001018679 001__ 1018679
001018679 005__ 20240116084325.0
001018679 0247_ $$2doi$$a10.1038/s41398-023-02344-2
001018679 0247_ $$2datacite_doi$$a10.34734/FZJ-2023-04973
001018679 0247_ $$2pmid$$a36797233
001018679 0247_ $$2WOS$$aWOS:000935891400001
001018679 037__ $$aFZJ-2023-04973
001018679 082__ $$a610
001018679 1001_ $$0P:(DE-HGF)0$$aGaebler, Arnim J.$$b0$$eCorresponding author
001018679 245__ $$aFunctional connectivity signatures of NMDAR dysfunction in schizophrenia—integrating findings from imaging genetics and pharmaco-fMRI
001018679 260__ $$aLondon$$bNature Publishing Group$$c2023
001018679 3367_ $$2DRIVER$$aarticle
001018679 3367_ $$2DataCite$$aOutput Types/Journal article
001018679 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1702473840_3807
001018679 3367_ $$2BibTeX$$aARTICLE
001018679 3367_ $$2ORCID$$aJOURNAL_ARTICLE
001018679 3367_ $$00$$2EndNote$$aJournal Article
001018679 520__ $$aBoth, pharmacological and genome-wide association studies suggest N-methyl-D-aspartate receptor (NMDAR) dysfunction and excitatory/inhibitory (E/I)-imbalance as a major pathophysiological mechanism of schizophrenia. The identification of shared fMRI brain signatures of genetically and pharmacologically induced NMDAR dysfunction may help to define biomarkers for patient stratification. NMDAR-related genetic and pharmacological effects on functional connectivity were investigated by integrating three different datasets: (A) resting state fMRI data from 146 patients with schizophrenia genotyped for the disease-associated genetic variant rs7191183 of GRIN2A (encoding the NMDAR 2 A subunit) as well as 142 healthy controls. (B) Pharmacological effects of the NMDAR antagonist ketamine and the GABA-A receptor agonist midazolam were obtained from a double-blind, crossover pharmaco-fMRI study in 28 healthy participants. (C) Regional gene expression profiles were estimated using a postmortem whole-brain microarray dataset from six healthy donors. A strong resemblance was observed between the effect of the genetic variant in schizophrenia and the ketamine versus midazolam contrast of connectivity suggestive for an associated E/I-imbalance. This similarity became more pronounced for regions with high density of NMDARs, glutamatergic neurons, and parvalbumin-positive interneurons. From a functional perspective, increased connectivity emerged between striato-pallido-thalamic regions and cortical regions of the auditory-sensory-motor network, while decreased connectivity was observed between auditory (superior temporal gyrus) and visual processing regions (lateral occipital cortex, fusiform gyrus, cuneus). Importantly, these imaging phenotypes were associated with the genetic variant, the differential effect of ketamine versus midazolam and schizophrenia (as compared to healthy controls). Moreover, the genetic variant was associated with language-related negative symptomatology which correlated with disturbed connectivity between the left posterior superior temporal gyrus and the superior lateral occipital cortex. Shared genetic and pharmacological functional connectivity profiles were suggestive of E/I-imbalance and associated with schizophrenia. The identified brain signatures may help to stratify patients with a common molecular disease pathway providing a basis for personalized psychiatry.
001018679 536__ $$0G:(DE-HGF)POF4-5252$$a5252 - Brain Dysfunction and Plasticity (POF4-525)$$cPOF4-525$$fPOF IV$$x0
001018679 588__ $$aDataset connected to DataCite
001018679 7001_ $$0P:(DE-HGF)0$$aFakour, Nilüfer$$b1
001018679 7001_ $$0P:(DE-HGF)0$$aStöhr, Felix$$b2
001018679 7001_ $$0P:(DE-HGF)0$$aZweerings, Jana$$b3
001018679 7001_ $$0P:(DE-HGF)0$$aTaebi, Arezoo$$b4
001018679 7001_ $$0P:(DE-HGF)0$$aSuslova, Mariia$$b5
001018679 7001_ $$0P:(DE-Juel1)177727$$aDukart, Jürgen$$b6$$ufzj
001018679 7001_ $$0P:(DE-HGF)0$$aHipp, Joerg F.$$b7
001018679 7001_ $$0P:(DE-HGF)0$$aAdhikari, Bhim M.$$b8
001018679 7001_ $$0P:(DE-HGF)0$$aKochunov, Peter$$b9
001018679 7001_ $$0P:(DE-HGF)0$$aMuthukumaraswamy, Suresh D.$$b10
001018679 7001_ $$0P:(DE-HGF)0$$aForsyth, Anna$$b11
001018679 7001_ $$0P:(DE-HGF)0$$aEggermann, Thomas$$b12
001018679 7001_ $$0P:(DE-HGF)0$$aKraft, Florian$$b13
001018679 7001_ $$0P:(DE-HGF)0$$aKurth, Ingo$$b14
001018679 7001_ $$0P:(DE-HGF)0$$aPaulzen, Michael$$b15
001018679 7001_ $$0P:(DE-HGF)0$$aGründer, Gerhard$$b16
001018679 7001_ $$0P:(DE-Juel1)171785$$aSchneider, Frank$$b17
001018679 7001_ $$0P:(DE-HGF)0$$aMathiak, Klaus$$b18
001018679 773__ $$0PERI:(DE-600)2609311-X$$a10.1038/s41398-023-02344-2$$gVol. 13, no. 1, p. 59$$n1$$p59$$tTranslational Psychiatry$$v13$$x2158-3188$$y2023
001018679 8564_ $$uhttps://juser.fz-juelich.de/record/1018679/files/9457_2_merged_1674735162.pdf$$yOpenAccess
001018679 8564_ $$uhttps://juser.fz-juelich.de/record/1018679/files/s41398-023-02344-2.pdf$$yOpenAccess
001018679 8564_ $$uhttps://juser.fz-juelich.de/record/1018679/files/9457_2_merged_1674735162.gif?subformat=icon$$xicon$$yOpenAccess
001018679 8564_ $$uhttps://juser.fz-juelich.de/record/1018679/files/9457_2_merged_1674735162.jpg?subformat=icon-1440$$xicon-1440$$yOpenAccess
001018679 8564_ $$uhttps://juser.fz-juelich.de/record/1018679/files/9457_2_merged_1674735162.jpg?subformat=icon-180$$xicon-180$$yOpenAccess
001018679 8564_ $$uhttps://juser.fz-juelich.de/record/1018679/files/9457_2_merged_1674735162.jpg?subformat=icon-640$$xicon-640$$yOpenAccess
001018679 8564_ $$uhttps://juser.fz-juelich.de/record/1018679/files/s41398-023-02344-2.gif?subformat=icon$$xicon$$yOpenAccess
001018679 8564_ $$uhttps://juser.fz-juelich.de/record/1018679/files/s41398-023-02344-2.jpg?subformat=icon-1440$$xicon-1440$$yOpenAccess
001018679 8564_ $$uhttps://juser.fz-juelich.de/record/1018679/files/s41398-023-02344-2.jpg?subformat=icon-180$$xicon-180$$yOpenAccess
001018679 8564_ $$uhttps://juser.fz-juelich.de/record/1018679/files/s41398-023-02344-2.jpg?subformat=icon-640$$xicon-640$$yOpenAccess
001018679 909CO $$ooai:juser.fz-juelich.de:1018679$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire
001018679 9101_ $$0I:(DE-588b)36225-6$$6P:(DE-HGF)0$$aRWTH Aachen$$b0$$kRWTH
001018679 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)177727$$aForschungszentrum Jülich$$b6$$kFZJ
001018679 9101_ $$0I:(DE-HGF)0$$6P:(DE-Juel1)177727$$a F. Hoffmann-La Roche, Pharma Research Early Development$$b6
001018679 9101_ $$0I:(DE-HGF)0$$6P:(DE-Juel1)177727$$a HHU Düsseldorf$$b6
001018679 9131_ $$0G:(DE-HGF)POF4-525$$1G:(DE-HGF)POF4-520$$2G:(DE-HGF)POF4-500$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$9G:(DE-HGF)POF4-5252$$aDE-HGF$$bKey Technologies$$lNatural, Artificial and Cognitive Information Processing$$vDecoding Brain Organization and Dysfunction$$x0
001018679 9141_ $$y2023
001018679 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
001018679 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0
001018679 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bTRANSL PSYCHIAT : 2022$$d2023-10-26
001018679 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-10-26
001018679 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-10-26
001018679 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central$$d2023-10-26
001018679 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2023-05-02T09:09:41Z
001018679 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2023-05-02T09:09:41Z
001018679 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Anonymous peer review$$d2023-05-02T09:09:41Z
001018679 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-10-26
001018679 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-10-26
001018679 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine$$d2023-10-26
001018679 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bTRANSL PSYCHIAT : 2022$$d2023-10-26
001018679 9201_ $$0I:(DE-Juel1)INM-7-20090406$$kINM-7$$lGehirn & Verhalten$$x0
001018679 980__ $$ajournal
001018679 980__ $$aVDB
001018679 980__ $$aUNRESTRICTED
001018679 980__ $$aI:(DE-Juel1)INM-7-20090406
001018679 9801_ $$aFullTexts