@article{Barr2004, author = {Barr, Christina S. and Newman, Timothy K. and Lindell, Stephen and Shannon, Courtney and Champoux, Maribeth and Lesch, Klaus Peter and Suomi, Stephen J. and Goldman, David and Dee Higley, J. and Higley, J. Dee}, doi = {10.1001/archpsyc.61.11.1146}, journal = {Archives of General Psychiatry}, month = {nov}, pages = {1146}, title = {Interaction Between Serotonin Transporter Gene Variation and RearingCondition in Alcohol Preference and Consumption in Female Primates}, url = {https://jamanetwork.com/journals/jamapsychiatry/articlepdf/482083/YOA30155.pdf}, volume = {61}, year = {2004} } @article{Bringmann2006, abstract = {Chloral-derived beta-carbolines, which are structurally similar to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 5), are discussed to contribute to neuronal cell death in idiopathic Parkinson's disease. The cytotoxicity of 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo, 4) to neuronal-like clonal pheochromocytoma PC12 cells was examined by the determination of lactate dehydrogenase (LDH) release. After incubation for 48 h, 4 showed a strong dose-dependent cytotoxic activity towards PC12 cells with an ED50 value of 230 microM. In PC12 cells reductive dehalogenation of 4 was observed giving rise to the formation of 1-dichloromethyl-1,2,3,4-tetrahydro-beta-carboline (6) as a main TaClo metabolite exhibiting a cytotoxic potential comparable to that of TaClo. An X-ray structure analysis, performed for the trifluoroacetyl derivative of 6, revealed the N-substituent of such a highly chlorinated agent to be dramatically pushed out of the beta-carboline ring 'plane' due to the high steric demand of the huge dichloromethyl group at C(1).}, author = {Bringmann, Gerhard and Feineis, Doris and Münchbach, Miriam and God, Ralf and Peters, Karl and Peters, Eva-Maria and Mössner, Rainald and Lesch, Klaus-Peter}, doi = {10.1515/znc-2006-7-822}, journal = {Zeitschrift für Naturforschung C}, month = {jan}, pages = {601-610}, title = {Toxicity and Metabolism of the Chloral-Derived Mammalian Alkaloid 1-Trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo) in PC12 Cells}, url = {http://www.degruyter.com/downloadpdf/j/znc.2006.61.issue-7-8/znc-2006-7-822/znc-2006-7-822.xml}, volume = {61}, year = {2006} } @article{Canli2005, abstract = { Prior work has highlighted the role of genetic variation within the repetitive sequence in the transcriptional control region of the serotonin (5-HT) transporter gene ( 5-HTT , SLC6A4 ) in modulating amygdala and prefrontal activation to negative emotional stimuli. However, these studies have not explicitly tested the assumption that the control condition (neutral baseline) does not itself produce changes in activation as a function of 5-HTT genotype. Using a fixation baseline condition, we show that variation in 5-HTT genotype is associated with differential activation to negative, positive, and neutral stimuli in limbic, striatal, and cortical regions. We replicate earlier reports of increased amygdala activation to negative, relative to neutral, stimuli, but then show that these differences are driven by decreased activation to neutral stimuli, rather than increased activation to negative stimuli, in carriers of the 5-HTT short allele. Using high-resolution structural images and automated processes to test for brain volume and gray matter density, we further report significant differences, as a function of 5-HTT genotype, in frontal cortical regions, anterior cingulate, and cerebellum. These functional and structural differences suggest a much broader role for 5-HT transport efficiency in brain processes than previously thought. 5-HTT genotype affects neural systems controlling affective, cognitive, and motor processes. }, author = {Canli, Turhan and Todd Constable, R. and Omura, Kazufumi and Haas, Brian W. and Fallgatter, Andreas and Constable, R. T. and Lesch, Klaus Peter}, doi = {10.1073/pnas.0503880102}, journal = {Proceedings of the National Academy of Sciences}, month = {aug}, pages = {12224-12229}, title = {Beyond affect: A role for genetic variation of the serotonin transporter in neural activation during a cognitive attention task}, url = {http://www.pnas.org/content/102/34/12224.full.pdf}, volume = {102}, year = {2005} } @article{Dreisbach2005, abstract = {One fundamental problem of intelligent organisms pursuing goal-directed behavior is how to dynamically regulate the balance between maintenance and flexibility. The authors show that central dopaminergic activity, as indicated by spontaneous eyeblink rate and dopamine gene polymorphisms, plays an important role in the modulation of this balance. Seventy-two young adults were examined. Participants with high blink rates showed increased cognitive flexibility but decreased cognitive stability compared with participants with low blink rates. This pattern of results was even more pronounced for carriers of the DRD4 exon III 4/7 genotype, even though no main effects were found for DRD4 and COMT polymorphisms. Results converge with neuropsychological models that suggest a modulatory role of prefrontal dopaminergic activity for processes of cognitive control.}, author = {Dreisbach, Gesine and Müller, Johannes and Goschke, Thomas and Strobel, Alexander and Schulze, Katja and Lesch, Klaus-Peter and Brocke, Burkhard}, month = {jan}, title = {Dopamine and Cognitive Control: The influence of spontaneous eye-blink rate and dopamine gene polymorphisms on perseveration and distractibility}, year = {2005} } @article{Dreisbach2005_2, abstract = {One fundamental problem of intelligent organisms pursuing goal-directed behavior is how to dynamically regulate the balance between maintenance and flexibility. The authors show that central dopaminergic activity, as indicated by spontaneous eyeblink rate and dopamine gene polymorphisms, plays an important role in the modulation of this balance. Seventy-two young adults were examined. Participants with high blink rates showed increased cognitive flexibility but decreased cognitive stability compared with participants with low blink rates. This pattern of results was even more pronounced for carriers of the DRD4 exon III 4/7 genotype, even though no main effects were found for DRD4 and COMT polymorphisms. Results converge with neuropsychological models that suggest a modulatory role of prefrontal dopaminergic activity for processes of cognitive control.}, author = {Dreisbach, Gesine and Müller, Johannes and Goschke, Thomas and Strobel, Alexander and Schulze, Katja and Lesch, Klaus-Peter and Brocke, Burkhard}, doi = {10.1037/0735-7044.119.2.483}, journal = {Behavioral Neuroscience}, month = {jan}, pages = {483-490}, title = {Dopamine and cognitive control: the influence of spontaneous eyeblink rate and dopamine gene polymorphisms on perseveration and distractibility.}, url = {https://www.researchgate.net/profile/Alexander_Strobel/publication/7897230_Dopamine_and_cognitive_control_the_influence_of_spontaneous_eyeblink_rate_and_dopamine_gene_polymorphisms_on_perseveration_and_distractibility/links/02e7e52120c44acab7000000.pdf}, volume = {119}, year = {2005} } @article{Jacob2005, abstract = {Genetic variants of the monoamine oxidase A (MAOA) have been associated with aggression-, anxiety-, and addiction-related behavior in several nonclinical and clinical populations. Here, we investigated the influence of allelic variation of MAOA activity on aggression-related personality traits and disease risk in patients with personality disorders. Personality disorders were diagnosed with the Structured Clinical Interview of DSM-IV and were allocated to cluster A, B, and C. Personality features were assessed by the revised NEO Personality Inventory and the Tridimensional Personality Questionnaire. The genotype of the MAOA gene-linked polymorphic region (MAOA-LPR) was determined in 566 patients with personality disorders and in 281 healthy controls. MAOA genotype was significantly associated with cluster B personality disorders (chi2=7.77, p=0.005, df=1) but not with cluster C personality disorders. In total, 26.0% of cluster B patients were hemi- or homozygous for the low-activity variant of the MAOA genotype, compared to 16.4% in the control group. Associations between MAOA variants and personality domains related to impulsivity and aggressiveness were inconsistent. Our findings further support the notion that allelic variation of MAOA activity contributes modestly to the balance of hyper- (impulsive-aggressive) and hyporeactive (anxious-depressive) traits.}, author = {Jacob, Christian P. and Müller, Johannes and Schmidt, Michael and Hohenberger, Katrin and Gutknecht, Lise and Reif, Andreas and Schmidtke, Armin and Mössner, Rainald and Lesch, Klaus Peter}, doi = {10.1038/sj.npp.1300737}, journal = {Neuropsychopharmacology}, month = {may}, pages = {1711-1718}, title = {Cluster B Personality Disorders are Associated with Allelic Variation of Monoamine Oxidase A Activity}, url = {https://www.nature.com/articles/1300737.pdf}, volume = {30}, year = {2005} } @article{Kim2005, abstract = {To evaluate the consequences of inactivation of the serotonin transporter (SERT) gene on 5-HT homeostasis and function, 5-HT synthesis and turnover rates were measured using the decarboxylase inhibition method in multiple brain regions (frontal cortex, striatum, brainstem, hippocampus and hypothalamus) from mice with a genetic disruption of SERT. 5-HT synthesis rates were increased 30-60% in the different brain regions of SERT -/- mice compared to littermate +/+ control mice despite 55-70% reductions in tissue 5-HT concentrations. Brain regions that possessed a greater capacity to increase synthesis and turnover (frontal cortex, striatum) demonstrated lesser reductions in tissue 5-HT. Female SERT -/- mice had greater increases (79%) in brain 5-HT synthesis than male -/- mice did (25%), a finding associated with higher brain tryptophan concentrations in females. Despite increased 5-HT synthesis, there was no change in either TPH2 or TPH1 mRNA levels or in maximal in vitro TPH activity in the brainstem of SERT -/- mice. Catecholamine homeostasis as reflected in brain tissue concentrations and in synthesis and turnover of dopamine and norepinephrine was unchanged in SERT -/- mice. Taken together, the results demonstrate a markedly altered homeostatic situation in SERT -/- mice that lack 5-HT reuptake, resulting in markedly depleted tissue stores that are inadequately compensated for by increased 5-HT synthesis, with brain region and gender specificity observed.}, author = {Kim, Dong-Kyu and Tolliver, Teresa J. and Huang, Su-Jan and Martin, Bradley J. and Andrews, Anne M. and Wichems, Christine and Holmes, Andrew and Lesch, Klaus-Peter and Murphy, Dennis L.}, doi = {10.1016/j.neuropharm.2005.08.010}, journal = {Neuropharmacology}, month = {nov}, pages = {798-810}, title = {Altered serotonin synthesis, turnover and dynamic regulation in multiple brain regions of mice lacking the serotonin transporter}, url = {https://www.researchgate.net/profile/Anne_Andrews/publication/7581289_Altered_serotonin_synthesis_turnover_and_dynamic_regulation_in_multiple_brain_regions_of_mice_lacking_the_serotonin_transporter/links/02bfe510b196125cd3000000.pdf}, volume = {49}, year = {2005} } @article{Lesch2005, abstract = {While multiple lines of evidence implicate the 5-HT1A receptor in the pathophysiology of anxiety and depression as well as in the mechanism of action of anxiolytics/antidepressants, its relevance to the therapeutic effectiveness of these drugs has been a matter of considerable debate (for review see Griebel, 1995; Hensler, 2003; Hjorth et al., 2000; Lesch et al., 2003). In the current issue of the International Journal of Neuropsychopharmacology, however, both Serretti et al. (2004) and Lemonde et al. (2004) make a strong argument for contribution of a functional 5-HT1A receptor gene variant in the pharmacogenetics of antidepressant treatment with prototypic tricyclics and selective serotonin reuptake inhibitors (SSRIs). Furthermore, the third study in this series by Huang and associates (2004) reveals an association of allelic variation of 5-HT1A receptor expression in a wide spectrum of psychopathology including schizophrenia, substance abuse, and panic disorder. Not unexpectedly, the failure to detect a consistent effect of this gene variation on 5-HT1A receptor functionality in the mature brain as indicated by both receptor binding in post-mortem brain and in-vivo receptor responsivity further supports a critical role of the 5-HT1A receptor in engineering neurodevelopmental processes which may have the potential to set the stage for the brain's permissiveness for psychopathology in later life. The availability of an increasing number of functional gene variants within the serotonergic pathway together with integration of emerging concepts of developmental genetics of complex traits will provide the groundwork for the molecular dissection of syndromal dimensions and treatment response.}, author = {Lesch, Klaus Peter and Gutknecht, Lise}, doi = {10.1017/s1461145704004845}, journal = {International Journal of Neuropsychopharmacology}, month = {jan}, pages = {381-385}, title = {Lesch KP, Gutknecht L. Focus on The 5-HT1A receptor: emerging role of a gene regulatory variant in psychopathology and pharmacogenetics. Int J Neuropsychopharmacol 7: 381-385}, url = {http://dx.doi.org/10.1017/s1461145704004845}, volume = {7}, year = {2005} } @article{Lesch2005_2, abstract = {Response to psychopharmacologic drugs is genetically complex, results from an interplay of multiple genomic variations with environmental influences, and depends on the structure or functional expression of gene products, which are direct drug targets or indirectly modify the development and synaptic plasticity of neural networks critically involved in their effects. During brain development, the serotonin (5HT) system, which is commonly targeted by antidepressant, anxiolytic, and antipsychotic drugs, controls neuronal specification, differentiation, and phenotype maintenance. While formation and integration of these neural networks is dependent on the action of multiple proteins, converging lines of evidence indicate that genetically controlled variability in the expression of the 5HT transporter (5HTT) is critical to the development and plasticity of distinct neurocircuits. The most promising finding to date indicate an association between the response time as well as overall response to serotonin reuptake inhibitors (SSRIs) and a common polymorphism (5HTTLPR) within the transcriptional control region of the 5HTT gene (SLC6A4) in patients with depressive disorders. The formation and maturation of serotonergic and associated systems, in turn, are influencing the efficacy of serotonergic compounds in a variety of psychiatric conditions. Based on the notion that complex gene x gene and gene x environment interactions in the regulation of brain plasticity are presumed to contribute to individual differences in psychopharmacologic drug response, the concept of developmental psychopharmacogenetics is emerging.}, author = {Lesch, Klaus Peter and Gutknecht, Lise}, doi = {10.1016/j.pnpbp.2005.03.012}, journal = {Progress in Neuro-Psychopharmacology and Biological Psychiatry}, month = {jul}, pages = {1062-1073}, title = {Pharmacogenetics of the serotonin transporter}, url = {https://www.researchgate.net/profile/Lise_Gutknecht/publication/7791779_Pharmacogenetics_of_the_serotonin_transporter/links/00b7d51a091092e605000000.pdf}, volume = {29}, year = {2005} } @article{Lesch2005_3, abstract = {Alcohol dependence is characterized by frequent, compulsive and uncontrolled consumption of alcohol associated with behavior of maladaption and destruction. It is an etiologically and clinically heterogeneous syndrome, moderately to highly heritable, and caused by interaction of genes and environment. Alcohol dependence is related to other psychiatric diseases by common neurobiological pathways, including those that modulate reward, behavioral control as well as anxiety and stress response. Alcohol induces adaptive changes in brain function providing the basis for tolerance, craving, withdrawal, and emotional disturbance. The differentiation of psychobiological traits of addictive behavior reflecting neurobiological processes is therefore of particular importance for the dissection of the complex genetic susceptibility to alcohol dependence. A central serotonin (5-HT) deficit is thought to be involved in the pathogenesis of alcohol dependence by modulating motivational behavior, neuroadaptive processes, and resulting emotional disturbance. 5-HT-related impulsive, aggressive, and suicidal behavior has been linked to a primordial personality that is susceptible to alcohol dependence. Although variations in many of the genes that encode receptors, enzymes, and transporters of the 5-HT system have been tested as risk factors for alcohol dependence, genetic analyses of 5-HT signaling in alcohol dependence have mainly been focused on the 5-HT transporter (5-HTT) gene. Due to its central role in the fine-tuning serotonergic neurotransmission, a regulatory variant of the 5-HTT, which is associated with anxiety related traits, is not only a key player in the neurobiological mechanism of gene x environment interaction in the etiology of depression, but also contributes to the risk to develop alcohol dependence with antisocial behavior and suicidality. Evidence for a modulatory effect of allelic variation of 5-HTT function on limbic circuit responses to emotional stimuli suggests that genotype-endophenotype correlations may be accessible to molecular functional imaging of the brain. These new developments have broad implications for our understanding how genetic vulnerability to alcohol dependence is manifested in the brain's response to emotional stimuli.}, author = {Lesch, Klaus-Peter}, doi = {10.1016/j.ejphar.2005.09.027}, journal = {European Journal of Pharmacology}, month = {dec}, pages = {113-124}, title = {Alcohol dependence and gene × environment interaction in emotion regulation: Is serotonin the link?}, url = {https://oadoi.org/10.1016/j.ejphar.2005.09.027}, volume = {526}, year = {2005} } @article{Meyer2006, abstract = {Recessive mutations of the potassium chloride co-transporter 3 gene ( SLC12A6 , KCC3 ) cause severe peripheral neuropathy frequently associated with agenesis of the corpus callosum and psychoses (ACCPN). SLC12A6 is localized on chromosome 15q14, a region where linkage to schizophrenia and bipolar disorder has previously been shown. Mutation analysis of SLC12A6 was carried out by direct sequencing of PCR-generated DNA fragments in two affected members of a multiplex family, and three non-affected individuals. A case-control study was performed to assess association of variants with bipolar disorder and schizophrenia in a large sample. Several variants including two rare single nucleotide polymorphisms (G/A, G/A) in the promoter and 5'-UTR, and a thymidine insertion in intron 4 were found. The two G variants and the insertion variant were co-inherited with chromosome 15-related schizophrenia in a large family that strongly supports the region on chromosome 15q14-15 between markers D15S144 and D15S132. Furthermore, they are in linkage disequilibrium with each other, and significantly associated with bipolar disorder in a case-control study. Our data strongly suggest that rare variants of SLC12A6 may represent risk factors for bipolar disorder.}, author = {Meyer, Jobst and Johannssen, Kirsten and Freitag, Christine M. and Schraut, Kerstin and Teuber, Isabel and Hahner, Astrid and Mainhardt, Christian and Mössner, Rainald and Volz, Hans-Peter and Wienker, Thomas F. and McKeane, Darleen and Stephan, Dietrich A. and Rouleau, Guy and Reif, Andreas and Lesch, Klaus-Peter}, doi = {10.1017/s1461145705005821}, journal = {International Journal of Neuropsychopharmacology}, month = {jan}, pages = {495}, title = {Rare variants of the gene encoding the potassium chloride co-transporter 3 are associated with bipolar disorder}, url = {http://dx.doi.org/10.1017/s1461145705005821}, volume = {8}, year = {2006} } @article{Mössner2005, author = {Mössner, Rainald and Weichselbaum, Annette and Marziniak, Martin and Freitag, Christine M. and Lesch, Klaus-Peter and Sommer, Claudia and Meyer, Jobst}, doi = {10.1111/j.1526-4610.2005.05027.x}, journal = {Headache: The Journal of Head and Face Pain}, month = {feb}, pages = {132-136}, title = {A Highly Polymorphic Poly‐Glutamine Stretch in the Potassium Channel KCNN3 in Migraine}, url = {https://www.researchgate.net/profile/Jobst_Meyer/publication/8028079_A_Highly_Polymorphic_Poly-Glutamine_Stretch_in_the_Potassium_Channel_KCNN3_in_Migraine/links/0fcfd50599e01c6caf000000.pdf}, volume = {45}, year = {2005} } @article{Mössner2005_2, abstract = {Obsessive-compulsive disorder (OCD) is characterized by recurrent, intrusive, and disturbing thoughts, as well as by repetitive stereotypic behaviour. Insight into the senseless nature of the symptoms is generally preserved. Patients try, albeit usually unsuccessfully, to suppress the obsessive thoughts and compulsive behaviours. Acting out the stereotypic behaviours reduces the anxiety generated by the obsessions and compulsions (APA, 2000). In 60% of patients OCD develops before the age of 25 yr, and onset of disease can already occur in childhood (Flament et al., 1990). Familial loading is higher in early-onset OCD, indicating that genetic factors may be of greater importance in OCD with early onset (Pauls et al., 1995).}, author = {Mössner, Rainald and Walitza, Susanne and Lesch, Klaus-Peter and Geller, Frank and Barth, Nikolaus and Remschmidt, Helmut and Hahn, Freya and Herpertz-Dahlmann, Beate and Fleischhaker, Christian and Schulz, Eberhard and Warnke, Andreas and Hinney, Anke and Wewetzer, Christoph}, doi = {10.1017/s146114570400495x}, journal = {International Journal of Neuropsychopharmacology}, month = {apr}, pages = {133-136}, title = {Brain-derived neurotrophic factor V66M polymorphism in childhood-onset obsessive-compulsive disorder}, url = {http://dx.doi.org/10.1017/s146114570400495x}, volume = {8}, year = {2005} } @article{Newman2005, author = {Newman, Timothy K. and Syagailo, Yana V. and Barr, Christina S. and Wendland, Jens R. and Champoux, Maribeth and Graessle, Markus and Suomi, Stephen J. and Dee Higley, J. and Higley, J. Dee and Lesch, Klaus-Peter}, doi = {10.1016/j.biopsych.2004.10.012}, journal = {Biological Psychiatry}, month = {jan}, pages = {167-172}, title = {Monoamine oxidase A gene promoter variation and rearing experience influences aggressive behavior in rhesus monkeys}, url = {https://www.researchgate.net/profile/Jens_Wendland/publication/8078267_Monoamine_oxidase_A_gene_promoter_variation_and_rearing_experience_influences_aggressive_behavior_in_rhesus_monkeys/links/00b7d52bcbaf347e51000000.pdf}, volume = {57}, year = {2005} } @article{Reif2004, abstract = {In recent years, the use of valproic acid (VPA) as a mood-stabilizing agent has continuously increased. Although VPA usually is well tolerated, its use in combination with other psychotropic compounds might bear an elevated risk of adverse reactions. Here, we present the case of a 42-year-old male suffering from treatment-resistant psychotic depression, who was prescribed VPA additionally to lithium, clomipramine, flupentixol and risperidone. By doing so, he developed myoclonus, tremor and encephalopathy with sedation and marked EEG background slowing. Most notably, these side effects occurred in the presence of normal VPA and ammonia serum concentrations. On VPA discontinuation, all symptoms vanished and EEG normalized. We thus suggest that direct VPA-induced encephalopathy in the absence of ammonemia does exist, in this case probably facilitated by psychotropic polypharmacy.}, author = {Reif, Andreas and Leonhard, Christine and Mössner, Rainald and Lesch, Klaus-Peter and Fallgatter, Andreas J.}, doi = {10.1016/j.pnpbp.2004.05.041}, journal = {Progress in Neuro-Psychopharmacology and Biological Psychiatry}, month = {sep}, pages = {1061-1063}, title = {Encephalopathy and myoclonus triggered by valproic acid}, url = {https://www.researchgate.net/profile/Andreas_Fallgatter/publication/8333814_Encephalopathy_and_myoclonus_triggered_by_valproic_acid/links/0912f510a55ca18d88000000.pdf}, volume = {28}, year = {2004} } @article{Reif2004_2, abstract = {The 22q11 microdeletion syndrome (22q11-DS) is strongly associated with schizophreniform disorders and, in turn, the 22q11 deletion region harbours several candidate genes for schizophrenia. Here, we present the case of an adolescent female patient with 22q11-DS associated with impaired cognitive abilities and behavioural abnormalities. The patient was studied with magnetic resonance imaging (MRI) and positron emission tomography (PET) as well as extensive neurophysiological investigations. Although no structural or functional abnormalities were found in MRI and PET, assessment of event-related potentials elicited during the Continuous Performance Test revealed a lack of NoGo anteriorisation. The latter was replicated in a second case of 22q11-DS with schizoaffective disorder but devoid of a severe somatic syndrome. This electrophysiological finding, which indicates modified functioning of the cingulate gyrus, has previously been demonstrated only in patients suffering from schizophrenia and attention deficit/hyperactivity disorder, two psychopathological conditions frequently associated with 22q11-DS. We conclude that more extensive study of NoGo anteriorisation as a potential endophenotype of 22q11-DS patients at risk for 22q11-associated psychiatric conditions is warranted.}, author = {Reif, Andreas and Fallgatter, Andreas J. and Ehlis, Ann-Christine and Lesch, Klaus-Peter}, doi = {10.1016/j.pscychresns.2004.08.003}, journal = {Psychiatry Research: Neuroimaging}, month = {dec}, pages = {273-278}, title = {Altered functioning of the cingulate gyrus in two cases of chromosome 22q11 deletion syndrome}, url = {https://www.researchgate.net/profile/Andreas_Fallgatter/publication/8066423_Altered_functioning_of_the_cingulate_gyrus_in_two_cases_of_chromosome_22q11_deletion_syndrome/links/0912f510a55ca5365c000000.pdf}, volume = {132}, year = {2004} } @article{Reif2005, abstract = {In the recent years, elevated homocysteine plasma levels have been reported to represent a risk factor not only for atherosclerosis, but also to be associated with dementia, depression and-in a gender-specific manner-schizophrenia. Here, we explored a possible association between homocysteinemia and psychiatric disorders. Fasting homocysteine, vitamin B12 and folate were determined in an ethnically homogeneous female population with different psychiatric disorders. Homocysteine was not elevated in females suffering from schizophrenia (mean, 11.6+/-5.8 micromol/l). As shown previously, increased homocysteine concentrations were associated not only with dementia of different aetiology (mean, 17.2+/-6.7 micromol/l; chi2=23.39, p<0.001, compared to the schizophrenia group), but also with depressive disorders (mean, 12.9+/-3.8 micromol/l; chi2=6.88, p=0.009). B12 and folate levels did not differ between different diagnostic groups. To further explore the connection between homocysteinemia and affective psychoses, a case-control study examining the C677T and the A1298C variants of methylenetetrahydrofolate reductase was conducted. The latter polymorphism not only was associated with affective psychoses in general, but also when divided in unipolar depression and bipolar affective disorder. In conclusion, we suggest that in females homocysteinemia is an unspecific risk factor for organic brain disorders like dementia, and possibly depression, but not for schizophrenia.}, author = {Reif, Andreas and Pfuhlmann, Bruno and Lesch, Klaus-Peter}, doi = {10.1016/j.pnpbp.2005.06.027}, journal = {Progress in Neuro-Psychopharmacology and Biological Psychiatry}, month = {sep}, pages = {1162-1168}, title = {Homocysteinemia as well as methylenetetrahydrofolate reductase polymorphism are associated with affective psychoses}, url = {https://www.researchgate.net/profile/Andreas_Reif/publication/7691149_Homocysteinemia_as_well_as_methylenetetrahydrofolate_reductase_polymorphism_are_associated_with_affective_psychoses/links/00b7d52e8a74dd82f9000000.pdf}, volume = {29}, year = {2005} } @article{Ren Patterson2005, abstract = {To study the neurochemical and behavioral effects of altered brain-derived neurotrophic factor (BDNF) expression on a brain serotonin system with diminished serotonin transport capability, a double-mutant mouse model was developed by interbreeding serotonin transporter (SERT) knockout mice with BDNF heterozygous knockout mice (BDNF +/-), producing SERT -/- x BDNF +/- (sb) mice. Prior evidence implicates serotonin and SERT in anxiety and stress responses. Some studies have shown that BDNF supports serotonergic neuronal development, leading to our hypothesis that reduced BDNF availability during development might exaggerate the consequences of absent SERT function. In the present study, brain serotonin and 5-hydroxyindol acetic acid concentrations in male sb mice were significantly reduced in the hippocampus and hypothalamus compared with wild-type control SB mice, BDNF-deficient Sb mice, and serotonin transporter knockout sB mice. The sb mice had significantly increased anxiety-like behaviors compared with SB, Sb, and sB mice as measured on the elevated plus maze test. These sb mice also had significantly greater increases in plasma adrenocorticotrophic hormone than mice with other genotypes after a stressful stimulus. Analysis of neuronal morphology showed that hypothalamic and hippocampal neurons exhibited 25-30% reductions in dendrites in sb mice compared with SB control mice. These findings support the hypothesis that genetic changes in BDNF expression interact with serotonin and other circuits that modulate anxiety and stress-related behaviors. Thus, this double-mutant mouse model should prove valuable in studying other gene x gene consequences for brain plasticity as well as in evaluating epistatic interactions of BDNF and serotonin transporter gene polymorphisms in neuropsychiatric disorders.}, author = {Ren Patterson, Renee F. and Cochran, Lauren W. and Holmes, Andrew and Sherrill, Suzanne and Huang, Su-Jan and Tolliver, Teresa and Lesch, Klaus-Peter and Lu, Bai and Murphy, Dennis L.}, doi = {10.1002/jnr.20410}, journal = {Journal of Neuroscience Research}, month = {jan}, pages = {756-771}, title = {Loss of brain-derived neurotrophic factor gene allele exacerbates brain monoamine deficiencies and increases stress abnormalities of serotonin transporter knockout mice}, url = {https://oadoi.org/10.1002/jnr.20410}, volume = {79}, year = {2005} } @article{Strobel2004, abstract = {The functional implications of the dopamine D4 receptor gene (DRD4) exon III polymorphism and its role in the modulation of temperament and in the pathophysiology of psychiatric disorders are still a matter of debate. Based on evidence from animal studies, we hypothesised that this polymorphism is involved in the modulation of the cortical response to novelty as reflected by the auditory evoked novelty P3 event-related potential. In a sample of 46 healthy volunteers, we observed an interactive effect of DRD4 exon III genotype and the eye-blink rate, a measure of central dopaminergic activity, on the novelty P3. These findings suggest that the DRD4 exon III polymorphism influences the processing of novelty and that this influence depends on tonic dopaminergic activity.}, author = {Strobel, Alexander and Debener, Stefan and Anacker, Kristin and Müller, Johannes and Lesch, Klaus-Peter and Brocke, Burkhard}, doi = {10.1097/00001756-200410250-00022}, journal = {NeuroReport}, month = {oct}, pages = {2411-2415}, title = {Dopamine D4 receptor exon III genotype influence on the auditory evoked novelty P3}, url = {https://www.researchgate.net/profile/Alexander_Strobel/publication/8090109_Dopamine_D4_receptor_exon_III_genotype_influence_on_the_auditory_evoked_novelty_P3/links/0046352272f1a39889000000.pdf}, volume = {15}, year = {2004} } @article{Wendland2005, abstract = {Functional allelic variation in the transcriptional control region of the serotonin transporter and monoamine oxidase A genes has been associated with anxiety- and aggression-related behavior in humans and, more recently, in nonhuman primates. Here, we have genotyped these polymorphic regions in seven species of the genus Macaca. Macaques exhibit exceptional inter-species variation in aggression-related social behavior as illustrated by recent studies showing overlapping patterns of aggression-based social organization grades and macaque phylogeny. We cloned and sequenced two new alleles of the serotonin transporter gene-linked polymorphic region in Barbary and Tibetan macaques. In addition, we observed that species displaying tolerant societies, with relaxed dominance and high levels of conciliatory tendency, were monomorphic for both the serotonin transporter gene and, with the exception of Tonkean macaques, the monoamine oxidase A gene. In contrast, those species known to exhibit intolerant, hierarchical and nepotistic societies were polymorphic at one or more of these loci. Rhesus (M. mulatta), the most intolerant and hierarchical species of macaques, showed the greatest degree of allelic variation in both genes. Additional investigation of a polymorphic repeat in exon III of the dopamine receptor D4 as well as a repeat/single nucleotide polymorphism in the 3' untranslated region of the dopamine transporter which have both been implicated in the modulation of complex behavior failed to reveal a relationship between allelic variability and social organization grade. Taken together, these findings suggest that genetic variation of serotonergic neurotransmission may play an important role in determining inter-species differences in aggression related behavior in macaques.}, author = {Wendland, Jens R. and Lesch, Klaus-Peter and Newman, Timothy K. and Timme, Angelika and Gachot-Neveu, Hélène and Thierry, Bernard and Suomi, Stephen J.}, doi = {10.1007/s10519-005-9017-8}, journal = {Behavior Genetics}, month = {dec}, pages = {163-172}, title = {Differential Functional Variability of Serotonin Transporter and Monoamine Oxidase A Genes in Macaque Species Displaying Contrasting Levels of Aggression-Related Behavior}, url = {https://www.researchgate.net/profile/Bernard_Thierry/publication/7370166_Differential_Functional_Variability_of_Serotonin_Transporter_and_Monoamine_Oxidase_A_Genes_in_Macaque_Species_Displaying_Contrasting_Levels_of_Aggression-Related_Behavior/links/0deec53bd9d87443e5000000.pdf}, volume = {36}, year = {2005} }