To explore the relationship of treatment-related changes in electrophysiology and those in metabolomics for identification of the underlying metabolic mechanisms for the electrophysiological effects of methylphenidate in children with ADHD.
Although the efficacy of methylphenidate in reducing the core symptoms of attentiondeficit/ hyperactivity disorder (ADHD) is well documented in clinical trials, no definite biomarker has been identified to differentiate responders from non-responders to methylphenidate treatment for children with ADHD. In addition, the neural and metabolic mechanisms underlying the therapeutic effects of methylphenidate remain to be elucidated. In this 4-year prospective project, the investigators will explore the effects of 12-week treatment with methylphenidate on the electrophysiology and metabolomics of children with ADHD to identify the biomarkers for predicting the clinical response to methylphenidate. In addition, the investigators will explore the metabolic mechanisms through which methylphenidate treatment may modulate the abnormality in the electrophysiology of children with ADHD. Specific Aims: 1. To examine the differences in electrophysiology and metabolomics between children with ADHD and neurotypical controls. 2. To examine the differences in the change of electrophysiology and metabolomics after 12-week treatment with methylphenidate between responders and non-responders in children with ADHD. 3. To explore the relationship of treatment-related changes in electrophysiology and those in metabolomics for identification of the underlying metabolic mechanisms for the electrophysiological effects of methylphenidate in children with ADHD.
Study Type
OBSERVATIONAL
Enrollment
160
The patients with ADHD will receive 12-week treatment with methylphenidate.
National Taiwan University Hospital
Taipei, Taiwan
RECRUITINGDiagnostic interview
We will interview all the participants and their parents to examine whether the participants have any psychiatric disorder by employing the Kiddie Epidemiologic version of the Schedule for Affective Disorders and Schizophrenia (K-SADS-E).
Time frame: 1 hour
ADHD symptoms
Subjects will be interviewed by ADHD rating scale , which consists of 18 items to measure the symptomatology of ADHD . Each question in this questionnaire is scaled from 0 to 3. The higher the total score, the more severe the symptoms.
Time frame: 15 minutes
Questionnaire
Cases and parents assisted in filling out the Achenbach child behavior check list (CBCL).Each question in this questionnaire is scaled from 1 to 3. The higher the total score, the more severe the emotional and behavioral distress.
Time frame: 5minutes
Questionnaire
Cases and parents assisted in filling out the Swanson, Nolan, and Pelham Rating Scale Fourth Edition (SNAP-IV).Each question in this questionnaire is scaled from 0 to 3. The higher the total score, the more severe the symptoms.
Time frame: 5minutes
Questionnaire
Cases and parents assisted in filling out the Family APGAR questionnaire.Each question in this questionnaire is scaled from 0 to 2. The higher the total score, the better the family function.
Time frame: 5minutes
Questionnaire
Cases and parents assisted in filling out the Social Adjustment Inventory for Children and Adolescents questionnaire (SAICA).The scale for each question in this questionnaire ranges from 1 to 4. The higher the total score, the worse the social adaptation status.
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Time frame: 5minutes
Questionnaire
Cases and parents assisted in filling out the Behavior Rating Inventory of Executive Function questionnaire(BRIEF).Each question in this questionnaire is scaled from 1 to 3. The higher the total score, the lower the executive function status.
Time frame: 5minutes
Neurobiological assessments
Resting state EEG will be recorded in NTUH ERP lab.The EEG will be processed for functional connectivity indices between regions are calculated using the magnitude squared coherence (Coh) in the delta(delta)/theta(theta)/alpha(alpha)/beta(beta) frequency bands and the nonlinear index (L) of generalized synchronization.
Time frame: 10minutes
Neurobiological assessments
Resting state EEG will be recorded in NTUH ERP lab. Phase transfer entropy (PTE) will be used to construct the effective connectivity. The topological properties of networks and flow gain are measured separately in four bands (delta, theta, alpha, and beta).
Time frame: 10minutes
Neurobiological assessments
Resting state EEG will be recorded in NTUH ERP lab. We will perform Fast Fourier Transform using the pwelch algorithm, with a 128 sample triangular window, to obtain time-frequency domain measures. Mean spectral estimates in various power bands are computed. As a measure of intraindividual variability in neural activity, the standard deviation of the power in each 2-second trial is calculated for each band for each participant.
Time frame: 10minutes
Neurobiological assessments
auditory MMN/P3a (task-free ERP) will be recorded in NTUH ERP .
Time frame: 30minutes
Neurobiological assessments
dichotic continuous performance task(DCPT, task-related ERP modified from Conner's CATA) will be recorded in NTUH ERP lab.
Time frame: 20minutes
liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry
Whole blood samples will be collected after 8 hours of fasting at baseline and week 12 for neurotypical controls and for patients with ADHD. The investigators will employ both liquid chromatography coupled to mass spectrometry (LC/MS) and gas chromatography coupled to mass spectrometry (GC/MS) to conduct the experiments of metabolomic profiling of the serum at the Metabolomics Core Laboratory, National Taiwan University.
Time frame: 5 minutes
Neuropsychological testing
Subjects will be assessed by the WISC-V(Wechsler Intelligence Scale for Children),WISC-V scores between 90 and 109 represent moderate general intelligence, and higher scores represent relatively better cognitive function.
Time frame: 1.5 hours