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

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 wit...

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Detalles Bibliográficos
Autores: Almodóvar Payá, Carmen, Guardiola Ripoll, Maria, Giralt López, Maria, Gallego, Carme, 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10459.1/83669
Acceso en línea:https://doi.org/10.3390/ijms23137456
http://hdl.handle.net/10459.1/83669
Access Level:acceso abierto
Palabra clave:NRN1
Age at onset
Functional magnetic resonance imaging (fMRI)
Schizophrenia-spectrum disorders
Working memory
Descripción
Sumario: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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