Schumann G

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 : Donepezil in Parkinson's disease dementia: a randomized, double-blind efficacy and safety study - Dubois_2012_Mov.Disord_27_1230
Author(s) : Dubois B , Tolosa E , Katzenschlager R , Emre M , Lees AJ , Schumann G , Pourcher E , Gray J , Thomas G , Swartz J , Hsu T , Moline ML
Ref : Movement Disordersord , 27 :1230 , 2012
Abstract : Parkinson's disease dementia (PDD) is associated with cholinergic deficits. This report presents an efficacy and safety study of the acetylcholinesterase inhibitor donepezil hydrochloride in PDD. PDD patients (n = 550) were randomized to donepezil (5 or 10 mg) or placebo for 24 weeks. Coprimary end points were the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Clinician's Interview-Based Impression of Change plus caregiver input (CIBIC+; global function). Secondary end points measured executive function, attention, activities of daily living (ADLs), and behavioral symptoms. Safety and tolerability were assessed. ADAS-cog mean changes from baseline to week 24 (end point) were not significant for donepezil in the intent-to-treat population by the predefined statistical model (difference from placebo: -1.45, P = .050, for 5 mg; -1.45, P = .076, for 10 mg). Alternative ADAS-cog analysis, removing the treatment-by-country interaction term from the model, revealed significant, dose-dependent benefit with donepezil (difference from placebo: -2.08, P = .002, for 5 mg; -3.31, P < .001, for 10 mg). The 10-mg group, but not the 5-mg group, had significantly better CIBIC+ scores compared with placebo (3.7 vs 3.9, P = .113, for 5 mg; 3.6 vs 3.9, P = .040, for 10 mg). Secondary end points-Mini-Mental State Exam; Delis-Kaplan Executive Function System; Brief Test of Attention, representing cognitive functions particularly relevant to PDD-showed significant benefit for both donepezil doses (P <= .007). There were no significant differences in ADLs or behavior. Adverse events were more common with donepezil but mostly mild/moderate in severity. Although the study did not achieve its predefined primary end points, it presents evidence suggesting that donepezil can improve cognition, executive function, and global status in PDD. Tolerability was consistent with the known safety profile of donepezil. (c) 2012 Movement Disorder Society.
ESTHER : Dubois_2012_Mov.Disord_27_1230
PubMedSearch : Dubois_2012_Mov.Disord_27_1230
PubMedID: 22915447