "Acting in Awareness" dimension, perhaps because of shared items reflecting attentional variability. The current findings support that a large portion of variability in trait mindfulness can be explained by ADHD status and personality traits of self-directedness and self-transcendence. It further suggests that interventions that increase mindfulness might improve symptoms of ADHD and increase self-directedness and/or self-transcendence.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Conscientização , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Personalidade , Análise de Regressão , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Trigeminal nerve stimulation (TNS), a minimal-risk noninvasive neuromodulation method, showed potential benefits for attention-deficit/hyperactivity disorder (ADHD) in an unblinded open study. The present blinded sham-controlled trial was conducted to assess the efficacy and safety of TNS for ADHD and potential changes in brain spectral power using resting-state quantitative electroencephalography. METHOD: Sixty-two children 8 to 12 years old, with full-scale IQ of at least 85 and Schedule for Affective Disorders and Schizophrenia-diagnosed ADHD, were randomized to 4 weeks of nightly treatment with active or sham TNS, followed by 1 week without intervention. Assessments included weekly clinician-administered ADHD Rating Scales (ADHD-RS) and Clinical Global Impression (CGI) scales and quantitative electroencephalography at baseline and week 4. RESULTS: ADHD-RS total scores showed significant group-by-time interactions (F1,228 = 8.12, p = .005; week 4 Cohen d = 0.5). CGI-Improvement scores also favored active treatment (χ21,168 = 8.75, p = .003; number needed to treat = 3). Resting-state quantitative electroencephalography showed increased spectral power in the right frontal and frontal midline frequency bands with active TNS. Neither group had clinically meaningful adverse events. CONCLUSION: This study demonstrates TNS efficacy for ADHD in a blinded sham-controlled trial, with estimated treatment effect size similar to non-stimulants. TNS is well tolerated and has minimal risk. Additional research should examine treatment response durability and potential impact on brain development with sustained use. CLINICAL TRIAL REGISTRATION INFORMATION: Trigeminal Nerve Stimulation for ADHD; http://clinicaltrials.gov/; NCT02155608.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/terapia , Terapia por Estimulação Elétrica/métodos , Nervo Trigêmeo/fisiologia , Criança , Método Duplo-Cego , Função Executiva , Feminino , Humanos , Modelos Logísticos , Masculino , Projetos Piloto , Escalas de Graduação Psiquiátrica , Resultado do Tratamento , Estados UnidosRESUMO
BACKGROUND: This paper examines familiality and candidate gene associations of cognitive measures as potential endophenotypes in attention-deficit/hyperactivity disorder (ADHD). METHODS: The sample consists of 540 participants, aged 6 to 18, who were diagnosed with ADHD from 251 families recruited for a larger genetic study of ADHD. All members of the family underwent psychiatric interviews and children were administered a large battery of cognitive tasks. Subjects were genotyped for several dopaminergic candidate genes (DAT1, DRD4, and DRD5). RESULTS: Performance on measures of intelligence, working memory, and set-shifting had the highest sibling correlations and exhibited significant familial clustering. The 7-repeat allele of the dopamine receptor D4 (DRD4) gene was associated with poor performance on measures of intelligence, color naming, interference control, and working memory. There were no significant associations with DAT1 and DRD5. CONCLUSIONS: Sibling correlations, familial clustering and candidate gene associations provide strong support for verbal working memory as a candidate endophenotype for ADHD. More complex models of, and larger sample sizes for, genetic association with cognitive functions are encouraged for future study.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtornos Cognitivos/epidemiologia , Dopamina/genética , Relações entre Irmãos , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Criança , Transtornos Cognitivos/diagnóstico , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Feminino , Genótipo , Humanos , Masculino , Testes Neuropsicológicos , Fenótipo , Polimorfismo Genético , Receptores de Dopamina D4/genética , Receptores de Dopamina D5/genéticaRESUMO
INTRODUCTION: Lisdexamfetamine dimesylate (LDX), a prodrug stimulant, is indicated for attention-deficit/hyperactivity disorder (ADHD) in children 6-12 years of age and in adults. In short-term studies, once-daily LDX provided efficacy throughout the day. This study presented here was conducted to assess the long-term safety, tolerability, and effectiveness of LDX in 6- to 12-year-olds with ADHD. METHODS: This open-label, multicenter, single-arm study enrolled children with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision criteria for ADHD. Following 1-week screening and washout periods, subjects were titrated to LDX 30, 50, or 70 mg/day over 4 weeks and placed on maintenance treatment for 11 months. The ADHD Rating Scale and Clinical Global Impression-Improvement scale measured effectiveness. RESULTS: Of 272 subjects receiving LDX, 147 completed the study. Most adverse events were mild to moderate and occurred during the first 4 weeks. There were no clinically meaningful changes in blood pressure or electrocardiographic parameters. From baseline to endpoint, mean ADHD Rating Scale scores improved by 27.2 points (P<.0001). Improvements occurred during each of the first 4 weeks, and were maintained throughout. Based on Clinical Global Impression-Improvement scale scores, >80% of subjects at endpoint and >95% of completers at 12 months were rated "improved." CONCLUSION: Long-term 30, 50, and 70 mg/day LDX was generally well tolerated and effective in children with ADHD.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Dextroanfetamina/uso terapêutico , Administração Oral , Apetite/efeitos dos fármacos , Criança , Dextroanfetamina/administração & dosagem , Dextroanfetamina/efeitos adversos , Manual Diagnóstico e Estatístico de Transtornos Mentais , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Cefaleia/induzido quimicamente , Humanos , Dimesilato de Lisdexanfetamina , Masculino , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Fatores de Tempo , Resultado do Tratamento , Redução de Peso/efeitos dos fármacosRESUMO
Attention deficit hyperactivity disorder (ADHD) treatment is often determined empirically through trial and error until an adequate response is obtained or side effects occur. ADHD is highly heritable and individuals experience wide individual variability in response to ADHD medications, suggesting that the mechanism of action of stimulant medications may provide clues for genetic predictors of response. The promise of ADHD pharmacogenetics is far-reaching and includes the potential to develop individualized medication regimens that improve symptom response, decrease risk for side effects, improve long-term tolerability, and thus contribute to long-term treatment compliance and improved effectiveness. Early ADHD pharmacogenetic studies have focused predominantly on catecholamine pathway genes and response to methylphenidate. Future efforts will also examine a wider range of stimulant and nonstimulant medications on a range of outcome measures and durations. Based on these studies, the potential for personalizing ADHD treatment in clinical practice will be determined.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/genética , Estimulantes do Sistema Nervoso Central/uso terapêutico , Farmacogenética , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/sangue , Biotransformação , Estimulantes do Sistema Nervoso Central/efeitos adversos , Estimulantes do Sistema Nervoso Central/farmacocinética , Criança , Pré-Escolar , Citocromo P-450 CYP2D6 , Citocromo P-450 CYP3A/genética , Relação Dose-Resposta a Droga , Previsões , Marcadores Genéticos/genética , Humanos , Receptores de Neurotransmissores/efeitos dos fármacos , Receptores de Neurotransmissores/genética , Resultado do TratamentoRESUMO
We conducted a genome-wide association study of symptom response in an open-label study of a methylphenidate transdermal system (MTS). All DNA extraction and genotyping was conducted at SUNY Upstate Medical University using the Affymetrix Genome-Wide Human SNP Array 6.0. All quality control and association analyses were conducted using the software package PLINK. After data cleaning and quality control, there were 187 subjects (72% (N = 135) male) with mean age 9.2 +/- 2.0 years and 319,722 SNPs available for analysis. The most statistically significant association (rs9627183 and rs11134178; P = 3 x 10(-6)) fell short of the threshold for a genome-wide significant association. The most intriguing association among suggestive findings (rs3792452; P = 2.6 x 10(-5)) was with the metabotropic glutamate receptor 7 gene (GRM7) as it is expressed in brain structures also previously associated with ADHD. Among the 102 available SNPs covering previously studied candidate genes, two SNPs within the norepinephrine transporter gene (NET, SLC6A2) were significant at P < or = 1 x 10(-2). These results should be considered preliminary until replicated in larger adequately powered, controlled samples but do suggest that noradrenergic and possibly glutaminergic genes may be involved with response to methylphenidate.