Smolka MN

References (3)

Title : Brain networks. Correlated gene expression supports synchronous activity in brain networks - Richiardi_2015_Science_348_1241
Author(s) : Richiardi J , Altmann A , Milazzo AC , Chang C , Chakravarty MM , Banaschewski T , Barker GJ , Bokde AL , Bromberg U , Buchel C , Conrod P , Fauth-Buhler M , Flor H , Frouin V , Gallinat J , Garavan H , Gowland P , Heinz A , Lemaitre H , Mann KF , Martinot JL , Nees F , Paus T , Pausova Z , Rietschel M , Robbins TW , Smolka MN , Spanagel R , Strohle A , Schumann G , Hawrylycz M , Poline JB , Greicius MD
Ref : Science , 348 :1241 , 2015
Abstract : 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.
ESTHER : Richiardi_2015_Science_348_1241
PubMedSearch : Richiardi_2015_Science_348_1241
PubMedID: 26068849

Title : Genomic architecture of human neuroanatomical diversity - Toro_2015_Mol.Psychiatry_20_1011
Author(s) : Toro R , Poline JB , Huguet G , Loth E , Frouin V , Banaschewski T , Barker GJ , Bokde A , Buchel C , Carvalho FM , Conrod P , Fauth-Buhler M , Flor H , Gallinat J , Garavan H , Gowland P , Heinz A , Ittermann B , Lawrence C , Lemaitre H , Mann K , Nees F , Paus T , Pausova Z , Rietschel M , Robbins T , Smolka MN , Strohle A , Schumann G , Bourgeron T
Ref : Mol Psychiatry , 20 :1011 , 2015
Abstract : Human brain anatomy is strikingly diverse and highly inheritable: genetic factors may explain up to 80% of its variability. Prior studies have tried to detect genetic variants with a large effect on neuroanatomical diversity, but those currently identified account for <5% of the variance. Here, based on our analyses of neuroimaging and whole-genome genotyping data from 1765 subjects, we show that up to 54% of this heritability is captured by large numbers of single-nucleotide polymorphisms of small-effect spread throughout the genome, especially within genes and close regulatory regions. The genetic bases of neuroanatomical diversity appear to be relatively independent of those of body size (height), but shared with those of verbal intelligence scores. The study of this genomic architecture should help us better understand brain evolution and disease.
ESTHER : Toro_2015_Mol.Psychiatry_20_1011
PubMedSearch : Toro_2015_Mol.Psychiatry_20_1011
PubMedID: 25224261

Title : Galantamine reduces smoking in alcohol-dependent patients: a randomized, placebo-controlled trial - Diehl_2006_Int.J.Clin.Pharmacol.Ther_44_614
Author(s) : Diehl A , Nakovics H , Croissant B , Smolka MN , Batra A , Mann K
Ref : Int J Clinical Pharmacology & Therapeutics , 44 :614 , 2006
Abstract : INTRODUCTION: The high morbidity and mortality caused by smoking highlights the importance of investigating new strategies for smoking cessation or reduction. Galantamine is an acetylcholinesterase inhibitor that increases the effect of acetylcholine (ACh). The nicotinic ACh receptor is activated via positive allosteric modulation (APL).
METHODS: We investigated whether galantamine reduces smoking by performing a 24-week randomized, placebo-controlled, multicentric clinical trial in recently detoxified alcohol-dependent patients. We included all study subjects irrespective of an intention or motivation to abstain from nicotine. Specific treatment for cessation or reduction of smoking was not provided. Smoking behavior was assessed by means of patients' diaries. The nicotine metabolite cotinine was measured to verify the number of smoked cigarettes as documented in the patient's diary.
RESULTS: 114 randomized smokers received galantamine (n = 56) or placebo (n = 58) for 12 weeks. Follow-up examinations were terminated after an additional 12 weeks without treatment. Smoking behavior did not differ between both groups at baseline. After treatment, the intention-to-treat analysis revealed significant differences with a 20% lower cumulative number of smoked cigarettes and a 15% lower number of smoking days in the galantamine group compared to placebo. The average number of smoked cigarettes per smoking day as well as the cotinine values decreased about 10%. Cotinine values showed a positive correlation with the number of documented cigarettes, validating the patients' diaries. CONCLUSION: Our tentative data indicate that galantamine reduces smoking behavior even without any additional specific intervention. We suggest introducing the term "substitution therapy" into the treatment of smoking. This result could open up a new treatment approach for groups of patients which usually have a low motivation for change.
ESTHER : Diehl_2006_Int.J.Clin.Pharmacol.Ther_44_614
PubMedSearch : Diehl_2006_Int.J.Clin.Pharmacol.Ther_44_614
PubMedID: 17190371