@article{NeufangAkhrifHerrmannetal.2016,
  author    = {Neufang, S. and Akhrif, A. and Herrmann, C.G. and Drepper, C. and Homola, G.A. and Nowak, J. and Waider, J. and Schmitt, A.G. and Lesch, K.-P. and Romanos, M.},
  title     = {Serotonergic modulation of 'waiting impulsivity' is mediated by the impulsivity phenotype in humans},
  series = {Translational Psychiatry},
  journal   = {Translational Psychiatry},
  number    = {6},
  doi       = {10.1038/tp.2016.210},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164418},
  pages     = {e940},
  year      = {2016},
  abstract  = {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.},
  language  = {en}
}
@article{AboagyeWeberMerdianetal.2021,
  author    = {Aboagye, B. and Weber, T. and Merdian, H. L. and Bartsch, D. and Lesch, K. P. and Waider, J.},
  title     = {Serotonin deficiency induced after brain maturation rescues consequences of early life adversity},
  series = {Scientific Reports},
  volume    = {11},
  journal   = {Scientific Reports},
  number    = {1},
  issn      = {2045-2322},
  doi       = {10.1038/s41598-021-83592-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258626},
  year      = {2021},
  abstract  = {Brain serotonin (5-HT) system dysfunction is implicated in depressive disorders and acute depletion of 5-HT precursor tryptophan has frequently been used to model the influence of 5-HT deficiency on emotion regulation. Tamoxifen (TAM)-induced Cre/loxP-mediated inactivation of the tryptophan hydroxylase-2 gene (Tph2) was used to investigate the effects of provoked 5-HT deficiency in adult mice (Tph2 icKO) previously subjected to maternal separation (MS). The efficiency of Tph2 inactivation was validated by immunohistochemistry and HPLC. The impact of Tph2 icKO in interaction with MS stress (Tph2 icKOxMS) on physiological parameters, emotional behavior and expression of 5-HT system-related marker genes were assessed. Tph2 icKO mice displayed a significant reduction in 5-HT immunoreactive cells and 5-HT concentrations in the rostral raphe region within four weeks following TAM treatment. Tph2 icKO and MS differentially affected food and water intake, locomotor activity as well as panic-like escape behavior. Tph2 icKO prevented the adverse effects of MS stress and altered the expression of the genes previously linked to stress and emotionality. In conclusion, an experimental model was established to study the behavioral and neurobiological consequences of 5-HT deficiency in adulthood in interaction with early-life adversity potentially affecting brain development and the pathogenesis of depressive disorders.},
  language  = {en}
}