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New developments in human neurocognition: clinical, genetic, and brain imaging correlates of impulsivity and compulsivity.

ABSTRACT: Impulsivity and compulsivity represent useful conceptualizations that involve dissociable cognitive functions, which are mediated by neuroanatomically and neurochemically distinct components of cortico-subcortical circuitry. The constructs were historically viewed as diametrically opposed, with impulsivity being associated with risk-seeking and compulsivity with harm-avoidance. However, they are increasingly recognized to be linked by shared neuropsychological mechanisms involving dysfunctional inhibition of thoughts and behaviors. In this article, we selectively review new developments in the investigation of the neurocognition of impulsivity and compulsivity in humans, in order to advance our understanding of the pathophysiology of impulsive, compulsive, and addictive disorders and indicate new directions for research.

SUBMITTER: Fineberg NA

PROVIDER: S-EPMC4113335 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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New developments in human neurocognition: clinical, genetic, and brain imaging correlates of impulsivity and compulsivity.

Fineberg Naomi A NA Chamberlain Samuel R SR Goudriaan Anna E AE Stein Dan J DJ Vanderschuren Louk J M J LJ Gillan Claire M CM Shekar Sameer S Gorwood Philip A P M PA Voon Valerie V Morein-Zamir Sharon S Denys Damiaan D Sahakian Barbara J BJ Moeller F Gerard FG Robbins Trevor W TW Potenza Marc N MN

CNS spectrums 20140201 1

Impulsivity and compulsivity represent useful conceptualizations that involve dissociable cognitive functions, which are mediated by neuroanatomically and neurochemically distinct components of cortico-subcortical circuitry. The constructs were historically viewed as diametrically opposed, with impulsivity being associated with risk-seeking and compulsivity with harm-avoidance. However, they are increasingly recognized to be linked by shared neuropsychological mechanisms involving dysfunctional ...[more]

PMID: 24512640

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Project description:BackgroundTourette syndrome (TS) is often found comorbid with other neurodevelopmental disorders across the impulsivity-compulsivity spectrum, with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) as most prevalent. This points to the possibility of a common etiological thread along an impulsivity-compulsivity continuum.MethodsInvestigating the shared genetic basis across TS, ADHD, ASD, and OCD, we undertook an evaluation of cross-disorder genetic architecture and systematic meta-analysis, integrating summary statistics from the latest genome-wide association studies (93,294 individuals, 6,788,510 markers).ResultsAs previously identified, a common unifying factor connects TS, ADHD, and ASD, while TS and OCD show the highest genetic correlation in pairwise testing among these disorders. Thanks to a more homogeneous set of disorders and a targeted approach that is guided by genetic correlations, we were able to identify multiple novel hits and regions that seem to play a pleiotropic role for the specific disorders analyzed here and could not be identified through previous studies. In the TS-ADHD-ASD genome-wide association study single nucleotide polymorphism-based and gene-based meta-analysis, we uncovered 13 genome-wide significant regions that host single nucleotide polymorphisms with a high posterior probability for association with all three studied disorders (m-value > 0.9), 11 of which were not identified in previous cross-disorder analysis. In contrast, we also identified two additional pleiotropic regions in the TS-OCD meta-analysis. Through conditional analysis, we highlighted genes and genetic regions that play a specific role in a TS-ADHD-ASD genetic factor versus TS-OCD. Cross-disorder tissue specificity analysis implicated the hypothalamus-pituitary-adrenal gland axis in TS-ADHD-ASD.ConclusionsOur work underlines the value of redefining the framework for research across traditional diagnostic categories.

Dataset Information

New developments in human neurocognition: clinical, genetic, and brain imaging correlates of impulsivity and compulsivity.

Publications

New developments in human neurocognition: clinical, genetic, and brain imaging correlates of impulsivity and compulsivity.

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