The Metabolome Profiling and Pathway Analysis of ADHD
Condition: Attention-deficit/Hyperactivity Disorder
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity
Study type: Observational

Summary: 
      The purpose of this study is to understand the pathophysiological mechanisms of ADHD,
      especially the metabolomic pathway related to the behavioral/neuropsychological deficits of
      ADHD.

      To identify specific metabolites that show significant differences between ADHD and control
      groups, both liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry
      will be performed. In addition, the behavioral measures include ADHDRS-IV, SNAP-IV, CBCL,
      CGI-ADHD-S, SAICA, and Family APGAR-C. Neuropsychological testing, including CPT and CANTAB,
      will be performed. Conditional logistic regression and partial least squares discriminant
      analysis will be applied to identify significant metabolites for ADHD. Pathway enrichment and
      topology analyses will be conducted to evaluate the regulated pathways.
    

Detailed description: 
      Because attention deficit hyperactivity disorder (ADHD) is an early onset and long-term
      impairing disorder with tremendous impact on individuals, families, and societies, detection
      and diagnosis are very important for ADHD. Current diagnosis of ADHD relies mainly on
      clinical observation and interview tools that may involve a great subjective variability, and
      thus the investigation of objective biomarkers for ADHD is warranted. Metabolomics is the
      study of a biologic process involving all metabolites that are end products of the cellular
      process in a whole organism. Because metabolites represent the downstream expression of
      genome, transcriptome, and proteome, metabolomic profiles are more proximal to the behavioral
      phenotypes of ADHD. Analyzing metabolic differences between children with ADHD and healthy
      controls will provide insight into underlying disease pathology. To date, there has been no
      metabolomics study on ADHD. In this 3-year project, the investigators will perform a
      metabolomics analysis of serum to identify potential biomarkers for the behavioral and
      neuropsychological deficits of ADHD.

      This is a 3-year project. After careful calculation of sample size, the investigators will
      recruit 120 drug-naïve children with ADHD, aged 7-18, and 120 healthy controls with matched
      age, sex and BMI. Using both liquid chromatography-mass spectrometry and gas
      chromatography-mass spectrometry, serum-based metabolomic profiling will be performed. The
      behavioral measures include ADHDRS-IV, SNAP-IV, CBCL, CGI-ADHD-S, SAICA, and Family APGAR-C.
      Neuropsychological testing, including CPT and CANTAB, will be performed. Conditional logistic
      regression and partial least squares discriminant analysis will be applied to identify
      significant metabolites for ADHD. Pathway enrichment and topology analyses will be conducted
      to evaluate the regulated pathways.

      Using a matched study design, the investigators anticipate to identify specific metabolites
      that show significant differences between ADHD and control groups. In addition, results of
      pathway analysis may offer more biological understanding in explaining the underlying
      metabolic regulation among children with ADHD. This findings will significantly contribute to
      the knowledge of the pathophysiological mechanisms of ADHD, especially the metabolomic
      pathway related to the behavioral/neuropsychological deficits of ADHD.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        We plan to recruit 120 ADHD subjects and 120 control subjects.
      
Biospecimen description: 
      The investigators will collect blood samples from each participant after 8-hour fasting.
      Blood samples will be transferred into evacuated tubes that contain anticoagulant sodium
      dihydrogen phosphate (EDTA), centrifuged at 2000g for 10 minutes at 4°C. Serum will be
      extracted and stored at -80°C for sample analysis. The collection of blood sample will be
      conducted at the NTUH.
    
Keywords: Attention-deficit/hyperactivity disorder; metabolomics; neuropsychological deficits; pathway analysis