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Serotonergic modulation of 'waiting impulsivity' is mediated by the impulsivity phenotype in humans

Please always quote using this URN: urn:nbn:de:bvb:20-opus-164418
  • 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 inIn 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.show moreshow less

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Metadaten
Author: S. Neufang, A. Akhrif, C.G. Herrmann, C. Drepper, G.A. Homola, J. Nowak, J. Waider, A.G. Schmitt, K.-P. Lesch, M. Romanos
URN:urn:nbn:de:bvb:20-opus-164418
Document Type:Journal article
Faculties:Medizinische Fakultät / Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie
Medizinische Fakultät / Institut für diagnostische und interventionelle Radiologie (Institut für Röntgendiagnostik)
Medizinische Fakultät / Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Medizinische Fakultät / Abteilung für Neuroradiologie
Language:English
Parent Title (English):Translational Psychiatry
Year of Completion:2016
Issue:6
Pagenumber:e940
Source:Transl Psychiatry (2016) 6, e940; doi:10.1038/tp.2016.210
DOI:https://doi.org/10.1038/tp.2016.210
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:Clinical Genetics
Release Date:2019/07/09
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International