Biomedical subjects

Martin Reuter

Publications and source records attributed to Martin Reuter.

16 recordsLinked to original sources

PubMed2006

Association between a polymorphism in the promoter region of the TPH2 gene and the personality trait of harm avoidance.

In a genetic association study the role of the -703 G/T (rs4570625) polymorphism, located in the promoter region of the tryptophan hydroxylase 2 gene (TPH2), in personality traits was investigated in a sample of 404 healthy Caucasian subjects. A significant association between harm avoidance (HA), a trait related to anxiety, and the -703 G/T polymorphism was detected supporting the findings by Gutknecht and colleagues.

Adult↗

PubMed2006

S-Citalopram in neuroendocrine challenge-tests: serotonergic responsivity in healthy male and female human participants.

The aim of the present study was to assess the usefulness of the selective serotonin-reuptake-inhibitor S-Citalopram as a serotonergic challenge probe in 24 healthy male and 24 healthy female participants. The participants received a single oral dose of 10 and 20mg of S-Citalopram in a placebo-controlled double blind crossover design. In female subjects phases of the menstrual cycle were controlled. Changes in concentrations of cortisol in saliva were used to indicate serotonergic reactivity. S-Citalopram induced a reliable dose dependent rise in cortisol concentrations. Results reveal a clear dose-response relationship in both sexes. However, in contrast to the 10mg condition the dosage of 20mg led to significantly higher cortisol levels in females, whereas no differences could be observed with respect to different phases of the menstrual cycle (follicular vs. luteal). Adverse side effects were reported only after 20mg. The results clearly indicate that the dosage of 10mg should be preferred when challenging males and females. Results will be discussed with regard to the further use of S-Citalopram in neuroendocrine challenge tests.

Adult↗

PubMed2006

Association of THR105Ile, a functional polymorphism of histamine N-methyltransferase (HNMT), with alcoholism in German Caucasians.

BACKGROUND: CNS histamine has been shown to have an inhibitory effect on reward and it is implicated in the etiology of addiction and stress. Histamine N-methyltransferase (HNMT) is believed to be the sole pathway for termination of the neurotransmitter action of histamine in mammalian brain. A common, functional polymorphism, a C314T transition in the HNMT gene, results in a Thr105Ile substitution of the protein encoded. A recent study has shown that the frequency of the Ile105 allele was significantly lower in alcoholics compared to that in non-alcoholics in Finns and Plains American Indians. Following up these results, we tested whether the Thr105Ile polymorphism was associated with alcoholism in German Caucasians. METHODS: Thr105Ile was genotyped in n=366 psychiatrically interviewed German Caucasian ICD-10 lifetime alcoholics, along with n=200 ethnically matched controls. RESULTS: No significant difference was found in the frequency of the Ile105 allele between alcoholics (0.11) and controls (0.10) (chi(2)=0.21, d.f.=1, p=0.647). Likewise, genotype distributions did not differ significantly. However, the frequency of the Ile105 allele was significantly lower in male alcoholics with a family history of alcoholism compared to that in male alcoholics without a family history of alcoholism (chi(2)=4.07, d.f.=1, p=0.044). CONCLUSIONS: In German Caucasians the association of the HNMT Thr105Ile polymorphism with alcoholism was not replicated per se, but a congruent association was found between the Ile105 allele and family history of alcoholism supporting the protective role of the Ile105 allele against alcoholism.

Adult↗

PubMed2006

Imaging gene-substance interactions: the effect of the DRD2 TaqIA polymorphism and the dopamine agonist bromocriptine on the brain activation during the anticipation of reward.

Dopamine is known as the main neurotransmitter modulating the activation of the reward system of the brain. The DRD2 TaqIA polymorphism is associated with dopamine D2 receptor density which plays an important role in the context of reward. Persons carrying an A1 allele have a lower D2 receptor density and a higher risk to show substance abuse. The present study was designed to investigate the influence of the DRD2 TaqIA polymorphism and the selective D2 receptor agonist bromociptine on the activation of the reward system by means of functional magnetic resonance imaging (fMRI). In a double-blind crossover study with 24 participants we found an increase of reward system activation from placebo to bromocriptine only in subjects carrying the A1 allele. Furthermore, only A1 carrier showed an increase of performance under bromocriptine. The results are interpreted as reflecting a specific sensitivity for dopamine agonists in persons carrying an A1 allele and may complement actual data and theories of the development of addiction disorders postulating a higher genetic risk for substance abuse in carrier of the A1 allele.

Adolescent↗

PubMed2006

Identification of first candidate genes for creativity: a pilot study.

Studies from behavioral genetics have demonstrated the high heritability of intelligence. However, the endeavor to detect the genes forming the molecular basis of intelligence has been rather unsuccessful until now. Pharmacological studies have demonstrated the influence of the dopaminergic (DA) and the serotonergic (5-HT) system on subcomponents of cognitive functioning, and first studies from molecular genetics have demonstrated that genes related to the DA metabolism are associated with mental abilities. However, candidate genes for creativity have not been identified so far. Therefore, the influence of the catechol-O-methyltransferase (locus: COMT VAL158MET) gene and the dopamine D2 receptor gene (locus: DRD2 TAQ IA) on creativity was tested in addition to a serotonergic gene, TPH1 (locus: TPH-A779C), in a sample of N = 92 healthy Caucasian subjects while controlling for intelligence. Results showed that the DRD2 gene and the TPH gene were both associated with total creativity, explaining 9% of the variance, while COMT was not related to creativity at all. With respect to the subcomponents, the A1+ allele of DRD2 was related to higher verbal creativity as compared to the A1- allele, and carriers of the A allele of TPH1 showed significantly higher scores in figural and in numeric creativity, indicating that the two gene loci discriminate between higher cortical functions according to the organization of cognitive functions in the respective hemispheres.

Adolescent↗

PubMed2005

The influence of the dopaminergic system on cognitive functioning: A molecular genetic approach.

Many pharmacological and clinical studies have demonstrated the importance of the dopaminergic (DA) system for cognitive functioning but little is known about the genetic basis of general cognitive ability that has been demonstrated to be highly heritable. Attempts to detect associations between certain gene loci and endophenotypes of general cognitive ability have turned out to be more promising. Therefore, the aim of the present study was to investigate two dopaminergic candidate genes (COMT VAL158MET and DRD2 TAQ IA) for endophenotypes of cognitive functioning i.e. attention, vigilance, interference, time estimation and sensoric and motoric reaction times. Out of a gene data bank of more than 600 healthy Caucasian participants, 96 subjects (n = 48 males and n = 48 females) were recruited according to their genotype/allele pattern, resulting in six independent groups (COMT: VAL/VAL, VAL/MET, MET/MET)x(DRD2: A1-, A1+) of n = 16 subjects each. Results showed associations of the COMT gene with attention and with time estimation but most noteworthy was an interaction effect DRD2xVAL on interference performance as measured by the STROOP-test explaining 13% of the variance. Findings suggest that a balance between DA related catabolic enzyme activity and receptor density are good predictors for the endophenotype of cognitive interference and that the COMT gene is in accordance with previous studies related to cognitive functioning.

Analysis of Variance↗

PubMed2005

Evidence for a common biological basis of the Absorption trait, hallucinogen effects, and positive symptoms: epistasis between 5-HT2a and COMT polymorphisms.

Absorption represents a disposition to experience altered states of consciousness characterized by intensively focused attention. It is correlated with hypnotic susceptibility and includes phenomena ranging from vivid perceptions and imaginations to mystical experiences. Based on the assumption that drug-induced and naturally occurring mystical experiences share common neural mechanisms, we hypothesized that Absorption is influenced by the T102C polymorphism affecting the 5-HT2a receptor, which is known to be an important target site of hallucinogens like LSD. Based on the pivotal role ascribed to the prefrontal executive control network for absorbed attention and positive symptoms in schizophrenia, it was further hypothesized that Absorption is associated with the VAL158MET polymorphism of the catechol-O-methyltransferase (COMT) gene affecting the dopaminergic neurotransmitter system. The Tellegen Absorption Scale was administered to 336 subjects (95 male, 241 female). Statistical analysis revealed that the group with the T/T genotype of the T102C polymorphism, implying a stronger binding potential of the 5-HT2a receptor, indeed had significantly higher Absorption scores (F = 10.00, P = 0.002), while no main effect was found for the COMT polymorphism. However, the interaction between T102C and COMT genotypes yielded significance (F = 3.89; P = 0.049), underlining the known functional interaction between the 5-HT and the dopaminergic system. These findings point to biological foundations of the personality trait of Absorption.

Adult↗

PubMed2005

Association of the functional catechol-O-methyltransferase VAL158MET polymorphism with the personality trait of extraversion.

Across different personality theories, there is agreement that dopamine is the neurochemical basis of extraversion. However, evidence from molecular genetics for the validity of this hypothesis is far from convincing. The functional polymorphism of the catechol-O-methyltransferase gene (COMT VAL158MET) has not been related to extraversion before, although it is a promising candidate gene locus for extraversion because of its great influence on the catabolism of dopamine. In a sample of n=363 healthy study participants, the catechol-O-methyltransferase VAL158MET polymorphism was related to extraversion and novelty seeking.Results showed a significant association between catechol-O-methyltransferase, extraversion and the subscale exploratory excitement (NS1) of novelty seeking but not with the total novelty-seeking scale supporting the psychometric analyses of the personality scales. The findings support the hypothesis that the dopamine system is involved in positive emotionality and incentive motivation, which has implications for the understanding of the neurochemical correlates of normal and psychopathological behaviors.

Adult↗

PubMed2005

Molecular genetics support Gray's personality theory: the interaction of COMT and DRD2 polymorphisms predicts the behavioural approach system.

The present study provides the first direct molecular genetics support for Gray's Reinforcement Sensitivity Theory (RST), which is one of the most influential biologically oriented personality theories. It was investigated whether the DRD2 TaqIA and the COMT polymorphisms were related to the dimensions of Gray's personality theory, as measured by the Carver and White BIS/BAS scales. In a sample of 295 healthy subjects results revealed significant DRD2xCOMT interactions (i.e. epistasis) for the total BAS scale (related to positive emotionality) and for the subscales Drive (D) and Fun Seeking (FS). High BAS scores were observed if the catabolic enzyme activity and the D2 receptor density as indicated by the two polymorphisms were in disequilibrium, i.e. in the presence of the Val-/A1- (low enzyme activity/high receptor density) or the Val+/A1+ (high enzyme activity/low receptor density) alleles. In a random subsample (n=48), it could be demonstrated that those allele combinations of COMT and DRD2 associated with high BAS scores also had significantly lower prolactin levels under resting conditions, indicating high dopamine activity, compared to those allele combinations with low BAS scores. Furthermore, two-way interactions of DRD2 TaqIAxsmoking status and of the Met allele of COMTxsmoking status on FS and Metxgender on BIS could be shown.

Adult↗

PubMed2005

Sexually dimorphic link between dopamine D2 receptor gene and neuroticism-anxiety.

Prior theory-driven research probing the association between dopaminergic candidate genes and human personality has focused on the trait of novelty seeking. Here, we examined the association between the dopamine D2 receptor (DRD2) TaqI A polymorphism and two other personality traits, neuroticism-anxiety and agentic extraversion. We found no significant associations for agentic extraversion. However, for men, but not for women, we observed a strong and specific association between low neuroticism-anxiety and the A1+ allele of the DRD2 TaqI A polymorphism across two independent samples and across two alternative personality scales. We conclude that new theoretical models are needed to account for these and other recent reports of associations between neuroticism-anxiety and brain dopamine, which cannot be interpreted within the traditional framework.

Adult↗

PubMed2005

Coursework selection: a frame of reference approach using structural equation modelling.

BACKGROUND: Choice behaviour has far-reaching consequences on students' educational careers. Previous models on course selection for example, the model of achievement-related choices (Wigfield & Eccles, 2000) and of self-efficacy theory (Bandura, 1997), stress the importance of ability perceptions (self-concept of ability) as major determinants of choice. AIM: This article suggests a model of course selection, which assumes that comparisons within an internal frame of reference (as proposed by Marsh, 1986, for the association between achievement and self-concepts) can also be applied to the association between self-concepts and course selection. It is therefore hypothesized that course selection is not only positively influenced by the self-concept with respect to the corresponding subject, but also negatively with respect to alternative subjects. Moreover, it should be tested whether the effects of previous achievement on course selection are completely mediated by the self-concepts. SAMPLE: These assumptions were empirically tested using a sample of 296 students from secondary school classes, who were specializing in, for example, chemistry or biology in the following school term. METHOD: Self-concepts and course selection were assessed via questionnaire. The postulated models were tested using a structural equation modelling approach for ordinal variables. RESULTS: The core assumption, that course selection is determined by dimensional comparisons, was supported by significant negative paths from self-concepts on the selection of non-corresponding subjects. Furthermore, the effects of previous achievement on selection were completely mediated by self-concepts. CONCLUSION: Previous models of choice behaviour should be extended, by considering not only the selected alternatives, but also the unselected ones. The finding that the influence of achievement on choice is completely mediated by self-concepts, demonstrates that subjective interpretations of previous achievement determine subsequent behaviour.

Adolescent↗

PubMed2005

Cost of illness and its predictors for Parkinson's disease in Germany.

OBJECTIVE: To prospectively evaluate the health economic burden of patients with Parkinson's disease (PD) in Germany over a 6-month observation period and to identify the predictors of these costs. STUDY DESIGN AND METHODS: Direct and indirect costs were evaluated in 145 patients with PD (mean age 67.3 +/- 9.6 years). PD patients were recruited from an outpatient department for movement disorders, a specialised PD clinic, two office-based neurologists and general practitioners, all located in Germany, and were enrolled between January and June 2000. Relevant economic data were documented in a patient diary over the 6-month period. Clinical evaluations (Unified Parkinson's Disease Rating Scale [UPDRS]) were performed at baseline and at 3 and 6 months. Costs were derived from various German medical economic resources. Costs were calculated from the perspective of healthcare and transfer payment providers and the individual patient. Indirect costs for lost productivity were also calculated. Costs are presented as means +/- standard deviation (SD). Multivariate regression analyses were performed to identify independent cost predictors. Costs are in year 2000-02 values. RESULTS: We estimated average per patient direct, indirect and total costs for the 6-month observation period. The costs from the perspective of statutory health insurance (Gesetzliche Krankenkversicherung [GKV]) consisted of direct medical costs 1370 euro +/- 3240 euro, including rehabilitation (420 euro +/- 1630 euro), hospitalisation (710 euro +/-2520 euro), outpatient treatment (40 euro +/- 30 euro), ancillary treatment (190 euro +/- 280 euro) and ambulatory diagnostic procedures (10 euro +/-30 euro). In addition, parkinsonian drug costs were 1520 euro +/-euro1250. Non-medical direct costs calculated from the GKV perspective were estimated to be euro480 +/-euro1710, which included transportation (10 euro+/- 20 euro), special equipment (420 euro +/- 1640 euro), social/home-help services (10 euro +/-110 euro) and sickness benefit (40 euro +/- 540 euro). The total medical (including drug costs) and non-medical direct costs for the GKV were 3380 euro +/- 4230 euro. Univariate predictors for GKV direct costs included occurrence of motor complications and falls, disease severity, nightmares and dementia. However, multivariate analyses only suggested disease severity and health-related quality of life as significant predictors. For nursing insurance, payments of 1330 euro +/- 2890 euro were calculated. For retirement insurance, payments were 650 euro +/- 1510 euro and there were patient (or caregiver) costs of 1490 euro +/- 2730 euro. Total indirect costs amounted to 3180 euro +/-6480 euro. CONCLUSION: According to our study, PD puts a high financial burden on society and underscores the need for further economic and medical research to optimise treatment for PD.

Aged↗

PubMed2004

Relationship between DRD4 polymorphism and lipid metabolism: what is the role of novelty seeking?

OBJECTIVE: This study examined the association of the dopamine receptor D4 (DRD4) gene polymorphism with the temperament dimension of novelty seeking (NS) on cardiovascular heart disease risk factors [the levels of high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides]. METHOD: From the ongoing population-based study of 'Cardiovascular Risk in Young Finns', 125 participants were DRD4 genotyped in 1997 and responded to the NS scale of the Temperament and Character Inventory in 2001. Their cholesterol and triglyceride concentrations were assessed in 2001. RESULTS: Having a 2- or 5-allele DRD4 polymorphism was related to high HDL cholesterol levels in men, but to low HDL cholesterol levels in women. NS was related to triglycerides in men and to LDL in women, but this was mediated by behavioral, age, and weight factors, and NS was not the underlying factor for the association between the polymorphism and lipids. CONCLUSION: Our preliminary findings suggest that there is a link between the dopaminergic receptor gene DRD4 and lipid metabolism, but this link is dependent on gender.

Adolescent↗

PubMed2004

Using Latent Mixed Markov Models for the choice of the best pharmacological treatment.

The choice of the best pharmacological treatment for an individual patient is crucial to optimize convalescence. Due to their effects on pharmacokinetics variables like gender and age are important factors when the pharmacological regimen is planned. By means of an example from anaesthesiology the usefulness of Latent Mixed Markov Models for choosing the optimal anaesthetic considering patient characteristics is demonstrated. Latent Mixed Markov models allow to predict and compare the quality of recovery from anaesthesia for different patient groups (defined by age and gender and treated with different anaesthetic regimens) in a multivariate non-parametric approach. On the basis of observed symptoms immediately after surgery and a few days later the probabilities for the respective dynamic latent status (like health or illness) and the probabilities for transition from one status to another are estimated depending on latent class membership (patient group).

Adolescent↗

PubMed2004

Do smoking intensity-related differences in vigilance indicate altered glucocorticoid receptor sensitivity?

The relationship of critical flicker fusion frequency (CFF) and a pharmacologically induced cortisol suppression by means of dexamethasone (DEX) and metyrapone (MET) was investigated during nicotine deprivation in a between-subjects design in 60 male smokers divided into light, medium and heavy smokers. DEX reduced vigilance in medium smokers and improved it in heavy smokers compared to placebo, whereas MET was more detrimental in heavy smokers. The hypothesis was put forward that the intensity of nicotine consumption is related to differences in glucocorticoid and mineralocorticoid receptor sensitivity.

Adult↗

PubMed2002

Dopamine agonist and antagonist responders as related to types of nicotine craving and facets of extraversion.

The role of dopamine (DA) in drug seeking behavior has been a matter of debate in the literature: One theory claims that DA triggers incentive motivational behavior, the other one favors the idea that DA itself is the rewarding property induced by the positive stimuli. The present experiment tries to contribute to a solution of the controversy by the approach of relating DA-associated motivational behavior to constellations of hormone response to a DA agonistic and DA antagonistic challenge performed in the same subjects and by relating their responses to different aspects of personality and smoking motivation. DA agonist (lisuride = LIS), DA antagonist (fluphenazine = FLU), and placebo (P) were applied to 36 male smokers who were deprived from smoking for 3.5 h in a balanced crossover design. Cigarette craving and prolactin (PRL) responses to the drugs were compared under the three pharmacological conditions and related to personality and smoking motivation. Results showed that PRL responder types to LIS and FLU, defined as differences from respective placebo values, emerged as pure agonist or antagonist responders in two-thirds of the cases and as mixed types in one-third. PRL-LIS responders developed more craving in the LIS condition and PRL-FLU responders when exposed to FLU. Furthermore, the first group scored high on the sensation seeking scale (SSS), which related to the concept of incentive motivation and the FLU responders high on extraversion and smoking motivation for stimulating purposes suggesting the endeavor to replace DA. Thus, evidence for the validity of both theories is proven.

Adult↗