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000154290 1001_ $$0P:(DE-2719)2812914$$aAssmann, Anne$$b0$$eFirst author
000154290 245__ $$aNeurocan genome-wide psychiatric risk variant affects explicit memory performance and hippocampal function in healthy humans.
000154290 260__ $$aOxford [u.a.]$$bWiley$$c2021
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000154290 520__ $$aAlterations of the brain extracellular matrix (ECM) can perturb the structure and function of brain networks like the hippocampus, a key region in human memory that is commonly affected in psychiatric disorders. Here, we investigated the potential effects of a genome-wide psychiatric risk variant in the NCAN gene encoding the ECM proteoglycan neurocan (rs1064395) on memory performance, hippocampal function and cortical morphology in young, healthy volunteers. We assessed verbal memory performance in two cohorts (N = 572, 302) and found reduced recall performance in risk allele (A) carriers across both cohorts. In 117 participants, we performed functional magnetic resonance imaging using a novelty-encoding task with visual scenes. Risk allele carriers showed higher false alarm rates during recognition, accompanied by inefficiently increased left hippocampal activation. To assess effects of rs1064395 on brain morphology, we performed voxel-based morphometry in 420 participants from four independent cohorts and found lower grey matter density in the ventrolateral and rostral prefrontal cortex of risk allele carriers. In silico eQTL analysis revealed that rs1064395 SNP is linked not only to increased prefrontal expression of the NCAN gene itself, but also of the neighbouring HAPLN4 gene, suggesting a more complex effect of the SNP on ECM composition. Our results suggest that the NCAN rs1064395 A allele is associated with lower hippocampus-dependent memory function, variation of prefrontal cortex structure and ECM composition. Considering the well-documented hippocampal and prefrontal dysfunction in bipolar disorder and schizophrenia, our results may reflect an intermediate phenotype by which NCAN rs1064395 contributes to disease risk.
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000154290 650_7 $$2Other$$aepisodic memory
000154290 650_7 $$2Other$$aextracellular matrix
000154290 650_7 $$2Other$$afMRI
000154290 650_7 $$2Other$$aimaging genetics
000154290 650_7 $$2Other$$avoxel-based morphometry
000154290 650_2 $$2MeSH$$aBipolar Disorder
000154290 650_2 $$2MeSH$$aBrain Mapping
000154290 650_2 $$2MeSH$$aChondroitin Sulfate Proteoglycans: genetics
000154290 650_2 $$2MeSH$$aHippocampus: diagnostic imaging
000154290 650_2 $$2MeSH$$aHippocampus: physiology
000154290 650_2 $$2MeSH$$aHumans
000154290 650_2 $$2MeSH$$aLectins, C-Type: genetics
000154290 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000154290 650_2 $$2MeSH$$aMemory
000154290 650_2 $$2MeSH$$aNerve Tissue Proteins: genetics
000154290 650_2 $$2MeSH$$aNeurocan: genetics
000154290 650_2 $$2MeSH$$aSchizophrenia
000154290 7001_ $$0P:(DE-HGF)0$$aRichter, Anni$$b1
000154290 7001_ $$0P:(DE-2719)9001467$$aSchütze, Hartmut$$b2$$udzne
000154290 7001_ $$0P:(DE-2719)9000770$$aSoch, Joram$$b3
000154290 7001_ $$0P:(DE-HGF)0$$aBarman, Adriana$$b4
000154290 7001_ $$0P:(DE-HGF)0$$aBehnisch, Gusalija$$b5
000154290 7001_ $$0P:(DE-HGF)0$$aKnopf, Lea$$b6
000154290 7001_ $$0P:(DE-HGF)0$$aRaschick, Matthias$$b7
000154290 7001_ $$0P:(DE-HGF)0$$aSchult, Annika$$b8
000154290 7001_ $$0P:(DE-HGF)0$$aWüstenberg, Torsten$$b9
000154290 7001_ $$0P:(DE-HGF)0$$aBehr, Joachim$$b10
000154290 7001_ $$0P:(DE-2719)2000005$$aDüzel, Emrah$$b11
000154290 7001_ $$0P:(DE-HGF)0$$aSeidenbecher, Constanze I$$b12
000154290 7001_ $$0P:(DE-2719)2814326$$aSchott, Björn$$b13$$eLast author
000154290 773__ $$0PERI:(DE-600)2005178-5$$a10.1111/ejn.14872$$gp. ejn.14872$$n12$$p3942-3959$$tEuropean journal of neuroscience$$v53$$x1460-9568$$y2021
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