Michael N. Smolka
Dresden University of Technology
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Featured researches published by Michael N. Smolka.
The Journal of Neuroscience | 2005
Michael N. Smolka; Gunter Schumann; Jana Wrase; Sabine M. Grüsser; Herta Flor; Karl Mann; Dieter F. Braus; David Goldman; Christian Büchel; Andreas Heinz
Catechol-O-methyltransferase (COMT) degrades the catecholamine neurotransmitters dopamine, epinephrine, and norepinephrine. A functional polymorphism in the COMT gene (val158met) accounts for a fourfold variation in enzyme activity. The low-activity met158 allele has been associated with improved working memory but with higher risk for anxiety-related behaviors. Using functional magnetic resonance imaging, we assessed the effects of COMT genotype on brain activation by standardized affective visual stimuli (unpleasant, pleasant, and neutral) in 35 healthy subjects. The analysis of genotype effects was restricted to brain areas with robust activation by the task. To determine genedose effects, the number of met158 alleles (0, 1, or 2) was correlated with the blood oxygen level-dependent (BOLD) response elicited by pleasant or unpleasant stimuli compared with neutral stimuli. COMT genotype had no significant impact on brain activation by pleasant stimuli but was related to the neural response to unpleasant stimuli: reactivity to unpleasant stimuli was significantly positively correlated with the number of met158 alleles in the limbic system (left hippocampus, right amygdala, right thalamus), connected prefrontal areas (bilateral ventrolateral prefrontal cortex, right dorsolateral prefrontal cortex), and the visuospatial attention system (bilateral fusiform gyrus, left inferior parietal lobule). Genotype explained up to 38% of interindividual variance in BOLD response elicited by unpleasant stimuli. We conclude that (1) genetic variations can account for a substantial part of interindividual variance in task-related brain activation and that (2) increased limbic and prefrontal activation elicited by unpleasant stimuli in subjects with more met158 alleles might contribute to the observed lower emotional resilience against negative mood states.
Nature Neuroscience | 2012
Robert Whelan; Patricia J. Conrod; Jean-Baptiste Poline; Anbarasu Lourdusamy; Tobias Banaschewski; Gareth J. Barker; Mark A. Bellgrove; Christian Büchel; Mark Byrne; Tarrant D.R. Cummins; Mira Fauth-Bühler; Herta Flor; Jürgen Gallinat; Andreas Heinz; Bernd Ittermann; Karl Mann; Jean-Luc Martinot; Edmund C. Lalor; Mark Lathrop; Eva Loth; Frauke Nees; Tomáš Paus; Marcella Rietschel; Michael N. Smolka; Rainer Spanagel; David N. Stephens; Maren Struve; Benjamin Thyreau; Sabine Vollstaedt-Klein; Trevor W. Robbins
The impulsive behavior that is often characteristic of adolescence may reflect underlying neurodevelopmental processes. Moreover, impulsivity is a multi-dimensional construct, and it is plausible that distinct brain networks contribute to its different cognitive, clinical and behavioral aspects. As these networks have not yet been described, we identified distinct cortical and subcortical networks underlying successful inhibitions and inhibition failures in a large sample (n = 1,896) of 14-year-old adolescents. Different networks were associated with drug use (n = 1,593) and attention-deficit hyperactivity disorder symptoms (n = 342). Hypofunctioning of a specific orbitofrontal cortical network was associated with likelihood of initiating drug use in early adolescence. Right inferior frontal activity was related to the speed of the inhibition process (n = 826) and use of illegal substances and associated with genetic variation in a norepinephrine transporter gene (n = 819). Our results indicate that both neural endophenotypes and genetic variation give rise to the various manifestations of impulsive behavior.
Science | 2015
Jonas Richiardi; Andre Altmann; Anna-Clare Milazzo; Catie Chang; M. Mallar Chakravarty; Tobias Banaschewski; Gareth J. Barker; Arun L.W. Bokde; Uli Bromberg; Christian Büchel; Patricia J. Conrod; Mira Fauth-Bühler; Herta Flor; Vincent Frouin; Jürgen Gallinat; Hugh Garavan; Penny A. Gowland; Andreas Heinz; Hervé Lemaitre; Karl Mann; Jean-Luc Martinot; Frauke Nees; Tomáš Paus; Zdenka Pausova; Marcella Rietschel; Trevor W. Robbins; Michael N. Smolka; Rainer Spanagel; Andreas Ströhle; Gunter Schumann
Cooperating brain regions express similar genes When the brain is at rest, a number of distinct areas are functionally connected. They tend to be organized in networks. Richiardi et al. compared brain imaging and gene expression data to build computational models of these networks. These functional networks are underpinned by the correlated expression of a core set of 161 genes. In this set, genes coding for ion channels and other synaptic functions such as neurotransmitter release dominate. Science, this issue p. 1241 Gene expression is more similar than expected by chance in brain regions that are functionally connected. During rest, brain activity is synchronized between different regions widely distributed throughout the brain, forming functional networks. However, the molecular mechanisms supporting functional connectivity remain undefined. We show that functional brain networks defined with resting-state functional magnetic resonance imaging can be recapitulated by using measures of correlated gene expression in a post mortem brain tissue data set. The set of 136 genes we identify is significantly enriched for ion channels. Polymorphisms in this set of genes significantly affect resting-state functional connectivity in a large sample of healthy adolescents. Expression levels of these genes are also significantly associated with axonal connectivity in the mouse. The results provide convergent, multimodal evidence that resting-state functional networks correlate with the orchestrated activity of dozens of genes linked to ion channel activity and synaptic function.
American Journal of Psychiatry | 2011
Jan Peters; Uli Bromberg; Sophia Schneider; Stefanie Brassen; Mareike M. Menz; Tobias Banaschewski; Patricia J. Conrod; Herta Flor; Jürgen Gallinat; Hugh Garavan; Andreas Heinz; Bernd Itterman; Mark Lathrop; Jean-Luc Martinot; Tomáš Paus; Jean-Baptiste Poline; Trevor W. Robbins; Marcella Rietschel; Michael N. Smolka; Andreas Ströhle; Maren Struve; Eva Loth; Gunter Schumann; Christian Büchel
OBJECTIVE Adolescents are particularly vulnerable to addiction, and in the case of smoking, this often leads to long-lasting nicotine dependence. The authors investigated a possible neural mechanism underlying this vulnerability. METHOD Functional MRI was performed during reward anticipation in 43 adolescent smokers and 43 subjects matched on age, gender, and IQ. The authors also assessed group differences in novelty seeking, impulsivity, and reward delay discounting. RESULTS In relation to the comparison subjects, the adolescent smokers showed greater reward delay discounting and higher scores for novelty seeking. Neural responses in the ventral striatum during reward anticipation were significantly lower in the smokers than in the comparison subjects, and in the smokers this response was correlated with smoking frequency. Notably, the lower response to reward anticipation in the ventral striatum was also observed in smokers (N=14) who had smoked on fewer than 10 occasions. CONCLUSIONS The present findings suggest that a lower response to reward anticipation in the ventral striatum may be a vulnerability factor for the development of early nicotine use.
Nature | 2014
Robert Whelan; Richard Watts; Catherine Orr; Robert R. Althoff; Eric Artiges; Tobias Banaschewski; Gareth J. Barker; Arun L.W. Bokde; Christian Büchel; Fabiana Carvalho; Patricia J. Conrod; Herta Flor; Mira Fauth-Bühler; Vincent Frouin; Juergen Gallinat; Gabriela Gan; Penny A. Gowland; Andreas Heinz; Bernd Ittermann; Claire Lawrence; Karl Mann; Jean-Luc Martinot; Frauke Nees; Nick Ortiz; Marie-Laure Paillère-Martinot; Tomáš Paus; Zdenka Pausova; Marcella Rietschel; Trevor W. Robbins; Michael N. Smolka
A comprehensive account of the causes of alcohol misuse must accommodate individual differences in biology, psychology and environment, and must disentangle cause and effect. Animal models can demonstrate the effects of neurotoxic substances; however, they provide limited insight into the psycho-social and higher cognitive factors involved in the initiation of substance use and progression to misuse. One can search for pre-existing risk factors by testing for endophenotypic biomarkers in non-using relatives; however, these relatives may have personality or neural resilience factors that protect them from developing dependence. A longitudinal study has potential to identify predictors of adolescent substance misuse, particularly if it can incorporate a wide range of potential causal factors, both proximal and distal, and their influence on numerous social, psychological and biological mechanisms. Here we apply machine learning to a wide range of data from a large sample of adolescents (n = 692) to generate models of current and future adolescent alcohol misuse that incorporate brain structure and function, individual personality and cognitive differences, environmental factors (including gestational cigarette and alcohol exposure), life experiences, and candidate genes. These models were accurate and generalized to novel data, and point to life experiences, neurobiological differences and personality as important antecedents of binge drinking. By identifying the vulnerability factors underlying individual differences in alcohol misuse, these models shed light on the aetiology of alcohol misuse and suggest targets for prevention.
Archives of General Psychiatry | 2012
Anne Beck; Alexander Genauck; Jana Wrase; Florian Schlagenhauf; Michael N. Smolka; Karl Mann; Andreas Heinz
CONTEXT In alcohol-dependent patients, brain atrophy and functional brain activation elicited by alcohol-associated stimuli may predict relapse. However, to date, the interaction between both factors has not been studied. OBJECTIVE To determine whether results from structural and functional magnetic resonance imaging are associated with relapse in detoxified alcohol-dependent patients. DESIGN A cue-reactivity functional magnetic resonance experiment with alcohol-associated and neutral stimuli. After a follow-up period of 3 months, the group of 46 detoxified alcohol-dependent patients was subdivided into 16 abstainers and 30 relapsers. SETTING Faculty for Clinical Medicine Mannheim at the University of Heidelberg, Germany. PARTICIPANTS A total of 46 detoxified alcohol-dependent patients and 46 age- and sex-matched healthy control subjects MAIN OUTCOME MEASURES Local gray matter volume, local stimulus-related functional magnetic resonance imaging activation, joint analyses of structural and functional data with Biological Parametric Mapping, and connectivity analyses adopting the psychophysiological interaction approach. RESULTS Subsequent relapsers showed pronounced atrophy in the bilateral orbitofrontal cortex and in the right medial prefrontal and anterior cingulate cortex, compared with healthy controls and patients who remained abstinent. The local gray matter volume-corrected brain response elicited by alcohol-associated vs neutral stimuli in the left medial prefrontal cortex was enhanced for subsequent relapsers, whereas abstainers displayed an increased neural response in the midbrain (the ventral tegmental area extending into the subthalamic nucleus) and ventral striatum. For alcohol-associated vs neutral stimuli in abstainers compared with relapsers, the analyses of the psychophysiological interaction showed a stronger functional connectivity between the midbrain and the left amygdala and between the midbrain and the left orbitofrontal cortex. CONCLUSIONS Subsequent relapsers displayed increased brain atrophy in brain areas associated with error monitoring and behavioral control. Correcting for gray matter reductions, we found that, in these patients, alcohol-related cues elicited increased activation in brain areas associated with attentional bias toward these cues and that, in patients who remained abstinent, increased activation and connectivity were observed in brain areas associated with processing of salient or aversive stimuli.
American Journal of Psychiatry | 2012
Sophia Schneider; Jan Peters; Uli Bromberg; Stefanie Brassen; Stephan F. Miedl; Tobias Banaschewski; Gareth J. Barker; Patricia J. Conrod; Herta Flor; Hugh Garavan; Andreas Heinz; Bernd Ittermann; Mark Lathrop; Eva Loth; Karl Mann; Jean-Luc Martinot; Frauke Nees; Tomáš Paus; Marcella Rietschel; Trevor W. Robbins; Michael N. Smolka; Rainer Spanagel; Andreas Ströhle; Maren Struve; Gunter Schumann; Christian Büchel
OBJECTIVE Increased risk-taking behavior has been associated with addiction, a disorder also linked to abnormalities in reward processing. Specifically, an attenuated response of reward-related areas (e.g., the ventral striatum) to nondrug reward cues has been reported in addiction. One unanswered question is whether risk-taking preference is associated with striatal reward processing in the absence of substance abuse. METHOD Functional and structural MRI was performed in 266 healthy young adolescents and in 31 adolescents reporting potentially problematic substance use. Activation during reward anticipation (using the monetary incentive delay task) and to gray matter density were measured. Risk-taking bias was assessed by the Cambridge Gamble Task. RESULTS With increasing risk-taking bias, the ventral striatum showed decreased activation bilaterally during reward anticipation. Voxel-based morphometry showed that greater risk-taking bias was also associated with and partially mediated by lower gray matter density in the same structure. The decreased activation was also observed when participants with virtually any substance use were excluded. The group with potentially problematic substance use showed greater risk taking as well as lower striatal activation relative to matched comparison subjects from the main sample. CONCLUSIONS Risk taking and functional and structural properties of the reward system in adolescents are strongly linked prior to a possible onset of substance abuse, emphasizing their potential role in the predisposition to drug abuse.
Translational Psychiatry | 2011
Simone Kühn; Alexander Romanowski; Christina Schilling; Robert C. Lorenz; Chantal Mörsen; Nina Y. Seiferth; Tobias Banaschewski; Alexis Barbot; Gareth J. Barker; Christian Büchel; Patricia J. Conrod; Jeffrey W. Dalley; Herta Flor; Hugh Garavan; Bernd Ittermann; K. Mann; J.-L. Martinot; Tomáš Paus; Marcella Rietschel; Michael N. Smolka; A Ströhle; Bernadeta Walaszek; Gunter Schumann; Andreas Heinz; Jürgen Gallinat
Video game playing is a frequent recreational activity. Previous studies have reported an involvement of dopamine-related ventral striatum. However, structural brain correlates of video game playing have not been investigated. On magnetic resonance imaging scans of 154 14-year-olds, we computed voxel-based morphometry to explore differences between frequent and infrequent video game players. Moreover, we assessed the Monetary Incentive Delay (MID) task during functional magnetic resonance imaging and the Cambridge Gambling Task (CGT). We found higher left striatal grey matter volume when comparing frequent against infrequent video game players that was negatively correlated with deliberation time in CGT. Within the same region, we found an activity difference in MID task: frequent compared with infrequent video game players showed enhanced activity during feedback of loss compared with no loss. This activity was likewise negatively correlated with deliberation time. The association of video game playing with higher left ventral striatum volume could reflect altered reward processing and represent adaptive neural plasticity.
American Journal of Psychiatry | 2011
Li Dong; Ainhoa Bilbao; Manfred Laucht; Richard Henriksson; Tatjana Yakovleva; Monika Ridinger; Sylvane Desrivières; Toni-Kim Clarke; Anbarasu Lourdusamy; Michael N. Smolka; Sven Cichon; Dorothea Blomeyer; Stéphanie Perreau-Lenz; Stephanie H. Witt; Fernando Leonardi-Essmann; Norbert Wodarz; Peter Zill; Michael Soyka; Urs Albrecht; Marcella Rietschel; Mark Lathrop; Georgy Bakalkin; Rainer Spanagel; Gunter Schumann
OBJECTIVE Circadian and stress-response systems mediate environmental changes that affect alcohol drinking. Psychosocial stress is an environmental risk factor for alcohol abuse. Circadian rhythm gene period 1 (Per1) is targeted by stress hormones and is transcriptionally activated in corticotropin releasing factor-expressing cells. The authors hypothesized that Per1 is involved in integrating stress response and circadian rhythmicity and explored its relevance to alcohol drinking. METHOD In mice, the effects of stress on ethanol intake in mPer1-mutant and wild-type mice were assessed. In humans, single nucleotide polymorphisms (SNPs) in hPer1 were tested for association with alcohol drinking behavior in 273 adolescents and an adult case-control sample of 1,006 alcohol-dependent patients and 1,178 comparison subjects. In vitro experiments were conducted to measure genotype-specific expression and transcription factor binding to hPer1. RESULTS The mPer1-mutant mice showed enhanced alcohol consumption in response to social defeat stress relative to their wild-type littermates. An association with the frequency of heavy drinking in adolescents with the hPer1 promoter SNP rs3027172 and with psychosocial adversity was found. There was significant interaction between the rs3027172 genotype and psychosocial adversity on this drinking measure. In a confirmatory analysis, association of hPer1 rs3027172 with alcohol dependence was shown. Cortisol-induced transcriptional activation of hPer1 was reduced in human B-lymphoblastoid cells carrying the risk genotype of rs3027172. Binding affinity of the transcription factor Snail1 to the risk allele of the hPer1 SNP rs3027172 was also reduced. CONCLUSIONS The findings indicate that the hPer1 gene regulates alcohol drinking behavior during stressful conditions and provide evidence for underlying neurobiological mechanisms.
Neuropsychopharmacology | 2012
Frauke Nees; Jelka Tzschoppe; Christopher J. Patrick; Sabine Vollstädt-Klein; Sabina Steiner; Luise Poustka; Tobias Banaschewski; Gareth J. Barker; Christian Büchel; Patricia J. Conrod; Hugh Garavan; Andreas Heinz; Jürgen Gallinat; Mark Lathrop; Karl Mann; Eric Artiges; Tomáš Paus; Jean-Baptiste Poline; Trevor W. Robbins; Marcella Rietschel; Michael N. Smolka; Rainer Spanagel; Maren Struve; Eva Loth; Gunter Schumann; Herta Flor
Individual variation in reward sensitivity may have an important role in early substance use and subsequent development of substance abuse. This may be especially important during adolescence, a transition period marked by approach behavior and a propensity toward risk taking, novelty seeking and alteration of the social landscape. However, little is known about the relative contribution of personality, behavior, and brain responses for prediction of alcohol use in adolescents. In this study, we applied factor analyses and structural equation modeling to reward-related brain responses assessed by functional magnetic resonance imaging during a monetary incentive delay task. In addition, novelty seeking, sensation seeking, impulsivity, extraversion, and behavioral measures of risk taking were entered as predictors of early onset of drinking in a sample of 14-year-old healthy adolescents (N=324). Reward-associated behavior, personality, and brain responses all contributed to alcohol intake with personality explaining a higher proportion of the variance than behavior and brain responses. When only the ventral striatum was used, a small non-significant contribution to the prediction of early alcohol use was found. These data suggest that the role of reward-related brain activation may be more important in addiction than initiation of early drinking, where personality traits and reward-related behaviors were more significant. With up to 26% of explained variance, the interrelation of reward-related personality traits, behavior, and neural response patterns may convey risk for later alcohol abuse in adolescence, and thus may be identified as a vulnerability factor for the development of substance use disorders.