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      ANKK1 and TH gene variants in combination with paternal maltreatment increase susceptibility to both cognitive and attentive impulsivity

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          Abstract

          Recent scientific findings suggest that dopamine exerts a central role on impulsivity, as well as that aversive life experiences may promote the high levels of impulsivity that often underlie violent behavior. To deepen our understanding of the complex gene by environment interplay on impulsive behavior, we genotyped six dopaminergic allelic variants ( ANKK1-rs1800497, TH-rs6356, DRD4-rs1800955, DRD4-exonIII-VNTR, SLC6A3-VNTR and COMT-rs4680) in 655 US White male inmates convicted for violent crimes, whose impulsivity was assessed by BIS-11 (Barratt Impulsiveness Scale). Furthermore, in a subsample of 216 inmates from the whole group, we also explored the potential interplay between the genotyped dopaminergic variants and parental maltreatment measured by MOPS (Measure of Parental Style) in promoting impulsivity. We found a significant interaction among paternal MOPS scores, ANKK1-rs1800497-T allele and TH-rs6356-A allele, which increased the variance of BIS-11 cognitive/attentive scores explained by paternal maltreatment from 1.8 up to 20.5%. No direct association between any of the individual genetic variants and impulsivity was observed. Our data suggest that paternal maltreatment increases the risk of attentive/cognitive impulsivity and that this risk is higher in carriers of specific dopaminergic alleles that potentiate the dopaminergic neurotransmission. These findings add further evidence to the mutual role that genetics and early environmental factors exert in modulating human behavior and highlight the importance of childhood care interventions.

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          Most cited references106

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          Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement.

          Stimulant addiction is often linked to excessive risk taking, sensation seeking, and impulsivity, but in ways that are poorly understood. We report here that a form of impulsivity in rats predicts high rates of intravenous cocaine self-administration and is associated with changes in dopamine (DA) function before drug exposure. Using positron emission tomography, we demonstrated that D2/3 receptor availability is significantly reduced in the nucleus accumbens of impulsive rats that were never exposed to cocaine and that such effects are independent of DA release. These data demonstrate that trait impulsivity predicts cocaine reinforcement and that D2 receptor dysfunction in abstinent cocaine addicts may, in part, be determined by premorbid influences.
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            Psychiatric aspects of impulsivity.

            The authors discuss the relationship of impulsivity to psychiatric disorders and present selected hypotheses regarding the reasons for these relationships. Previous research has shown significantly higher levels of impulsivity among patients with conduct disorder, personality disorders, substance use disorders, and bipolar disorder, compared to other psychiatric patients or healthy comparison subjects. A literature review of the theoretical bases of the relationship between these disorders and impulsivity is presented. Measurements of impulsivity and treatment options are discussed in relation to the physiology of impulsivity and the disorders in which it is a prominent feature. Impulsivity, as defined on the basis of a biopsychosocial approach, is a key feature of several psychiatric disorders. Behavioral and pharmacological interventions that are effective for treating impulsivity should be incorporated into treatment plans for these disorders. The high comorbidity of impulsivity and selected psychiatric disorders, including personality disorders, substance use disorders, and bipolar disorder, is in a large part related to the association between impulsivity and the biological substrates of these disorders. Before treatment studies on impulsivity can move forward, measures of impulsivity that capture the core aspects of this behavior need to be refined and tested on the basis of an ideologically neutral model of impulsivity.
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              The role of default network deactivation in cognition and disease.

              A considerable body of evidence has accumulated over recent years on the functions of the default-mode network (DMN)--a set of brain regions whose activity is high when the mind is not engaged in specific behavioral tasks and low during focused attention on the external environment. In this review, we focus on DMN suppression and its functional role in health and disease, summarizing evidence that spans several disciplines, including cognitive neuroscience, pharmacological neuroimaging, clinical neuroscience, and theoretical neuroscience. Collectively, this research highlights the functional relevance of DMN suppression for goal-directed cognition, possibly by reducing goal-irrelevant functions supported by the DMN (e.g., mind-wandering), and illustrates the functional significance of DMN suppression deficits in severe mental illness. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                22 July 2022
                2022
                : 13
                : 868804
                Affiliations
                [1] 1Department of Surgical, Medical and Molecular Pathology and Critical Care, University of Pisa , Pisa, Italy
                [2] 2Department of Clinical and Experimental Medicine, University of Pisa , Pisa, Italy
                [3] 3The Mind Research Network and Lovelace Biomedical and Environmental Research Institute , Albuquerque, NM, United States
                [4] 4Molecular Mind Lab, IMT School for Advanced Studies Lucca , Lucca, Italy
                [5] 5Department of Psychology, University of New Mexico , Albuquerque, NM, United States
                Author notes

                Edited by: Mauro Ceccanti, Sapienza University of Rome, Italy

                Reviewed by: Christopher Thomas Smith, Virginia Tech, United States; Mario Vitali, ASUR Marche, Italy

                *Correspondence: Silvia Pellegrini, silvia.pellegrini@ 123456unipi.it

                This article was submitted to Behavioral and Psychiatric Genetics, a section of the journal Frontiers in Psychiatry

                Article
                10.3389/fpsyt.2022.868804
                9352854
                98f58400-d652-48f6-81b8-9648e42a0714
                Copyright © 2022 Palumbo, Mariotti, Vellucci, Antonelli, Anderson, Harenski, Pietrini, Kiehl and Pellegrini.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 22 March 2022
                : 28 June 2022
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 106, Pages: 10, Words: 7558
                Categories
                Psychiatry
                Original Research

                Clinical Psychology & Psychiatry
                cognitive/attentive impulsivity,parenting,gene variants,dopamine,ankk1,rs1800497,th,rs6356

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