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Giegling, I.* ; Hartmann, A.M.* ; Genius, J.* ; Konte, B.* ; Maul, S.* ; Straube, A.* ; Eggert, T.* ; Mulert, C.* ; Leicht, G.* ; Karch, S.* ; Hegerl, U.* ; Pogarell, O.* ; Hölter, S.M. ; Möller, H.J.* ; Graw, J. ; Rujescu, D.*

Polymorphisms in CRYBB2 encoding βB2-crystallin are associated with antisaccade performance and memory function.

Transl. Psychiatry 10:113 (2020)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
beta B2-crystallin (gene symbol: Crybb2/CRYBB2) was first described as a structural protein of the ocular lens before it was detected in various brain regions of the mouse, including the hippocampus and the cerebral cortex. Mutations in the mouse Crybb2 gene lead to alterations of sensorimotor gating measured as prepulse inhibition (PPI) and reduced hippocampal size, combined with an altered number of parvalbumin-positive GABAergic interneurons. Decreased PPI and alterations of parvalbumin-positive interneurons are also endophenotypes that typically occur in schizophrenia. To verify the results found in mice, we genotyped 27 single nucleotide polymorphisms (SNPs) within the CRYBB2 gene and its flanking regions and investigated different schizophrenia typical endophenotypes in a sample of 510 schizophrenia patients and 1322 healthy controls. In the case-control study, no association with schizophrenia was found. However, 3 of the 4 investigated haplotype blocks indicated a decreased CRYBB2 mRNA expression. Two of these blocks were associated with poorer antisaccade task performance and altered working memory-linked functional magnetic resonance imaging signals. For the two haplotypes associated with antisaccade performance, suggestive evidence was found with visual memory and in addition, haplotype block 4 showed a nominally significant association with reduced sensorimotor gating, measured as P50 ratio. These results were not schizophrenia-specific, but could be detected in a combined sample of patients and healthy controls. This is the first study to demonstrate the importance of beta B2-crystallin for antisaccade performance and memory function in humans and therefore provides implications for beta B2-crystallin function in the human brain.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Prepulse Inhibition; Calcium-binding; Working-memory; Schizophrenia; Heritability; Startle; Crystallin; Mutation; Deficits; Receptor
Sprache englisch
Veröffentlichungsjahr 2020
HGF-Berichtsjahr 2020
ISSN (print) / ISBN 2158-3188
e-ISSN 2158-3188
Zeitschrift Translational Psychiatry
Quellenangaben Band: 10, Heft: 1, Seiten: , Artikelnummer: 113 Supplement: ,
Verlag Nature Publishing Group
Verlagsort Macmillan Building, 4 Crinan St, London N1 9xw, England
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Developmental Genetics (IDG)
POF Topic(s) 30204 - Cell Programming and Repair
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500500-001
G-500500-002
DOI 10.1038/s41398-020-0791-0
WOS ID WOS:000529508900004
Scopus ID 85083768337
PubMed ID 32317624
Erfassungsdatum 2020-05-15
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