ArticleEuropean archives of psychiatry and clinical neuroscience2022
A functional neuroimaging association study on the interplay between two schizophrenia genome-wide associated genes (CACNA1C and ZNF804A).
Article in European archives of psychiatry and clinical neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 5 citations in OpenAlex.
- NRN1 epistasis with BDNF and CACNA1C: mediation effects on symptom severity through neuroanatomical changes in schizophrenia.Brain structure & function · 2024Article
- Neurodevelopmental disturbances in schizophrenia: evidence from genetic and environmental factors.Journal of neural transmission (Vienna, Austria : 1996) · 2023Review
- Post-mortem gene expression of calcium channels Cav1.2 and Cav1.3 in schizophrenia.European archives of psychiatry and clinical neuroscience · 2022Article
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16 authors at 6 institutions in 3 countries.
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Abstract
The CACNA1C and the ZNF804A genes are among the most relevant schizophrenia GWAS findings. Recent evidence shows that the interaction of these genes with the schizophrenia diagnosis modulates brain functional response to a verbal fluency task. To better understand how these genes might influence the risk for schizophrenia, we aimed to study the interplay between CACNA1C and ZNF804A on working memory brain functional correlates. The analyses included functional and behavioural N-back task data (obtained from an fMRI protocol) and CACNA1C-rs1006737 and ZNF804A-rs1344706 genotypes for 78 healthy subjects and 78 patients with schizophrenia (matched for age, sex and premorbid IQ). We tested the effects of the epistasis between these genes as well as of the three-way interaction (CACNA1C × ZNAF804A × diagnosis) on working memory-associated activity (N-back: 2-back vs 1-back). We detected a significant CACNA1C × ZNAF804A interaction on working memory functional response in regions comprising the ventral caudate medially and within the left hemisphere, the superior and inferior orbitofrontal gyrus, the superior temporal pole and the ventral-anterior insula. The individuals with the GWAS-identified risk genotypes (CACNA1C-AA/AG and ZNF804A-AA) displayed a reduced working memory modulation response. This genotypic combination was also associated with opposite brain activity patterns between patients and controls. While further research will help to comprehend the neurobiological mechanisms of this interaction, our data highlight the role of the epistasis between CACNA1C and ZNF804A in the functional mechanisms underlying the pathophysiology of schizophrenia.
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