NRN1 Gene as a Potential Marker of Early-Onset Schizophrenia: Evidence from Genetic and Neuroimaging Approaches

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2022Author
Almodóvar Payá, Carmen
Guardiola Ripoll, Maria
Giralt López, Maria
Salgado Pineda, Pilar
Miret, Salvador
Salvador, Raymond
Muñoz, María J.
Lázaro, Luisa
Guerrero Pedraza, Amalia
Parellada, Mara
Carrión, María I.
Cuesta, Manuel J.
Maristany, Teresa
Sarró, Salvador
Fañanás Saura, Lourdes
Callado, Luis F.
Arias, Bárbara
Pomarol-Clotet, Edith
Fatjó-Vilas, Mar
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Almodóvar Payá, Carmen;
Guardiola Ripoll, Maria;
Giralt López, Maria;
Gallego, Carme;
Salgado Pineda, Pilar;
Miret, Salvador;
...
Fatjó-Vilas, Mar.
(2022)
.
NRN1 Gene as a Potential Marker of Early-Onset Schizophrenia: Evidence from Genetic and Neuroimaging Approaches.
International Journal of Molecular Science, 2022, vol. 23, núm. 13.
https://doi.org/10.3390/ijms23137456.
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Included in the neurotrophins family, the Neuritin 1 gene (NRN1) has emerged as an attractive candidate gene for schizophrenia (SZ) since it has been associated with the risk for the disorder and general cognitive performance. In this work, we aimed to further investigate the association of NRN1 with SZ by exploring its role on age at onset and its brain activity correlates. First, we developed two genetic association analyses using a family-based sample (80 early-onset (EO) trios (offspring onset ≤ 18 years) and 71 adult-onset (AO) trios) and an independent case-control sample (120 healthy subjects (HS), 87 EO and 138 AO patients). Second, we explored the effect of NRN1 on brain activity during a working memory task (N-back task; 39 HS, 39 EO and 39 AO; matched by age, sex and estimated IQ). Different haplotypes encompassing the same three Single Nucleotide Polymorphisms(SNPs, rs3763180-rs10484320-rs4960155) were associated with EO in the two samples (GCT, TCC and GTT). Besides, the GTT haplotype was associated with worse N-back task performance in EO and was linked to an inefficient dorsolateral prefrontal cortex activity in subjects with EO compared to HS. Our results show convergent evidence on the NRN1 association with EO both from genetic and neuroimaging approaches, highlighting the role of neurotrophins in the pathophysiology of SZ.
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International Journal of Molecular Science, 2022, vol. 23, núm. 13European research projects
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