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

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.

SUBMITTER: Blasi V

PROVIDER: S-EPMC8427043 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPoor working memory, lower IQ and maladaptive behaviour form a triple disability known to have negative effects on the academic and social development of children with borderline intellectual functioning (BIF; IQ: 70 < IQ < 85) and neuropsychiatric disorders [attention-deficit hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD)]. Treatment possibilities for these children are scarce and hardly evidence based. This study primarily investigated whether adaptive computerised working memory training (WMT) may lead to significantly more improvement on a non-trained visuospatial WM task compared with a non-adaptive control WMT (placebo) in children with BIF and neuropsychiatric disorders. As secondary outcome measures, we used the scores on several non-trained neuropsychological near-transfer and far-transfer tasks as well as behavioural measures.MethodWe conducted a triple-blind placebo-controlled randomised clinical trial in 72 children (aged 10;0-13;11 years, 53 boys, 19 girls) with BIF and comorbid neuropsychiatric disorders (ADHD = 37, ASD = 21, both = 14) that were referred to child and adolescent psychiatry care, between May 2012 and March 2019. Children completed the Dutch version of Cogmed WMT, either the adaptive training version or the non-adaptive placebo version, 25 sessions (30-45 min a day), for 5 weeks. The primary outcome measure was the score on a non-trained visuospatial working memory task. The primary outcome was measured before and directly after 5 weeks of WMT and again 6 months after training.ResultsA total of 375 children were screened for eligibility and 72 were randomised. No significantly higher levels of improvement over time were found on our primary outcome measure in the experimental WMT group compared with the placebo control WMT, nor in the secondary (near-transfer and far-transfer tasks) or tertiary (behavioural measures) outcome measures. However, this study did show changes over time for these measurements for both the experimental and placebo conditions.ConclusionsThis study was unable to document superior training effects over time of an adaptive WMT in children with BIF and neuropsychiatric disorders, compared with a placebo (non-adaptive) WMT. The objectively documented changes over time in the non-adaptive WMT arm suggest that these children with persistent impairments in WM may benefit from a structured learning environment that is associated with improvement of neurocognitive functioning and coping strategies. Further research is needed to examine which elements of cognitive training may be useful for which specific patients and to study long-term effects of training.

Project description:BackgroundThe demand for support for persons with mild intellectual disability or borderline intellectual functioning is growing rapidly. These persons often encounter individual and familial limitations that influence their human functioning, and often have difficulty coping with the demands of modern society. Although in the areas of policy, research and practice, people with mild intellectual disability or borderline intellectual functioning are generally approached as one group, important differences between them have been reported. Current support seems to be both suboptimal and insufficiently differentiated.MethodsIn this Delphi study we aimed to explore the need for appropriate and differentiated support for individuals with mild intellectual disability or borderline intellectual functioning. The study was based on five unique profiles of persons with mild intellectual disability or borderline intellectual functioning that are associated with individual and environmental variables. The opinions of expert primary caregivers, professional caregivers and scientists were analysed for potentially appropriate types of support for each of the five profiles.ResultsA total of 174 statements, divided over the five profiles, were presented to the participants. For 74 statements, consensus was reached between the expert groups. For each profile, these consensual statements represented specific items (e.g. concrete personal goals) and non-specific items (e.g. the attitude towards persons with mild intellectual disability or borderline intellectual functioning, and the coordination of health care) related to the support needs.ConclusionThis Delphi-based study generated consensual opinions contributing to a more differentiated system of support for individuals with mild intellectual disability or borderline intellectual functioning. Although these findings need additional investigation, they address actions that might enhance the support programmes for these individuals into more personalized support.

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

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