A common variant in ERBB4 regulates gaba concentrations in human cerebrospinal fluid

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A common variant in ERBB4 regulates gaba concentrations in human cerebrospinal fluid. / Luykx, Jurjen J.; Vinkers, Christiaan H.; Bakker, Steven C.; Visser, Wouter F.; Van Boxmeer, Loes; Strengman, Eric; Van Eijk, Kristel R.; Lens, Judith A.; Borgdorff, Paul; Keijzers, Peter; Kappen, Teus H.; Van Dongen, Eric P.A.; Bruins, Peter; Verhoeven, Nanda M.; De Koning, Tom J.; Kahn, René S.; Ophoff, Roel A.

I: Neuropsychopharmacology, Vol. 37, Nr. 9, 01.08.2012, s. 2088-2092.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Luykx, JJ, Vinkers, CH, Bakker, SC, Visser, WF, Van Boxmeer, L, Strengman, E, Van Eijk, KR, Lens, JA, Borgdorff, P, Keijzers, P, Kappen, TH, Van Dongen, EPA, Bruins, P, Verhoeven, NM, De Koning, TJ, Kahn, RS & Ophoff, RA 2012, 'A common variant in ERBB4 regulates gaba concentrations in human cerebrospinal fluid', Neuropsychopharmacology, vol. 37, nr. 9, s. 2088-2092. https://doi.org/10.1038/npp.2012.57

APA

Luykx, J. J., Vinkers, C. H., Bakker, S. C., Visser, W. F., Van Boxmeer, L., Strengman, E., Van Eijk, K. R., Lens, J. A., Borgdorff, P., Keijzers, P., Kappen, T. H., Van Dongen, E. P. A., Bruins, P., Verhoeven, N. M., De Koning, T. J., Kahn, R. S., & Ophoff, R. A. (2012). A common variant in ERBB4 regulates gaba concentrations in human cerebrospinal fluid. Neuropsychopharmacology, 37(9), 2088-2092. https://doi.org/10.1038/npp.2012.57

CBE

Luykx JJ, Vinkers CH, Bakker SC, Visser WF, Van Boxmeer L, Strengman E, Van Eijk KR, Lens JA, Borgdorff P, Keijzers P, Kappen TH, Van Dongen EPA, Bruins P, Verhoeven NM, De Koning TJ, Kahn RS, Ophoff RA. 2012. A common variant in ERBB4 regulates gaba concentrations in human cerebrospinal fluid. Neuropsychopharmacology. 37(9):2088-2092. https://doi.org/10.1038/npp.2012.57

MLA

Vancouver

Luykx JJ, Vinkers CH, Bakker SC, Visser WF, Van Boxmeer L, Strengman E et al. A common variant in ERBB4 regulates gaba concentrations in human cerebrospinal fluid. Neuropsychopharmacology. 2012 aug 1;37(9):2088-2092. https://doi.org/10.1038/npp.2012.57

Author

Luykx, Jurjen J. ; Vinkers, Christiaan H. ; Bakker, Steven C. ; Visser, Wouter F. ; Van Boxmeer, Loes ; Strengman, Eric ; Van Eijk, Kristel R. ; Lens, Judith A. ; Borgdorff, Paul ; Keijzers, Peter ; Kappen, Teus H. ; Van Dongen, Eric P.A. ; Bruins, Peter ; Verhoeven, Nanda M. ; De Koning, Tom J. ; Kahn, René S. ; Ophoff, Roel A. / A common variant in ERBB4 regulates gaba concentrations in human cerebrospinal fluid. I: Neuropsychopharmacology. 2012 ; Vol. 37, Nr. 9. s. 2088-2092.

RIS

TY - JOUR

T1 - A common variant in ERBB4 regulates gaba concentrations in human cerebrospinal fluid

AU - Luykx, Jurjen J.

AU - Vinkers, Christiaan H.

AU - Bakker, Steven C.

AU - Visser, Wouter F.

AU - Van Boxmeer, Loes

AU - Strengman, Eric

AU - Van Eijk, Kristel R.

AU - Lens, Judith A.

AU - Borgdorff, Paul

AU - Keijzers, Peter

AU - Kappen, Teus H.

AU - Van Dongen, Eric P.A.

AU - Bruins, Peter

AU - Verhoeven, Nanda M.

AU - De Koning, Tom J.

AU - Kahn, René S.

AU - Ophoff, Roel A.

PY - 2012/8/1

Y1 - 2012/8/1

N2 - The neuregulin 1 (NRG1) receptor ErbB4 is involved in the development of cortical inhibitory GABAergic circuits and NRG1-ErbB4 signaling has been implicated in schizophrenia (SCZ). A magnetic resonance spectroscopy (1 H-MRS) study has demonstrated that a single-nucleotide polymorphism in ERBB4, rs7598440, influences human cortical GABA concentrations. Other work has highlighted the significant impact of this genetic variant on expression of ERBB4 in the hippocampus and dorsolateral prefrontal cortex in human post mortem tissue. Our aim was to examine the association of rs7598440 with cerebrospinal fluid (CSF) GABA levels in healthy volunteers (n155). We detected a significant dose-dependent association of the rs7598440 genotype with CSF GABA levels (G-allele standardized Β0.23; 95% CIs: 0.39 to 0.07; P0.0066). GABA concentrations were highest in A homozygous, intermediate in heterozygous, and lowest in G homozygous subjects. When excluding subjects on psychotropic medication (three subjects using antidepressants), the results did not change (G-allele standardized Β0.23; 95% CIs: 0.40 to 0.07; P0.0051). The explained variance in CSF GABA by rs7598440 in our model is 5.2% (P0.004). The directionality of our findings agrees with the aforementioned 1 H-MRS and gene expression studies. Our observation therefore strengthens the evidence that the A-allele of rs7598440 in ERBB4 is associated with increased GABA concentrations in the human central nervous system (CNS). To our knowledge, our finding constitutes the first confirmation that CSF can be used to study genotype-phenotype correlations of GABA levels in the CNS. Such quantitative genetic analyses may be extrapolated to other CSF constituents relevant to SCZ in future studies.

AB - The neuregulin 1 (NRG1) receptor ErbB4 is involved in the development of cortical inhibitory GABAergic circuits and NRG1-ErbB4 signaling has been implicated in schizophrenia (SCZ). A magnetic resonance spectroscopy (1 H-MRS) study has demonstrated that a single-nucleotide polymorphism in ERBB4, rs7598440, influences human cortical GABA concentrations. Other work has highlighted the significant impact of this genetic variant on expression of ERBB4 in the hippocampus and dorsolateral prefrontal cortex in human post mortem tissue. Our aim was to examine the association of rs7598440 with cerebrospinal fluid (CSF) GABA levels in healthy volunteers (n155). We detected a significant dose-dependent association of the rs7598440 genotype with CSF GABA levels (G-allele standardized Β0.23; 95% CIs: 0.39 to 0.07; P0.0066). GABA concentrations were highest in A homozygous, intermediate in heterozygous, and lowest in G homozygous subjects. When excluding subjects on psychotropic medication (three subjects using antidepressants), the results did not change (G-allele standardized Β0.23; 95% CIs: 0.40 to 0.07; P0.0051). The explained variance in CSF GABA by rs7598440 in our model is 5.2% (P0.004). The directionality of our findings agrees with the aforementioned 1 H-MRS and gene expression studies. Our observation therefore strengthens the evidence that the A-allele of rs7598440 in ERBB4 is associated with increased GABA concentrations in the human central nervous system (CNS). To our knowledge, our finding constitutes the first confirmation that CSF can be used to study genotype-phenotype correlations of GABA levels in the CNS. Such quantitative genetic analyses may be extrapolated to other CSF constituents relevant to SCZ in future studies.

KW - cerebrospinal fluid

KW - ErbB4

KW - GABA

KW - neuregulin

KW - rs7598440

KW - schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=84863988697&partnerID=8YFLogxK

U2 - 10.1038/npp.2012.57

DO - 10.1038/npp.2012.57

M3 - Article

C2 - 22549119

AN - SCOPUS:84863988697

VL - 37

SP - 2088

EP - 2092

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

SN - 1740-634X

IS - 9

ER -