@article{Chen2011, abstract = {Abstract Background The role of serotonin (5-hydroxytrptamine, 5-HT) in the modulation of pain has been widely studied. Previous work led to the hypothesis that 5-hydroxyindolacetic acid (5-HIAA), a main metabolite of serotonin, might by itself influence pain thresholds. Results In the present study, we investigated the role of 5-HIAA in inflammatory pain induced by intraplantar injection of complete Freund's adjuvant (CFA) into the hind paw of mice. Wild-type mice were compared to mice deficient of the 5-HT transporter (5-HTT-/- mice) using behavioral tests for hyperalgesia and high-performance liquid chromatography (HPLC) to determine tissue levels of 5-HIAA. Wild-type mice reproducibly developed thermal hyperalgesia and paw edema for 5 days after CFA injection. 5-HTT-/- mice treated with CFA had reduced thermal hyperalgesia on day 1 after CFA injection and normal responses to heat thereafter. The 5-HIAA levels in spinal cord and sciatic nerve as measured with HPLC were lower in 5-HTT-/- mice than in wild-type mice after CFA injection. Pretreatment of wild-type mice with intraperitoneal injection of para-chlorophenylalanine (p-CPA), a serotonin synthesis inhibitor, resulted in depletion of the 5-HIAA content in spinal cord and sciatic nerve and decrease in thermal hyperalgesia in CFA injected mice. The application of exogenous 5-HIAA resulted in potentiation of thermal hyperalgesia induced by CFA in 5-HTT-/- mice and in wild-type mice pretreated with p-CPA, but not in wild-type mice without p-CPA pretreatment. Further, methysergide, a broad-spectrum serotonin receptor antagonist, had no effect on 5-HIAA-induced potentiation of thermal hyperalgesia in CFA-treated wild-type mice. Conclusion Taken together, the present results suggest that 5-HIAA plays an important role in modulating peripheral thermal hyperalgesia in CFA induced inflammation, probably via a non-serotonin receptor mechanism.}, author = {Chen, Yong and Palm, Florian and Lesch, Klaus-Peter and Gerlach, Manfred and Moessner, Rainald and Sommer, Claudia}, doi = {10.1186/1744-8069-7-21}, journal = {Molecular Pain}, month = {jan}, pages = {1744-8069-7-21}, title = {5-hydroxyindolacetic acid (5-HIAA), a main metabolite of serotonin, is responsible for complete Freund's adjuvant-induced thermal hyperalgesia in mice}, url = {http://dx.doi.org/10.1186/1744-8069-7-21}, volume = {7}, year = {2011} } @article{Dawson2011, author = {Dawson, Neil and Ferrington, Linda and Lesch, Klaus-Peter and Kelly, Paul A. T.}, doi = {10.1016/j.euroneuro.2010.10.006}, journal = {European Neuropsychopharmacology}, month = {jan}, pages = {117-128}, title = {Cerebral metabolic responses to 5-HT2A/C receptor activation in mice with genetically modified serotonin transporter (SERT) expression}, url = {https://oadoi.org/10.1016/j.euroneuro.2010.10.006}, volume = {21}, year = {2011} } @article{Enge2011, abstract = {Ascending serotonergic projections from the raphe nuclei to frontal brain areas and the dense distribution of receptor and transporter sites in prefrontal and sensory regions support the idea that serotonin exerts influence on cognitive functioning. Indeed, growing evidence suggests serotonin to be an important factor in learning and memory; however, its precise role in executive processes particularly in voluntary attention is less clear. Event-related EEG studies showed the N1 potential to predict top-down attention allocation and implicated the auditory N1 in central serotonergic activity. Dipole analyses and single-trial coupling of EEG and fMRI revealed N1 sources in the primary auditory cortex and in the anterior cingulate. In the present study, amplitude variation of the event-related N1 potential was investigated on 72 healthy subjects while performing an auditory novelty oddball paradigm to tap top-down and bottom-up attention allocation. Possible serotonergic effects on voluntary attention were analyzed using allele variants of a functional polymorphism (5-HTTLPR) of the gene encoding the serotonin transporter, a key regulator of serotonergic neurotransmission. Because mental effort has been related to top-down attention and N1 modulation, a measure of stable individual differences in cognitive effort was included. The main result was a strong interaction of 5-HTTLPR and cognitive effort on target N1 amplitude. Greater target-related attention allocation was evident in those carriers of the 5-HTTLPR s-allele who described themselves as being more engaged in effortful processing. We suggest that the observed interaction mirrors the interplay between effort-mediated top-down attention by the ACC and serotonergic adjustment on attentional systems.}, author = {Enge, Sören and Fleischhauer, Monika and Lesch, Klaus-Peter and Strobel, Alexander}, doi = {10.1016/j.bbr.2010.07.021}, journal = {Behavioural Brain Research}, month = {jan}, pages = {122-128}, title = {Enge S, Fleischhauer M, Lesch KP, Strobel A. On the role of serotonin and effort in voluntary attention: evidence of genetic variation in N1 modulation. Behav Brain Res 216: 122-128}, url = {https://oadoi.org/10.1016/j.bbr.2010.07.021}, volume = {216}, year = {2011} } @article{Fabre2011, abstract = {Transcriptome analyses were performed in the anterior raphe area of mutant mice deficient in the serotonin transporter (5-HTT KO) or overexpressing this protein (5-HTT TG), which exhibit opposite changes in anxiety-related behavior. Among genes with altered expression, the gene encoding the neuropeptide urocortin 1 was down-regulated in 5-HTT KO and up-regulated in 5-HTT TG mice. Expression of the gene encoding cocaine-and-amphetamine-related-peptide, which colocalizes with urocortin 1, was also increased in 5-HTT TG mutants. Real-time RT-PCR confirmed these data and immunoautoradiographic labeling showed that parallel changes in neuropeptide levels were confined to the non-preganglionic Edinger-Westphal nucleus. Thus, 5-HTT expression correlates with that of urocortin 1, suggesting that this peptide can be involved in the behavioral changes observed in 5-HTT mutant mice.}, author = {Fabre, Véronique and Massart, Renaud and Rachalski, Adeline and Jennings, Katie and Brass, Andrew and Sharp, Trevor and Lesch, Klaus-Peter and Lanfumey, Laurence and Hamon, Michel}, doi = {10.1016/j.euroneuro.2010.10.004}, journal = {European Neuropsychopharmacology}, month = {jan}, pages = {33-44}, title = {Differential gene expression in mutant mice overexpressing or deficient in the serotonin transporter: a focus on urocortin 1.}, url = {https://www.researchgate.net/profile/Laurence_LANFUMEY-MONGREDIEN/publication/47791041_Differential_gene_expression_in_mutant_mice_overexpressing_or_deficient_in_the_serotonin_transporter_A_focus_on_urocortin_1/links/54b52bf30cf28ebe92e4cb09.pdf}, volume = {21}, year = {2011} } @article{Hahn2010, author = {Hahn, Tim and Dresler, Thomas and Plichta, Michael M. and Ehlis, Ann-Christine and Ernst, Lena H. and Markulin, Falko and Polak, Thomas and Blaimer, Martin and Deckert, Jürgen and Lesch, Klaus-Peter and Jakob, Peter M. and Fallgatter, Andreas J.}, doi = {10.1016/j.biopsych.2010.04.033}, journal = {Biological Psychiatry}, month = {sep}, pages = {459-464}, title = {Functional Amygdala-Hippocampus Connectivity During Anticipation of Aversive Events is Associated with Gray's Trait “Sensitivity to Punishment”}, url = {https://oadoi.org/10.1016/j.biopsych.2010.04.033}, volume = {68}, year = {2010} } @article{Hahn2010_2, abstract = {The impact of individual differences on human reward processing has been a focus of research in recent years, particularly, as they are associated with a variety of neuropsychiatric diseases including addiction and attention-deficit/hyperactivity disorder. Studies exploring the neural basis of individual differences in reward sensitivity have consistently implicated the ventral striatum (VS) as a core component of the human reward system. However, the mechanisms of dopaminergic neurotransmission underlying ventral striatal activation as well as trait reward sensitivity remain speculative. We addressed this issue by investigating the triadic interplay between VS reactivity during reward anticipation using functional magnetic resonance imaging, trait reward sensitivity, and dopamine (DA) transporter genotype (40-bp 3'VNTR of DAT, SLC6A3) affecting synaptic DA neurotransmission. Our results show that DAT variation moderates the association between VS-reactivity and trait reward sensitivity. Specifically, homozygote carriers of the DAT 10-repeat allele exhibit a strong positive correlation between reward sensitivity and reward-related VS activity whereas this relationship is absent in the DAT 9-repeat allele carriers. We discuss the possibility that this moderation of VS-trait relation might arise from DAT-dependent differences in DA availability affecting synaptic plasticity within the VS. Generally, studying the impact of dopaminergic gene variations on the relation between reward-related brain activity and trait reward sensitivity might facilitate the investigation of complex mechanisms underlying disorders linked to dysregulation of DA neurotransmission.}, author = {Hahn, Tim and Heinzel, Sebastian and Dresler, Thomas and Plichta, Michael M. and Renner, Tobias J. and Markulin, Falko and Jakob, Peter M. and Lesch, Klaus-Peter and Fallgatter, Andreas J.}, doi = {10.1002/hbm.21127}, journal = {Human Brain Mapping}, month = {sep}, pages = {1557-1565}, title = {Association Between Reward-Related Activation in the Ventral Striatum and Trait Reward Sensitivity is Moderated by Dopamine Transporter Genotype}, url = {https://doi.org/10.1002/hbm.21127}, volume = {32}, year = {2010} } @article{Hahn2010_3, author = {Hahn, Tim and Heinzel, Sebastian and Plichta, Michael M. and Reif, Andreas and Lesch, Klaus-Peter and Fallgatter, Andreas J.}, doi = {10.1093/cercor/bhq236}, journal = {Cerebral Cortex}, month = {nov}, pages = {1659-1666}, title = {Neurovascular Coupling in the Human Visual Cortex Is Modulated by Cyclooxygenase-1 (COX-1) Gene Variant}, url = {https://academic.oup.com/cercor/article-pdf/21/7/1659/17305144/bhq236.pdf}, volume = {21}, year = {2010} } @article{Hahn2010_4, author = {Hahn, Tim and Marquand, Andre F. and Ehlis, Ann-Christine and Dresler, Thomas and Kittel-Schneider, Sarah and Jarczok, Tomasz A. and Lesch, Klaus-Peter and Jakob, Peter M. and Mourao-Miranda, Janaina and Brammer, Michael J. and Fallgatter, Andreas J.}, doi = {10.1001/archgenpsychiatry.2010.178}, journal = {Archives of General Psychiatry}, month = {dec}, pages = {361}, title = {Integrating Neurobiological Markers of Depression}, url = {https://jamanetwork.com/journals/jamapsychiatry/articlepdf/211204/yoa05074_361_368.pdf}, volume = {68}, year = {2010} } @article{Hall2010, abstract = {Norepinephrine and serotonin involvement in nociceptive functions is supported by observations of analgesic effects of norepinephrine transporter (NET) and serotonin transporter (SERT) inhibitors such as amitriptyline. However, the relative contribution of NET and SERT to baseline nociception, as well as amitriptyline analgesia, is unclear. Amitriptyline and morphine analgesia in wild-type (WT) mice and littermates with gene knockout (KO) of SERT, NET or both transporters was conducted using the hotplate and tail-flick tests. Hypoalgesia was observed in NET KO mice, and to a lesser extent in SERT KO mice. The magnitude of this hypoalgesia in NET KO mice was so profound that it limited the assessment of drug-induced analgesia. Nonetheless, the necessary exclusion of these subjects because of profound baseline hypoalgesia strongly supports the role of norepinephrine and NET in basal nociceptive behavior while indicating a much smaller role for serotonin and SERT. To further clarify the role of NET and SERT in basal nociceptive sensitivity further experiments were conducted in SERT KO and NET KO mice across a range of temperatures. NET KO mice were again found to have pronounced thermal hypoalgesia compared to WT mice in both the hotplate and tail-flick tests, while only limited effects were observed in SERT KO mice. Furthermore, in the acetic acid writhing test of visceral nociception pronounced hypoalgesia was again found in NET KO mice, but no change in SERT KO mice. As some of these effects may have resulted from developmental consequences of NET KO, the effects of the selective NET blocker nisoxetine and the selective SERT blocker fluoxetine were also examined in WT mice: only nisoxetine produced analgesia in these mice. Collectively these data suggest that NET has a far greater role in determining baseline analgesia, and perhaps other analgesic effects, than SERT in mice.}, author = {Hall, F. Scott and Schwarzbaum, Joshua M. and Perona, Maria T. G. and Templin, J. Scott and Caron, Marc G. and Lesch, Klaus-Peter and Murphy, Dennis L. and Uhl, George R.}, doi = {10.1016/j.neuroscience.2010.11.057}, journal = {Neuroscience}, month = {dec}, pages = {315-327}, title = {A greater role for the norepinephrine transporter than the serotonin transporter in murine nociception}, url = {http://www.ncbi.nlm.nih.gov/pubmed/21129446}, volume = {175}, year = {2010} } @article{Hinney2011, abstract = {The heritability of attention deficit hyperactivity disorder (ADHD) is approximately 0.8. Despite several larger scale attempts, genome-wide association studies (GWAS) have not led to the identification of significant results. We performed a GWAS based on 495 German young patients with ADHD (according to DSM-IV criteria; Human660W-Quadv1; Illumina, San Diego, CA) and on 1,300 population-based adult controls (HumanHap550v3; Illumina). Some genes neighboring the single nucleotide polymorphisms (SNPs) with the lowest P-values (best P-value: 8.38 × 10(-7)) have potential relevance for ADHD (e.g., glutamate receptor, metabotropic 5 gene, GRM5). After quality control, the 30 independent SNPs with the lowest P-values (P-values ≤ 7.57 × 10(-5) ) were chosen for confirmation. Genotyping of these SNPs in up to 320 independent German families comprising at least one child with ADHD revealed directionally consistent effect-size point estimates for 19 (10 not consistent) of the SNPs. In silico analyses of the 30 SNPs in the largest meta-analysis so far (2,064 trios, 896 cases, and 2,455 controls) revealed directionally consistent effect-size point estimates for 16 SNPs (11 not consistent). None of the combined analyses revealed a genome-wide significant result. SNPs in previously described autosomal candidate genes did not show significantly lower P-values compared to SNPs within random sets of genes of the same size. We did not find genome-wide significant results in a GWAS of German children with ADHD compared to controls. The second best SNP is located in an intron of GRM5, a gene located within a recently described region with an infrequent copy number variation in patients with ADHD.}, author = {Hinney, Anke and Scherag, André and Jarick, Ivonne and Albayrak, Ö. and Albayrak, Özgür and Albayrak, O. and Pütter, Carolin and Pechlivanis, Sonali and Dauvermann, Maria R. and Beck, Sebastian and Weber, Heike and Scherag, Susann and Nguyen, Trang T. and Volckmar, Anna-Lena and Knoll, Nadja and Faraone, Stephen V. and Neale, Benjamin M. and Franke, Barbara and Cichon, Sven and Hoffmann, Per and Nöthen, Markus M. and Schreiber, Stefan and Jockel, Karl-Heinz and Wichmann, H.-Erich and Freitag, Christine and Lempp, Thomas and Meyer, Jobst and Gilsbach, Susanne and Herpertz-Dahlmann, Beate and Sinzig, Judith and Lehmkuhl, Gerd and Renner, Tobias J. and Warnke, Andreas and Romanos, Marcel and Lesch, Klaus-Peter and Reif, Andreas and Schimmelmann, Benno G. and Hebebrand, Johannes and Adhd, subgroup Psychiatric Gwas Consortium}, doi = {10.1002/ajmg.b.31246}, journal = {American Journal of Medical Genetics Part B: Neuropsychiatric Genetics}, month = {jan}, pages = {888-897}, title = {Genome-wide association study in German patients with attention deficit/hyperactivity disorder.}, url = {http://www.researchgate.net/profile/Andreas_Reif/publication/281758557_Genome-wide_association_study_in_German_patients_with_attention_deficithyperactivity_disorder/links/563a221708ae45b5d284a058.pdf}, volume = {156}, year = {2011} } @article{Homberg2011, abstract = {Converging evidence indicates an association of the short (s), low-expressing variant of the repeat length polymorphism, serotonin transporter-linked polymorphic region (5-HTTLPR), in the human serotonin transporter gene (5-HTT, SERT, SLC6A4) with anxiety-related traits and increased risk for depression in interaction with psychosocial adversity across the life span. However, genetically driven deficient serotonin transporter (5-HTT) function would not have been maintained throughout evolution if it only exerted negative effects without conveying any gain of function. Here, we review recent findings that humans and nonhuman primates carrying the s variant of the 5-HTTLPR outperform subjects carrying the long allele in an array of cognitive tasks and show increased social conformity. In addition, studies in 5-HTT knockout rodents are included that provide complementary insights in the beneficial effects of the 5-HTTLPR s-allele. We postulate that hypervigilance, mediated by hyperactivity in corticolimbic structures, may be the common denominator in the anxiety-related traits and (social) cognitive superiority of s-allele carriers and that environmental conditions determine whether a response will turn out to be negative (emotional) or positive (cognitive, in conformity with the social group). Taken together, these findings urge for a conceptual change in the current deficit-oriented connotation of the 5-HTTLPR variants. In fact, these factors may counterbalance or completely offset the negative consequences of the anxiety-related traits. This notion may not only explain the modest effect size of the 5-HTTLPR and inconsistent reports but may also lead to a more refined appreciation of allelic variation in 5-HTT function.}, author = {Homberg, Judith R. and Lesch, Klaus-Peter and Buckley, P. F.}, doi = {10.1016/j.biopsych.2010.09.024}, journal = {Biological Psychiatry}, month = {jan}, pages = {513-519}, title = {Looking on the bright side of serotonin transporter gene variation.}, url = {https://oadoi.org/10.1016/j.biopsych.2010.09.024}, volume = {69}, year = {2011} } @article{Jennings2010, author = {Jennings, Katie Ann and Lesch, Klaus-Peter and Sharp, Trevor and Cragg, Stephanie Jane}, doi = {10.1111/j.1471-4159.2010.07001.x}, journal = {Journal of Neurochemistry}, month = {oct}, pages = {965-973}, title = {Non-linear relationship between 5-HT transporter gene expression and frequency sensitivity of 5-HT signals}, url = {http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2010.07001.x/pdf}, volume = {115}, year = {2010} } @article{Kriegebaum2010, abstract = {Several lines of evidence implicate a dysregulation of tryptophan hydroxylase (TPH)-dependent serotonin (5-HT) synthesis in emotional behaviour and stress, and point to its relevance for the etiology and pathogenesis of various neuropsychiatric disorders. We therefore studied different animal models featuring reduced Tph2 expression to investigate the consequences of impaired brain 5-HT synthesis on neuronal development. Specifically, brain-specific conditional and time-specific inducible Tph2 knockout (KO) models were generated and investigated for altered serotonergic neuron-specific gene expression. Raphe neurons of a brain-specific constitutive Tph2 KO were completely devoid of Tph2-positive neurons and, consequently, 5-HT in the brain, and also displayed no compensatory up-regulation of Tph1 expression. In contrast, an inducible Tph2 KO mouse facilitates the generation of a brain-specific 5-HT-reduction model selectively during adult life. This resulted in a highly reduced number of Tph2-positive cells and thus 5-HT in the brain. Intriguingly, expression studies detected no alteration in the expression of genes relevant to the 5-HT system in the brain-specific Tph2 KO and the 5-HT-reduction models. These findings confirm the specificity of Tph2 in brain 5-HT synthesis across the lifespan, yet also suggest that neither developmental nor adult 5-HT synthesis is required for the expression of genes specific for serotonergic signalling. The formation of the serotonergic system thus seems to be a preserved expressional pattern due to intrinsic cellular programs which occurs also in the absence of its key molecule, namely 5-HT.}, author = {Kriegebaum, Claudia and Gutknecht, Lise and Huang, Ying and Schmitt, Angelika and Song, Ning and Reif, Andreas and Ding, Yu-Qiang and Lesch, Klaus-Peter}, doi = {10.1016/j.neuint.2010.06.015}, journal = {Neurochemistry International}, month = {nov}, pages = {512-517}, title = {Brain-specific conditional and time-specific inducible Tph2 knockout mice possess normal serotonergic gene expression in the absence of serotonin during adult life}, url = {https://www.researchgate.net/profile/Yu-Qiang_Ding2/publication/45090574_Brain-specific_conditional_and_time-specific_inducible_Tph2_knockout_mice_possess_normal_serotonergic_gene_expression_in_the_absence_of_serotonin_during_adult_life/links/02bfe511dbf3c3c8b1000000.pdf}, volume = {57}, year = {2010} } @article{Lazary2011, abstract = {G protein-activated K+ channel 2 (GIRK2) and cAMP-response element binding protein (CREB1) are involved in synaptic plasticity and their genes have been implicated depression and memory processing. Excessive rumination is a core cognitive feature of depression which is also present in remission. High scores on the Ruminative Response Scale (RRS) questionnaire are predictive of relapse and recurrence. Since rumination involves memory, we tested the hypothesis that variation in the genes encoding GIRK2 (KCNJ6) and CREB1 mechanisms would influence RRS scores. GIRK2 and CREB1 polymorphisms were studied in two independent samples (n=651 and n=1174) from the general population. Strongly significant interaction between the TT genotype of rs2070995 (located in KCNJ6) and the GG genotype of rs2253206 (located in CREB1) on RRS were found in both samples. These results were validated in an independent third sample (n=565; individuals with personality disorders) showing significant main effect of the variants mentioned as well as significant interaction on a categorical diagnosis of Cluster C personality disorder (obsessional-compulsive, avoidant and dependent) in which rumination is a prominent feature. Our results suggest that genetic epistasis in post-receptor signaling pathways in memory systems may have relevance for depression and its treatment.}, author = {Lazary, Judit and Trang Nguyen, T. and William Deakin, J. F. and Juhasz, Gabriella and Anderson, Ian M. and Jacob, Christian P. and Nguyen, T. Trang and Lesch, Klaus-Peter and Reif, Andreas and Deakin, J. F. William and Bagdy, Gyorgy}, doi = {10.1016/j.euroneuro.2010.09.009}, journal = {European Neuropsychopharmacology}, month = {jan}, pages = {63-70}, title = {Epistatic interaction of CREB1 and KCNJ6 on rumination and negative emotionality.}, url = {https://www.researchgate.net/profile/Judit_Lazary/publication/47414286_Epistatic_interaction_of_CREB1_and_KCNJ6_on_rumination_and_negative_emotionality/links/54d223d60cf25ba0f0426795.pdf}, volume = {21}, year = {2011} } @incollection{Lesch2011, author = {Lesch, Klaus-Peter}, doi = {10.1007/7854_2010_109}, journal = {Molecular and Functional Models in Neuropsychiatry}, month = {jan}, pages = {251-280}, title = {When the Serotonin Transporter Gene Meets Adversity: The Contribution of Animal Models to Understanding Epigenetic Mechanisms in Affective Disorders and Resilience}, url = {https://oadoi.org/10.1007/7854_2010_109}, year = {2011} } @misc{Song2011, author = {Song, Ning-Ning and Xiu, Jian-Bo and Huang, Ying and Chen, Jia-Yin and Zhang, Lei and Gutknecht, Lise and Lesch, Klaus Peter and Li, He and Ding, Yu-Qiang}, month = {jan}, title = {Figure S1}, year = {2011} } @misc{Song2011_2, author = {Song, Ning-Ning and Xiu, Jian-Bo and Huang, Ying and Chen, Jia-Yin and Zhang, Lei and Gutknecht, Lise and Lesch, Klaus Peter and Li, He and Ding, Yu-Qiang}, month = {jan}, title = {Figure S2}, year = {2011} } @article{Weiland2011, abstract = {Recently, research on olfactory functions in attention-deficit/hyperactivity disorder (ADHD) has become prominent, whereas gustation has never been investigated. Increased odor sensitivity was found in medication-naïve children with ADHD, but not in adult ADHD, which might be due to a dopaminergic dysregulation presumed to underlie this disorder. Taste sensitivity, in particular bitter sensitivity as a hereditary trait, also might be altered in ADHD. To examine olfactory and gustatory functions in adult ADHD patients, we assessed odor sensitivity by Sniffin' Sticks, taste sensitivity by taste strips, and bitter sensitivity by the one-solution test in women with ADHD (n = 12), Bulimia Nervosa (n = 12), and healthy control women (n = 12). Bulimia Nervosa as second patient group was included to control for effects of impulsivity. Preliminary results indicate that ADHD patients were significantly more often classified as tasters, i.e. perceived the bitter taste as more intense, compared to both bulimic patients and healthy controls. No group differences were found with regard to general odor and taste sensitivity. It is proposed that the higher frequency of tasters in ADHD patients might underlie a genetic variation of the bitter receptor-dependent signaling pathway associated with ADHD.}, author = {Weiland, Romy and Macht, Michael and Ellgring, Heiner and Gross-Lesch, Silke and Lesch, Klaus-Peter and Pauli, Paul}, doi = {10.1007/s12402-010-0052-9}, journal = {ADHD Attention Deficit and Hyperactivity Disorders}, month = {jan}, pages = {53-60}, title = {Olfactory and gustatory sensitivity in adults with attention-deficit/hyperactivity disorder}, url = {https://www.researchgate.net/profile/Romy_Weiland/publication/50833910_Olfactory_and_gustatory_sensitivity_in_adults_with_attention-deficithyperactivity_disorder/links/0912f50f6c60f911c9000000.pdf}, volume = {3}, year = {2011} } @article{Xiu2011, abstract = {The transcription factor Lmx1b is essential for the differentiation and survival of central serotonergic (5-HTergic) neurons during embryonic development. However, the role of Lmx1b in adult 5-HTergic neurons is unknown. We used an inducible Cre-LoxP system to selectively inactivate Lmx1b expression in the raphe nuclei of adult mice. Pet1-CreER(T2) mice were generated and crossed with Lmx1b(flox/flox) mice to obtain Pet1-CreER(T2); Lmx1b(flox/flox) mice (which termed as Lmx1b iCKO). After administration of tamoxifen, the level of 5-HT in the brain of Lmx1b iCKO mice was reduced to 60% of that in control mice, and the expression of tryptophan hydroxylase 2 (Tph2), serotonin transporter (Sert) and vesicular monoamine transporter 2 (Vmat2) was greatly down-regulated. On the other hand, the expression of dopamine and norepinephrine as well as aromatic L-amino acid decarboxylase (Aadc) and Pet1 was unchanged. Our results reveal that Lmx1b is required for the biosynthesis of 5-HT in adult mouse brain, and it may be involved in maintaining normal functions of central 5-HTergic neurons by regulating the expression of Tph2, Sert and Vmat2.}, author = {Xiu, Jian-Bo and Huang, Ying and Song, Ning and Zhang, Lei and Chen, Jia-Yin and Gutknecht, Lise and Lesch, Klaus Peter and Li, He and Ding, Yu-Qiang}, doi = {10.1371/journal.pone.0015998}, journal = {PLoS ONE}, month = {jan}, pages = {e15998}, title = {Adult Raphe-Specific Deletion of Lmx1b Leads to Central Serotonin Deficiency}, url = {https://doi.org/10.1371/journal.pone.0015998}, volume = {6}, year = {2011} } @article{Ádori2010, author = {Ádori, Csaba and Lőw, Péter and Andó, Rómeó D. and Gutknecht, Lise and Pap, Dorottya and Truszka, Ferencné and Takács, József and Kovács, Gábor G. and Lesch, Klaus-Peter and Bagdy, György}, doi = {10.1007/s00213-010-2041-2}, journal = {Psychopharmacology}, month = {oct}, pages = {377-391}, title = {Ultrastructural characterization of tryptophan hydroxylase 2-specific cortical serotonergic fibers and dorsal raphe neuronal cell bodies after MDMA treatment in rat}, url = {https://www.researchgate.net/profile/Csaba_Adori/publication/47680519_Ultrastructural_characterization_of_tryptophan_hydroxylase_2-specific_cortical_serotonergic_fibers_and_dorsal_raphe_neuronal_cell_bodies_after_MDMA_treatment_in_rat_Psychopharmacology_2132-3_377-391/links/0c960516c35fe479ec000000.pdf}, volume = {213}, year = {2010} }