Metabolic Mechanisms of the Electrophysiological Biomarkers for Response to Methylphenidate Treatment in Children With ADHD

Exploration of the Metabolic Mechanisms of the Electrophysiological Biomarkers for Response to Methylphenidate Treatment in Children With Attention-Deficit/Hyperactivity Disorder

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.

1. Patients with ADHD

   1. Inclusion Criteria

      • Patients, aged 6 to 18 years, meet the DSM-5 diagnostic criteria for ADHD.
      • At baseline, patients have a Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) score greater than 4.
      • Patients have a Full IQ (FIQ) score greater than 80.

   2. Exclusion Criteria

      • Patients have a major psychiatric disorder, such as autism spectrum disorder, schizophrenia, affective disorders, or substance use disorders.
      • Patients have a major disorder of central nervous system, such as epilepsy.
      • Patients have a major systemic disease, such as diabetes mellitus or cardiovascular diseases.
      • Patients have ever received any medication to treat the clinical symptoms of ADHD.

2. Neurotypical participants:

   1. Inclusion Criteria

      • aged 6 to 18 years
      • All of the neurotypical participants have no psychiatric disorder in lifetime according to the diagnostic criteria of DSM-5.

   2. Exclusion Criteria

      • participants have any disorder of central nervous system or major systemic disease
      • participants have ever taken any psychotropic drug, or who have FIQ scores less than 80, will be excluded from the present study.