A preliminary study on methylphenidate-regulated gene expression in lymphoblastoid cells of ADHD patients

Ricarda Schwarz; Andreas Reif; Claus-Jürgen Scholz; Lena Weissflog; Brigitte Schmidt; Klaus-Peter Lesch; Christian Jacob; Susanne Reichert; Julia Heupel; Julia Volkert; Juliane Kopf; Max Hilscher; Heike Weber; Sarah Kittel-Schneider

doi:10.3109/15622975.2014.948064

A preliminary study on methylphenidate-regulated gene expression in lymphoblastoid cells of ADHD patients

Ricarda Schwarz, Andreas Reif, Claus-Jürgen Scholz, Lena Weissflog, Brigitte Schmidt, Klaus-Peter Lesch, Christian Jacob, Susanne Reichert, Julia Heupel, Julia Volkert, Juliane Kopf, Max Hilscher, Heike Weber, Sarah Kittel-Schneider^*

^*Corresponding author for this work

MHeNs - Neuroscience

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

OBJECTIVES: 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.

Original language	English
Pages (from-to)	180-9
Number of pages	10
Journal	World Journal of Biological Psychiatry
Volume	16
Issue number	3
DOIs	https://doi.org/10.3109/15622975.2014.948064
Publication status	Published - Apr 2015

Keywords

Adult
Ataxin-1
Attention Deficit Disorder with Hyperactivity
Basic Helix-Loop-Helix Transcription Factors
Case-Control Studies
Cell Cycle Proteins
Cell Line
Female
Gene Expression Regulation
Glucose Transporter Type 3
Guanylate Cyclase
Humans
MAP Kinase Kinase Kinases
Male
Methylphenidate
Microarray Analysis
Middle Aged
Nerve Tissue Proteins
Proto-Oncogene Proteins
Real-Time Polymerase Chain Reaction
Receptors, Cytoplasmic and Nuclear
Young Adult

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Cite this

Schwarz, R., Reif, A., Scholz, C.-J., Weissflog, L., Schmidt, B., Lesch, K.-P., Jacob, C., Reichert, S., Heupel, J., Volkert, J., Kopf, J., Hilscher, M., Weber, H., & Kittel-Schneider, S. (2015). A preliminary study on methylphenidate-regulated gene expression in lymphoblastoid cells of ADHD patients. World Journal of Biological Psychiatry, 16(3), 180-9. https://doi.org/10.3109/15622975.2014.948064

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title = "A preliminary study on methylphenidate-regulated gene expression in lymphoblastoid cells of ADHD patients",

abstract = "OBJECTIVES: 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.",

keywords = "Adult, Ataxin-1, Attention Deficit Disorder with Hyperactivity, Basic Helix-Loop-Helix Transcription Factors, Case-Control Studies, Cell Cycle Proteins, Cell Line, Female, Gene Expression Regulation, Glucose Transporter Type 3, Guanylate Cyclase, Humans, MAP Kinase Kinase Kinases, Male, Methylphenidate, Microarray Analysis, Middle Aged, Nerve Tissue Proteins, Proto-Oncogene Proteins, Real-Time Polymerase Chain Reaction, Receptors, Cytoplasmic and Nuclear, Young Adult",

author = "Ricarda Schwarz and Andreas Reif and Claus-J{\"u}rgen Scholz and Lena Weissflog and Brigitte Schmidt and Klaus-Peter Lesch and Christian Jacob and Susanne Reichert and Julia Heupel and Julia Volkert and Juliane Kopf and Max Hilscher and Heike Weber and Sarah Kittel-Schneider",

year = "2015",

month = apr,

doi = "10.3109/15622975.2014.948064",

language = "English",

volume = "16",

pages = "180--9",

journal = "World Journal of Biological Psychiatry",

issn = "1562-2975",

publisher = "Routledge/Taylor & Francis Group",

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Schwarz, R, Reif, A, Scholz, C-J, Weissflog, L, Schmidt, B, Lesch, K-P, Jacob, C, Reichert, S, Heupel, J, Volkert, J, Kopf, J, Hilscher, M, Weber, H & Kittel-Schneider, S 2015, 'A preliminary study on methylphenidate-regulated gene expression in lymphoblastoid cells of ADHD patients', World Journal of Biological Psychiatry, vol. 16, no. 3, pp. 180-9. https://doi.org/10.3109/15622975.2014.948064

TY - JOUR

T1 - A preliminary study on methylphenidate-regulated gene expression in lymphoblastoid cells of ADHD patients

AU - Schwarz, Ricarda

AU - Reif, Andreas

AU - Scholz, Claus-Jürgen

AU - Weissflog, Lena

AU - Schmidt, Brigitte

AU - Lesch, Klaus-Peter

AU - Jacob, Christian

AU - Reichert, Susanne

AU - Heupel, Julia

AU - Volkert, Julia

AU - Kopf, Juliane

AU - Hilscher, Max

AU - Weber, Heike

AU - Kittel-Schneider, Sarah

PY - 2015/4

Y1 - 2015/4

N2 - OBJECTIVES: 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.

AB - OBJECTIVES: 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.

KW - Adult

KW - Ataxin-1

KW - Attention Deficit Disorder with Hyperactivity

KW - Basic Helix-Loop-Helix Transcription Factors

KW - Case-Control Studies

KW - Cell Cycle Proteins

KW - Cell Line

KW - Female

KW - Gene Expression Regulation

KW - Glucose Transporter Type 3

KW - Guanylate Cyclase

KW - Humans

KW - MAP Kinase Kinase Kinases

KW - Male

KW - Methylphenidate

KW - Microarray Analysis

KW - Middle Aged

KW - Nerve Tissue Proteins

KW - Proto-Oncogene Proteins

KW - Real-Time Polymerase Chain Reaction

KW - Receptors, Cytoplasmic and Nuclear

KW - Young Adult

U2 - 10.3109/15622975.2014.948064

DO - 10.3109/15622975.2014.948064

M3 - Article

C2 - 25162476

SN - 1562-2975

VL - 16

SP - 180

EP - 189

JO - World Journal of Biological Psychiatry

JF - World Journal of Biological Psychiatry

IS - 3

ER -