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Tph2 gene variants modulate response control processes in adult ADHD patients and healthy individuals.

Abstract：

:Although therapeutic interventions in attention-deficit/hyperactivity disorder (ADHD) still focus on the dopaminergic system, recent studies indicate a serotonergic dysfunction in this disease as well. In that respect, several variants of the tryptophan hydroxylase gene (TPH2), which codes for the rate-limiting enzyme in the biosynthesis of serotonin (5-HT), have been associated with ADHD. The rs4570625 G-allele polymorphisms of the TPH2 gene have already been related to altered reactivity of the brain during perception tasks with emotional stimuli in healthy adults. Here we investigated the influence of the ADHD related risk alleles for rs4570625 and for rs11178997 on prefrontal brain function during cognitive response control in large samples of adult ADHD patients (n=124) and healthy controls (n=84). Response control was elicited with a Go-NoGo task (continuous performance test; CPT) performed during recording of an ongoing EEG. From the resulting event-related potentials in the Go- and NoGo conditions of the CPT, the NoGo-anteriorization (NGA) has been calculated as a valid neurophysiological parameter for prefrontal brain function. In the current study, ADHD risk alleles of both polymorphisms were found to be associated with a reduction in the NGA in both healthy controls and ADHD patients. These findings are in line with the notion that genetic variations associated with altered serotonergic neurotransmission are also associated with the function of the prefrontal cortex during response inhibition. This mechanism might also be relevant in the pathophysiology of ADHD.

journal_name

Mol Psychiatry

journal_title

Molecular psychiatry

authors

Baehne CG,Ehlis AC,Plichta MM,Conzelmann A,Pauli P,Jacob C,Gutknecht L,Lesch KP,Fallgatter AJ

doi

10.1038/mp.2008.39

subject

Has Abstract

pub_date

2009-11-01 00:00:00

pages

1032-9

issue

11

eissn

1359-4184

issn

1476-5578

pii

mp200839

journal_volume

14

pub_type

杂志文章

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