title: Complexin2 modulates working memory-related neural activity in patients with schizophrenia.
abstract: The specific contribution of risk or candidate gene variants to the complex phenotype of schizophrenia is largely unknown. Studying the effects of such variants on brain function can provide insight into disease-associated mechanisms on a neural systems level. Previous studies found common variants in the complexin2 (CPLX2) gene to be highly associated with cognitive dysfunction in schizophrenia patients. Similarly, cognitive functioning was found to be impaired in Cplx2 gene-deficient mice if they were subjected to maternal deprivation or mild brain trauma during puberty. Here, we aimed to study seven common CPLX2 single-nucleotide polymorphisms (SNPs) and their neurogenetic risk mechanisms by investigating their relationship to a schizophrenia-related functional neuroimaging intermediate phenotype. We examined functional MRI and genotype data collected from 104 patients with DSM-IV-diagnosed schizophrenia and 122 healthy controls who participated in the Mind Clinical Imaging Consortium study of schizophrenia. Seven SNPs distributed over the whole CPLX2 gene were tested for association with working memory-elicited neural activity in a frontoparietal neural network. Three CPLX2 SNPs were significantly associated with increased neural activity in the dorsolateral prefrontal cortex and intraparietal sulcus in the schizophrenia sample, but showed no association in healthy controls. Since increased working memory-related neural activity in individuals with or at risk for schizophrenia has been interpreted as 'neural inefficiency,' these findings suggest that certain variants of CPLX2 may contribute to impaired brain function in schizophrenia, possibly combined with other deleterious genetic variants, adverse environmental events, or developmental insults.
authors.affiliation: Department of Child and Adolescent Psychiatry, Faculty of Medicine Carl Gustav Carus of the Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Hass
authors.forename: Esther
authors.initials: E
authors.lastname: Walton
authors.forename: Holger
authors.initials: H
authors.lastname: Kirsten
authors.forename: Jessica
authors.initials: J
authors.lastname: Turner
authors.forename: Rick
authors.initials: R
authors.lastname: Wolthusen
authors.forename: Veit
authors.initials: V
authors.lastname: Roessner
authors.forename: Scott R
authors.initials: SR
authors.lastname: Sponheim
authors.forename: Daphne
authors.initials: D
authors.lastname: Holt
authors.forename: Randy
authors.initials: R
authors.lastname: Gollub
authors.forename: Vince D
authors.initials: VD
authors.lastname: Calhoun
authors.forename: Stefan
authors.initials: S
authors.lastname: Ehrlich
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics*; D000328:Adult; D001921:Brain / Q000098:blood supply / Q000473:pathology*; D001931:Brain Mapping; D005260:Female; D007839:Functional Laterality; D056726:Genetic Association Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000209:etiology*; D008570:Memory, Short-Term / Q000502:physiology*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D025341:Principal Component Analysis; D021641:Recognition, Psychology / Q000502:physiology; D012559:Schizophrenia / Q000150:complications / Q000235:genetics / Q000473:pathology; D055815:Young Adult
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D009419:Nerve Tissue Proteins; C095993:complexin II; D010100:Oxygen