Jürgen Gallinat

Publications (131)640.71 Total impact

• Article: Functional Polymorphism in the Neuropeptide Y Gene Promoter (rs16147) Is Associated with Serum Leptin Levels and Waist-Hip Ratio in Women.

  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
• Article: The risk variant in ODZ4 for bipolar disorder impacts on amygdala activation during reward processing.

  Angela Heinrich, Anbarasu Lourdusamy, Jelka Tzschoppe, Sabine Vollstädt-Klein, Mira Bühler, Sabina Steiner, Christiane Bach, Luise Poustka, Tobias Banaschewski, Gareth Barker, [......], Tomáš Paus, Zdenka Pausova, Michael Smolka, Andreas Ströhle, Maren Struve, Stephanie Witt, Herta Flor, Gunter Schumann, Marcella Rietschel, Frauke Nees
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  ABSTRACT: OBJECTIVES: Bipolar disorder is a severe mood disorder, which normally begins during adolescence or early adulthood and has a heritability of up to 80%. The largest genome-wide association analysis of bipolar disorder recently identified a new genome-wide associated variant in OZD4 (rs12576775). The aim of the present study was to further elucidate the role of this risk variant in the disease process using an imaging genetics approach. As increased amygdala and striatal responses during the processing of reward and emotion are characteristic for bipolar disorder patients, it was tested whether the risk variant has an influence on this endophenotype in healthy adolescents. METHODS: We examined the impact of the risk variant rs12576775 on functional magnetic resonance imaging data in an adolescent sample (N = 485). Differential activation between carriers of the risk allele (G-allele) and homozygous A-allele carriers in the amygdala and the striatum during a modification of the monetary incentive delay task (examining reward) and a face task (examining emotion) was analyzed. RESULTS: Carriers of the risk allele showed an increased blood oxygen level-dependent response in the amygdala during reward sensitivity (p = 0.05) and reward expectation (p < 0.05) but not during the face task. No significant group differences were found in the striatum during both reward and emotion processing. CONCLUSION: Our results indicate that the ODZ4 risk variant influences reward processing in the amygdala. Alterations in the processing of emotion may have different underlying mechanisms and need to be further examined.
  Bipolar Disorders 04/2013; · 5.29 Impact Factor
• Source

  Available from: Corinde E Wiers

  Article: Automatic approach bias towards smoking cues is present in smokers but not in ex-smokers.

  Corinde E Wiers, Simone Kühn, Amir Homayoun Javadi, Ozlem Korucuoglu, Reinout W Wiers, Henrik Walter, Jürgen Gallinat, Felix Bermpohl
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  ABSTRACT: RATIONALE: Drug-addicted individuals show automatic approach tendencies towards drug-related cues, i.e., an approach bias (ApB). Nevertheless, little is known about ApB in tobacco smokers and about the presence of ApB after smoking abstinence. OBJECTIVES: We investigated ApB to smoking cues in heavy tobacco smokers versus never-smokers and studied its relation to smoking characteristics and craving. Second, we compared ApBs of heavy smokers with biases of abstinent heavy smokers. METHOD: A group of current heavy smokers (n = 24), ex-smokers who were abstinent for at least 5 years (n = 20), and never-smokers (n = 20) took part in the experiment. An indirect smoking approach avoidance task was performed, in which participants were required to respond to pictures of smoking and neutral cues by pulling (approach) or pushing (avoid) on a joystick, according to the content-irrelevant format of the picture (landscape or portrait). Craving scores were examined using the Questionnaire of Smoking Urges. RESULTS: Heavy smokers showed an ApB for smoking cues compared to ex-smokers and never-smokers, which correlated positively to craving scores. There were no group differences in ApB scores for ex-smokers and never-smokers. CONCLUSION: These results suggest that ApBs for smoking cues are present in heavy smokers and decrease after long-term successful smoking cessation.
  Psychopharmacologia 04/2013; · 4.08 Impact Factor
• Article: Effects of age and sex on the concentrations of glutamate and glutamine in the human brain.

  Sven Hädel, Christoph Wirth, Michael Rapp, Jürgen Gallinat, Florian Schubert
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  ABSTRACT: PURPOSE: To determine the effects of age and sex on cerebral glutamate and glutamine concentrations in a large sample of healthy humans using a dedicated measuring and evaluation procedure. Exploratory examinations of other brain metabolites were also conducted. MATERIALS AND METHODS: In 118 healthy subjects aged 19 to 55 years (59 female) absolute concentrations of glutamate, glutamine, N-acetylaspartate (NAA), total creatine, and total choline (tCho) in voxels comprising the left hippocampus (HC) and the anterior cingulate cortex (ACC) were investigated using point-resolved spectroscopy with an echo time of 80 ms at 3 Tesla in combination with a reliable quantification procedure. Special care was taken to correct for multiple comparisons. RESULTS: An age-related decline of the concentrations of glutamate in both regions studied was observed whereas glutamine levels in ACC increased with age. Statistically significant sex-related differences were detected for glutamate in the HC and for tCho in the ACC. NAA decreased with age in both regions, the significance not surviving Bonferroni correction. CONCLUSION: The results demonstrate effects of age and gender on glutamate, glutamine, choline containing compounds, and NAA in healthy human brain. They add to the growing evidence for gender-specific differences in cerebral neurotransmission, metabolism, and structure across the lifespan. J. Magn. Reson. Imaging 2013. © 2013 Wiley Periodicals, Inc.
  Journal of Magnetic Resonance Imaging 04/2013; · 2.70 Impact Factor
• Article: From gene to brain to behavior: schizophrenia-associated variation in AMBRA1 alters impulsivity-related traits.

  Angela Heinrich, Frauke Nees, Anbarasu Lourdusamy, Jelka Tzschoppe, Sandra Meier, Sabine Vollstädt-Klein, Mira Fauth-Bühler, Sabina Steiner, Christiane Bach, Luise Poustka, [......], Tomáš Paus, Claire Lawrence, Zdenka Pausova, Michael N Smolka, Andreas Ströhle, Maren Struve, Stephanie H Witt, Gunter Schumann, Herta Flor, Marcella Rietschel
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  ABSTRACT: Recently, genome-wide association between schizophrenia and an intronic variant in AMBRA1 (rs11819869) was reported. Additionally, in a reverse genetic approach in adult healthy subjects, risk allele carriers showed a higher medial prefrontal cortex blood oxygen level-dependent (BOLD) response during a flanker task examining motor inhibition as an aspect of impulsivity. To test whether this finding can be expanded to further aspects of impulsivity, we analysed the effects of the rs11819869 genotype on impulsivity-related traits on a behavioral, temperament and neural level in a large sample of healthy adolescents. We consider this reverse genetic approach specifically suited for use in a healthy adolescent sample, as these individuals comprise those who will eventually develop mental disorders in which impulsivity is implicated. Healthy adolescents from the IMAGEN study were included in the neuropsychological analysis (n = 848) and a functional magnetic resonance imaging (fMRI) task (n = 512). Various aspects of impulsivity were assessed using the Temperament and Character Inventory-Revised, the Substance Use Risk Profile Scale, the Cambridge Cognition Neuropsychological Test Automated Battery, and the Stop Signal Task (SST) in the fMRI paradigm. On a behavioral level, increased delay aversion was observed in risk allele carriers. Furthermore, risk allele carriers showed a higher BOLD response in an orbito-frontal target region during the SST, which declined to trend status after Family Wise Error correction. Our findings support the hypothesis that the schizophrenia-related risk variant of rs11819869 is involved in various aspects of impulsivity, and that this involvement occurs on a behavioral as well as an imaging genetics level.
  European Journal of Neuroscience 04/2013; · 3.63 Impact Factor
• Article: Neural activation during processing of aversive faces predicts treatment outcome in alcoholism.

  Katrin Charlet, Florian Schlagenhauf, Anne Richter, Karina Naundorf, Lina Dornhof, Christopher E J Weinfurtner, Friederike König, Bernadeta Walaszek, Florian Schubert, Christian A Müller, Stefan Gutwinski, Annette Seissinger, Lioba Schmitz, Henrik Walter, Anne Beck, Jürgen Gallinat, Falk Kiefer, Andreas Heinz
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  ABSTRACT: Neuropsychological studies reported decoding deficits of emotional facial expressions in alcohol-dependent patients, and imaging studies revealed reduced prefrontal and limbic activation during emotional face processing. However, it remains unclear whether this reduced neural activation is mediated by alcohol-associated volume reductions and whether it interacts with treatment outcome. We combined analyses of neural activation during an aversive face-cue-comparison task and local gray matter volumes (GM) using Biological Parametric Mapping in 33 detoxified alcohol-dependent patients and 33 matched healthy controls. Alcoholics displayed reduced activation toward aversive faces-neutral shapes in bilateral fusiform gyrus [FG; Brodmann areas (BA) 18/19], right middle frontal gyrus (BA46/47), right inferior parietal gyrus (BA7) and left cerebellum compared with controls, which were explained by GM differences (except for cerebellum). Enhanced functional activation in patients versus controls was found in left rostral anterior cingulate cortex (ACC) and medial frontal gyrus (BA10/11), even after GM reduction control. Increased ACC activation correlated significantly with less (previous) lifetime alcohol intake [Lifetime Drinking History (LDH)], longer abstinence and less subsequent binge drinking in patients. High LDH appear to impair treatment outcome via its neurotoxicity on ACC integrity. Thus, high activation of the rostral ACC elicited by affective faces appears to be a resilience factor predicting better treatment outcome. Although no group differences were found, increased FG activation correlated with patients' higher LDH. Because high LDH correlated with worse task performance for facial stimuli in patients, elevated activation in the fusiform 'face' area may reflect inefficient compensatory activation. Therapeutic interventions (e.g. emotion evaluation training) may enable patients to cope with social stress and to decrease relapses after detoxification.
  Addiction Biology 03/2013; · 4.83 Impact Factor
• Article: Segregating cognitive functions within hippocampal formation: A quantitative meta-analysis on spatial navigation and episodic memory.

  Simone Kühn, Jürgen Gallinat
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  ABSTRACT: The most important cognitive domains where hippocampal formation is crucially involved are navigation and memory. Some evidence suggests that different hippocampal subregions mediate these domains. However, a quantitative meta-analysis on neuroimaging studies of spatial navigation versus memory is lacking. By means of activation likelihood estimation (ALE), we investigate concurrence of brain regions activated during spatial navigation encoding and retrieval as well as during episodic memory encoding and retrieval tasks in humans. During encoding in spatial navigation, activity was located in more posterior regions of the hippocampal formation, whereas episodic memory encoding was located in more anterior regions. Retrieval in spatial navigation was more strongly lateralized to the right compared to episodic memory retrieval. Within studies on spatial navigation retrieval, immediate recall was located more posterior and delayed recall more anterior. Overlap between concurrence of activation in spatial navigation and episodic memory was rather limited in comparison to uniquely involved regions. This argues in favor of two distinct networks, one for spatial navigation the other for episodic memory within the hippocampal formation. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.
  Human Brain Mapping 01/2013; · 5.88 Impact Factor
• Article: Lack of Association of a Functional Catechol-O-Methyltransferase Gene Polymorphism With Risk of Tobacco Smoking: Results From a Multicenter Case-Control Study.

  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
• Article: Does taste matter? How anticipation of cola brands influences gustatory processing in the brain.

  Simone Kühn, Jürgen Gallinat
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  ABSTRACT: Brands surround us everywhere in daily life. Here we investigate the influences of brand cues on gustatory processing of the same beverage. Participants were led to believe that the brand that announced the administration of a Cola mixture provided correct information about the drink to come. We found stronger fMRI signal in right mOFC during weak compared to strong brand cues in a contrast of parametric modulation with subjective liking. When directly comparing the two strong brands cues, more activation in the right amygdala was found for Coca Cola cues compared with Pepsi Cola cues. During the taste phase the same beverage elicited stronger activation in left ventral striatum when it was previously announced by a strong compared with a weak brand. This effect was stronger in participants who drink Cola infrequently and might therefore point to a stronger reliance on brand cues in less experienced consumers. The present results reveal strong effects of brand labels on neural responses signalling reward.
  PLoS ONE 01/2013; 8(4):e61569. · 4.09 Impact Factor
• Article: RASGRF2 regulates alcohol-induced reinforcement by influencing mesolimbic dopamine neuron activity and dopamine release.

  David Stacey, Ainhoa Bilbao, Matthieu Maroteaux, Tianye Jia, Alanna C Easton, Sophie Longueville, Charlotte Nymberg, Tobias Banaschewski, Gareth J Barker, Christian Büchel, [......], Michael N Smolka, Oliver Staehlin, Marjo-Riitta Jarvelin, Paul Elliott, Wolfgang H Sommer, Manuel Mameli, Christian P Müller, Rainer Spanagel, Jean-Antoine Girault, Gunter Schumann
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  ABSTRACT: The firing of mesolimbic dopamine neurons is important for drug-induced reinforcement, although underlying genetic factors remain poorly understood. In a recent genome-wide association metaanalysis of alcohol intake, we identified a suggestive association of SNP rs26907 in the ras-specific guanine-nucleotide releasing factor 2 (RASGRF2) gene, encoding a protein that mediates Ca(2+)-dependent activation of the ERK pathway. We performed functional characterization of this gene in relation to alcohol-related phenotypes and mesolimbic dopamine function in both mice and adolescent humans. Ethanol intake and preference were decreased in Rasgrf2(-/-) mice relative to WT controls. Accordingly, ethanol-induced dopamine release in the ventral striatum was blunted in Rasgrf2(-/-) mice. Recording of dopamine neurons in the ventral tegmental area revealed reduced excitability in the absence of Ras-GRF2, likely because of lack of inhibition of the I(A) potassium current by ERK. This deficit provided an explanation for the altered dopamine release, presumably linked to impaired activation of dopamine neurons firing. Functional neuroimaging analysis of a monetary incentive-delay task in 663 adolescent boys revealed significant association of ventral striatal activity during reward anticipation with a RASGRF2 haplotype containing rs26907, the SNP associated with alcohol intake in our previous metaanalysis. This finding suggests a link between the RASGRF2 haplotype and reward sensitivity, a known risk factor for alcohol and drug addiction. Indeed, follow-up of these same boys at age 16 y revealed an association between this haplotype and number of drinking episodes. Together, these combined animal and human data indicate a role for RASGRF2 in the regulation of mesolimbic dopamine neuron activity, reward response, and alcohol use and abuse.
  Proceedings of the National Academy of Sciences 12/2012; · 9.68 Impact Factor
• Article: FTO, obesity and the adolescent brain.

  Melkaye G Melka, Jesse Gillis, Manon Bernard, Michal Abrahamowicz, M Mallar Chakravarty, Gabriel T Leonard, Michel Perron, Louis Richer, Suzanne Veillette, Tobias Banaschewski, [......], Andreas Ströhle, Jürgen Gallinat, Maren Struve, Eva Lattka, Melanie Waldenberger, Gunter Schumann, Paul Pavlidis, Daniel Gaudet, Tomás Paus, Zdenka Pausova
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  ABSTRACT: Genetic variations in FTO, a well-replicated gene locus of obesity, appear to be associated also with reduced regional brain volumes in elderly. Here, we examined whether FTO is associated with total brain-volume in adolescence, thus exploring possible developmental effects of FTO. We studied a population-based sample of 598 adolescents recruited from the French-Canadian founder population in whom we measured brain volume by magnetic resonance imaging. Total fat mass was assessed with bioimpedance and body mass index was determined with anthropometry. Genotype-phenotype associations were tested with Merlin under an additive model. We found that the G allele of fto (rs9930333) was associated with higher total body fat (p=0.002) and lower brain volume (p=0.005). The same allele was also associated with higher lean body mass (p=0.03) and no difference in height (p=0.99). Principal component analysis identified a shared inverse variance between the brain volume and total body fat, which was associated with FTO at p=5.5x10(-6). These results were replicated in two independent samples of 413 and 718 adolescents; in a meta-analysis of all three samples (n=1,729 adolescents), FTO was associated with this shared inverse variance at p=1.3x10(-9). Co-expression networks analysis supported the possibility that the underlying FTO effects may occur during embryogenesis. In conclusion, FTO is associated with shared inverse variance between body adiposity and brain volume, suggesting that this gene may exert inverse effects on adipose and brain tissues. Given the completion of the overall brain growth in early childhood, these effects may have their origins during early development.
  Human Molecular Genetics 11/2012; · 7.64 Impact Factor
• Source

  Available from: Patricia J Conrod

  Dataset: Whelan et al final nn.3092[1]

  Jean-Luc Martinot, Patricia J Conrod, Herta Flor, Gunter Schumann, Jean-Baptiste Poline, Jürgen Gallinat, Mira Fauth-Bühler, Hugh Garavan, Tarrant D R Cummins, Michael N Smolka, [......], Frauke Nees, Maren Struve, Christian Büchel, Tomas Paus, Benjamin Thyreau, Marcella Rietschel, Sabine Vollstaedt-Klein, Robert Whelan, Mark A Bellgrove, Trevor W Robbins
• Article: Imitation and speech: commonalities within Broca's area.

  Simone Kühn, Marcel Brass, Jürgen Gallinat
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  ABSTRACT: The so-called embodiment of communication has attracted considerable interest. Recently a growing number of studies have proposed a link between Broca's area's involvement in action processing and its involvement in speech. The present quantitative meta-analysis set out to test whether neuroimaging studies on imitation and overt speech show overlap within inferior frontal gyrus. By means of activation likelihood estimation (ALE), we investigated concurrence of brain regions activated by object-free hand imitation studies as well as overt speech studies including simple syllable and more complex word production. We found direct overlap between imitation and speech in bilateral pars opercularis (BA 44) within Broca's area. Subtraction analyses revealed no unique localization neither for speech nor for imitation. To verify the potential of ALE subtraction analysis to detect unique involvement within Broca's area, we contrasted the results of a meta-analysis on motor inhibition and imitation and found separable regions involved for imitation. This is the first meta-analysis to compare the neural correlates of imitation and overt speech. The results are in line with the proposed evolutionary roots of speech in imitation.
  Brain Structure and Function 11/2012; · 5.63 Impact Factor
• Article: Reduced thickness of anterior cingulate cortex in obsessive-compulsive disorder.

  Simone Kühn, Christian Kaufmann, Daniela Simon, Tanja Endrass, Jürgen Gallinat, Norbert Kathmann
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  ABSTRACT: INTRODUCTION: Obsessive-compulsive disorder (OCD) is characterized by a pattern of repetitive, intrusive thoughts and behaviours that patients do not want to but feel they have to perform. Functional brain imaging revealed dysfunctional pathways in OCD involving the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and basal ganglia. Structural alterations in OCD have been discussed but analysis tools focussing on specific morphometric aspects such as cortical thickness have rarely been employed. METHODS: We acquired MRI scans from 101 OCD patients and 95 healthy control subjects. FreeSurfer analysis software was employed to model the individual grey-white and pial surfaces to compute cortical thickness as our target measure. RESULTS: Relative to controls, OCD patients demonstrate cortical thinning in dorsal and subgenual ACC (false discovery rate corrected at p < .001), as well as in several other regions within the fronto-parietal network (false discovery rate corrected at p < .05). Cortical thickness could not be predicted in whole brain analyses from symptom state, but there was a modest correlation of left dorsal ACC thickness with the obsession subscore of the Yale-Brown Obsessive-Compulsive Scale as well as with the Beck Depression Inventory score. CONCLUSIONS: The findings confirm and extend previous reports showing that OCD is associated with morphometric alterations. The location of the most robust cortical thinning in ACC regions matches the previously reported topography of functional alterations at resting state and during cognitive task execution.
  Cortex 09/2012; · 6.08 Impact Factor
• Source

  Available from: Dieter Riemann

  Article: Impaired sleep quality and sleep duration in smokers-results from the German Multicenter Study on Nicotine Dependence.

  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
• Article: Gray Matter Correlates of Posttraumatic Stress Disorder: A Quantitative Meta-Analysis.

  Simone Kühn, Jürgen Gallinat
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  ABSTRACT: BACKGROUND: Since the inception of the diagnosis posttraumatic stress disorder (PTSD), attempts have been undertaken to understand why only a subpopulation of individuals exposed to trauma develops PTSD. Cerebral gray matter reductions have been suggested to be a crucial pathobiological marker of PTSD. However, a quantitative meta-analysis of whole-brain voxel-based morphometry studies is lacking. METHODS: Here, we investigated concurrence across voxel-based morphometry studies in PTSD compared with trauma-exposed individuals without PTSD (all together nine studies with 319 subjects) by means of activation likelihood estimation. RESULTS: We identified brain regions of consistent gray matter reduction in anterior cingulate cortex, ventromedial prefrontal cortex, left temporal pole/middle temporal gyrus, and left hippocampus in PTSD patients compared with individuals exposed to trauma without PTSD. CONCLUSIONS: This is the first quantitative whole-brain meta-analysis showing brain structure deficits in traumatized subjects with PTSD compared with trauma-exposed healthy control subjects. The gray matter deficit profile overlaps with brain networks of emotion processing, fear extinction, and emotion regulation known to be affected in PTSD. Although the data cannot clarify if this is a predisposition or a consequence of the disease, the results may facilitate the need to control for structural characteristics in future functional brain studies.
  Biological psychiatry 07/2012; · 8.93 Impact Factor
• Article: Early orbitofrontal hyperactivation in obsessive-compulsive disorder.

  Tobias Lagemann, Johannes Rentzsch, Christiane Montag, Jürgen Gallinat, Maria Jockers-Scherübl, Christine Winter, Friedel Martin Reischies
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  ABSTRACT: Dysfunctional activity in the orbitofrontal cortex (OFC) is one of the core features in the pathophysiology of obsessive-compulsive disorder (OCD). Neuroimaging studies indicate orbitofrontal hyperactivation during the resting state as well as during symptom provocation, whereas orbitofrontal hypoactivation has been reported during tasks designed to dissociate specific cognitive processes. Combined magnetoencephalic and functional magnetic resonance imaging studies show early involvement of the OFC in stimulus processing in healthy subjects. However, it is unclear whether OFC activation is dysfunctional at an early stage in patients with OCD. We investigated early electrical OFC activation evoked by reward and punishment feedback in a visual probabilistic object reversal task (pORT). Patients with OCD (n=23) and healthy controls (n=27), matched for gender, age and educational level, performed the pORT during a 29-channel electroencephalographic recording. Low resolution brain electromagnetic tomography was applied to localize orbitofrontal sources of neuronal activity at 80 to 200 ms post-stimulus. Group comparison showed significantly higher orbitofrontal activation in OCD patients at 100-120 ms after the reward stimulus. No group differences were found with respect to OFC activation in response to punishment stimuli and in task performance. Results substantiate dysfunctional OFC activity at a very early stage in the processing of reward stimuli in patients with OCD. Our results provide support for the assumption that the OFC plays a more active role in the processing of visual stimuli as previously supposed. As orbitofrontal hyperactivation following rewarding feedback occurred as early as 100 ms after receipt of the visual stimulus in patients with OCD, and as we did not find any OFC dysfunction following negative feedback, our findings may point towards a specific early disturbance of reward processing in OCD. This finding might have implications for cognitive behavioural therapy of this disorder.
  Psychiatry Research 07/2012; 202(3):257-63. · 2.52 Impact Factor
• Article: Allosteric alpha-7 nicotinic receptor modulation and P50 sensory gating in schizophrenia: A proof-of-mechanism study.

  Georg Winterer, Jürgen Gallinat, Jürgen Brinkmeyer, Francesco Musso, Johannes Kornhuber, Norbert Thuerauf, Dan Rujescu, Reyna Favis, Yu Sun, Monique A Franc, Sivi Ouwerkerk-Mahadevan, Luc Janssens, Maarten Timmers, Johannes R Streffer
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  ABSTRACT: In this multicenter, double-blind, placebo-controlled, randomized, four way cross-over proof-of-mechanism study, we tested the effect of the positive allosteric α7 nicotinic acetylcholine receptor (nAChR) modulator JNJ-39393406 in a key translational assay (sensory P50 gating) in 39 regularly smoking male patients with schizophrenia. All patients were clinically stable and JNJ-39393406 was administered as an adjunct treatment to antipsychotics. No indication was found that JNJ-39393406 has the potential to reverse basic deficits of information processing in schizophrenia (sensory P50 gating) or has a significant effect on other tested electrophysiological markers (MMN, P300 and quantitative resting EEG). Sensitivity analyses including severity of disease, baseline P50 gating, medication and gene variants of the CHRNA7 gene did not reveal any subgroups with consistent significant effects. It is discussed that potential positive effects in subgroups not present or not large enough in the current study or upon chronic dosing are possible, but unlikely to be developed. This article is part of a Special Issue entitled 'Cognitive Enhancers'.
  Neuropharmacology 07/2012; 64(1):197-204. · 4.81 Impact Factor
• Article: Neurophysiological effects of cannabinoids: implications for psychosis research.

  Jurgen Gallinat, Johannes Rentzsch, Patrik Roser
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  ABSTRACT: It is widely accepted that there is a close relationship between cannabis use, the endocannabinoid system, and psychosis. In particular, cannabis use has the potential to trigger the onset of psychosis in vulnerable individuals and to exacerbate psychotic symptomatology in schizophrenia patients, including positive, negative, and cognitive symptoms. With regard to the cognitive dysfunctions as a core feature of schizophrenia, overlapping deficits in the domains of attention, memory, and executive functioning have been observed between chronic cannabis use and the disease. In this overview, we report on human clinical and experimental studies investigating the acute and chronic effects of cannabinoids on specific neurophysiological measures, i.e., the P50 suppression, the mismatch negativity, and the P300 potential, that consistently showed characteristic abnormalities in schizophrenia. Based on the results, we discuss some explanations on the putative mechanisms involving the endocannabinoid system and its interactions with other neuromodulators that might form the neural substrates underlying cannabis-induced cognitive impairments and help understand the neurobiology underpinning the development of cognitive deficits in schizophrenia.
  Current pharmaceutical design 06/2012; 18(32):4938-49. · 4.41 Impact Factor
• Article: Oxytocin and oxytocin receptor gene polymorphisms and risk for schizophrenia: A case-control study.

  Christiane Montag, Eva-Maria Brockmann, Martin Bayerl, Dan Rujescu, Daniel J Müller, Jürgen Gallinat
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  ABSTRACT: Objectives. Dysfunctions of the "social brain" belong to the core features of schizophrenia. The neurohormone oxytocin (OXT), mediated through its specific receptor (OXTR), is involved in the regulation of social behaviour and social cognition. Previous research has suggested a role of OXT system genes in disorders of social reciprocity. Preliminary evidence points to an association of peripheral OXT levels as well as OXT and OXTR gene polymorphisms with psychotic symptoms and treatment response in schizophrenia. This study aims to determine a possible contribution of OXT and OXTR genetic variations to schizophrenia susceptibility. Methods. Using n = 406 individuals diagnosed with schizophrenia according to DSM-IV and n = 406 healthy controls matched for age and gender in a case-control design, two single nucleotide polymorphisms (SNPs) within the OXT gene (rs2740204, rs2740210) and four SNPs within the OXTR gene (rs53576, rs237880, rs237885, rs237902) that were previously investigated in other studies were genotyped. Results. Chi(2)-testing suggested significant associations of OXTR SNPs rs53576(A > G) (P = 0.008) and rs237885(T > G) (P = 0.025) with a diagnosis of schizophrenia. Post-hoc ANCOVA revealed significant associations of OXTR SNPs rs53576 with general psychopathology and rs237902 with negative symptom scores in schizophrenic patients. Conclusions. Our findings support hypotheses about an involvement of oxytocinergic gene variants in schizophrenia vulnerability and warrant independent replication.
  The World Journal of Biological Psychiatry 05/2012; · 2.38 Impact Factor