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Title: Complexin2 modulates working memory-related neural activity in patients with schizophrenia

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. In this paper, 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. Finally, since increased working memory-related neuralmore » 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.« less
Authors:
 [1] ;  [1] ;  [2] ;  [3] ;  [4] ;  [1] ;  [5] ;  [6] ;  [6] ;  [7] ;  [4]
  1. Faculty of Medicine Carl Gustav Carus of the Technische Univ. Dresden, Dresden (Germany)
  2. Univ. of Leipzig, Leipzig (Germany)
  3. The MIND Research Network, Albuquerque, NM (United States)
  4. Faculty of Medicine Carl Gustav Carus of the Technische Univ. Dresden, Dresden (Germany); Massachusetts General Hospital, Charlestown, MA (United States); Massachusetts General Hospital, Boston, MA (United States)
  5. Univ. of Minnesota, Minneapolis, MN (United States)
  6. Massachusetts General Hospital, Charlestown, MA (United States); Massachusetts General Hospital, Boston, MA (United States)
  7. The MIND Research Network, Albuquerque, NM (United States); Univ. of New Mexico, Albuquerque, NM (United States)
Publication Date:
Grant/Contract Number:
FG02-99ER62764; NIH/NCRR P41RR14075
Type:
Accepted Manuscript
Journal Name:
European Archives of Psychiatry and Clinical Neuroscience
Additional Journal Information:
Journal Volume: 265; Journal Issue: 2; Journal ID: ISSN 0940-1334
Research Org:
Univ. of New Mexico, Albuquerque, NM (United States); The MIND Research Network, Albuquerque, NM (United States); Massachusetts General Hospital, Boston, MA (United States)
Sponsoring Org:
USDOE Office of Science (SC); National Inst. of Health (NIH) (United States)
Contributing Orgs:
Faculty of Medicine Carl Gustav Carus of the Technische Univ. Dresden, Dresden (Germany); Univ. of Leipzig, Leipzig (Germany); Massachusetts General Hospital, Charlestown, MA (United States); Univ. of Minnesota, Minneapolis, MN (United States)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; Complexin2; imaging genetics; intermediate phenotype; working memory; frontoparietal circuit; schizophrenia
OSTI Identifier:
1343437

Hass, Johanna, Walton, Esther, Kirsten, Holger, Turner, Jessica, Wolthusen, Rick, Roessner, Veit, Sponheim, Scott R., Holt, Daphne, Gollub, Randy, Calhoun, Vince D., and Ehrlich, Stefan. Complexin2 modulates working memory-related neural activity in patients with schizophrenia. United States: N. p., Web. doi:10.1007/s00406-014-0550-4.
Hass, Johanna, Walton, Esther, Kirsten, Holger, Turner, Jessica, Wolthusen, Rick, Roessner, Veit, Sponheim, Scott R., Holt, Daphne, Gollub, Randy, Calhoun, Vince D., & Ehrlich, Stefan. Complexin2 modulates working memory-related neural activity in patients with schizophrenia. United States. doi:10.1007/s00406-014-0550-4.
Hass, Johanna, Walton, Esther, Kirsten, Holger, Turner, Jessica, Wolthusen, Rick, Roessner, Veit, Sponheim, Scott R., Holt, Daphne, Gollub, Randy, Calhoun, Vince D., and Ehrlich, Stefan. 2014. "Complexin2 modulates working memory-related neural activity in patients with schizophrenia". United States. doi:10.1007/s00406-014-0550-4. https://www.osti.gov/servlets/purl/1343437.
@article{osti_1343437,
title = {Complexin2 modulates working memory-related neural activity in patients with schizophrenia},
author = {Hass, Johanna and Walton, Esther and Kirsten, Holger and Turner, Jessica and Wolthusen, Rick and Roessner, Veit and Sponheim, Scott R. and Holt, Daphne and Gollub, Randy and Calhoun, Vince D. and Ehrlich, Stefan},
abstractNote = {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. In this paper, 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. Finally, 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.},
doi = {10.1007/s00406-014-0550-4},
journal = {European Archives of Psychiatry and Clinical Neuroscience},
number = 2,
volume = 265,
place = {United States},
year = {2014},
month = {10}
}