title: A preliminary study on methylphenidate-regulated gene expression in lymphoblastoid cells of ADHD patients.
abstract: OBJECTIVE
  Methylphenidate (MPH) is a commonly used stimulant medication for treating attention-deficit/hyperactivity disorder (ADHD). Besides inhibiting monoamine reuptake there is evidence that MPH also influences gene expression directly.
  
  
  METHODS
  We investigated the impact of MPH treatment on gene expression levels of lymphoblastoid cells derived from adult ADHD patients and healthy controls by hypothesis-free, genome-wide microarray analysis. Significant findings were subsequently confirmed by quantitative Real-Time PCR (qRT PCR) analysis.
  
  
  RESULTS
  The microarray analysis from pooled samples after correction for multiple testing revealed 138 genes to be marginally significantly regulated due to MPH treatment, and one gene due to diagnosis. By qRT PCR we could confirm that GUCY1B3 expression was differential due to diagnosis. We verified chronic MPH treatment effects on the expression of ATXN1, HEY1, MAP3K8 and GLUT3 in controls as well as acute treatment effects on the expression of NAV2 and ATXN1 specifically in ADHD patients.
  
  
  CONCLUSIONS
  Our preliminary results demonstrate MPH treatment differences in ADHD patients and healthy controls in a peripheral primary cell model. Our results need to be replicated in larger samples and also using patient-derived neuronal cell models to validate the contribution of those genes to the pathophysiology of ADHD and mode of action of MPH.
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg , Würzburg , Germany.
authors.forename: Ricarda
authors.initials: R
authors.lastname: Schwarz
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
authors.forename: Claus-Jürgen
authors.initials: CJ
authors.lastname: Scholz
authors.forename: Lena
authors.initials: L
authors.lastname: Weissflog
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schmidt
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Lesch
authors.forename: Christian
authors.initials: C
authors.lastname: Jacob
authors.forename: Susanne
authors.initials: S
authors.lastname: Reichert
authors.forename: Julia
authors.initials: J
authors.lastname: Heupel
authors.forename: Julia
authors.initials: J
authors.lastname: Volkert
authors.forename: Juliane
authors.initials: J
authors.lastname: Kopf
authors.forename: Max
authors.initials: M
authors.lastname: Hilscher
authors.forename: Heike
authors.initials: H
authors.lastname: Weber
authors.forename: Sarah
authors.initials: S
authors.lastname: Kittel-Schneider
mesh_terms: D000328:Adult; D000067696:Ataxin-1 / Q000235:genetics; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000235:genetics*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics; D002460:Cell Line; D004265:DNA Helicases; D005260:Female; D005786:Gene Expression Regulation; D051274:Glucose Transporter Type 3 / Q000235:genetics; D006162:Guanylate Cyclase / Q000235:genetics; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000235:genetics; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use*; D046228:Microarray Analysis; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D000071756:Soluble Guanylyl Cyclase; D055815:Young Adult
chemical_list: D000067696:Ataxin-1; D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D004265:DNA Helicases; D051274:Glucose Transporter Type 3; D006162:Guanylate Cyclase; D020930:MAP Kinase Kinase Kinases; D008774:Methylphenidate; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D000071756:Soluble Guanylyl Cyclase; C000593749:ATXN1 protein, human; C000605664:GUCY1B1 protein, human; C485631:HEY1 protein, human; C495687:SLC2A3 protein, human; C069937:MAP3K8 protein, human; C465311:NAV2 protein, human
keywords: attention-deficit-/hyperactivity disorder; disease models; gene expression; methylphenidate; microarray analysis