SNAP-25 Single Nucleotide Polymorphisms, Brain Morphology and Intelligence in Children With Borderline Intellectual Functioning: A Mediation Analysis.

Valeria Blasi,Elisabetta Bolognesi,Monia Cabinio,Gisella Baglio,Franca Rosa Guerini,Mario Clerici,Milena Zanzottera,Michela Zanette,Maria Paola Canevini,Mauro Walder,Cristian Ricci,Francesca Baglio

doi:10.3389/fnins.2021.715048

Valeria Blasi, Elisabetta Bolognesi + Show 10 more

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https://doi.org/10.3389/fnins.2021.715048

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Abstract

Borderline intellectual functioning (BIF) is a multifactorial condition in which both genetic and environmental factors are likely to contribute to the clinical outcome. Abnormal cortical development and lower IQ scores were shown to be correlated in BIF children, but the genetic components of this condition and their possible connection with intelligence and brain morphology have never been investigated in BIF. The synaptosomal-associated protein of 25 kD (SNAP-25) is involved in synaptic plasticity, neural maturation, and neurotransmission, affecting intellectual functioning. We investigated SNAP-25 polymorphisms in BIF and correlated such polymorphisms with intelligence and cortical thickness, using socioeconomic status and environmental stress as covariates as a good proxy of the variables that determine intellectual abilities. Thirty-three children with a diagnosis of BIF were enrolled in the study. SNAP-25 polymorphisms rs363050, rs363039, rs363043, rs3746544, and rs1051312 were analyzed by genotyping; cortical thickness was studied by MRI; intelligence was measured using the WISC-III/IV subscales; environmental stressors playing a role in neuropsychiatric development were considered as covariate factors. Results showed that BIF children carrying the rs363043(T) minor allele represented by (CT + TT) genotypes were characterized by lower performance Perceptual Reasoning Index and lower full-scale IQ scores (p = 0.04) compared to those carrying the (CC) genotype. This association was correlated with a reduced thickness of the left inferior parietal cortex (direct effect = 0.44) and of the left supramarginal gyrus (direct effect = 0.56). These results suggest a link between SNAP-25 polymorphism and intelligence with the mediation role of brain morphological features in children with BIF.

Highlights

Borderline intellectual functioning (BIF) is a condition characterized by a mental ability at the border between normal intellectual functioning and intellectual disability, with an Intellectual Quotient (IQ) within 1 and 2 standard deviations below the mean of the normal curve of the distribution of intelligence that impacts on adaptive abilities (Salvador-Carulla et al, 2013; Peltopuro et al, 2014)
Socioeconomic status, IQ evaluation scores, and synaptosomal-associated protein of 25 kD (SNAP-25) polymorphisms were similar in boys and girls; the Environmental Stress Check List (ESCL) score, on the other hand, was lower in girls compared to boys, not significantly (p = 0.3964)
We show that SNAP-25 rs363043(T) minor allele represented by (CT + that the rs3746544 (TT)) genotypes are associated with lower Perceptual Reasoning Index (PRI) scores in children with BIF; such association was found to be mediated by the left inferior parietal cortex thickness: lower thickness mediates lower PRI scores

Summary

Introduction

Borderline intellectual functioning (BIF) is a condition characterized by a mental ability at the border between normal intellectual functioning and intellectual disability, with an Intellectual Quotient (IQ) within 1 and 2 standard deviations below the mean of the normal curve of the distribution of intelligence that impacts on adaptive abilities (Salvador-Carulla et al, 2013; Peltopuro et al, 2014). Children with BIF are burdened with difficulties in school achievements due to learning difficulties in more than one executive functions domain, such as attention, concentration, planning, and inhibition of impulsive responses, as well as memory and motor skill limitations (Alloway, 2010; Vuijk et al, 2010; Salvador-Carulla et al, 2013; Peltopuro et al, 2014; Contena and Taddei, 2017). Children with BIF are at high risk of school failure and dropout (Fernell and Ek, 2010), and are more likely to develop psychiatric problems in adulthood (Douma et al, 2007; Emerson et al, 2010; Gigi et al, 2014; Hassiotis, 2015; Hassiotis et al, 2019). The negative social condition does not explain all the BIF cases and their development across the life span

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