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Multicenter Study
. 2015 Mar;265(2):137-45.
doi: 10.1007/s00406-014-0550-4. Epub 2014 Oct 9.

Complexin2 Modulates Working Memory-Related Neural Activity in Patients With Schizophrenia

Free PMC article
Multicenter Study

Complexin2 Modulates Working Memory-Related Neural Activity in Patients With Schizophrenia

Johanna Hass et al. Eur Arch Psychiatry Clin Neurosci. .
Free PMC article


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.

Conflict of interest statement

Conflict of interest

Veit Roessner has received lecture fees from Eli Lilly, Janssen-Cilag, Medice, Novartis and was a member of advisory boards of Eli Lilly and Novartis. All other authors declare that they have no conflicts of interest.


Fig 1
Fig 1. FreeSurfer cortical parcellation of the DLPFC and IPS in the schizophrenia sample
Cortical statistical map illustrating regions of working memory-related load-dependent neural activity in the dorsolateral prefrontal cortex (anterior outline) and the intraparietal sulcus (posterior outline) in the schizophrenia sample. This map is shown on the inflated surface of the standard average subject allowing visualization of data across the entire cortical surface without interference from cortical folding.

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