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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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ADHD GROUP | Subjects with clinical diagnosis of ADHD according to the DSM-V criteria |
| |
| TD GROUP | Typically development controls without lifetime diagnosis with ADHD |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| methylphenidate | Drug | The patients with ADHD will receive 12-week treatment with methylphenidate. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Diagnostic 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). | 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. | 15 minutes |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 5minutes |
| Questionnaire |
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Patients with ADHD
Inclusion Criteria
Exclusion Criteria
Neurotypical participants:
Inclusion Criteria
Exclusion Criteria
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80drug-naïve patients with ADHD, aged 6-18, and 80 age- and sex-matched typically developing controls will be recruited in this project
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Chi-Yung Shang, MD, PhD | Contact | +886-2-23123456 | 66965 | cyshang@ntu.edu.tw |
| Name | Affiliation | Role |
|---|---|---|
| Susan Shur-Fen Gau, MD, PhD | Department of Psychiatry, National Taiwan University Hospital | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Taiwan University Hospital | Recruiting | Taipei | 110 | Taiwan |
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| ID | Term |
|---|---|
| D008774 | Methylphenidate |
| ID | Term |
|---|---|
| D010648 | Phenylacetates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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plasma
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. |
| 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. | 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. | 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. | 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. | 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). | 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. | 10minutes |
| Neurobiological assessments | auditory MMN/P3a (task-free ERP) will be recorded in NTUH ERP . | 30minutes |
| Neurobiological assessments | dichotic continuous performance task(DCPT, task-related ERP modified from Conner's CATA) will be recorded in NTUH ERP lab. | 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. | 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. | 1.5 hours |
| D010880 |
| Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |