Epistasis between Dopamine Regulating Genes Identifies a Nonlinear Response of the Human Hippocampus During Memory Tasks

Alessandro Bertolino, Annabella Di Giorgio, Giuseppe Blasi, Fabio Sambataro, Grazia Caforio, Lorenzo Sinibaldi, Valeria Latorre, Antonio Rampino, Paolo Taurisano, Leonardo Fazio, Raffaella Romano, Sofia Douzgou, Teresa Popolizio, Bhaskar Kolachana, Marcello Nardini, Daniel R. Weinberger, Bruno Dallapiccola

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Background: Dopamine modulation of neuronal activity in prefrontal cortex maps to an inverted U-curve. Dopamine is also an important factor in regulation of hippocampal mediated memory processing. Here, we investigated the effect of genetic variation of dopamine inactivation via catechol-O-methyltransferase (COMT) and the dopamine transporter (DAT) on hippocampal activity in healthy humans during different memory conditions. Methods: Using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in 82 subjects matched for a series of demographic and genetic variables, we studied the effect of the COMT valine (Val)158methionine (Met) and the DAT 3′ variable number tandem repeat (VNTR) polymorphisms on function of the hippocampus during encoding of recognition memory and during working memory. Results: Our results consistently demonstrated a double dissociation so that DAT 9-repeat carrier alleles modulated activity in the hippocampus in the exact opposite direction of DAT 10/10-repeat alleles based on COMT Val158Met genotype during different memory conditions. Similar results were evident in ventrolateral and dorsolateral prefrontal cortex. Conclusions: These findings suggest that genetically determined dopamine signaling during memory processing maps to a nonlinear relationship also in the hippocampus. Our data also demonstrate in human brain epistasis of two genes implicated in dopamine signaling on brain activity during different memory conditions.

Original languageEnglish
Pages (from-to)226-234
Number of pages9
JournalBiological Psychiatry
Volume64
Issue number3
DOIs
Publication statusPublished - Aug 1 2008

Fingerprint

Hippocampus
Dopamine
Dopamine Plasma Membrane Transport Proteins
Catechol O-Methyltransferase
Genes
Prefrontal Cortex
Alleles
Minisatellite Repeats
Brain
Valine
Short-Term Memory
Genotype
Magnetic Resonance Imaging
Demography

Keywords

  • Dopamine
  • encoding
  • hippocampus
  • prefrontal cortex
  • working memory

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Epistasis between Dopamine Regulating Genes Identifies a Nonlinear Response of the Human Hippocampus During Memory Tasks. / Bertolino, Alessandro; Di Giorgio, Annabella; Blasi, Giuseppe; Sambataro, Fabio; Caforio, Grazia; Sinibaldi, Lorenzo; Latorre, Valeria; Rampino, Antonio; Taurisano, Paolo; Fazio, Leonardo; Romano, Raffaella; Douzgou, Sofia; Popolizio, Teresa; Kolachana, Bhaskar; Nardini, Marcello; Weinberger, Daniel R.; Dallapiccola, Bruno.

In: Biological Psychiatry, Vol. 64, No. 3, 01.08.2008, p. 226-234.

Research output: Contribution to journalArticle

Bertolino, A, Di Giorgio, A, Blasi, G, Sambataro, F, Caforio, G, Sinibaldi, L, Latorre, V, Rampino, A, Taurisano, P, Fazio, L, Romano, R, Douzgou, S, Popolizio, T, Kolachana, B, Nardini, M, Weinberger, DR & Dallapiccola, B 2008, 'Epistasis between Dopamine Regulating Genes Identifies a Nonlinear Response of the Human Hippocampus During Memory Tasks', Biological Psychiatry, vol. 64, no. 3, pp. 226-234. https://doi.org/10.1016/j.biopsych.2008.02.001
Bertolino, Alessandro ; Di Giorgio, Annabella ; Blasi, Giuseppe ; Sambataro, Fabio ; Caforio, Grazia ; Sinibaldi, Lorenzo ; Latorre, Valeria ; Rampino, Antonio ; Taurisano, Paolo ; Fazio, Leonardo ; Romano, Raffaella ; Douzgou, Sofia ; Popolizio, Teresa ; Kolachana, Bhaskar ; Nardini, Marcello ; Weinberger, Daniel R. ; Dallapiccola, Bruno. / Epistasis between Dopamine Regulating Genes Identifies a Nonlinear Response of the Human Hippocampus During Memory Tasks. In: Biological Psychiatry. 2008 ; Vol. 64, No. 3. pp. 226-234.
@article{d39d6f8f1c8b41bea01c6cfc43fff172,
title = "Epistasis between Dopamine Regulating Genes Identifies a Nonlinear Response of the Human Hippocampus During Memory Tasks",
abstract = "Background: Dopamine modulation of neuronal activity in prefrontal cortex maps to an inverted U-curve. Dopamine is also an important factor in regulation of hippocampal mediated memory processing. Here, we investigated the effect of genetic variation of dopamine inactivation via catechol-O-methyltransferase (COMT) and the dopamine transporter (DAT) on hippocampal activity in healthy humans during different memory conditions. Methods: Using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in 82 subjects matched for a series of demographic and genetic variables, we studied the effect of the COMT valine (Val)158methionine (Met) and the DAT 3′ variable number tandem repeat (VNTR) polymorphisms on function of the hippocampus during encoding of recognition memory and during working memory. Results: Our results consistently demonstrated a double dissociation so that DAT 9-repeat carrier alleles modulated activity in the hippocampus in the exact opposite direction of DAT 10/10-repeat alleles based on COMT Val158Met genotype during different memory conditions. Similar results were evident in ventrolateral and dorsolateral prefrontal cortex. Conclusions: These findings suggest that genetically determined dopamine signaling during memory processing maps to a nonlinear relationship also in the hippocampus. Our data also demonstrate in human brain epistasis of two genes implicated in dopamine signaling on brain activity during different memory conditions.",
keywords = "Dopamine, encoding, hippocampus, prefrontal cortex, working memory",
author = "Alessandro Bertolino and {Di Giorgio}, Annabella and Giuseppe Blasi and Fabio Sambataro and Grazia Caforio and Lorenzo Sinibaldi and Valeria Latorre and Antonio Rampino and Paolo Taurisano and Leonardo Fazio and Raffaella Romano and Sofia Douzgou and Teresa Popolizio and Bhaskar Kolachana and Marcello Nardini and Weinberger, {Daniel R.} and Bruno Dallapiccola",
year = "2008",
month = "8",
day = "1",
doi = "10.1016/j.biopsych.2008.02.001",
language = "English",
volume = "64",
pages = "226--234",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "3",

}

TY - JOUR

T1 - Epistasis between Dopamine Regulating Genes Identifies a Nonlinear Response of the Human Hippocampus During Memory Tasks

AU - Bertolino, Alessandro

AU - Di Giorgio, Annabella

AU - Blasi, Giuseppe

AU - Sambataro, Fabio

AU - Caforio, Grazia

AU - Sinibaldi, Lorenzo

AU - Latorre, Valeria

AU - Rampino, Antonio

AU - Taurisano, Paolo

AU - Fazio, Leonardo

AU - Romano, Raffaella

AU - Douzgou, Sofia

AU - Popolizio, Teresa

AU - Kolachana, Bhaskar

AU - Nardini, Marcello

AU - Weinberger, Daniel R.

AU - Dallapiccola, Bruno

PY - 2008/8/1

Y1 - 2008/8/1

N2 - Background: Dopamine modulation of neuronal activity in prefrontal cortex maps to an inverted U-curve. Dopamine is also an important factor in regulation of hippocampal mediated memory processing. Here, we investigated the effect of genetic variation of dopamine inactivation via catechol-O-methyltransferase (COMT) and the dopamine transporter (DAT) on hippocampal activity in healthy humans during different memory conditions. Methods: Using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in 82 subjects matched for a series of demographic and genetic variables, we studied the effect of the COMT valine (Val)158methionine (Met) and the DAT 3′ variable number tandem repeat (VNTR) polymorphisms on function of the hippocampus during encoding of recognition memory and during working memory. Results: Our results consistently demonstrated a double dissociation so that DAT 9-repeat carrier alleles modulated activity in the hippocampus in the exact opposite direction of DAT 10/10-repeat alleles based on COMT Val158Met genotype during different memory conditions. Similar results were evident in ventrolateral and dorsolateral prefrontal cortex. Conclusions: These findings suggest that genetically determined dopamine signaling during memory processing maps to a nonlinear relationship also in the hippocampus. Our data also demonstrate in human brain epistasis of two genes implicated in dopamine signaling on brain activity during different memory conditions.

AB - Background: Dopamine modulation of neuronal activity in prefrontal cortex maps to an inverted U-curve. Dopamine is also an important factor in regulation of hippocampal mediated memory processing. Here, we investigated the effect of genetic variation of dopamine inactivation via catechol-O-methyltransferase (COMT) and the dopamine transporter (DAT) on hippocampal activity in healthy humans during different memory conditions. Methods: Using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in 82 subjects matched for a series of demographic and genetic variables, we studied the effect of the COMT valine (Val)158methionine (Met) and the DAT 3′ variable number tandem repeat (VNTR) polymorphisms on function of the hippocampus during encoding of recognition memory and during working memory. Results: Our results consistently demonstrated a double dissociation so that DAT 9-repeat carrier alleles modulated activity in the hippocampus in the exact opposite direction of DAT 10/10-repeat alleles based on COMT Val158Met genotype during different memory conditions. Similar results were evident in ventrolateral and dorsolateral prefrontal cortex. Conclusions: These findings suggest that genetically determined dopamine signaling during memory processing maps to a nonlinear relationship also in the hippocampus. Our data also demonstrate in human brain epistasis of two genes implicated in dopamine signaling on brain activity during different memory conditions.

KW - Dopamine

KW - encoding

KW - hippocampus

KW - prefrontal cortex

KW - working memory

UR - http://www.scopus.com/inward/record.url?scp=46249114924&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=46249114924&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2008.02.001

DO - 10.1016/j.biopsych.2008.02.001

M3 - Article

C2 - 18374902

AN - SCOPUS:46249114924

VL - 64

SP - 226

EP - 234

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 3

ER -