Serotonergic modulation of 'waiting impulsivity' is mediated by the impulsivity phenotype in humans.
In rodents, the five-choice serial reaction time task (5-CSRTT) has been established as a reliable measure of waiting impulsivity being defined as the ability to regulate a response in anticipation of reinforcement. Key brain structures are the nucleus accumbens (NAcc) and prefrontal regions (for example, pre- and infralimbic cortex), which are, together with other transmitters, modulated by serotonin. In this functional magnetic resonance imaging study, we examined 103 healthy males while performing the 5-CSRTT measuring brain activation in humans by means of a paradigm that has been widely applied in rodents. Subjects were genotyped for the tryptophan hydroxylase-2 (TPH2; G-703T; rs4570625) variant, an enzyme specific for brain serotonin synthesis. We addressed neural activation patterns of waiting impulsivity and the interaction between the NAcc and the ventromedial prefrontal cortex (vmPFC) using dynamic causal modeling. Genetic influence was examined via interaction analyses between the TPH2 genotype (GG homozygotes vs T allele carriers) and the degree of impulsivity as measured by the 5-CSRTT. We found that the driving input of the vmPFC was reduced in highly impulsive T allele carriers (reflecting a reduced top-down control) in combination with an enhanced response in the NAcc after correct target processing (reflecting an augmented response to monetary reward). Taken together, we found a high overlap of our findings with reports from animal studies in regard to the underlying cognitive processes, the brain regions associated with waiting impulsivity and the neural interplay between the NAcc and vmPFC. Therefore, we conclude that the 5-CSRTT is a promising tool for translational studies.
Center of Mental Health, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany.
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S
Neufang
Center of Mental Health, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany.
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A
Akhrif
Center of Mental Health, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany.
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CG
Herrmann
Center of Mental Health, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany.
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0000-0002-7883-6479
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Drepper
Department of Neuroradiology, University of Wuerzburg, Wuerzburg, Germany.
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GA
Homola
Department of Neuroradiology, University of Wuerzburg, Wuerzburg, Germany.|Department of Radiology, University of Wuerzburg, Wuerzburg, Germany.
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J
Nowak
Center of Mental Health, Division of Molecular Psychiatry, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany.
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J
Waider
Center of Mental Health, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany.
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Schmitt
Center of Mental Health, Division of Molecular Psychiatry, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany.
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Lesch
Center of Mental Health, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany.
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Romanos
D000328:Adult; D000483:Alleles; D002755:Choice Behavior / Q000502:physiology*; D065786:Delay Discounting / Q000502:physiology*; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007175:Impulsive Behavior / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009714:Nucleus Accumbens / Q000502:physiology*; D010364:Pattern Recognition, Visual / Q000502:physiology; D010641:Phenotype; D017397:Prefrontal Cortex / Q000502:physiology*; D011930:Reaction Time / Q000502:physiology*; D012201:Reward; D012701:Serotonin / Q000502:physiology*; D057170:Translational Research, Biomedical; D014365:Tryptophan Hydroxylase / Q000235:genetics; D055815:Young Adult
D012701:Serotonin; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase