Systematic Overestimation of Reflection Impulsivity in the Information Sampling Task: Age Dependency in Children

Pokhvisneva, Irina; Léger, Étienne; Meaney, Michael J.; Silveira, Patrícia Pelufo

doi:10.1016/j.biopsych.2016.12.027

Cited by 3 publications

(1 citation statement)

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“…P Correct is the probability that the colour chosen by the subject at the point of decision would be correct, based only on the evidence available to the subject at the time (i.e., dependent on the amount of information they had sampled). There was a recent update in the mean P Correct formula, which was endorsed by the original authors of the measure [41,42], therefore in this study we calculated and used the new mean P Correct [43]. Moreover, as we have reported differences in impulsivity levels between boys and girls in MAVAN [44], and impulsivity is highly influenced by sex [45,46], we analyzed the effect of sex as well as sex by genetic score interactions on IST.…”

Section: Methodsmentioning

confidence: 99%

A biologically-informed polygenic score identifies endophenotypes and clinical conditions associated with the insulin receptor function on specific brain regions

et al. 2019

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Background Activation of brain insulin receptors modulates reward sensitivity, inhibitory control and memory. Variations in the functioning of this mechanism likely associate with individual differences in the risk for related mental disorders (attention deficit hyperactivity disorder or ADHD, addiction, dementia), in agreement with the high co-morbidity between insulin resistance and psychopathology. These neurobiological mechanisms can be explored using genetic studies. We propose a novel, biologically informed genetic score reflecting the mesocorticolimbic and hippocampal insulin receptor-related gene networks, and investigate if it predicts endophenotypes (impulsivity, cognitive ability) in community samples of children, and psychopathology (addiction, dementia) in adults. Methods Lists of genes co-expressed with the insulin receptor in the mesocorticolimbic system or hippocampus were created. SNPs from these genes (post-clumping) were compiled in a polygenic score using the association betas described in a conventional GWAS (ADHD in the mesocorticolimbic score and Alzheimer in the hippocampal score). Across multiple samples ( n = 4502), the biologically informed, mesocorticolimbic or hippocampal specific insulin receptor polygenic scores were calculated, and their ability to predict impulsivity, risk for addiction, cognitive performance and presence of Alzheimer's disease was investigated. Findings The biologically-informed ePRS-IR score showed better prediction of child impulsivity and cognitive performance, as well as risk for addiction and Alzheimer's disease in comparison to conventional polygenic scores for ADHD, addiction and dementia. Interpretation This novel, biologically-informed approach enables the use of genomic datasets to probe relevant biological processes involved in neural function and disorders. Fund Toxic Stress Research network of the JPB Foundation, Jacobs Foundation (Switzerland), Sackler Foundation.

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Section: Methodsmentioning

confidence: 99%

A biologically-informed polygenic score identifies endophenotypes and clinical conditions associated with the insulin receptor function on specific brain regions

et al. 2019

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Birth weight and catch up growth are associated with childhood impulsivity in two independent cohorts

Silveira

Pokhvisneva

Gaudreau

et al. 2018

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Individuals born after intrauterine growth restriction (IUGR) are more impulsive towards palatable foods, but it is not clear 1) if IUGR-related impulsivity is specific for foods and solely based on response inhibition and 2) if the development of impulsivity is due to being born IUGR per se or to growing up fast in the first few years of life (catch up growth). Children were classified in the IUGR group if the birth weight ratio was below 0.85. Delta z score for BMI was used as a measure of catch up growth. In MAVAN (N = 274), impulsivity was measured by the Information Sampling Task from the Cambridge Neuropsychological Test Automated Battery (IST - CANTAB), and in GUSTO using the Sticker Delay Task (N = 327). There is a significant effect of interaction between being born IUGR and the magnitude of catch up growth on the reflection impulsivity from IST-CANTAB at 60 months, in which greater catch up growth associates with greater impulsivity in the IST fixed condition in IUGR children. The finding was reproduced in children from the GUSTO cohort using the Sticker Delay Task. We confirmed that catch up growth interacts with IUGR, having a major role in the development of impulsivity in the first years of life and influencing inhibitory control and decision making processes.

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A novel, biologically-informed polygenic score reveals role of mesocorticolimbic insulin receptor gene network on impulsivity and addiction

McCracken

Dass

Pokhvisneva

et al. 2018

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Conventional polygenic scores derived from genome-wide association studies do not reflect gene networks that code for biological functions. We present an alternative approach creating a biologically-informed polygenic score based on the insulin receptor (IR) gene networks in the mesocorticolimbic system and hippocampus that regulate reward sensitivity/inhibitory control and memory, respectively. Across multiple samples (n = 4300) our biologically-informed IR-PRS score showed better prediction of child impulsivity and cognitive performance, as well as risk for early addiction onset and Alzheimer's disease in comparison to conventional polygenic scores for ADHD, addiction and dementia. This novel, biologicallyinformed approach enables the use of genomic datasets to probe relevant biological processes involved in neural function and disorders.One Sentence Summary: A polygenic score based on genes co-expressed with the insulin receptor predicts childhood behavior and adult disease. Main Text:The co-morbidity between metabolic and neuropsychiatric disorders is well-established, but poorly understood. The high co-occurrence of several psychiatric conditions (e.g. major depression, bipolar disorder, dementia) with insulin resistance suggests a common underlying mechanism (Anderson, Freedland et al. 2001). Insulin receptors (IR) are expressed throughout the brain, in areas including the ventral tegmental area, striatum, prefrontal cortex and hippocampus. Insulin is actively transported across the blood-brain barrier, and its action on mesocorticolimbic receptors modulates synaptic plasticity in dopaminergic neurons, affecting dopamine-related behaviors such as response to reward, impulsivity and decision-making (Kullmann, Heni et al. 2016). IR location on hippocampal glutamatergic synapses suggests a role of insulin in neurotransmission, synaptic plasticity and modulation of learning and memory, while its inhibition is described in Alzheimer's disease and related animal models (Bomfim, Forny-Germano et al. 2012).Genetic studies can be a pertinent tool to investigate the neurobiological mechanisms that explain the co-morbidity between metabolic and neuropsychiatric conditions. Genome-wide association studies (GWAS) provide the basis for cumulative variants that associate with health outcomes and reflect genetic predispositions to common disorders where individual variants carry small effects. The cumulative polygenetic risk of the individual can be used to estimate risk through polygenic risk scores (PRS), by multiplying the measured number of risk alleles at a locus by the effect size of the association between a particular genotype and the outcome from the relevant GWAS study, and summing across the genome (Wray and Goddard 2010). GWAS and PRS methodologies are focused on statistically significant candidate associations between scattered loci and a certain condition or trait, not accounting for the fact that genes operate in networks, and code for precise biological functions in specific tissues. Although recent studie...

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Systematic Overestimation of Reflection Impulsivity in the Information Sampling Task: Age Dependency in Children

Cited by 3 publications

References 9 publications

A biologically-informed polygenic score identifies endophenotypes and clinical conditions associated with the insulin receptor function on specific brain regions

A biologically-informed polygenic score identifies endophenotypes and clinical conditions associated with the insulin receptor function on specific brain regions

Birth weight and catch up growth are associated with childhood impulsivity in two independent cohorts

A novel, biologically-informed polygenic score reveals role of mesocorticolimbic insulin receptor gene network on impulsivity and addiction

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