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Jochen Mutschler,
Elvira Abbruzzese,
Klaus Wiedemann,
Christoph von der Goltz,
Christina Dinter,
Arian Mobascher,
Holger Thiele, Amalia Diaz-Lacava,
Norbert Dahmen,
Jürgen Gallinat, [......],
Nadine Petrovsky,
Norbert Thuerauf,
Johannes Kornhuber,
Gerhard Gründer,
Lena Rademacher,
Juergen Brinkmeyer,
Thomas Wienker,
Michael Wagner,
Georg Winterer,
Falk Kiefer
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ABSTRACT: Objective: The neuropeptide-Y (NP-Y) gene is a strong candidate gene in the pathophysiology of obesity-linked behavior, and several single-nucleotide polymorphisms of NP-Y have already been linked to body weight and appetite. However, the results from current studies remain inconclusive. The aim of the present study was to test whether a certain functional genetic variant (SNP rs16147) in the NP-Y promoter gene is associated with serum leptin levels and body fat distribution. Method: We genotyped and measured the serum leptin levels of the NP-Y rs16147 polymorphism in 1,097 Caucasian subjects in the context of a population-based, case-control multicenter study. We measured weight, height and waist circumference, from which we then calculated BMI and waist-to-hip ratio (WHR). Results: We found the CT-genotype of the SNP rs16147 to be significantly associated with lower WHRs and higher serum leptin levels in women, compared to homozygote gene carriers. No association between rs16147, WHR and serum leptin levels was found in men. Conclusion: Our results provide evidence that the functionally relevant SNP in the NP-Y promoter gene affects body fat distribution and serum leptin levels in women, pointing towards possible behavioral effects of NPY in obesity.
Annals of Nutrition and Metabolism 05/2013; 62(4):271-276. · 2.26 Impact Factor
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Jochen Mutschler,
Elvira Abbruzzese,
Christoph von der Goltz,
Christina Dinter,
Arian Mobascher,
Holger Thiele, Amalia Diaz-Lacava,
Norbert Dahmen,
Jürgen Gallinat,
Tomislav Majic,
Nadine Petrovsky,
Norbert Thuerauf,
Johannes Kornhuber,
Gerhard Gründer,
Lena Rademacher,
Juergen Brinkmeyer,
Thomas Wienker,
Michael Wagner,
Georg Winterer,
Falk Kiefer
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ABSTRACT: BACKGROUND: The catechol-O-methyltransferase (COMT) modulates dopaminergic neurotransmission in the prefrontal cortex as well as in the mesolimbic reward system. Since the reward system mediates addictive behavior, the COMT gene is a strong candidate gene regarding the pathophysiology of tobacco dependence and smoking behavior. Because of rather conflicting results in previous studies, the purpose of the present study was to test for association between a functional genetic variant in the COMT gene (single nucleotide polymorphism [SNP] rs4680) and tobacco smoking behavior. METHODS: In a population-based case-control multicenter study designed for tobacco addiction research, a total of 551 current smokers of European ancestry and 548 age-matched healthy volunteers (never-smokers) were genotyped for SNP rs4680 and extensively characterized concerning their smoking behavior. RESULTS: We found no association between smoking status and SNP rs4680 genotype nor did we find a significant association to the degree of tobacco dependence. CONCLUSIONS: Although prefrontal cortical and ventral striatal activity are highly relevant for addictive behavior, and under partial control of COMT rs4680 genotype, no association between COMT and smoking behavior was observed. Other genetic variants may account for the high heritability of behavioral smoking phenotypes.
Nicotine & Tobacco Research 01/2013; · 2.58 Impact Factor
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Stefan Cohrs,
Andrea Rodenbeck,
Dieter Riemann,
Bertram Szagun,
Andreas Jaehne,
Jürgen Brinkmeyer,
Gerhard Gründer,
Thomas Wienker, Amalia Diaz-Lacava,
Arian Mobascher,
Norbert Dahmen,
Norbert Thuerauf,
Johannes Kornhuber,
Falk Kiefer,
Jürgen Gallinat,
Michael Wagner,
Dieter Kunz,
Ulrike Grittner,
Georg Winterer
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ABSTRACT: Cigarette smoking is a severe health burden being related to a number of chronic diseases. Frequently, smokers report about sleep problems. Sleep disturbance, in turn, has been demonstrated to be involved in the pathophysiology of several disorders related to smoking and may be relevant for the pathophysiology of nicotine dependence. Therefore, determining the frequency of sleep disturbance in otherwise healthy smokers and its association with degree of nicotine dependence is highly relevant. In a population-based case-control study, 1071 smokers and 1243 non-smokers without lifetime Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Axis I disorder were investigated. Sleep quality (SQ) of participants was determined by the Pittsburgh Sleep Quality Index. As possible confounders, age, sex and level of education and income, as well as depressiveness, anxiety, attention deficit hyperactivity, alcohol drinking behaviour and perceived stress, were included into multiple regression analyses. Significantly more smokers than non-smokers (28.1% versus 19.1%; P < 0.0001) demonstrated a disturbed global SQ. After controlling for the confounders, impaired scores in the component scores of sleep latency, sleep duration and global SQ were found significantly more often in smokers than non-smokers. Consistently, higher degrees of nicotine dependence and intensity of smoking were associated with shorter sleep duration. This study demonstrates for the first time an elevated prevalence of sleep disturbance in smokers compared with non-smokers in a population without lifetime history of psychiatric disorders even after controlling for potentially relevant risk factors. It appears likely that smoking is a behaviourally modifiable risk factor for the occurrence of impaired SQ and short sleep duration.
Addiction Biology 08/2012; · 4.83 Impact Factor
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Jochen Mutschler,
Elvira Abbruzzese,
Christoph von der Goltz,
Christina Dinter,
Arian Mobascher,
Holger Thiele, Amalia Diaz-Lacava,
Norbert Dahmen,
Jürgen Gallinat,
Tomislav Majic,
Nadine Petrovsky,
Johannes Kornhuber,
Norbert Thuerauf,
Gerhard Gründer,
Jürgen Brinkmeyer,
Thomas Wienker,
Michael Wagner,
Georg Winterer,
Falk Kiefer
[show abstract]
[hide abstract]
ABSTRACT: Neuropeptide Y (NPY) is a strong candidate gene regarding the pathophysiology of tobacco dependence. It has been associated with various addictive and psychiatric disorders, and closely interacts with the brain reward system. The aim of the present study was to test for association between a functional genetic variant in the NP-Y promoter gene (SNP rs16147) and tobacco smoking.
In a population-based case-control multicenter study designed for tobacco addiction research, a total of 550 Caucasian current smokers, and 544 never-smokers were genotyped for SNP rs16147 and behaviorally characterized with the State-Trait Anxiety Inventory (STAI).
Subjects with TT genotype of the SNP rs16147 were significantly more frequently smokers than never-smokers (p = 0.046). In addition, TT genotype exhibited increased state anxiety scores compared to carriers of the C allele (p = 0.037).
Our results provide evidence for an involvement of the functionally relevant SNP rs16147 in the pathophysiology of tobacco dependence. Further studies are needed to confirm our findings.
European Addiction Research 05/2012; 18(5):246-52. · 2.53 Impact Factor
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Boris B Quednow,
Jürgen Brinkmeyer,
Arian Mobascher,
Michael Nothnagel,
Francesco Musso,
Gerhard Gründer,
Noah Savary,
Nadine Petrovsky,
Ingo Frommann,
Leonhard Lennertz, [......],
Tomislav Majic,
Rainald Mössner,
Wolfgang Maier,
Jürgen Gallinat, Amalia Diaz-Lacava,
Mohammad R Toliat,
Holger Thiele,
Peter Nürnberg,
Michael Wagner,
Georg Winterer
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ABSTRACT: Several polymorphisms of the transcription factor 4 (TCF4) have been shown to increase the risk for schizophrenia, particularly TCF4 rs9960767. This polymorphism is associated with impaired sensorimotor gating measured by prepulse inhibition--an established endophenotype of schizophrenia. We therefore investigated whether TCF4 polymorphisms also affect another proposed endophenotype of schizophrenia, namely sensory gating assessed by P50 suppression of the auditory evoked potential. Although sensorimotor gating and sensory gating are not identical, recent data suggest that they share genetic fundamentals. In a multicenter study at six academic institutions throughout Germany, we applied an auditory P50 suppression paradigm to 1,821 subjects (1,023 never-smokers, 798 smokers) randomly selected from the general population. Samples were genotyped for 21 TCF4 polymorphisms. Given that smoking is highly prevalent in schizophrenia and affects sensory gating, we also assessed smoking behavior, cotinine plasma concentrations, exhaled carbon monoxide, and the Fagerström Test (FTND). P50 suppression was significantly decreased in carriers of schizophrenia risk alleles of the TCF4 polymorphisms rs9960767, rs10401120rs, rs17597926, and 17512836 (P < 0.0002-0.00005). These gene effects were modulated by smoking behavior as indicated by significant interactions of TCF4 genotype and smoking status; heavy smokers (FTND score ≥ 4) showed stronger gene effects on P50 suppression than light smokers and never-smokers. Our finding suggests that sensory gating is modulated by an interaction of TCF4 genotype with smoking, and both factors may play a role in early information processing deficits also in schizophrenia. Consequently, considering smoking behavior may facilitate the search for genetic risk factors for schizophrenia.
Proceedings of the National Academy of Sciences 03/2012; 109(16):6271-6. · 9.68 Impact Factor
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Michael Wagner,
Svenja Schulze-Rauschenbach,
Nadine Petrovsky,
Juergen Brinkmeyer,
Christoph von der Goltz,
Gerd Gründer,
Katja N Spreckelmeyer,
Thomas Wienker, Amalia Diaz-Lacava,
Arian Mobascher,
Norbert Dahmen,
Marion Clepce,
Norbert Thuerauf,
Falk Kiefer,
J Walter de Millas,
Jürgen Gallinat,
Georg Winterer
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ABSTRACT: The aim of the present study was to examine neurocognitive function associated with chronic nicotine use. A total of 2163 healthy participants (1002 smokers, 1161 never-smoking controls) participated in a population-based case-control design. The main outcome measures were six cognitive domain factors derived from a neuropsychological test battery. In smokers, the battery was administered after controlled smoking of one cigarette. Analyses included age, sex and education as covariates. Results demonstrated small, but significant deficits in smokers for visual attention (P < 0.001) and cognitive impulsivity (P < 0.006), while verbal episodic memory, verbal fluency, verbal working memory, and Stroop-interference did not differ between groups. These attention/impulsivity deficits were also present in smokers with only a low amount of cigarette consumption. Lifetime nicotine use (pack-years) was not correlated with cognition in smokers. In conclusion, this study confirmed subtle and specific cognitive deficits in non-deprived smokers. The independence of these deficits from consumption intensity may argue for an a priori deficit of some cognitive abilities in smokers. These specific deficits may constitute intermediate phenotypes for genetic research on nicotine use.
Addiction Biology 02/2012; · 4.83 Impact Factor
