ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2017
Cognitive Characterization of Schizophrenia Risk Variants Involved in Synaptic Transmission: Evidence of CACNA1C's Role in Working Memory.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 48 citations in OpenAlex.
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- Cacna1c deficiency in forebrain glutamatergic neurons alters behavior and hippocampal plasticity in female mice.Translational psychiatry · 2024Article
- L-type calcium channel regulation of depression, anxiety and anhedonia-related behavioral phenotypes following chronic stress exposure.Neuropharmacology · 2024Article
- Identification of a psychiatric risk gene NISCH at 3p21.1 GWAS locus mediating dendritic spine morphogenesis and cognitive function.BMC medicine · 2023Article
- Neurodevelopmental disturbances in schizophrenia: evidence from genetic and environmental factors.Journal of neural transmission (Vienna, Austria : 1996) · 2023Review
- L-type calcium channel regulation of dopamine activity in the ventral tegmental area to nucleus accumbens pathway: Implications for substance use, mood disorders and co-morbidities.Neuropharmacology · 2023Review
- The association of genetic variation in CACNA1C with resting-state functional connectivity in youth bipolar disorder.International journal of bipolar disorders · 2023Article
- A functional neuroimaging association study on the interplay between two schizophrenia genome-wide associated genes (CACNA1C and ZNF804A).European archives of psychiatry and clinical neuroscience · 2022Article
- Unusual Molecular Regulation of Dorsolateral Prefrontal Cortex Layer III Synapses Increases Vulnerability to Genetic and Environmental Insults in Schizophrenia.Biological psychiatry · 2022Review
- Phenotypes, mechanisms and therapeutics: insights from bipolar disorder GWAS findings.Molecular psychiatry · 2022Review
- Clustering of cognitive subtypes in schizophrenia patients and their siblings: relationship with regional brain volumes.Schizophrenia (Heidelberg, Germany) · 2022Article
- Enhanced long-term potentiation and impaired learning in mice lacking alternative exon 33 of CaTranslational psychiatry · 2022Article
- Working memory deficits in children with schizophrenia and its mechanism, susceptibility genes, and improvement: A literature review.Frontiers in psychiatry · 2022Review
- A molecular approach to treating cognition in schizophrenia by calcium channel blockade: An open-label pilot study of the calcium-channel antagonist isradipine.Schizophrenia research. Cognition · 2020Article
- Analysis of KCNH2 and CACNA1C schizophrenia risk genes on EEG functional network modulation during an auditory odd-ball task.European archives of psychiatry and clinical neuroscience · 2020Article
- Polygenic Risk Scores Shed Light on the Relationship between Schizophrenia and Cognitive Functioning: Review and Meta-Analysis.Journal of clinical medicine · 2020Article
- Genetic Variation in the Psychiatric Risk Gene CACNA1C Modulates Reversal Learning Across Species.Schizophrenia bulletin · 2019Article
- Genetic Associations between Voltage-Gated Calcium Channels and Psychiatric Disorders.International journal of molecular sciences · 2019Review
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Authors and funding
18 authors at 4 institutions in 3 countries.
Funding
Abstract
With >100 common variants associated with schizophrenia risk, establishing their biological significance is a priority. We sought to establish cognitive effects of risk variants at loci implicated in synaptic transmission by (1) identifying GWAS schizophrenia variants whose associated gene function is related to synaptic transmission, and (2) testing for association between these and measures of neurocognitive function. We selected variants, reported in the largest GWAS to date, associated with genes involved in synaptic transmission. Associations between genotype and cognitive test score were analyzed in a discovery sample (988 Irish participants, including 798 with psychosis), and replication samples (528 UK patients with schizophrenia/schizoaffective disorder; 921 German participants including 362 patients with schizophrenia). Three loci showed significant associations with neuropsychological performance in the discovery samples. This included an association between the rs2007044 (risk allele G) within CACNA1C and poorer working memory performance (increased errors B (95% CI)=0.635-4.535, p=0.012), an effect driven mainly by the psychosis groups. In an fMRI analysis of working memory performance (n=84 healthy participants, a subset of the discovery sample), we further found evidence that the same CACNA1C allele was associated with decreased functional connectivity between the right dorsolateral prefrontal cortex and right superior occipital gyrus/cuneus and anterior cingulate cortex. In conclusion, these data provide evidence to suggest that the CACNA1C risk variant rs2007044 is associated with poorer memory function that may result from risk carriers' difficulty with top-down initiated responses caused by dysconnectivity between the right DLPFC and several cortical regions.
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