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Li J, Bi W, Xiong M, Nasifu L, Zhang L, Zhu C, He B. Association of the DRD and OXT Genetic Polymorphisms With Schizophrenia in a Chinese Population. J Nerv Ment Dis 2025; 213:71-77. [PMID: 39993143 DOI: 10.1097/nmd.0000000000001824] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/26/2025]
Abstract
ABSTRACT The polymorphism of dopamine receptor (DRD) and oxytocin (OXT) may be associated with schizophrenia. A case-control study of 248 schizophrenia patients and 236 controls was conducted using the Sequenom MassARRAY platform. The results showed that DRD2 rs1800497 was a heterozygote (AG vs. GG: adjusted odds ratio [OR] = 1.88; 95% confidence interval [CI]: 1.09-3.25) and DRD3 rs7631540 (TC vs. CC: adjusted OR = 0.60; 95% CI: 0.36-1.02) may be associated with an increased risk of developing schizophrenia. In addition, the DRD2 rs1800497 genotype GA showed a reduced risk of schizophrenia in the male subgroup and the late-onset subgroup (>27 years of age). For DRD3 polymorphisms, the rs7631540 TC genotype was associated with schizophrenia in the female subgroup. In OXT polymorphism analysis, rs2740210 codominant CA/AA was a risk factor for schizophrenia in the male and early-onset subgroup (≤27 years old). This study also concluded that OXT rs2740210 codominant CA/AA is associated with schizophrenia.
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Affiliation(s)
- Jingjing Li
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Wen Bi
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Mengqiu Xiong
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | | | | | - Chengbin Zhu
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Bangshun He
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
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Jin Y, Zheng D, Gu R, Fan Q, Dietz M, Wang C, Li X, Chen J, Hu Y, Zhou Y. Substantial Heritability Underlies Fairness Norm Adaptation Capability and its Neural Basis. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2411070. [PMID: 39679781 PMCID: PMC11884581 DOI: 10.1002/advs.202411070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 11/26/2024] [Indexed: 12/17/2024]
Abstract
The present research uncovers the shared genetic underpinnings of fairness norm adaptation capability, its neural correlates, and long-term mental health outcomes. One hundred and eighty-six twins are recruited and played as responders in the Ultimatum Game (UG) while undergoing fMRI scanning in their early adulthood (Study-1) and are measured on depressive symptoms eight years later (Study-2). With computational modeling, the process of norm adaptation is differentiated from that of fairness valuation in UG. The two processes both have moderate levels of heritability. The anterior insula has a significant phenotypic correlation, whereas the Supplementary Motor Area/Medial Frontal Gyrus (SMA/mSFG) shows both a significant phenotypic correlation and a shared genetic influence with the learning rate, an index for norm adaptation. The dopaminergic DRD2 polymorphisms correlate with both the learning rate and the SMA/mSFG encoding of prediction error, constituting of their common genetic basis. Regional gene expression analysis reveals the high expression of dopamine-related genes in the SMA/mSFG. Moreover, the learning rate can predict depressive symptom severity eight years later, with the DRD2 polymorphisms constituting their shared genetic basis. This suggests that heritability is a non-negligible driving force behind norm adaptation, which facilitates the learning of social norms in changing environments and preserves long-term mental health.
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Affiliation(s)
- Yuening Jin
- CAS Key Laboratory of Behavioral ScienceInstitute of PsychologyChinese Academy of SciencesBeijing100101China
- Department of PsychologyUniversity of Chinese Academy of SciencesBeijing100049China
| | - Dang Zheng
- CAS Key Laboratory of Behavioral ScienceInstitute of PsychologyChinese Academy of SciencesBeijing100101China
- Department of Early Childhood EducationChina National Children's CenterBeijing100035China
| | - Ruolei Gu
- CAS Key Laboratory of Behavioral ScienceInstitute of PsychologyChinese Academy of SciencesBeijing100101China
- Department of PsychologyUniversity of Chinese Academy of SciencesBeijing100049China
| | - Qingchen Fan
- CAS Key Laboratory of Behavioral ScienceInstitute of PsychologyChinese Academy of SciencesBeijing100101China
- Department of PsychologyUniversity of Chinese Academy of SciencesBeijing100049China
| | - Martin Dietz
- Center of Functionally Integrative NeuroscienceInstitute of Clinical MedicineAarhus UniversityUniversitetsbyen 3Aarhus8000Denmark
| | - Changshuo Wang
- CAS Key Laboratory of Behavioral ScienceInstitute of PsychologyChinese Academy of SciencesBeijing100101China
- Sino‐Danish CenterUniversity of Chinese Academy of SciencesBeijing100049China
- Brainnetome CenterInstitute of AutomationChinese Academy of SciencesBeijing100190China
| | - Xinying Li
- Department of PsychologyUniversity of Chinese Academy of SciencesBeijing100049China
- CAS Key Laboratory of Mental HealthInstitute of PsychologyChinese Academy of SciencesBeijing100101China
| | - Jie Chen
- Department of PsychologyUniversity of Chinese Academy of SciencesBeijing100049China
- CAS Key Laboratory of Mental HealthInstitute of PsychologyChinese Academy of SciencesBeijing100101China
| | - Yuanyuan Hu
- CAS Key Laboratory of Behavioral ScienceInstitute of PsychologyChinese Academy of SciencesBeijing100101China
- Department of PsychologyUniversity of Chinese Academy of SciencesBeijing100049China
| | - Yuan Zhou
- CAS Key Laboratory of Behavioral ScienceInstitute of PsychologyChinese Academy of SciencesBeijing100101China
- Department of PsychologyUniversity of Chinese Academy of SciencesBeijing100049China
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental DisordersBeijing Anding HospitalCapital Medical UniversityBeijingChina
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Emond JA, Renier TJ, Yeum D, Carlson DD, Ballarino GA, Gilbert-Diamond D. Association between the Taq1A polymorphism and problematic media use in preadolescent children. Front Psychol 2025; 15:1395957. [PMID: 39845554 PMCID: PMC11752389 DOI: 10.3389/fpsyg.2024.1395957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 12/24/2024] [Indexed: 01/24/2025] Open
Abstract
Objective Problematic media use (PMU) is addiction-like media use. No study has examined if genetic factors for addiction relate to PMU during childhood. This study tested the association between genetic risk factors for addiction and PMU among 9-to-12-year-olds. Method Data were from a cohort of 9-to-12-year-olds recruited from Northern New England, 2018-2022, for a study examining obesity risk among children. Two polymorphisms related to dopaminergic (ANNK1 rs1800497 [the Taq1A polymorphism] and COMT rs4680) and one related to nicotinic (CHRNA4 rs1044396) pathways that were previously associated with internet addiction or internet video game addiction in adolescents and young adults were genotyped. Parent-reported PMU for children was measured with a validated nine-item scale (range for final scores: 1 to 5); higher scores indicate more severe PMU. Results Among children (n = 180; 43.9% female; 90.0% white, non-Hispanic; 82.2% of parents were college graduates), the median PMU score was 2.22 (IQR: 1.78, 2.78). In a linear regression model adjusted for child age, sex, European ancestry, and parent education, there was an additive association between the number of Taq1A1 alleles and PMU among children. Specifically, geometric mean PMU scores were 8.6% greater for each additional copy of the Taq1A1 allele (p = 0.030; R 2 = 5.2%). No other polymorphisms were statistically associated with PMU at the p < 0.05 level. Conclusion These preliminary findings suggest that a genetic predisposition to reduced dopamine sensitivity as indicated by the Taq1A polymorphism may relate to PMU in early adolescence. Findings need confirmation in larger samples.
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Affiliation(s)
- Jennifer A. Emond
- Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth College, Lebanon, NH, United States
- Department of Pediatrics, Geisel School of Medicine at Dartmouth College, Lebanon, NH, United States
| | - Timothy J. Renier
- Department of Epidemiology, Geisel School of Medicine at Dartmouth College, Lebanon, NH, United States
| | - Dabin Yeum
- Department of Epidemiology, Geisel School of Medicine at Dartmouth College, Lebanon, NH, United States
| | - Delaina D. Carlson
- Department of Epidemiology, Geisel School of Medicine at Dartmouth College, Lebanon, NH, United States
| | - Grace A. Ballarino
- Department of Epidemiology, Geisel School of Medicine at Dartmouth College, Lebanon, NH, United States
| | - Diane Gilbert-Diamond
- Department of Pediatrics, Geisel School of Medicine at Dartmouth College, Lebanon, NH, United States
- Department of Epidemiology, Geisel School of Medicine at Dartmouth College, Lebanon, NH, United States
- Department of Medicine, Geisel School of Medicine at Dartmouth College, Lebanon, NH, United States
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Humińska-Lisowska K. Dopamine in Sports: A Narrative Review on the Genetic and Epigenetic Factors Shaping Personality and Athletic Performance. Int J Mol Sci 2024; 25:11602. [PMID: 39519153 PMCID: PMC11546834 DOI: 10.3390/ijms252111602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 10/22/2024] [Accepted: 10/27/2024] [Indexed: 11/16/2024] Open
Abstract
This narrative review examines the relationship between dopamine-related genetic polymorphisms, personality traits, and athletic success. Advances in sports genetics have identified specific single nucleotide polymorphisms (SNPs) in dopamine-related genes linked to personality traits crucial for athletic performance, such as motivation, cognitive function, and emotional resilience. This review clarifies how genetic variations can influence athletic predisposition through dopaminergic pathways and environmental interactions. Key findings reveal associations between specific SNPs and enhanced performance in various sports. For example, polymorphisms such as COMT Val158Met rs4680 and BDNF Val66Met rs6265 are associated with traits that could benefit performance, such as increased focus, stress resilience and conscientiousness, especially in martial arts. DRD3 rs167771 is associated with higher agreeableness, benefiting teamwork in sports like football. This synthesis underscores the multidimensional role of genetics in shaping athletic ability and advocates for integrating genetic profiling into personalized training to optimize performance and well-being. However, research gaps remain, including the need for standardized training protocols and exploring gene-environment interactions in diverse populations. Future studies should focus on how genetic and epigenetic factors can inform tailored interventions to enhance both physical and psychological aspects of athletic performance. By bridging genetics, personality psychology, and exercise science, this review paves the way for innovative training and performance optimization strategies.
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Affiliation(s)
- Kinga Humińska-Lisowska
- Faculty of Physical Education, Gdansk University of Physical Education and Sport, 80-336 Gdańsk, Poland
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Unterrainer JM, Petersen J, Schmidt P, Ernst M, Wirtz MA, Reinwarth AC, Wicke F, Ghaemi Kerahrodi J, Michal M, Münzel T, König J, Lackner KJ, Pfeiffer N, Tüscher O, Galle PR, Beutel M, Wild PS. Different risk and protective factors predict change of planning ability in middle versus older age. Sci Rep 2024; 14:25275. [PMID: 39455694 PMCID: PMC11511955 DOI: 10.1038/s41598-024-76784-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Accepted: 10/16/2024] [Indexed: 10/28/2024] Open
Abstract
Age-related cognitive decline has become an increasingly relevant public health issue. However, risk and protective factors of cognitive decline have yet to be investigated prospectively taking into account genetic, lifestyle, physical and mental health factors. Population-based data from middle-aged (40 to 59 years; N = 2,764) and older individuals (60 to 80 years; N = 1,254) were drawn from a prospective community cohort study using the Tower of London (TOL) planning task. Assessments were repeated at a 5-year interval to investigate age-related changes in planning performance and to determine the impact of risk and protective factors. Planning performance improved in middle-aged, but declined in older participants over 5 years. SNPs affecting the dopamine system (COMT, DRD2) and APOE polymorphisms differentially predicted cognitive performance in older vs. middle-aged individuals. For older individuals, high alcohol consumption, antidepressant medication and living without a partner had additional negative predictive power on cognition. In contrast, undiagnosed hypertension, no obstructive lung disease, and fewer years of education predicted cognitive decline in the middle-aged group. The results inform screening for individuals particularly vulnerable to cognitive decline and interventions (e.g., focusing on lifestyle factors) to help maintain cognitive performance into old age.
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Affiliation(s)
- Josef M Unterrainer
- Institute of Medical Psychology and Medical Sociology, Faculty of Medicine, University of Freiburg, Hebelstraße 29, Freiburg, 79104, Germany.
| | - Julia Petersen
- Department of Psychosomatic Medicine and Psychotherapy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Peter Schmidt
- Department of Psychosomatic Medicine and Psychotherapy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
- Department of Political Science and the Centre for International Development and Environment (ZEU), University of Giessen, Giessen, Germany
| | - Mareike Ernst
- Department of Psychosomatic Medicine and Psychotherapy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
- Department of Clinical Psychology, Psychotherapy and Psychoanalysis, Institute of Psychology, University of Klagenfurt, Klagenfurt am Wörthersee, Austria
| | - Markus A Wirtz
- Research Methods in the Health Sciences, University of Education Freiburg, Freiburg, Germany
| | - Anna C Reinwarth
- Department of Psychosomatic Medicine and Psychotherapy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
- Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Felix Wicke
- Department of Psychosomatic Medicine and Psychotherapy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Jasmin Ghaemi Kerahrodi
- Department of Psychosomatic Medicine and Psychotherapy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Matthias Michal
- Department of Psychosomatic Medicine and Psychotherapy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Thomas Münzel
- Partner Site RhineMain, German Center for Cardiovascular Research (DZHK), Mainz, Germany
| | - Jochem König
- Division of Pediatric Epidemiology, Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Karl J Lackner
- Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Norbert Pfeiffer
- Department of Ophthalmology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Oliver Tüscher
- Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
- Leibniz Institute for Resilience Research (LIR) Mainz, Mainz, Germany
- Institute of Molecular Biology (IMB) Mainz, Mainz, Germany
| | - Peter R Galle
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Manfred Beutel
- Department of Psychosomatic Medicine and Psychotherapy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Philipp S Wild
- Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
- Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg- University Mainz, Mainz, Germany
- Center for Translational Vascular Biology (CTVB), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
- Institute of Molecular Biology (IMB) Mainz, Mainz, Germany
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Tereshchenko SY, Afonicheva KV, Marchenko IV, Shubina MV, Smolnikova MV. Polymorphic variants of the dopamine receptor gene DRD2 (rs6277, rs1800497) in adolescents with problematic video game use. Vavilovskii Zhurnal Genet Selektsii 2024; 28:667-674. [PMID: 40200916 PMCID: PMC11975965 DOI: 10.18699/vjgb-24-74] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 06/30/2024] [Accepted: 07/15/2024] [Indexed: 04/10/2025] Open
Abstract
Problematic video games use, as a specific form of problematic Internet use, is widespread among adolescents and can have negative effects on their mental and somatic well-being. An increasing incidence of addictive video gaming, as well as the overuse of the Internet, among the young population makes the current study of susceptibility factors, including the genetic component, relevant. There has been a number of investigations related to the involvement of gene variants of the neurotransmitter system in the development of Internet addiction, with the results being different for various ethnic groups. The dopamine type 2 receptor gene (DRD2) is one of the candidate genes for susceptibility to video game addiction. The aim of the work was to study polymorphic variants of the dopamine receptor gene DRD2 (rs6277, rs1800497) in Russian adolescents with problematic use of computer video games. A sampling of 407 adolescents aged 14.1 ± 1.8 years was tested, of which 56 (13.8 %) were identified as having problems with the pathological use of video games use based on the GASA scale results. Boys in the sample proved to be addicted to video games more than girls (p = 0.041). As a result of comparing the allele frequency of DRD2 (rs6277), a tendency to a higher frequency of the minor allele T was revealed in the group of adolescents with problematic video game use compared with adolescents without problematic video game use (i. e. 0.563 and 0.466, respectively, p = 0.06). When using the dominant inheritance model, it was revealed that adolescents with problematic use of video games were statistically significantly more likely to carry the T (CT+TT) allele (p = 0.04, OR = 2.14, CI = 1.01-4.53). The T allele DRD2 (rs6277) is associated with low expression of the dopamine receptor D2 and leads to decreasing the density and affinity of extrastriatal dopamine type 2 receptors, which is associated with impaired social communication as well. We suggest that the presence of CT and TT genotypes of rs6277 DRD2 may be a potential risk factor for developing problematic video game use in adolescents.
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Affiliation(s)
- S Yu Tereshchenko
- Scientific Research Institute of Medical Problems of the North - a separate division of the Federal Research Center "Krasnoyarsk Science Center" of the Siberian Branch of the Russian Academy of Sciences, Krasnoyarsk, Russia
| | - K V Afonicheva
- Scientific Research Institute of Medical Problems of the North - a separate division of the Federal Research Center "Krasnoyarsk Science Center" of the Siberian Branch of the Russian Academy of Sciences, Krasnoyarsk, Russia
| | - I V Marchenko
- Scientific Research Institute of Medical Problems of the North - a separate division of the Federal Research Center "Krasnoyarsk Science Center" of the Siberian Branch of the Russian Academy of Sciences, Krasnoyarsk, Russia
| | - M V Shubina
- Scientific Research Institute of Medical Problems of the North - a separate division of the Federal Research Center "Krasnoyarsk Science Center" of the Siberian Branch of the Russian Academy of Sciences, Krasnoyarsk, Russia
| | - M V Smolnikova
- Scientific Research Institute of Medical Problems of the North - a separate division of the Federal Research Center "Krasnoyarsk Science Center" of the Siberian Branch of the Russian Academy of Sciences, Krasnoyarsk, Russia
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7
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Steiner AM, Roscoe RF, Booze RM, Mactutus CF. Motivational dysregulation with melanocortin 4 receptor haploinsufficiency. NEUROIMMUNE PHARMACOLOGY AND THERAPEUTICS 2024; 3:237-250. [PMID: 39741559 PMCID: PMC11683877 DOI: 10.1515/nipt-2024-0011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/19/2024] [Accepted: 10/18/2024] [Indexed: 01/03/2025]
Abstract
Obesity, by any standard, is a global health crisis. Both genetic and dietary contributions to the development and maintenance of obesity were integral factors of our experimental design. As mutations of the melanocortin 4 receptors (MC4R) are the leading monogenetic cause of obesity, MC4R haploinsufficient rats were fed a range of dietary fat (0-12 %) in a longitudinal design. Physiological and motivational assessments were performed using a locomotor task, a 5-choice sucrose preference task, an operant task with fixed and progressive ratios, as well as a distraction operant task. Dendritic spine morphology of medium spiny neurons (MSNs) of the nucleus accumbens (NAc), cells with ample D1 and D2 receptors, was also assessed. The percentage of lipid deposits in the liver of each rat was also analyzed using the Area Fraction Fractionator probe for stereological measurements. MC4R haploinsufficiency resulted in a phenotypic resemblance for adult-onset obesity that was exacerbated by the consumption of a high-fat diet. Results from the operant tasks indicate that motivational deficits due to MC4R haploinsufficiency were apparent prior to the onset of obesity and exacerbated by dietary fat consumption after obesity was well established. Moreover, MSN morphology shifted to longer spines with smaller head diameters for the MC4R+/- animals under the high-fat diet, suggesting a potential mechanism for the dysregulation of motivation to work for food. Increasing our knowledge of the neural circuitry/mechanisms responsible for the rewarding properties of food has significant implications for understanding energy balance and the development of obesity.
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Affiliation(s)
- Alex M. Steiner
- Cognitive and Neural Science Program, Department of Psychology, Barnwell College, University of South Carolina, Columbia, SC, USA
| | - Robert F. Roscoe
- Cognitive and Neural Science Program, Department of Psychology, Barnwell College, University of South Carolina, Columbia, SC, USA
| | - Rosemarie M. Booze
- Cognitive and Neural Science Program, Department of Psychology, Barnwell College, University of South Carolina, Columbia, SC, USA
| | - Charles F. Mactutus
- Cognitive and Neural Science Program, Department of Psychology, Barnwell College, University of South Carolina, Columbia, SC, USA
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Banuelos C, Creswell K, Walsh C, Manuck SB, Gianaros PJ, Verstynen T. D2 dopamine receptor expression, reactivity to rewards, and reinforcement learning in a complex value-based decision-making task. Soc Cogn Affect Neurosci 2024; 19:nsae050. [PMID: 38988197 PMCID: PMC11281849 DOI: 10.1093/scan/nsae050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 04/24/2024] [Accepted: 07/10/2024] [Indexed: 07/12/2024] Open
Abstract
Different dopamine (DA) subtypes have opposing dynamics at postsynaptic receptors, with the ratio of D1 to D2 receptors determining the relative sensitivity to gains and losses, respectively, during value-based learning. This effective sensitivity to different reward feedback interacts with phasic DA levels to determine the effectiveness of learning, particularly in dynamic feedback situations where the frequency and magnitude of rewards need to be integrated over time to make optimal decisions. We modeled this effect in simulations of the underlying basal ganglia pathways and then tested the predictions in individuals with a variant of the human dopamine receptor D2 (DRD2; -141C Ins/Del and Del/Del) gene that associates with lower levels of D2 receptor expression (N = 119) and compared their performance in the Iowa Gambling Task to noncarrier controls (N = 319). Ventral striatal (VS) reactivity to rewards was measured in the Cards task with fMRI. DRD2 variant carriers made less effective decisions than noncarriers, but this effect was not moderated by VS reward reactivity as is hypothesized by our model. These results suggest that the interaction between DA receptor subtypes and reactivity to rewards during learning may be more complex than originally thought.
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Affiliation(s)
- Cristina Banuelos
- Department of Psychology, Carnegie Mellon University, Pittsburgh, PA 15213, United States
- Carnegie Mellon Neuroscience Institute, Carnegie Mellon University, Pittsburgh, PA 15213, United States
- Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh, PA 15213, United States
| | - Kasey Creswell
- Department of Psychology, Carnegie Mellon University, Pittsburgh, PA 15213, United States
| | - Catherine Walsh
- Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260, United States
| | - Stephen B Manuck
- Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260, United States
| | - Peter J Gianaros
- Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260, United States
- Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA 15260, United States
| | - Timothy Verstynen
- Department of Psychology, Carnegie Mellon University, Pittsburgh, PA 15213, United States
- Carnegie Mellon Neuroscience Institute, Carnegie Mellon University, Pittsburgh, PA 15213, United States
- Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh, PA 15213, United States
- Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, United States
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9
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Kumar P, Chaudhary A, Rai V. Evaluation of the Relationship Between Dopamine Receptor D2 Gene TaqIA1 Polymorphism and Alcohol Dependence Risk. Indian J Clin Biochem 2024; 39:301-311. [PMID: 39005876 PMCID: PMC11239648 DOI: 10.1007/s12291-023-01122-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Accepted: 02/20/2023] [Indexed: 04/03/2023]
Abstract
Several studies are published, that investigated dopamine receptor 2 (DRD2) gene TaqIA polymorphism as a risk factor for alcohol dependence (AD) with positive and negative associations. To derive a more precise estimation of the relationship, a meta-analysis of case-control studies that examined the association between DRD2 gene Taq1A polymorphism and alcohol dependence was performed. Eligible articles were identified through a search of databases including PubMed, Science Direct, Springer link, and Google Scholar. The association between the DRD2 TaqIA polymorphism and AD susceptibility was conducted using odds ratios (ORs) and 95% confidence intervals (95% CIs) as association measures. A total of 69 studies with 9125 cases and 9123 healthy controls were included in the current meta-analysis. Results of the present analysis showed significant association between DRD2 TaqIA polymorphism and AD risk using five genetic modes (allele contrast model-OR 1.22, 95% CI 1.13-1.32, p < 0.0001; homozygote model-OR 1.35, 95%CI 1.18-1.55; p ≤ 0.0001; dominant model-OR 1.29; 95% CI 1.20-1.39; p < 0.0001; recessive model-OR 1.21; 95% CI 1.08-1.36; p = 0.0006). There was no significant association found in subgroup analysis, TaqIA polymorphism was not significantly associated with AD risk in the Asian population under all genetic models, but in the Caucasian population, TaqIA polymorphism was significantly associated with AD risk. Overall, results support the hypothesis that DRD2 Taq1A polymorphism plays a role in alcohol dependence.
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Affiliation(s)
- Pradeep Kumar
- Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur, UP 222003 India
| | - Amrita Chaudhary
- Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur, UP 222003 India
| | - Vandana Rai
- Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur, UP 222003 India
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10
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Koh AP, Smith MI, Dando R. Bitter taste function-related genes are implicated in the behavioral association between taste preference and ethanol preference in male mice. Physiol Behav 2024; 276:114473. [PMID: 38262572 DOI: 10.1016/j.physbeh.2024.114473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 01/08/2024] [Accepted: 01/19/2024] [Indexed: 01/25/2024]
Abstract
Alcohol use disorder in humans is highly heritable, and as a term is synonymous with alcoholism, alcohol dependence, and alcohol addiction. Defined by the NIAAA as a medical condition characterized by an impaired ability to stop or control alcohol use despite adverse social, occupational, or health consequences, the genetic basis of alcohol dependence is much studied. However, an intriguing component to alcohol acceptance exists outside of genetics or social factors. In fact, mice of identical genetic backgrounds without any prior experience of tasting ethanol display widely varying preferences to it, far beyond those seen for typical taste solutions. Here, we hypothesized that a preference for ethanol, which tastes both bitter and sweet to humans, would be influenced by taste function. Using a mouse model of taste behavior, we tested preferences for bitter and sweet in mice that, without training or previous experience, either preferred or avoided ethanol solutions in consumption trials. Data showed clear sex differences, in which male mice that preferred ethanol also preferred a bitter quinine solution, whereas female mice that preferred ethanol also preferred a sweet sucralose solution. Male mice preferring ethanol also exhibited lower expression levels of mRNA for genes encoding the bitter taste receptors T2R26 and T2R37, and the bitter transducing G-protein subunit GNAT3, suggesting that the higher ethanol preference observed in the male mice may be due to bitter signaling, including that arising from ethanol, being weaker in this group. Results further support links between ethanol consumption and taste response, and may be relevant to substance abuse issues in human populations.
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Affiliation(s)
- Anna P Koh
- Department of Food Science, Cornell University, Ithaca, NY 14853, United States
| | - Molly I Smith
- Department of Food Science, Cornell University, Ithaca, NY 14853, United States
| | - Robin Dando
- Department of Food Science, Cornell University, Ithaca, NY 14853, United States.
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11
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Qin Y, Sun Q, Wang L, Hu F, Zhang Q, Wang W, Li W, Wang Y. DRD2 TaqIA polymorphism-related functional connectivity between anterior insula and dorsolateral prefrontal cortex predicts the retention time in heroin-dependent individuals under methadone maintenance treatment. Eur Arch Psychiatry Clin Neurosci 2024; 274:433-443. [PMID: 37400684 DOI: 10.1007/s00406-023-01626-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 05/22/2023] [Indexed: 07/05/2023]
Abstract
BACKGROUND Dopamine receptor D2 (DRD2) TaqIA polymorphism has an influence on addiction treatment response and prognosis by mediating brain dopaminergic system efficacy. Insula is crucial for conscious urges to take drugs and maintain drug use. However, it remains unclear about the contribution of DRD2 TaqIA polymorphism to the regulation of insular on addiction behavioral and its relation with the therapeutic effect of methadone maintenance treatment (MMT). METHODS 57 male former heroin dependents receiving stable MMT and 49 matched male healthy controls (HC) were enrolled. Salivary genotyping for DRD2 TaqA1 and A2 alleles, brain resting-state functional MRI scan and a 24-month follow-up for collecting illegal-drug-use information was conducted and followed by clustering of functional connectivity (FC) patterns of HC insula, insula subregion parcellation of MMT patients, comparing the whole brain FC maps between the A1 carriers and non-carriers and analyzing the correlation between the genotype-related FC of insula sub-regions with the retention time in MMT patients by Cox regression. RESULTS Two insula subregions were identified: the anterior insula (AI) and the posterior insula (PI) subregion. The A1 carriers had a reduced FC between the left AI and the right dorsolateral prefrontal cortex (dlPFC) relative to no carriers. And this reduced FC was a poor prognostic factor for the retention time in MMT patients. CONCLUSION DRD2 TaqIA polymorphism affects the retention time in heroin-dependent individuals under MMT by mediating the functional connectivity strength between left AI and right dlPFC, and the two brain regions are promising therapeutic targets for individualized treatment.
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Affiliation(s)
- Yue Qin
- Department of Radiology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, People's Republic of China
- Department of Radiology, Xi'an Daxing Hospital, Xi'an, People's Republic of China
| | - Qinli Sun
- Department of Radiology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, People's Republic of China
| | - Lei Wang
- Department of Radiology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, People's Republic of China
- Department of Radiology, Xi'an Daxing Hospital, Xi'an, People's Republic of China
| | - Feng Hu
- Department of Radiology, Hospital of Shaannxi Provincial Geology and Mineral Resources Bureau, Xi'an, People's Republic of China
| | - Qiuli Zhang
- Department of Radiology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, People's Republic of China
| | - Wei Wang
- Department of Radiology, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi'an, 710038, People's Republic of China
| | - Wei Li
- Department of Radiology, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi'an, 710038, People's Republic of China.
| | - Yarong Wang
- Department of Radiology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, People's Republic of China.
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12
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Kogure M, Kanahara N, Miyazawa A, Shiko Y, Otsuka I, Matsuyama K, Takase M, Kimura M, Kimura H, Ota K, Idemoto K, Tamura M, Oda Y, Yoshida T, Okazaki S, Yamasaki F, Nakata Y, Watanabe Y, Niitsu T, Hishimoto A, Iyo M. Association of SLC6A3 variants with treatment-resistant schizophrenia: a genetic association study of dopamine-related genes in schizophrenia. Front Psychiatry 2024; 14:1334335. [PMID: 38476817 PMCID: PMC10929739 DOI: 10.3389/fpsyt.2023.1334335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 12/21/2023] [Indexed: 03/14/2024] Open
Abstract
Background Most genetic analyses that have attempted to identify a locus or loci that can distinguish patients with treatment-resistant schizophrenia (TRS) from those who respond to treatment (non-TRS) have failed. However, evidence from multiple studies suggests that patients with schizophrenia who respond well to antipsychotic medication have a higher dopamine (DA) state in brain synaptic clefts whereas patients with TRS do not show enhanced DA synthesis/release pathways. Patients and methods To examine the contribution (if any) of genetics to TRS, we conducted a genetic association analysis of DA-related genes in schizophrenia patients (TRS, n = 435; non-TRS, n = 539) and healthy controls (HC: n = 489). Results The distributions of the genotypes of rs3756450 and the 40-bp variable number tandem repeat on SLC6A3 differed between the TRS and non-TRS groups. Regarding rs3756450, the TRS group showed a significantly higher ratio of the A allele, whereas the non-TRS group predominantly had the G allele. The analysis of the combination of COMT and SLC6A3 yielded a significantly higher ratio of the putative low-DA type (i.e., high COMT activity + high SLC6A3 activity) in the TRS group compared to the two other groups. Patients with the low-DA type accounted for the minority of the non-TRS group and exhibited milder psychopathology. Conclusion The overall results suggest that (i) SLC6A3 could be involved in responsiveness to antipsychotic medication and (ii) genetic variants modulating brain DA levels may be related to the classification of TRS and non-TRS.
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Affiliation(s)
- Masanobu Kogure
- Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Nobuhisa Kanahara
- Division of Medical Treatment and Rehabilitation, Center for Forensic Mental Health, Chiba University, Chiba, Japan
| | - Atsuhiro Miyazawa
- Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan
- Doujin-kai Kisarazu Hospital, Kisarazu, Japan
| | - Yuki Shiko
- Biostatistics Section, Clinical Research Center, Chiba University Hospital, Chiba, Japan
| | - Ikuo Otsuka
- Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Koichi Matsuyama
- Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan
- Douwa-kai Chiba Hospital, Funabashi, Japan
| | | | - Makoto Kimura
- Chiba Psychiatric Medical Center, Chiba, Japan
- Department of Psychiatry, Kameda Medical Center, Kamogawa, Japan
| | - Hiroshi Kimura
- Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan
- Gakuji-kai Kimura Hospital, Chiba, Japan
- Department of Psychiatry, School of Medicine, International University of Health and Welfare, Narita, Japan
| | - Kiyomitsu Ota
- Doujin-kai Kisarazu Hospital, Kisarazu, Japan
- Choshi-kokoro Clinic, Choshi, Japan
| | - Keita Idemoto
- Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan
- Doujin-kai Kisarazu Hospital, Kisarazu, Japan
| | - Masaki Tamura
- Doujin-kai Kisarazu Hospital, Kisarazu, Japan
- Department of Cognitive Behavioral Psychology, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Yasunori Oda
- Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan
| | | | - Satoshi Okazaki
- Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Fumiaki Yamasaki
- Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Yusuke Nakata
- Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan
| | | | - Tomihisa Niitsu
- Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Akitoyo Hishimoto
- Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Masaomi Iyo
- Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan
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13
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Moore SC, Vaz de Castro PAS, Yaqub D, Jose PA, Armando I. Anti-Inflammatory Effects of Peripheral Dopamine. Int J Mol Sci 2023; 24:13816. [PMID: 37762126 PMCID: PMC10530375 DOI: 10.3390/ijms241813816] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 08/18/2023] [Accepted: 08/29/2023] [Indexed: 09/29/2023] Open
Abstract
Dopamine is synthesized in the nervous system where it acts as a neurotransmitter. Dopamine is also synthesized in a number of peripheral organs as well as in several types of cells and has organ-specific functions and, as demonstrated more recently, is involved in the regulation of the immune response and inflammatory reaction. In particular, the renal dopaminergic system is very important in the regulation of sodium transport and blood pressure and is particularly sensitive to stimuli that cause oxidative stress and inflammation. This review is focused on how dopamine is synthesized in organs and tissues and the mechanisms by which dopamine and its receptors exert their effects on the inflammatory response.
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Affiliation(s)
| | | | | | | | - Ines Armando
- Division of Kidney Diseases and Hypertension, Department of Medicine, The George Washington School of Medicine and Health Sciences, Washington, DC 20037, USA; (S.C.M.); (P.A.S.V.d.C.); (D.Y.); (P.A.J.)
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14
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Montalban E, Walle R, Castel J, Ansoult A, Hassouna R, Foppen E, Fang X, Hutelin Z, Mickus S, Perszyk E, Petitbon A, Berthelet J, Rodrigues-Lima F, Cebrian-Serrano A, Gangarossa G, Martin C, Trifilieff P, Bosch-Bouju C, Small DM, Luquet S. The Addiction-Susceptibility TaqIA/Ankk1 Controls Reward and Metabolism Through D 2 Receptor-Expressing Neurons. Biol Psychiatry 2023; 94:424-436. [PMID: 36805080 DOI: 10.1016/j.biopsych.2023.02.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 01/21/2023] [Accepted: 02/09/2023] [Indexed: 02/18/2023]
Abstract
BACKGROUND A large body of evidence highlights the importance of genetic variants in the development of psychiatric and metabolic conditions. Among these, the TaqIA polymorphism is one of the most commonly studied in psychiatry. TaqIA is located in the gene that codes for the ankyrin repeat and kinase domain containing 1 kinase (Ankk1) near the dopamine D2 receptor (D2R) gene. Homozygous expression of the A1 allele correlates with a 30% to 40% reduction of striatal D2R, a typical feature of addiction, overeating, and other psychiatric pathologies. The mechanisms by which the variant influences dopamine signaling and behavior are unknown. METHODS Here, we used transgenic and viral-mediated strategies to reveal the role of Ankk1 in the regulation of activity and functions of the striatum. RESULTS We found that Ankk1 is preferentially enriched in striatal D2R-expressing neurons and that Ankk1 loss of function in the dorsal and ventral striatum leads to alteration in learning, impulsivity, and flexibility resembling endophenotypes described in A1 carriers. We also observed an unsuspected role of Ankk1 in striatal D2R-expressing neurons of the ventral striatum in the regulation of energy homeostasis and documented differential nutrient partitioning in humans with or without the A1 allele. CONCLUSIONS Overall, our data demonstrate that the Ankk1 gene is necessary for the integrity of striatal functions and reveal a new role for Ankk1 in the regulation of body metabolism.
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Affiliation(s)
- Enrica Montalban
- Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, Paris, France.
| | - Roman Walle
- Université Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, Bordeaux, France
| | - Julien Castel
- Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, Paris, France
| | - Anthony Ansoult
- Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, Paris, France
| | - Rim Hassouna
- Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, Paris, France
| | - Ewout Foppen
- Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, Paris, France
| | - Xi Fang
- Modern Diet and Physiology Research Center, New Haven, Connecticut; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
| | - Zach Hutelin
- Modern Diet and Physiology Research Center, New Haven, Connecticut; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
| | - Sophie Mickus
- Modern Diet and Physiology Research Center, New Haven, Connecticut; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
| | - Emily Perszyk
- Modern Diet and Physiology Research Center, New Haven, Connecticut; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
| | - Anna Petitbon
- Université Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, Bordeaux, France
| | - Jérémy Berthelet
- Université Paris Cité, CNRS, Unité Epigenetique et Destin Cellulaire, Paris, France
| | | | - Alberto Cebrian-Serrano
- Institute for Diabetes and Obesity, Helmholtz Diabetes Center (HDC), Helmholtz Zentrum München, Neuherberg, Germany; German Center for Diabetes Research, Neuherberg, Germany
| | - Giuseppe Gangarossa
- Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, Paris, France
| | - Claire Martin
- Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, Paris, France
| | - Pierre Trifilieff
- Université Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, Bordeaux, France
| | | | - Dana M Small
- Modern Diet and Physiology Research Center, New Haven, Connecticut; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
| | - Serge Luquet
- Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, Paris, France; Modern Diet and Physiology Research Center, New Haven, Connecticut.
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15
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Ahlström SE, Bergman PH, Jokela RM, Olkkola KT, Kaunisto MA, Kalso EA. Clinical and genetic factors associated with post-operative nausea and vomiting after propofol anaesthesia. Acta Anaesthesiol Scand 2023; 67:1018-1027. [PMID: 37156489 DOI: 10.1111/aas.14261] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Revised: 04/15/2023] [Accepted: 04/20/2023] [Indexed: 05/10/2023]
Abstract
BACKGROUND The incidence of post-operative nausea and vomiting (PONV) remains at about 30% despite all therapeutic efforts to reduce it. The clinical risk factors guiding the prophylactic treatment are well established, but genetic factors associated with PONV remain poorly known. The aim of this study was to explore clinical and genetic factors impacting PONV by performing a genome-wide association study (GWAS) together with relevant clinical factors as covariates, and systematically attempt to replicate previously reported PONV associations. Relevant clinical factors are explored with logistic regression model. METHODS This was an observational case control study in Helsinki University Hospital between 1 August 2006 and 31 December 2010. One thousand consenting women with elevated risk for PONV, undergoing breast cancer surgery with standardised propofol anaesthesia and antiemetics. After exclusions for clinical reasons and failed genotyping, 815 patients were included with 187 PONV cases and 628 controls. Emergence of PONV up to 7th post-operative day was recorded. PONV at 2-24 h after surgery was selected to be the primary outcome. The GWAS explored associations between PONV and 653 034 genetic variants. Replication attempts included 31 variants in 16 genes. RESULTS The overall incidence of PONV up to 7th post-operative day was 35%, where 3% had PONV at 0-2 h and 23% at 2-24 h after surgery. Age, American Society of Anaesthesiologists status, the amount of oxycodone used in the post-anaesthesia care unit, smoking status, previous PONV, and history of motion sickness were statistically significant predictive factors in the logistic model. The receiver operating characteristic-area under the curve of 0.75 (95% CI 0.71-0.79) was calculated for the model. The GWAS identified six variants with suggestive association to PONV (p < 1 × 10-5 ). Of the previously reported variants, association with the DRD2 variant rs18004972 (TaqIA) was replicated (p = .028). CONCLUSIONS Our GWAS approach did not identify any high-impact PONV susceptibility variants. The results provide some support for a role of dopamine D2 receptors in PONV.
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Affiliation(s)
- Sirkku E Ahlström
- Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and HUS Helsinki University Hospital, Helsinki, Finland
| | - Paula H Bergman
- Biostatistics Consulting, Department of Public Health, University of Helsinki and HUS Helsinki University Hospital, Helsinki, Finland
| | - Ritva M Jokela
- HUS Joint Resources, University of Helsinki and HUS Helsinki University Hospital, Helsinki, Finland
| | - Klaus T Olkkola
- Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and HUS Helsinki University Hospital, Helsinki, Finland
- INDIVIDRUG Research Programme, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Mari A Kaunisto
- Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland
| | - Eija A Kalso
- Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and HUS Helsinki University Hospital, Helsinki, Finland
- Department of Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- SleepWell Research Programme, Faculty of Medicine, University of Helsinki, Helsinki, Finland
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16
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Vrantsidis DM, Clark CAC, Volk A, Wakschlag LS, Andrews Espy K, Wiebe SA. Exploring the interplay of dopaminergic genotype and parental behavior in relation to executive function in early childhood. Dev Psychopathol 2023; 35:1147-1158. [PMID: 34779374 PMCID: PMC9107528 DOI: 10.1017/s0954579421001061] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Child genotype is an important biologically based individual difference conferring differential sensitivity to the effect of parental behavior. This study explored dopaminergic polygenic composite × parental behavior interactions in relation to young children's executive function. Participants were 135 36-month-old children and their mothers drawn from a prospective cohort followed longitudinally from pregnancy. A polygenic composite was created based on the number of COMT, DAT1, DRD2, and DRD4 alleles associated with increased reward sensitivity children carried. Maternal negative reactivity and responsiveness were coded during a series of structured mother-child interactions. Executive function was operationalized as self-control and working memory/inhibitory control. Path analysis supported a polygenic composite by negative reactivity interaction for self-control. The nature of the interaction was one of diathesis-stress, such that higher negative reactivity was associated with poorer self-control for children with higher polygenic composite scores. This result suggests that children with a higher number of alleles may be more vulnerable to the negative effect of negative reactivity. Negative reactivity may increase the risk for developing behavior problems in this population via an association with poorer self-control. Due to the small sample size, these initial findings should be treated with caution until they are replicated in a larger independent sample.
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Affiliation(s)
- Daphne M Vrantsidis
- Center for Biobehavioral Health, Nationwide Children's Hospital, Columbus, OH, USA
| | - Caron A C Clark
- Department of Educational Psychology, University of Nebraska-Lincoln, Lincoln, NE, USA
| | - Auriele Volk
- Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
| | - Lauren S Wakschlag
- Department of Medical Social Sciences, Feinberg School of Medicine and Institute for Innovations in Developmental Sciences, Northwestern University, Evanston, IL, USA
| | - Kimberly Andrews Espy
- Departments of Psychology and Biology, University of Texas at San Antonio, San Antonio, TX, USA
- Department of Psychiatry and Behavioral Science, University of Texas Health San Antonio, San Antonio, TX, USA
| | - Sandra A Wiebe
- Department of Psychology and Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Canada
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17
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Niu YM, Zhang J, Tang H, Cao LH, Jiang TY, Hu YY. Association between DRD2/ANKK1 rs1800497 C > T polymorphism and post-traumatic stress disorder susceptibility: a multivariate meta-analysis. Front Neurosci 2023; 17:1102573. [PMID: 37274216 PMCID: PMC10232825 DOI: 10.3389/fnins.2023.1102573] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Accepted: 03/10/2023] [Indexed: 06/06/2023] Open
Abstract
Background Previous studies have suggested that the DRD2/ANKK1 rs1800497 C > T polymorphism plays a critical role in the risk of post-traumatic stress disorder (PTSD). However, published data are inconsistent or even contradictory. Therefore, we conducted a meta-analysis to explore the underlying correlation between the rs1800497 C > T polymorphism and PTSD risk. Materials and methods A total of five online databases were searched, and all related studies were reviewed up to 1 October 2022. Critical information was extracted, and quality assessment was conducted for all included studies. Multivariate meta-analyses were performed for the genetic model choice, and the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to examine the statistical power of the genetic models. In addition, heterogeneity, sensitivity, cumulative analysis, and publication bias were analyzed to guarantee statistical power. Result Overall, 12 observational studies involving 5,515 subjects were included and analyzed in this meta-analysis. Multivariate analysis indicated that a co-dominant genetic model was most likely the best choice. Pooled results revealed an elevated PTSD risk in mutated homozygote TT carriers in the general population (TT vs. CC: OR = 1.73, 95% CI = 1.14-2.62, P = 0.01, I2 = 58.9%) and other specific subgroups. Moreover, similar results were observed in other genetic models using univariate analysis. Conclusion Current evidence suggests that the DRD2/ANKK1 rs1800497 C > T polymorphism may contribute to PTSD susceptibility.
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Affiliation(s)
- Yu-Ming Niu
- Department of Stomatology and Center for Evidence-Based Medicine and Clinical Research, Gongli Hospital of Shanghai Pudong New Area, Shanghai, China
- Department of Psychiatry and Joint Laboratory of Psychiatric Genetic Research, The Third People's Hospital of Zhongshan, Zhongshan, Guangdong Province, China
- Department of Psychiatry, Gannan Medical University, Ganzhou, Jiangxi Province, China
| | - Jie Zhang
- Department of Psychiatry and Joint Laboratory of Psychiatric Genetic Research, The Third People's Hospital of Zhongshan, Zhongshan, Guangdong Province, China
- Department of Psychiatry, Gannan Medical University, Ganzhou, Jiangxi Province, China
| | - Hong Tang
- Department of Psychiatry, Gannan Medical University, Ganzhou, Jiangxi Province, China
| | - Lu-Hua Cao
- Information Department, Gongli Hospital of Shanghai Pudong New Area, Shanghai, China
| | - Ting-Yun Jiang
- Department of Psychiatry and Joint Laboratory of Psychiatric Genetic Research, The Third People's Hospital of Zhongshan, Zhongshan, Guangdong Province, China
| | - Yuan-Yuan Hu
- Department of Stomatology and Center for Evidence-Based Medicine and Clinical Research, Gongli Hospital of Shanghai Pudong New Area, Shanghai, China
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18
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Liu MN, Tian XY, Fang T, Wu N, Li H, Li J. Insights into the Involvement and Therapeutic Target Potential of the Dopamine System in the Posttraumatic Stress Disorder. Mol Neurobiol 2023; 60:3708-3723. [PMID: 36933147 DOI: 10.1007/s12035-023-03312-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 03/09/2023] [Indexed: 03/19/2023]
Abstract
Posttraumatic stress disorder (PTSD) is a neuropsychiatric disease closely related to life-threatening events and psychological stress. Re-experiencing, hyperarousal, avoidance, and numbness are the hallmark symptoms of PTSD, but their underlying neurological processes have not been clearly elucidated. Therefore, the identification and development of drugs for PTSD that targets brain neuronal activities have stalled. Considering that the persistent fear memory induced by traumatic stimulation causes high alertness, high arousal, and cognitive impairment of PTSD symptoms. While the midbrain dopamine system can affect physiological processes such as aversive fear memory learning, consolidation, persistence, and extinction, by altering the functions of the dopaminergic neurons, our viewpoint is that the dopamine system plays a considerable role in the PTSD occurrence and acts as a potential therapeutic target of the disorder. This paper reviews recent findings on the structural and functional connections between ventral tegmental area neurons and the core synaptic circuits involved in PTSD, gene polymorphisms related to the dopamine system that confer susceptibility to clinical PTSD. Moreover, the progress of research on medications that target the dopamine system as PTSD therapies is also discussed. Our goal is to offer some hints for early detection and assist in identifying novel, efficient approaches for treating PTSD.
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Affiliation(s)
- Meng-Nan Liu
- Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, 100850, China
| | - Xiao-Yu Tian
- Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, 100850, China.,Medical School of Chinese PLA, Beijing, 100853, China
| | - Ting Fang
- Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, 100850, China
| | - Ning Wu
- Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, 100850, China
| | - Hong Li
- Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, 100850, China.
| | - Jin Li
- Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, 100850, China.
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Noroozian M, Kormi-Nouri R, Nyberg L, Persson J. Hippocampal and motor regions contribute to memory benefits after enacted encoding: cross-sectional and longitudinal evidence. Cereb Cortex 2023; 33:3080-3097. [PMID: 35802485 DOI: 10.1093/cercor/bhac262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 05/25/2022] [Accepted: 05/26/2022] [Indexed: 11/13/2022] Open
Abstract
The neurobiological underpinnings of action-related episodic memory and how enactment contributes to efficient memory encoding are not well understood. We examine whether individual differences in level (n = 338) and 5-year change (n = 248) in the ability to benefit from motor involvement during memory encoding are related to gray matter (GM) volume, white matter (WM) integrity, and dopamine-regulating genes in a population-based cohort (age range = 25-80 years). A latent profile analysis identified 2 groups with similar performance on verbal encoding but with marked differences in the ability to benefit from motor involvement during memory encoding. Impaired ability to benefit from enactment was paired with smaller HC, parahippocampal, and putamen volume along with lower WM microstructure in the fornix. Individuals with reduced ability to benefit from encoding enactment over 5 years were characterized by reduced HC and motor cortex GM volume along with reduced WM microstructure in several WM tracts. Moreover, the proportion of catechol-O-methyltransferase-Val-carriers differed significantly between classes identified from the latent-profile analysis. These results provide converging evidence that individuals with low or declining ability to benefit from motor involvement during memory encoding are characterized by low and reduced GM volume in regions critical for memory and motor functions along with altered WM microstructure.
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Affiliation(s)
- Maryam Noroozian
- Department of Psychiatry, School of Medicine, South Kargar Str., Tehran 13185/1741, Iran
| | - Reza Kormi-Nouri
- School of Law, Psychology and Social Work, Örebro University, Fakultetsgatan 1, Örebro 702 81, Sweden
| | - Lars Nyberg
- Department of Radiation Sciences, Radiology, Umeå University, Universitetstorget 4, Umeå 901 87, Sweden
- Department of Integrative Medical Biology, Umeå University, Universitetstorget 4, Umeå 901 87, Sweden
- Umeå Center for Functional Brain Imaging, Umeå University, Universitetstorget 4, Umeå 901 87, Sweden
| | - Jonas Persson
- School of Law, Psychology and Social Work, Center for Lifespan Developmental Research (LEADER), Örebro University, Fakultetsgatan 1, Örebro 702 81, Sweden
- Aging Research Center (ARC), Stockholm University and Karolinska Institute, Tomtebodavägen 18A, Solna 171 65, Sweden
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20
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Trempler I, Binder E, Reuter M, Plieger T, Standke I, Mecklenbrauck F, Meinert S, Forstner AJ, Nöthen MM, Rietschel M, Stürmer S, Dannlowski U, Tittgemeyer M, Lencer R, Fink GR, Schubotz RI. Effects of DRD2/ANKK1 and COMT Val158Met polymorphisms on stabilization against and adaptation to unexpected events. Cereb Cortex 2022; 32:5698-5715. [PMID: 35235645 DOI: 10.1093/cercor/bhac046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 01/19/2022] [Accepted: 01/20/2022] [Indexed: 01/25/2023] Open
Abstract
Genetic variations affecting dopaminergic neuromodulation such as the DRD2/ANKK1 and the COMT Val158Met polymorphisms contribute to goal-directed behavior that requires a balance between stabilization and updating of current states and behaviors. Dopamine is also thought to be relevant for encoding of surprise signals to sensory input and adaptive learning. A link between goal-directed behavior and learning from surprise is therefore plausible. In the present fMRI study, we investigated whether DRD2 and COMT polymorphisms are related to behavioral responses and neural signals in the caudate nucleus and dlPFC during updating or stabilizing internal models of predictable digit sequences. To-be-detected switches between sequences and to-be-ignored digit omissions within a sequence varied by information-theoretic quantities of surprise and entropy. We found that A1 noncarriers and Val-carriers showed a lower response threshold along with increased caudate and dlPFC activation to surprising switches compared with A1-carriers and Met-homozygotes, whose dlPFC activity increased with decreasing switch surprise. In contrast, there were overall smaller differences in behavioral and neural modulation by drift surprise. Our results suggest that the impact of dopamine-relevant polymorphisms in the flexibility-stability trade-off may result in part from the role of dopamine in encoding the weight afforded to events requiring updating or stabilization.
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Affiliation(s)
- Ima Trempler
- Department of Psychology, University of Muenster, Fliednerstr. 21, Muenster D48149, Germany.,Otto-Creutzfeldt-Center for Cognitive and Behavioural Neuroscience, University of Muenster, Fliednerstr. 21, Muenster D48149, Germany
| | - Ellen Binder
- Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, Cologne D50937, Germany
| | - Martin Reuter
- Department of Psychology, University of Bonn, Kaiser-Karl-Ring 9, Bonn D53111, Germany.,Laboratory of Neurogenetics, Center for Economics and Neuroscience, University of Bonn, Am Hofgarten 8, Bonn D53113, Germany
| | - Thomas Plieger
- Department of Psychology, University of Bonn, Kaiser-Karl-Ring 9, Bonn D53111, Germany.,Laboratory of Neurogenetics, Center for Economics and Neuroscience, University of Bonn, Am Hofgarten 8, Bonn D53113, Germany
| | - Isabel Standke
- Institute for Translational Psychiatry, University of Muenster, Albert-Schweitzer-Str. 11, Muenster D48149, Germany
| | - Falko Mecklenbrauck
- Department of Psychology, University of Muenster, Fliednerstr. 21, Muenster D48149, Germany.,Otto-Creutzfeldt-Center for Cognitive and Behavioural Neuroscience, University of Muenster, Fliednerstr. 21, Muenster D48149, Germany
| | - Susanne Meinert
- Institute for Translational Psychiatry, University of Muenster, Albert-Schweitzer-Str. 11, Muenster D48149, Germany.,Institute for Translational Neuroscience, University of Muenster, Albert-Schweitzer-Str. 11, Muenster D48149, Germany
| | - Andreas J Forstner
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Sigmund-Freud-Str. 25, Bonn D53127, Germany.,Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Wilhelm-Johnen-Str., Juelich D52428, Germany
| | - Markus M Nöthen
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Sigmund-Freud-Str. 25, Bonn D53127, Germany
| | - Marcella Rietschel
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, Mannheim D68159, Germany
| | - Sophie Stürmer
- Department of Psychiatry, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, Cologne D50937, Germany
| | - Udo Dannlowski
- Institute for Translational Psychiatry, University of Muenster, Albert-Schweitzer-Str. 11, Muenster D48149, Germany
| | - Marc Tittgemeyer
- Translational Neurocircuitry Group, Max-Planck-Institute for Metabolism Research, Gleueler Str. 50, Cologne D50931, Germany.,Cluster of Excellence in Cellular Stress Responses in Aging-associated Diseases (CECAD), Joseph-Stelzmann-Str. 26, Cologne D50931, Germany
| | - Rebekka Lencer
- Institute for Translational Psychiatry, University of Muenster, Albert-Schweitzer-Str. 11, Muenster D48149, Germany.,Department of Psychiatry and Psychotherapy, University of Luebeck, Ratzeburger Allee 160, Luebeck, D23538, Germany
| | - Gereon R Fink
- Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, Cologne D50937, Germany.,Institute of Neuroscience and Medicine (INM3), Research Centre Juelich, Wilhelm-Johnen-Str., Juelich D52428, Germany
| | - Ricarda I Schubotz
- Department of Psychology, University of Muenster, Fliednerstr. 21, Muenster D48149, Germany.,Otto-Creutzfeldt-Center for Cognitive and Behavioural Neuroscience, University of Muenster, Fliednerstr. 21, Muenster D48149, Germany.,Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, Cologne D50937, Germany
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21
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Yuan M, Zhu H, Li Y, Ge F, Lui S, Gong Q, Qiu C, Song H, Zhang W. The DRD2 Taq1A polymorphism moderates the effect of PTSD symptom severity on the left hippocampal CA3 volume: a pilot study. Psychopharmacology (Berl) 2022; 239:3431-3438. [PMID: 34086098 PMCID: PMC9585014 DOI: 10.1007/s00213-021-05882-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 05/21/2021] [Indexed: 02/08/2023]
Abstract
RATIONALE AND OBJECTIVES The hippocampus, especially the CA1, CA3, and dentate gyrus (DG) subfields, is reported to be associated with post-traumatic stress disorder (PTSD) after trauma. However, neuroimaging studies of the associations between PTSD and hippocampal subfield volumes have failed to yield consistent findings. The aim of this study is to examine whether the dopamine D2 receptor (DRD2) Taq1A polymorphism, which is associated with both hippocampal function and PTSD, moderated the association between PTSD severity and hippocampal CA1, CA3 and DG volumes. METHODS T1-weighted images were acquired from 142 trauma survivors from the 2008 Wenchuan earthquake using a 3.0-T magnetic resonance imaging system. Hippocampal subfield segmentations were performed with FreeSurfer v6.0. We used the simple moderation model from the PROCESS v3.4 tool for SPSS 23.0 to examine the association between the rs1800497 polymorphism, PTSD severity, and hippocampal CA3 and DG volumes. RESULTS A significant genotype × PTSD symptom severity interaction was found for the left CA3 volume (ΔF = 5.01, p = 0.008, ΔR2 = 0.05). Post hoc, exploratory analyses deconstructing the interaction revealed that severe PTSD symptomatology were associated with reduced left CA3 volume among TC heterozygotes (t = - 2.86, p = 0.005). CONCLUSIONS This study suggests that DRD2 Taq1A polymorphism moderates the association between PTSD symptomatology and left CA3 volume, which promotes an etiological understanding of the hippocampal atrophy at the subfield level. This highlights the complex effect of environmental stress, and provides possible mechanism for the relationship between the dopaminergic system and hippocampal function in PTSD.
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Affiliation(s)
- Minlan Yuan
- Mental Health Center and Psychiatric Laboratory, the State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, 610041, Chengdu, China
- Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Hongru Zhu
- Mental Health Center and Psychiatric Laboratory, the State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, 610041, Chengdu, China
- Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Yuchen Li
- Mental Health Center and Psychiatric Laboratory, the State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, 610041, Chengdu, China
- Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Fenfen Ge
- Mental Health Center and Psychiatric Laboratory, the State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, 610041, Chengdu, China
- Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Su Lui
- Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
- Radiology Department of the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Qiyong Gong
- Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Changjian Qiu
- Mental Health Center and Psychiatric Laboratory, the State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, 610041, Chengdu, China
- Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Huan Song
- West China Biomedical Big Data Center, West China Hospital, Sichuan University, 610041, Chengdu, China.
- Medical Big Data Center, Sichuan University, Chengdu, 610041, China.
| | - Wei Zhang
- Mental Health Center and Psychiatric Laboratory, the State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, 610041, Chengdu, China.
- Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, China.
- West China Biomedical Big Data Center, West China Hospital, Sichuan University, 610041, Chengdu, China.
- Medical Big Data Center, Sichuan University, Chengdu, 610041, China.
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22
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Devoto F, Coricelli C, Paulesu E, Zapparoli L. Neural circuits mediating food cue-reactivity: Toward a new model shaping the interplay of internal and external factors. Front Nutr 2022; 9:954523. [PMID: 36276811 PMCID: PMC9579536 DOI: 10.3389/fnut.2022.954523] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 09/14/2022] [Indexed: 11/13/2022] Open
Affiliation(s)
- Francantonio Devoto
- Psychology Department and NeuroMi—Milan Centre for Neuroscience, University of Milano-Bicocca, Milan, Italy,*Correspondence: Francantonio Devoto
| | - Carol Coricelli
- Psychology Department, Western University, London, ON, Canada
| | - Eraldo Paulesu
- Psychology Department and NeuroMi—Milan Centre for Neuroscience, University of Milano-Bicocca, Milan, Italy,fMRI Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Galeazzi, Milan, Italy
| | - Laura Zapparoli
- Psychology Department and NeuroMi—Milan Centre for Neuroscience, University of Milano-Bicocca, Milan, Italy,fMRI Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Galeazzi, Milan, Italy,Laura Zapparoli
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23
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Boroń A, Śmiarowska M, Grzywacz A, Chmielowiec K, Chmielowiec J, Masiak J, Pawłowski T, Larysz D, Ciechanowicz A. Association of Polymorphism within the Putative miRNA Target Site in the 3'UTR Region of the DRD2 Gene with Neuroticism in Patients with Substance Use Disorder. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:9955. [PMID: 36011589 PMCID: PMC9408599 DOI: 10.3390/ijerph19169955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Revised: 08/08/2022] [Accepted: 08/10/2022] [Indexed: 06/15/2023]
Abstract
The study aims at looking into associations between the polymorphism rs6276 that occurs in the putative miRNA target site in the 3'UTR region of the DRD2 gene in patients with substance use disorder (SUD) comorbid with a maniacal syndrome (SUD MANIA). In our study, we did not state any essential difference in DRD2 rs6276 genotype frequencies in the studied samples of SUD MANIA, SUD, and control subjects. A significant result was found for the SUD MANIA group vs. SUD vs. controls on the Neuroticism Scale of NEO FFI test, and DRD2 rs6276 (p = 0.0320) accounted for 1.7% of the variance. The G/G homozygous variants were linked with lower results on the neuroticism scale in the SUD MANIA group because G/G alleles may serve a protective role in the expression of neuroticism in patients with SUD MANIA. So far, there have been no data in the literature on the relationship between the miRSNP rs6276 region in the DRD2 gene and neuroticism (personal traits) in patients with a diagnosis of substance use disorder comorbid with the affective, maniacal type disturbances related to SUD. This is the first report on this topic.
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Affiliation(s)
- Agnieszka Boroń
- Department of Clinical and Molecular Biochemistry, Pomeranian Medical University in Szczecin, Aleja Powstańców Wielkopolskich 72 St., 70-111 Szczecin, Poland
| | - Małgorzata Śmiarowska
- Department of Pharmacokinetics and Therapeutic Drug Monitoring, Pomeranian Medical University in Szczecin, Aleja Powstańcόw Wielkopolskich 72 St., 70-111 Szczecin, Poland
| | - Anna Grzywacz
- Independent Laboratory of Health Promotion, Pomeranian Medical University in Szczecin, Aleja Powstańcόw Wielkopolskich 72 St., 70-111 Szczecin, Poland
| | - Krzysztof Chmielowiec
- Department of Hygiene and Epidemiology, Collegium Medicum, University of Zielona Góra, Zyty 28 St., 65-046 Zielona Gora, Poland
| | - Jolanta Chmielowiec
- Department of Hygiene and Epidemiology, Collegium Medicum, University of Zielona Góra, Zyty 28 St., 65-046 Zielona Gora, Poland
| | - Jolanta Masiak
- Second Department of Psychiatry and Psychiatric Rehabilitation, Medical University of Lublin, Głuska 1 St., 20-059 Lublin, Poland
| | - Tomasz Pawłowski
- Division of Psychotherapy and Psychosomatic Medicine, Wroclaw Medical University, Wyb. L. Pasteura 10 St., 50-367 Wroclaw, Poland
| | - Dariusz Larysz
- 109 Military Hospital with Cutpatient Cinic in Szczecin, Piotra Skargi 9-11 St., 70-965 Szczecin, Poland
| | - Andrzej Ciechanowicz
- Department of Clinical and Molecular Biochemistry, Pomeranian Medical University in Szczecin, Aleja Powstańców Wielkopolskich 72 St., 70-111 Szczecin, Poland
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24
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Kanarik M, Grimm O, Mota NR, Reif A, Harro J. ADHD co-morbidities: A review of implication of gene × environment effects with dopamine-related genes. Neurosci Biobehav Rev 2022; 139:104757. [PMID: 35777579 DOI: 10.1016/j.neubiorev.2022.104757] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 06/25/2022] [Accepted: 06/26/2022] [Indexed: 02/07/2023]
Abstract
ADHD is a major burden in adulthood, where co-morbid conditions such as depression, substance use disorder and obesity often dominate the clinical picture. ADHD has substantial shared heritability with other mental disorders, contributing to comorbidity. However, environmental risk factors exist but their interaction with genetic makeup, especially in relation to comorbid disorders, remains elusive. This review for the first time summarizes present knowledge on gene x environment (GxE) interactions regarding the dopamine system. Hitherto, mainly candidate (GxE) studies were performed, focusing on the genes DRD4, DAT1 and MAOA. Some evidence suggest that the variable number tandem repeats in DRD4 and MAOA may mediate GxE interactions in ADHD generally, and comorbid conditions specifically. Nevertheless, even for these genes, common variants are bound to suggest risk only in the context of gender and specific environments. For other polymorphisms, evidence is contradictory and less convincing. Particularly lacking are longitudinal studies testing the interaction of well-defined environmental with polygenic risk scores reflecting the dopamine system in its entirety.
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Affiliation(s)
- Margus Kanarik
- Chair of Neuropsychopharmacology, Institute of Chemistry, University of Tartu, Ravila 14A Chemicum, 50411 Tartu, Estonia
| | - Oliver Grimm
- Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital, Goethe University, Frankfurt, Germany
| | - Nina Roth Mota
- Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Andreas Reif
- Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital, Goethe University, Frankfurt, Germany
| | - Jaanus Harro
- Chair of Neuropsychopharmacology, Institute of Chemistry, University of Tartu, Ravila 14A Chemicum, 50411 Tartu, Estonia; Psychiatry Clinic, North Estonia Medical Centre, Paldiski Road 52, 10614 Tallinn, Estonia.
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25
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Neuman J, Roeder N, Richardson B, Quattrin T, Hamilton J, Thanos PK. High Fat Diet Increases [ 3H] Flunitrazepam Binding in the Mouse Brain that is Dependent on the Expression of the Dopamine D2 Gene. Neurochem Res 2022; 47:3003-3011. [PMID: 35708880 DOI: 10.1007/s11064-022-03644-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 05/16/2022] [Accepted: 05/22/2022] [Indexed: 11/24/2022]
Abstract
Dopamine is an important neuromodulator in the brain that binds to dopamine D1-like receptors (D1, D5) as well as dopamine D2-like receptors (D2, D3, D4). The D2 receptor is known to play an integral role in a variety of physiological processes including addictive behaviors, locomotion, motivation, feeding behavior, and more. It was recently reported that dopamine is a direct-acting modulator of mammalian GABA(A) receptors. To this end, we wanted to examine how the expression of the dopamine D2 gene impacts the expression of GABA(A) receptors in the brain under different dietary conditions. Adult female Drd2 wild-type (WT), heterozygous (HT), and knockout (KO) mice were given either normal or high-fat diet for a period of 30 weeks. Following this, their brains were collected for [3H] Flunitrazepam binding in order to assess GABA(A) receptor expression. A high fat diet significantly increased [3H] Flunitrazepam binding in the regions of the somatosensory cortex, striatum, and various other cortical areas within WT mice. In contrast, no effect of diet was observed in HT or KO mice. As such, HT and KO mice displayed reduced [3H] Flunitrazepam binding in these areas relative to WT mice under high-fat dietary conditions. The effect of a high-fat diet on [3H] Flunitrazepam binding is consistent with recent evidence showing increases in GABA neurotransmitter levels following a high-fat diet. We demonstrate for the first time that the expression of the D2 gene plays a prominent role in the ability of a high-fat diet to impact GABA(A) receptors in the mouse brain.
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Affiliation(s)
- Josh Neuman
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, NY, USA
| | - Nicole Roeder
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, NY, USA
| | - Brittany Richardson
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, NY, USA
| | - Teresa Quattrin
- University at Buffalo, UBMD Pediatrics, JR Oishei Children's Hospital, Buffalo, NY, USA
| | - John Hamilton
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, NY, USA
| | - Panayotis K Thanos
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, NY, USA.
- Department of Psychology, State University at Buffalo, Buffalo, NY, USA.
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26
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Bell K, McMillin K, Ethridge LE. Bereft and Left: The interplay between insecure attachment, isolation, and neurobiology. DEVELOPMENTAL REVIEW 2022. [DOI: 10.1016/j.dr.2022.101020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
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27
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Grant CE, Flis A, Ryan BM. Understanding the Role of Dopamine in Cancer: Past, Present, and Future. Carcinogenesis 2022; 43:517-527. [PMID: 35616105 DOI: 10.1093/carcin/bgac045] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 05/12/2022] [Accepted: 05/23/2022] [Indexed: 11/14/2022] Open
Abstract
Dopamine (DA, 3-hydroxytyramine) is member of the catecholamine family and is classically characterized according to its role in the central nervous system as a neurotransmitter. In recent decades, many novel and intriguing discoveries have been made about the peripheral expression of DA receptors (DRs) and the role of DA signaling in both normal and pathological processes. Drawing from decades of evidence suggesting a link between DA and cancer, the DA pathway (DAP) has recently emerged as a potential target in antitumor therapies. Due to the onerous, expensive, and frequently unsuccessful nature of drug development, the repurposing of dopaminergic drugs for cancer therapy has the potential to greatly benefit patients and drug developers alike. However, the lack of clear mechanistic data supporting the direct involvement of DRs and their downstream signaling components in cancer represents an ongoing challenge that has limited the translation of these drugs to the clinic. Despite this, the breadth of evidence linking DA to cancer and non-tumor cells in the tumor microenvironment (TME) justifies further inquiry into the potential applications of this treatment modality in cancer. Herein, we review the literature characterizing the interplay between the DA signaling axis and cancer, highlighting key findings, and then propose rational lines of investigation to follow.
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Affiliation(s)
- Christopher E Grant
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD
| | - Amy Flis
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD
| | - Bríd M Ryan
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD
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28
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Thuan ND, Nhung VP, Dung HT, Son ND, Hai Ha N, Ton ND. Acute Extrapyramidal Side Effects Following Domperidone Intake in a 48-Year-Old Female Patient: The First Genetic Alteration and Drug Interaction Characterized. J Mov Disord 2022; 15:193-195. [PMID: 35531621 PMCID: PMC9171318 DOI: 10.14802/jmd.21151] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 01/18/2022] [Indexed: 11/24/2022] Open
Affiliation(s)
- Nguyen Duc Thuan
- Department of Neurology, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam
- Corresponding author: Nguyen Duc Thuan, MD, PhD Department of Neurology, Military Hospital 103, Vietnam Military Medical University, 261 Phung Hung Str., Ha Dong, Hanoi, Vietnam / Tel: +84-979-363-097 / Fax: +84-69566401 / E-mail:
| | - Vu Phuong Nhung
- Institute of Genome Research, Vietnam Academy of Science and Technology, Hanoi, Vietnam
| | - Hoang Thi Dung
- Department of Neurology, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam
| | - Nhu Dinh Son
- Department of Neurology, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam
| | - Nguyen Hai Ha
- Institute of Genome Research, Vietnam Academy of Science and Technology, Hanoi, Vietnam
- Graduate University of Science and Technology, Vietnam Academy of Science and Technology, Hanoi, Vietnam
| | - Nguyen Dang Ton
- Institute of Genome Research, Vietnam Academy of Science and Technology, Hanoi, Vietnam
- Graduate University of Science and Technology, Vietnam Academy of Science and Technology, Hanoi, Vietnam
- Corresponding author: Nguyen Dang Ton, PhD Institute of Genome Research, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Str., Cau Giay, Hanoi, Vietnam / Tel: +84-983-384-288 / Fax: +84-2437918010 / E-mail:
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29
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Vereczkei A, Barta C, Magi A, Farkas J, Eisinger A, Király O, Belik A, Griffiths MD, Szekely A, Sasvári-Székely M, Urbán R, Potenza MN, Badgaiyan RD, Blum K, Demetrovics Z, Kotyuk E. FOXN3 and GDNF Polymorphisms as Common Genetic Factors of Substance Use and Addictive Behaviors. J Pers Med 2022; 12:jpm12050690. [PMID: 35629112 PMCID: PMC9144496 DOI: 10.3390/jpm12050690] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 04/20/2022] [Accepted: 04/21/2022] [Indexed: 12/15/2022] Open
Abstract
Epidemiological and phenomenological studies suggest shared underpinnings between multiple addictive behaviors. The present genetic association study was conducted as part of the Psychological and Genetic Factors of Addictions study (n = 3003) and aimed to investigate genetic overlaps between different substance use, addictive, and other compulsive behaviors. Association analyses targeted 32 single-nucleotide polymorphisms, potentially addictive substances (alcohol, tobacco, cannabis, and other drugs), and potentially addictive or compulsive behaviors (internet use, gaming, social networking site use, gambling, exercise, hair-pulling, and eating). Analyses revealed 29 nominally significant associations, from which, nine survived an FDRbl correction. Four associations were observed between FOXN3 rs759364 and potentially addictive behaviors: rs759364 showed an association with the frequency of alcohol consumption and mean scores of scales assessing internet addiction, gaming disorder, and exercise addiction. Significant associations were found between GDNF rs1549250, rs2973033, CNR1 rs806380, DRD2/ANKK1 rs1800497 variants, and the “lifetime other drugs” variable. These suggested that genetic factors may contribute similarly to specific substance use and addictive behaviors. Specifically, FOXN3 rs759364 and GDNF rs1549250 and rs2973033 may constitute genetic risk factors for multiple addictive behaviors. Due to limitations (e.g., convenience sampling, lack of structured scales for substance use), further studies are needed. Functional correlates and mechanisms underlying these relationships should also be investigated.
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Affiliation(s)
- Andrea Vereczkei
- Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, 1094 Budapest, Hungary; (A.V.); (A.B.); (M.S.-S.)
| | - Csaba Barta
- Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, 1094 Budapest, Hungary; (A.V.); (A.B.); (M.S.-S.)
- Correspondence: (C.B.); (Z.D.)
| | - Anna Magi
- Institute of Psychology, ELTE Eötvös Loránd University, 1075 Budapest, Hungary; (A.M.); (J.F.); (A.E.); (O.K.); (A.S.); (R.U.); (E.K.)
- Doctoral School of Psychology, ELTE Eötvös Loránd University, 1075 Budapest, Hungary
| | - Judit Farkas
- Institute of Psychology, ELTE Eötvös Loránd University, 1075 Budapest, Hungary; (A.M.); (J.F.); (A.E.); (O.K.); (A.S.); (R.U.); (E.K.)
- Nyírő Gyula National Institute of Psychiatry and Addictions, 1135 Budapest, Hungary
| | - Andrea Eisinger
- Institute of Psychology, ELTE Eötvös Loránd University, 1075 Budapest, Hungary; (A.M.); (J.F.); (A.E.); (O.K.); (A.S.); (R.U.); (E.K.)
- Doctoral School of Psychology, ELTE Eötvös Loránd University, 1075 Budapest, Hungary
| | - Orsolya Király
- Institute of Psychology, ELTE Eötvös Loránd University, 1075 Budapest, Hungary; (A.M.); (J.F.); (A.E.); (O.K.); (A.S.); (R.U.); (E.K.)
| | - Andrea Belik
- Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, 1094 Budapest, Hungary; (A.V.); (A.B.); (M.S.-S.)
| | - Mark D. Griffiths
- International Gaming Research Unit, Psychology Department, Nottingham Trent University, Nottingham NG1 4FQ, UK;
| | - Anna Szekely
- Institute of Psychology, ELTE Eötvös Loránd University, 1075 Budapest, Hungary; (A.M.); (J.F.); (A.E.); (O.K.); (A.S.); (R.U.); (E.K.)
| | - Mária Sasvári-Székely
- Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, 1094 Budapest, Hungary; (A.V.); (A.B.); (M.S.-S.)
| | - Róbert Urbán
- Institute of Psychology, ELTE Eötvös Loránd University, 1075 Budapest, Hungary; (A.M.); (J.F.); (A.E.); (O.K.); (A.S.); (R.U.); (E.K.)
| | - Marc N. Potenza
- Departments of Psychiatry, Child Study and Neuroscience, Yale University School of Medicine, New Haven, CT 06511, USA;
- Connecticut Council on Problem Gambling, Wethersfield, CT 06109, USA
- Connecticut Mental Health Center, New Haven, CT 06519, USA
| | - Rajendra D. Badgaiyan
- Department of Psychiatry, Ichan School of Medicine at Mount Sinai, New York, NY 10029, USA;
| | - Kenneth Blum
- Division of Addiction Research & Education, Center for Psychiatry, Medicine, & Primary Care (Office of the Provost), Western University Health Sciences, Pomona, CA 91766, USA;
| | - Zsolt Demetrovics
- Institute of Psychology, ELTE Eötvös Loránd University, 1075 Budapest, Hungary; (A.M.); (J.F.); (A.E.); (O.K.); (A.S.); (R.U.); (E.K.)
- Division of Addiction Research & Education, Center for Psychiatry, Medicine, & Primary Care (Office of the Provost), Western University Health Sciences, Pomona, CA 91766, USA;
- Correspondence: (C.B.); (Z.D.)
| | - Eszter Kotyuk
- Institute of Psychology, ELTE Eötvös Loránd University, 1075 Budapest, Hungary; (A.M.); (J.F.); (A.E.); (O.K.); (A.S.); (R.U.); (E.K.)
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DRD2 Taq1A Polymorphism-Related Brain Volume Changes in Parkinson's Disease: Voxel-Based Morphometry. PARKINSON'S DISEASE 2022; 2022:8649195. [PMID: 35386951 PMCID: PMC8979712 DOI: 10.1155/2022/8649195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 03/01/2022] [Accepted: 03/10/2022] [Indexed: 01/18/2023]
Abstract
Taq1A polymorphism is a DRD2 gene variant located in an exon of the ANKK1 gene and has an important role in the brain's dopaminergic functions. Some studies have indicated that A1 carriers have an increased risk of developing Parkinson's disease (PD) and show poorer clinical performance than A2 homo carriers. Previous studies have suggested that A1 carriers had fewer dopamine D2 receptors in the caudate and increased cortical activity as a compensatory mechanism. However, there is little information about morphological changes associated with this polymorphism in patients with PD. The study's aim was to investigate the relationship between brain volume and Taq1A polymorphism in PD using voxel-based morphometry (VBM). Based on Taq1A polymorphism, 103 patients with PD were divided into two groups: A1 carriers (A1/A1 and A1/A2) and A2 homo carriers (A2/A2). The volume of the left prefrontal cortex (PFC) was significantly decreased in A2 homo carriers compared to A1 carriers. This finding supports the association between Taq1A polymorphism and brain volume in PD and may explain the compensation of cortical function in A1 carriers with PD.
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del Casale A, Paolini M, Gentile G, Borro M, Zocchi C, Fiaschè F, Padovano A, Zoppi T, Modesti MN, De Luca O, Pomes LM, Brugnoli R, Ferracuti S, Girardi P, Pompili M, Simmaco M. Dopamine DRD2 and DRD3 Polymorphisms Involvement in Nicotine Dependence in Patients with Treatment-Resistant Mental Disorders. J Pers Med 2022; 12:565. [PMID: 35455685 PMCID: PMC9033085 DOI: 10.3390/jpm12040565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 03/08/2022] [Accepted: 03/28/2022] [Indexed: 12/04/2022] Open
Abstract
Patients affected by mental disorders smoke more than the general population. The reasons behind this habit are genetic, environmental, etc. This study aims to investigate the correlations between some polymorphisms and the smoking habits and nicotine dependence in patients with psychiatric disorders. We recruited 88 patients with treatment-resistant mental disorders, including 35 with major depressive disorder, 43 with bipolar spectrum disorder, and 10 with schizophrenia spectrum disorder. We carried out a clinical and psychometric assessment on current smoking habits, years of smoking, number of daily cigarettes, and level of nicotine addiction. The patients performed a peripheral blood sample for DNA analyses of different polymorphisms. We searched for correlations between the measures of nicotine addiction and analysed genotypes. The expression of the T allele of the DRD2 rs1800497 and DRD3 rs6280 polymorphisms significantly correlated with a lower level of nicotine dependence and lower use of cigarettes. We did not find significant correlations between nicotine dependence and OPRM1 rs1799971, COMT rs4680 and rs4633 polymorphisms, CYP2A6 rs1801272 and rs28399433, or 5-HTTLPR genotype. Concluding, DRD2 rs1800497 and DRD3 rs6280 polymorphisms are involved in nicotine dependence and cigarette smoking habits in patients with treatment-resistant mental disorders.
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Affiliation(s)
- Antonio del Casale
- Department of Dynamic and Clinical Psychology, and Health Studies, Faculty of Medicine and Psychology, Sapienza University, Via degli Apuli 2, 00185 Rome, Italy;
- Unit of Psychiatry, ‘Sant’Andrea’ University Hospital, Via di Grottarossa, 00189 Rome, Italy; (M.P.); (C.Z.); (F.F.); (A.P.); (T.Z.); (M.N.M.); (R.B.); (M.P.)
| | - Marco Paolini
- Unit of Psychiatry, ‘Sant’Andrea’ University Hospital, Via di Grottarossa, 00189 Rome, Italy; (M.P.); (C.Z.); (F.F.); (A.P.); (T.Z.); (M.N.M.); (R.B.); (M.P.)
- Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University, Via di Grottarossa, 00189 Rome, Italy; (G.G.); (M.B.); (O.D.L.); (L.M.P.); (M.S.)
| | - Giovanna Gentile
- Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University, Via di Grottarossa, 00189 Rome, Italy; (G.G.); (M.B.); (O.D.L.); (L.M.P.); (M.S.)
- Unit of Laboratory and Advanced Molecular Diagnostics, ‘Sant’Andrea’ University Hospital, Via di Grottarossa, 00189 Rome, Italy
| | - Marina Borro
- Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University, Via di Grottarossa, 00189 Rome, Italy; (G.G.); (M.B.); (O.D.L.); (L.M.P.); (M.S.)
- Unit of Laboratory and Advanced Molecular Diagnostics, ‘Sant’Andrea’ University Hospital, Via di Grottarossa, 00189 Rome, Italy
| | - Clarissa Zocchi
- Unit of Psychiatry, ‘Sant’Andrea’ University Hospital, Via di Grottarossa, 00189 Rome, Italy; (M.P.); (C.Z.); (F.F.); (A.P.); (T.Z.); (M.N.M.); (R.B.); (M.P.)
- Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University, Via di Grottarossa, 00189 Rome, Italy; (G.G.); (M.B.); (O.D.L.); (L.M.P.); (M.S.)
| | - Federica Fiaschè
- Unit of Psychiatry, ‘Sant’Andrea’ University Hospital, Via di Grottarossa, 00189 Rome, Italy; (M.P.); (C.Z.); (F.F.); (A.P.); (T.Z.); (M.N.M.); (R.B.); (M.P.)
- Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University, Via di Grottarossa, 00189 Rome, Italy; (G.G.); (M.B.); (O.D.L.); (L.M.P.); (M.S.)
| | - Alessio Padovano
- Unit of Psychiatry, ‘Sant’Andrea’ University Hospital, Via di Grottarossa, 00189 Rome, Italy; (M.P.); (C.Z.); (F.F.); (A.P.); (T.Z.); (M.N.M.); (R.B.); (M.P.)
- Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University, Via di Grottarossa, 00189 Rome, Italy; (G.G.); (M.B.); (O.D.L.); (L.M.P.); (M.S.)
| | - Teodolinda Zoppi
- Unit of Psychiatry, ‘Sant’Andrea’ University Hospital, Via di Grottarossa, 00189 Rome, Italy; (M.P.); (C.Z.); (F.F.); (A.P.); (T.Z.); (M.N.M.); (R.B.); (M.P.)
- Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University, Via di Grottarossa, 00189 Rome, Italy; (G.G.); (M.B.); (O.D.L.); (L.M.P.); (M.S.)
| | - Martina Nicole Modesti
- Unit of Psychiatry, ‘Sant’Andrea’ University Hospital, Via di Grottarossa, 00189 Rome, Italy; (M.P.); (C.Z.); (F.F.); (A.P.); (T.Z.); (M.N.M.); (R.B.); (M.P.)
- Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University, Via di Grottarossa, 00189 Rome, Italy; (G.G.); (M.B.); (O.D.L.); (L.M.P.); (M.S.)
| | - Ottavia De Luca
- Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University, Via di Grottarossa, 00189 Rome, Italy; (G.G.); (M.B.); (O.D.L.); (L.M.P.); (M.S.)
- Unit of Laboratory and Advanced Molecular Diagnostics, ‘Sant’Andrea’ University Hospital, Via di Grottarossa, 00189 Rome, Italy
| | - Leda Marina Pomes
- Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University, Via di Grottarossa, 00189 Rome, Italy; (G.G.); (M.B.); (O.D.L.); (L.M.P.); (M.S.)
- Unit of Laboratory and Advanced Molecular Diagnostics, ‘Sant’Andrea’ University Hospital, Via di Grottarossa, 00189 Rome, Italy
| | - Roberto Brugnoli
- Unit of Psychiatry, ‘Sant’Andrea’ University Hospital, Via di Grottarossa, 00189 Rome, Italy; (M.P.); (C.Z.); (F.F.); (A.P.); (T.Z.); (M.N.M.); (R.B.); (M.P.)
- Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University, Via di Grottarossa, 00189 Rome, Italy; (G.G.); (M.B.); (O.D.L.); (L.M.P.); (M.S.)
| | - Stefano Ferracuti
- Department of Human Neuroscience, Sapienza University, Viale dell’Università 30, 00185, Rome, Italy;
- Unit of Risk Management, ‘Sant’Andrea’University Hospital, Via di Grottarossa, 00189 Rome, Italy
| | - Paolo Girardi
- Department of Dynamic and Clinical Psychology, and Health Studies, Faculty of Medicine and Psychology, Sapienza University, Via degli Apuli 2, 00185 Rome, Italy;
- Unit of Psychiatry, ‘Sant’Andrea’ University Hospital, Via di Grottarossa, 00189 Rome, Italy; (M.P.); (C.Z.); (F.F.); (A.P.); (T.Z.); (M.N.M.); (R.B.); (M.P.)
| | - Maurizio Pompili
- Unit of Psychiatry, ‘Sant’Andrea’ University Hospital, Via di Grottarossa, 00189 Rome, Italy; (M.P.); (C.Z.); (F.F.); (A.P.); (T.Z.); (M.N.M.); (R.B.); (M.P.)
- Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University, Via di Grottarossa, 00189 Rome, Italy; (G.G.); (M.B.); (O.D.L.); (L.M.P.); (M.S.)
| | - Maurizio Simmaco
- Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University, Via di Grottarossa, 00189 Rome, Italy; (G.G.); (M.B.); (O.D.L.); (L.M.P.); (M.S.)
- Unit of Laboratory and Advanced Molecular Diagnostics, ‘Sant’Andrea’ University Hospital, Via di Grottarossa, 00189 Rome, Italy
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Atlas of type 2 dopamine receptors in the human brain: Age and sex dependent variability in a large PET cohort. Neuroimage 2022; 255:119149. [PMID: 35367652 DOI: 10.1016/j.neuroimage.2022.119149] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 03/22/2022] [Accepted: 03/24/2022] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND The dopamine system contributes to a multitude of functions ranging from reward and motivation to learning and movement control, making it a key component in goal-directed behavior. Altered dopaminergic function is observed in neurological and psychiatric conditions. Numerous factors have been proposed to influence dopamine function, but due to small sample sizes and heterogeneous data analysis methods in previous studies their specific and joint contributions remain unresolved. METHODS In this cross-sectional register-based study we investigated how age, sex, body mass index (BMI), as well as cerebral hemisphere and regional volume influence striatal type 2 dopamine receptor (D2R) availability in the human brain. We analyzed a large historical dataset (n=156, 120 males and 36 females) of [11C]raclopride PET scans performed between 2004 and 2018. RESULTS Striatal D2R availability decreased through age for both sexes (2-5 % in striatal ROIs per 10 years) and was higher in females versus males throughout age (7-8% in putamen). BMI and striatal D2R availability were weakly associated. There was no consistent lateralization of striatal D2R. The observed effects were independent of regional volumes. These results were validated using two different spatial normalization methods, and the age and sex effects also replicated in an independent sample (n=135). CONCLUSIONS D2R availability is dependent on age and sex, which may contribute to the vulnerability of neurological and psychiatric conditions involving altering D2R expression.
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White-Matter Integrity and Working Memory: Links to Aging and Dopamine-Related Genes. eNeuro 2022; 9:ENEURO.0413-21.2022. [PMID: 35346961 PMCID: PMC9014983 DOI: 10.1523/eneuro.0413-21.2022] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 01/22/2022] [Accepted: 02/07/2022] [Indexed: 11/21/2022] Open
Abstract
Working memory, a core function underlying many higher-level cognitive processes, requires cooperation of multiple brain regions. White matter refers to myelinated axons, which are critical to interregional brain communication. Past studies on the association between white-matter integrity and working memory have yielded mixed findings. Using voxelwise tract-based spatial statistics analysis, we investigated this relationship in a sample of 328 healthy adults from 25 to 80 years of age. Given the important role of dopamine (DA) in working-memory functioning and white matter, we also analyzed the effects of dopamine-related genes on them. There were associations between white-matter integrity and working memory in multiple tracts, indicating that working-memory functioning relies on global connections between different brain areas across the adult life span. Moreover, a mediation analysis suggested that white-matter integrity contributes to age-related differences in working memory. Finally, there was an effect of the COMT Val158Met polymorphism on white-matter integrity, such that Val/Val carriers had lower fractional anisotropy values than any Met carriers in the internal capsule, corona radiata, and posterior thalamic radiation. As this polymorphism has been associated with dopaminergic tone in the prefrontal cortex, this result provides evidence for a link between DA neurotransmission and white matter. Together, the results support a link between white-matter integrity and working memory, and provide evidence for its interplay with age- and DA-related genes.
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Rapp C, Hamilton J, Blum K, Thanos PK. The long-term interaction of diet and dopamine D2 gene expression on brain microglial activation. Psychiatry Res Neuroimaging 2022; 320:111430. [PMID: 34953329 DOI: 10.1016/j.pscychresns.2021.111430] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 12/16/2021] [Accepted: 12/17/2021] [Indexed: 12/11/2022]
Abstract
Dopamine D2 receptors are expressed on microglial in the central nervous system and promote anti-inflammatory responses. Little work has been done on the interaction between the dopamine D2 receptors and diet on activated microglial expression in the brain. To assess this, the current study uses in vitro autoradiography to look at microglial activation in the brain as a marker for neuroinflammation. Mice with different levels of expression of the DA D2 gene were given a chronic diet of either normal diet chow or high fat diet chow for 30 weeks. Mice were then euthanized and their brains were processed for [3H]PK11195 autoradiography. Mice with reductions or lack of the D2 gene showed higher [3H]PK11195 binding in a diet-specific manner within somatosensory and striatal regions, as well as the piriform, frontal, insular, and entorhinal regions compared to mice with normal D2 gene levels. These brain regions are important for sensory processing, habit formation, as well as cognitive function tasks related to learning, motivation, and memory. These results suggest that decreased D2R levels may increase vulnerability to specific inflammatory markers. Future studies will need to examine the implications of these inflammatory changes on brain function and behavior.
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Affiliation(s)
- Cecilia Rapp
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, 1021 Main Street, Buffalo, NY 14203-1016, USA; Department of Biomedical Engineering, State University at New York at Buffalo, Buffalo, NY USA
| | - John Hamilton
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, 1021 Main Street, Buffalo, NY 14203-1016, USA; Department of Psychology, State University at Buffalo, Buffalo, NY, USA
| | - Kenneth Blum
- Graduate College, Western University Health Sciences, Pomona, CA, USA
| | - Panayotis K Thanos
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, 1021 Main Street, Buffalo, NY 14203-1016, USA; Department of Psychology, State University at Buffalo, Buffalo, NY, USA.
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Differential Relations of Parental Behavior to Children's Early Executive Function as a Function of Child Genotype: A Systematic Review. Clin Child Fam Psychol Rev 2022; 25:435-470. [PMID: 35195834 DOI: 10.1007/s10567-022-00387-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/10/2022] [Indexed: 11/03/2022]
Abstract
Child genotype is an important biologically based indicator of sensitivity to the effects of parental behavior on children's executive function (EF) in early childhood, birth to age 5. While evidence for gene × parental behavior interactions on children's early EF is growing, researchers have called the quality of evidence provided by gene × environment interaction studies into question. For this reason, this review comprehensively examined the literature and evaluated the evidence for gene × parental behavior interactions on children's early EF abilities. Psychology and psychiatry databases were searched for published peer-reviewed studies. A total of 18 studies met inclusion criteria. Twenty-nine of 89 (33%) examined interactions were significant. However, a p-curve analysis did not find the significant interactions to be of evidential value. A high rate of false positives, due to the continued use of candidate gene and haplotype measures of child genotype and small sample sizes, likely contributed to the high rate of significant interactions and low evidential value. The use of contemporary molecular genetic measures and larger sample sizes are necessary to advance our understanding of child genotype as a moderator of parental effects on children's EF during early childhood and the biopsychosocial mechanisms underlying children's EF development during this critical period. Without these changes, future research is likely to be stymied by the same limitations as current research.
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Balakrishnan R, Mohammed V, Veerabathiran R. The role of genetic mutation in alcoholic liver disease. EGYPTIAN LIVER JOURNAL 2022; 12:14. [DOI: 10.1186/s43066-022-00175-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 01/26/2022] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Alcoholic liver disease (ALD) is the world’s most common type of liver disease caused due to overconsumption of alcohol. The liver supports the best level of tissue damage by hefty drinking since it is the binding site of ethanol digestion. This disease can progress to alcoholic steatohepatitis from alcoholic fatty liver, which implies steatosis has become the most punctual reaction to hefty drinking and is portrayed by the deposition of fat hepatocytes. In addition, steatosis can advance to steatohepatitis, a more extreme, provocative sort of liver damage described by hepatic inflammation. Constant and unnecessary liquor utilization delivers a wide range of hepatic sores, fibrosis and cirrhosis, and sometimes hepatocellular carcinoma. Most people consuming > 40 g of liquor each day create alcoholic fatty liver (AFL); notwithstanding, just a subset of people will grow further developed infection. Hereditary, epigenetic, and non-hereditary components may clarify the impressive interindividual variety in the ALD phenotype.
Main body
This systematic review is to classify new candidate genes associated with alcoholic liver disorders, such as RASGRF2, ALDH2, NFE2L2, ADH1B, PNPLA3, DRD2, MTHFR, TM6SF2, IL1B, and CYP2E1, MBOAT7 as well as to revise the functions of each gene in its polymorphic sequence. The information obtained from the previously published articles revealed the crucial relationship between the genes and ALD and discussed each selected gene’s mechanism.
Conclusion
The aim of this review is to highlight the candidate genes associated with the ALD, and the evidence of this study is to deliberate the part of genetic alterations and modifications that can serve as an excellent biological maker, risk predictors, and therapeutic targets for this disease.
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Palumbo S, Mariotti V, Vellucci S, Antonelli K, Anderson N, Harenski C, Pietrini P, Kiehl KA, Pellegrini S. ANKK1 and TH gene variants in combination with paternal maltreatment increase susceptibility to both cognitive and attentive impulsivity. Front Psychiatry 2022; 13:868804. [PMID: 35935430 PMCID: PMC9352854 DOI: 10.3389/fpsyt.2022.868804] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Accepted: 06/28/2022] [Indexed: 11/13/2022] Open
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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Affiliation(s)
- Sara Palumbo
- Department of Surgical, Medical and Molecular Pathology and Critical Care, University of Pisa, Pisa, Italy
| | - Veronica Mariotti
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Stefano Vellucci
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Klizia Antonelli
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Nathaniel Anderson
- The Mind Research Network and Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM, United States
| | - Carla Harenski
- The Mind Research Network and Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM, United States
| | - Pietro Pietrini
- Molecular Mind Lab, IMT School for Advanced Studies Lucca, Lucca, Italy
| | - Kent A Kiehl
- The Mind Research Network and Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM, United States.,Department of Psychology, University of New Mexico, Albuquerque, NM, United States
| | - Silvia Pellegrini
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
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Elsheikh SSM, Müller DJ, Pouget JG. Pharmacogenetics of Antipsychotic Treatment in Schizophrenia. Methods Mol Biol 2022; 2547:389-425. [PMID: 36068471 DOI: 10.1007/978-1-0716-2573-6_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Antipsychotics are the mainstay treatment for schizophrenia. There is large variability between individuals in their response to antipsychotics, both in efficacy and adverse effects of treatment. While the source of interindividual variability in antipsychotic response is not completely understood, genetics is a major contributing factor. The identification of pharmacogenetic markers that predict antipsychotic efficacy and adverse reactions is a growing area of research and holds the potential to replace the current trial-and-error approach to treatment selection in schizophrenia with a personalized medicine approach.In this chapter, we provide an overview of the current state of pharmacogenetics in schizophrenia treatment. The most promising pharmacogenetic findings are presented for both antipsychotic response and commonly studied adverse reactions. The application of pharmacogenetics to schizophrenia treatment is discussed, with an emphasis on the clinical utility of pharmacogenetic testing and directions for future research.
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Affiliation(s)
| | - Daniel J Müller
- The Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada.
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
| | - Jennie G Pouget
- The Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
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39
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Erkoreka L, Zumarraga M, Arrue A, Zamalloa MI, Arnaiz A, Olivas O, Moreno-Calle T, Saez E, Garcia J, Marin E, Varela N, Gonzalez-Pinto A, Basterreche N. Genetics of adult attachment: An updated review of the literature. World J Psychiatry 2021; 11:530-542. [PMID: 34631458 PMCID: PMC8474999 DOI: 10.5498/wjp.v11.i9.530] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/04/2021] [Accepted: 07/29/2021] [Indexed: 02/06/2023] Open
Abstract
Attachment style, which has been theorized to be rooted in childhood bonding experiences, influences adult cognitive, emotional and interpersonal functioning. Despite its relationship with early experiences, research indicates that the continuity of attachment style across childhood and adulthood is only partial, being a malleable tendency that is shaped throughout development, with an increasing influence of genetics, as it occurs in other cognitive and behavioral phenotypes. Genetic research indicates that up to 45% of the variability in anxious and 39% in avoidant adult attachment style could be explained by genetic causes, but the precise mechanisms remain unclear. A narrative review is conducted analyzing the existing literature regarding the implication of candidate genes related to oxytocin, dopaminergic pathways, serotonergic pathways and brain-derived neurotrophic factor in adult attachment, with both vulnerability and differential susceptibility approaches, yielding mixed results. We highlight the lack of genome-wide studies and the scarcity of epigenetic investigation. Based on the existing data, we conclude that the genetics of adult attachment is an area that requires further research to clarify its etiological role and that it should be preferably approached as an interaction between nature and nurture.
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Affiliation(s)
- Leire Erkoreka
- Department of Psychiatry, Galdakao-Usansolo Hospital, Osakidetza Basque Health Service, Galdakao 48960, Spain
- Department of Neurosciences, University of the Basque Country UPV/EHU, Leioa 48940, Spain
- Grupo Red de Salud Mental, Biocruces Bizkaia Health Research Institute, Barakaldo 48903, Spain
| | - Mercedes Zumarraga
- Grupo Red de Salud Mental, Biocruces Bizkaia Health Research Institute, Barakaldo 48903, Spain
- Department of Neurochemical Research, Bizkaia Mental Health Network, Osakidetza Basque Health Service, Barakaldo 48903, Spain
| | - Aurora Arrue
- Grupo Red de Salud Mental, Biocruces Bizkaia Health Research Institute, Barakaldo 48903, Spain
- Department of Neurochemical Research, Bizkaia Mental Health Network, Osakidetza Basque Health Service, Barakaldo 48903, Spain
| | - M Isabel Zamalloa
- Grupo Red de Salud Mental, Biocruces Bizkaia Health Research Institute, Barakaldo 48903, Spain
- Department of Neurochemical Research, Bizkaia Mental Health Network, Osakidetza Basque Health Service, Barakaldo 48903, Spain
| | - Ainara Arnaiz
- Grupo Red de Salud Mental, Biocruces Bizkaia Health Research Institute, Barakaldo 48903, Spain
- Erandio Mental Health Center, Bizkaia Mental Health Network, Osakidetza Basque Health Service, Erandio 48950, Spain
| | - Olga Olivas
- Grupo Red de Salud Mental, Biocruces Bizkaia Health Research Institute, Barakaldo 48903, Spain
- Zaldibar Hospital, Bizkaia Mental Health Network, Osakidetza Basque Health Service, Zaldibar 48250, Spain
| | - Teresa Moreno-Calle
- Department of Psychiatry, Galdakao-Usansolo Hospital, Osakidetza Basque Health Service, Galdakao 48960, Spain
- Grupo Red de Salud Mental, Biocruces Bizkaia Health Research Institute, Barakaldo 48903, Spain
| | - Estela Saez
- Department of Psychiatry, Galdakao-Usansolo Hospital, Osakidetza Basque Health Service, Galdakao 48960, Spain
| | - Jon Garcia
- Department of Neurosciences, University of the Basque Country UPV/EHU, Leioa 48940, Spain
- Grupo Red de Salud Mental, Biocruces Bizkaia Health Research Institute, Barakaldo 48903, Spain
- Zamudio Hospital, Bizkaia Mental Health Network, Osakidetza Basque Health Service, Zamudio 48170, Spain
| | - Elena Marin
- Grupo Red de Salud Mental, Biocruces Bizkaia Health Research Institute, Barakaldo 48903, Spain
- Bermeo Hospital, Bizkaia Mental Health Network, Osakidetza Basque Health Service, Bermeo 48370, Spain
| | - Noemi Varela
- Grupo Red de Salud Mental, Biocruces Bizkaia Health Research Institute, Barakaldo 48903, Spain
- Zamudio Hospital, Bizkaia Mental Health Network, Osakidetza Basque Health Service, Zamudio 48170, Spain
| | - Ana Gonzalez-Pinto
- Department of Psychiatry, BioAraba Research Institute, Araba University Hospital, University of the Basque Country (UPV/EHU), CIBERSAM, Vitoria-Gasteiz 01004, Spain
| | - Nieves Basterreche
- Zamudio Hospital, Bizkaia Mental Health Network, Osakidetza Basque Health Service, Zamudio 48170, Spain
- Grupo de investigación integradora en Salud Mental, Biocruces Bizkaia Health Research Institute, Barakaldo 48903, Spain
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40
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Ho AMC, Weinshilboum RM, Frye MA, Biernacka JM. Genetics and antiepileptic mood stabilizer treatment response in bipolar disorder: what do we know? Pharmacogenomics 2021; 22:913-925. [PMID: 34486896 DOI: 10.2217/pgs-2021-0041] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
Antiepileptic mood stabilizers (AED-MS) are often used to treat bipolar disorder (BD). Similar to other mood disorder medications, AED-MS treatment response varies between patients. Identification of biomarkers associated with treatment response may ultimately help with the delivery of individualized treatment and lead to improved treatment efficacy. Here, we conducted a narrative review of the current knowledge of the pharmacogenomics of AED-MS (valproic acid, lamotrigine and carbamazepine) treatment response in BD, including genetic contributions to AED-MS pharmacokinetics. Genes involved in neurotransmitter systems and drug transport have been shown to be associated with AED-MS treatment response. As more studies are conducted, and experimental and analytical methods advance, knowledge of AED-MS pharmacogenomics is expected to grow and contribute to precision medicine in BD.
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Affiliation(s)
- Ada Man-Choi Ho
- Department of Psychiatry & Psychology, Mayo Clinic, Rochester, MN 55905, USA
| | - Richard M Weinshilboum
- Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA
| | - Mark A Frye
- Department of Psychiatry & Psychology, Mayo Clinic, Rochester, MN 55905, USA
| | - Joanna M Biernacka
- Department of Psychiatry & Psychology, Mayo Clinic, Rochester, MN 55905, USA.,Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA
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41
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Dobewall H, Keltikangas-Järvinen L, Saarinen A, Lyytikäinen LP, Zwir I, Cloninger R, Raitakari OT, Lehtimäki T, Hintsanen M. Genetic differential susceptibility to the parent-child relationship quality and the life span development of compassion. Dev Psychobiol 2021; 63:e22184. [PMID: 34423428 DOI: 10.1002/dev.22184] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 06/26/2021] [Accepted: 07/06/2021] [Indexed: 11/11/2022]
Abstract
The development of compassion for others might be influenced by the social experiences made during childhood and has a genetic component. No research has yet investigated whether the parent-child relationship quality interacts with genetic variation in the oxytocin and dopamine systems in predicting compassion over the life span. In the prospective Young Finns Study (N = 2099, 43.9% men), we examined the interaction between mother-reported emotional warmth and intolerance toward their child assessed in 1980 (age of participants, 3-18 years) and two established genetic risk scores for oxytocin levels and dopamine signaling activity. Dispositional compassion for others was measured with the Temperament and Character Inventory 1997, 2001, and 2012 (age of participants, 20-50 years). We found a gene-environment interaction (p = .031) that remained marginally significant after adjustment for multiple testing. In line with the differential susceptibility hypothesis, only participants who carry alleles associated with low dopamine signaling activity had higher levels of compassion when growing up with emotionally warm parents, whereas they had lower levels of compassion when their parents were emotionally cold. Children's genetic variability in the dopamine system might result in plasticity to early environmental influences that have a long-lasting effect on the development of compassion. However, our findings need replication.
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Affiliation(s)
- Henrik Dobewall
- Division of Psychology, Faculty of Education, University of Oulu, Oulu, Finland.,Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | | | - Aino Saarinen
- Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Leo-Pekka Lyytikäinen
- Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.,Finnish Cardiovascular Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Igor Zwir
- Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, United States.,Department of Computer Science, University of Granada, Granada, Spain
| | - Robert Cloninger
- Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, United States
| | - Olli T Raitakari
- Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland.,Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.,Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland
| | - Terho Lehtimäki
- Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.,Finnish Cardiovascular Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Mirka Hintsanen
- Division of Psychology, Faculty of Education, University of Oulu, Oulu, Finland
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Habibzadeh P, Nemati A, Dastsooz H, Taghipour‐Sheshdeh A, Paul PM, Sahraian A, Faghihi MA. Investigating the association between common DRD2/ANKK1 genetic polymorphisms and schizophrenia: a meta-analysis. J Genet 2021. [DOI: 10.1007/s12041-021-01306-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Fisher ML, Pauly JR, Froeliger B, Turner JR. Translational Research in Nicotine Addiction. Cold Spring Harb Perspect Med 2021; 11:cshperspect.a039776. [PMID: 32513669 DOI: 10.1101/cshperspect.a039776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
While commendable strides have been made in reducing smoking initiation and improving smoking cessation rates, current available smoking cessation treatment options are still only mildly efficacious and show substantial interindividual variability in their therapeutic responses. Therefore, the primary goal of preclinical research has been to further the understanding of the neural substrates and genetic influences involved in nicotine's effects and reassess potential drug targets. Pronounced advances have been made by investing in new translational approaches and placing more emphasis on bridging the gap between human and rodent models of dependence. Functional neuroimaging studies have identified key brain structures involved with nicotine-dependence phenotypes such as craving, impulsivity, withdrawal symptoms, and smoking cessation outcomes. Following up with these findings, rodent-modeling techniques have made it possible to dissect the neural circuits involved in these motivated behaviors and ascertain mechanisms underlying nicotine's interactive effects on brain structure and function. Likewise, translational studies investigating single-nucleotide polymorphisms (SNPs) within the cholinergic, dopaminergic, and opioid systems have found high levels of involvement of these neurotransmitter systems in regulating the reinforcing aspects of nicotine in both humans and mouse models. These findings and coordinated efforts between human and rodent studies pave the way for future work determining gene by drug interactions and tailoring treatment options to each individual smoker.
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Affiliation(s)
- Miranda L Fisher
- Department of Pharmaceutical Sciences, University of Kentucky College of Pharmacy, Lexington, Kentucky 40536-0596, USA
| | - James R Pauly
- Department of Pharmaceutical Sciences, University of Kentucky College of Pharmacy, Lexington, Kentucky 40536-0596, USA
| | - Brett Froeliger
- Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina 29425, USA
| | - Jill R Turner
- Department of Pharmaceutical Sciences, University of Kentucky College of Pharmacy, Lexington, Kentucky 40536-0596, USA
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Oishi K, Niitsu T, Kanahara N, Sato Y, Iwayama Y, Toyota T, Hashimoto T, Sasaki T, Takase M, Shiina A, Yoshikawa T, Iyo M. Genetic risks of schizophrenia identified in a matched case-control study. Eur Arch Psychiatry Clin Neurosci 2021; 271:775-781. [PMID: 32623490 DOI: 10.1007/s00406-020-01158-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Accepted: 06/24/2020] [Indexed: 11/25/2022]
Abstract
It has been suggested that dopaminergic neurotransmission plays important roles for the psychotic symptoms and probably etiology of schizophrenia. In our recent preliminary study, we demonstrated that the specific allele combinations of dopamine-related functional single nucleotide polymorphisms (SNPs), rs10770141, rs4680, and rs1800497 could indicate risks for schizophrenia. The present validation study involved a total of 2542 individuals who were age- and sex-matched in a propensity score matching analysis, and the results supported the statistical significances of the proposed genetic risks described in our previous reports. The estimated odds ratios were 1.24 (95% CI 1.06-1.45, p < 0.001) for rs4680, 1.73 (95% CI 1.47-2.02, p < 0.0001) for rs1800497, and 1.79 (95% CI 1.35-2.36, p < 0.0001) for rs10770141. A significant relationship was also revealed among these three polymorphisms and schizophrenia, with corresponding coefficients (p < 0.0001). In this study, we also present a new scoring model for the identification of individuals with the disease risks. Using the cut-off value of 2, our model exhibited sensitivity for almost two-thirds of all of the schizophrenia patients: odds ratio 1.87, 95% CI 1.59-2.19, p < 0.0001. In conclusion, we identified significant associations of dopamine-related genetic combinations with schizophrenia. These findings suggest that some types of dopaminergic neurotransmission play important roles for development of schizophrenia, and this type of approach may also be applicable for other multifactorial diseases, providing a potent new risk predictor.
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Affiliation(s)
- Kengo Oishi
- Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuou-ku, Chiba, Chiba, 260-8670, Japan.
| | - Tomihisa Niitsu
- Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuou-ku, Chiba, Chiba, 260-8670, Japan
| | - Nobuhisa Kanahara
- Division of Medical Treatment and Rehabilitation, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chuou-ku, Chiba, Chiba, 260-8670, Japan
| | - Yasunori Sato
- Department of Preventive Medicine and Public Health, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo, 160-0016, Japan
| | - Yoshimi Iwayama
- Laboratory for Molecular Psychiatry, RIKEN Center for Brain Science, Wako, Saitama, 351-0198, Japan
- Support Unit for Bio-Material Analysis, Research Resources Division, RIKEN Center for Brain Science, Wako, Saitama, 351-0198, Japan
| | - Tomoko Toyota
- Laboratory for Molecular Psychiatry, RIKEN Center for Brain Science, Wako, Saitama, 351-0198, Japan
| | - Tasuku Hashimoto
- Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuou-ku, Chiba, Chiba, 260-8670, Japan
| | - Tsuyoshi Sasaki
- Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuou-ku, Chiba, Chiba, 260-8670, Japan
- Department of Child Psychiatry, Chiba University Hospital, 1-8-1 Inohana, Chuou-ku, Chiba, Chiba, 260-8670, Japan
| | - Masayuki Takase
- Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuou-ku, Chiba, Chiba, 260-8670, Japan
| | - Akihiro Shiina
- Division of Medical Treatment and Rehabilitation, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chuou-ku, Chiba, Chiba, 260-8670, Japan
| | - Takeo Yoshikawa
- Laboratory for Molecular Psychiatry, RIKEN Center for Brain Science, Wako, Saitama, 351-0198, Japan
| | - Masaomi Iyo
- Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuou-ku, Chiba, Chiba, 260-8670, Japan
- Division of Medical Treatment and Rehabilitation, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chuou-ku, Chiba, Chiba, 260-8670, Japan
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Brown JT, Campo-Soria C, Bishop JR. Current strategies for predicting side effects from second generation antipsychotics in youth. Expert Opin Drug Metab Toxicol 2021; 17:655-664. [PMID: 33896324 DOI: 10.1080/17425255.2021.1922668] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Introduction: Antipsychotic medications are used to treat a number of conditions in children and adolescents. While side effect profiles from second generation antipsychotics (SGAs) may differ from older antipsychotics, they do not come without risk. Knowing which children may be at higher risk for specific outcomes is important clinical information for prescribers. Common side effects and toxicities of SGAs in children include movement disorders, weight gain, and hormonal changes. There are also rare, but potentially dangerous adverse events including neuroleptic malignant syndrome, hypersensitivity and suicidal ideation.Areas covered: This review will summarize and comment on clinical, pharmacological, and genetic factors having evidence as predictors of SGA-associated side effects and toxicities in children.Expert opinion: Observations across studies note that older children and those that do not respond early in treatment may be more at risk for movement disorders, while younger, antipsychotic naive children are at increased risk for weight gain. Relatively fewer studies have looked at pharmacogenetic relationships, although variations in pharmacokinetic and pharmacodynamic genes hold promise to advance drug dosing or selection strategies. Future efforts to assimilate multiple clinical, pharmacological, and genetic factors to facilitate predictive analytics and clinical decision support for prescribers will advance precision care to patients.
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Affiliation(s)
- Jacob T Brown
- Department of Pharmacy Practice and Pharmaceutical Sciences, College of Pharmacy, University of Minnesota, Duluth, MN, USA
| | - Claudia Campo-Soria
- Department of Psychiatry, Children's Hospitals and Clinics of Minnesota, Minneapolis, MN, USA
| | - Jeffrey R Bishop
- Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA.,Department of Psychiatry and Behavioral Sciences, School of Medicine, University of Minnesota, Minneapolis, MN, USA
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46
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Dobewall H, Saarinen A, Lyytikäinen LP, Keltikangas-Järvinen L, Lehtimäki T, Hintsanen M. Functional Polymorphisms in Oxytocin and Dopamine Pathway Genes and the Development of Dispositional Compassion Over Time: The Young Finns Study. Front Psychol 2021; 12:576346. [PMID: 33897514 PMCID: PMC8060576 DOI: 10.3389/fpsyg.2021.576346] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Accepted: 03/03/2021] [Indexed: 12/21/2022] Open
Abstract
Background: We define compassion as an enduring disposition that centers upon empathetic concern for another person's suffering and the motivation to act to alleviate it. The contribution of specific candidate genes to the development of dispositional compassion for others is currently unknown. We examine candidate genes in the oxytocin and dopamine signaling pathways. Methods: In a 32-year follow-up of the Young Finns Study (N = 2,130, 44.0% men), we examined with multiple indicators latent growth curve modeling the molecular genetic underpinnings of dispositional compassion for others across the life span. We selected five single nucleotide polymorphisms (SNPs) whose functions are known in humans: rs2268498 (OXTR), rs3796863 (CD38) (related to lower oxytocin levels), rs1800497 (ANKK1/DRD2), rs4680 (COMT), and rs1611115 (DBH) (related to higher dopamine levels). Compassion was measured with Cloninger's Temperament and Character Inventory on three repeated observations spanning 15 years (1997–2012). Differences between gender were tested. Results: We did not find an effect of the five SNPs in oxytocin and dopamine pathway genes on the initial levels of dispositional compassion for others. Individuals who carry one or two copies of the T-allele of DBH rs1611115, however, tend to increase faster in compassion over time than those homozygotes for the C-allele, b = 0.063 (SE = 0.027; p = 0.018). This effect was largely driven by male participants, 0.206 (SE = 0.046; p < 0.001), and was not significant in female participants when analyzed separately. Conclusions: Men who are known to have, on average, lower compassion than women seem to reduce this difference over time if they carry the T-allele of DBH rs1611115. The direction of the association indicates that dopamine signaling activity rather than overall dopamine levels might drive the development of compassion.
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Affiliation(s)
- Henrik Dobewall
- Research Unit of Psychology, University of Oulu, Oulu, Finland.,Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Fimlab Laboratories, and Finnish Cardiovascular Research Center - Tampere, Department of Clinical Chemistry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Aino Saarinen
- Research Unit of Psychology, University of Oulu, Oulu, Finland.,Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Leo-Pekka Lyytikäinen
- Fimlab Laboratories, and Finnish Cardiovascular Research Center - Tampere, Department of Clinical Chemistry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | | | - Terho Lehtimäki
- Fimlab Laboratories, and Finnish Cardiovascular Research Center - Tampere, Department of Clinical Chemistry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Mirka Hintsanen
- Research Unit of Psychology, University of Oulu, Oulu, Finland
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47
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Magistrelli L, Ferrari M, Furgiuele A, Milner AV, Contaldi E, Comi C, Cosentino M, Marino F. Polymorphisms of Dopamine Receptor Genes and Parkinson's Disease: Clinical Relevance and Future Perspectives. Int J Mol Sci 2021; 22:ijms22073781. [PMID: 33917417 PMCID: PMC8038729 DOI: 10.3390/ijms22073781] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 03/26/2021] [Accepted: 04/01/2021] [Indexed: 12/20/2022] Open
Abstract
Parkinson’s disease (PD) is a neurodegenerative disease caused by loss of dopaminergic neurons in the midbrain. PD is clinically characterized by a variety of motor and nonmotor symptoms, and treatment relies on dopaminergic replacement. Beyond a common pathological hallmark, PD patients may present differences in both clinical progression and response to drug therapy that are partly affected by genetic factors. Despite extensive knowledge on genetic variability of dopaminergic receptors (DR), few studies have addressed their relevance as possible influencers of clinical heterogeneity in PD patients. In this review, we summarized available evidence regarding the role of genetic polymorphisms in DR as possible determinants of PD development, progression and treatment response. Moreover, we examined the role of DR in the modulation of peripheral immunity, in light of the emerging role of the peripheral immune system in PD pathophysiology. A better understanding of all these aspects represents an important step towards the development of precise and personalized disease-modifying therapies for PD.
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Affiliation(s)
- Luca Magistrelli
- PhD Program in Clinical and Experimental Medicine and Medical Humanities, University of Insubria, 21100 Varese, Italy; (L.M.); (A.F.)
- Movement Disorders Centre, Neurology Unit, Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy; (A.V.M.); (E.C.)
| | - Marco Ferrari
- Centre of Research in Medical Pharmacology, University of Insubria, 21100 Varese, Italy; (M.F.); (M.C.); (F.M.)
| | - Alessia Furgiuele
- PhD Program in Clinical and Experimental Medicine and Medical Humanities, University of Insubria, 21100 Varese, Italy; (L.M.); (A.F.)
- Centre of Research in Medical Pharmacology, University of Insubria, 21100 Varese, Italy; (M.F.); (M.C.); (F.M.)
| | - Anna Vera Milner
- Movement Disorders Centre, Neurology Unit, Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy; (A.V.M.); (E.C.)
| | - Elena Contaldi
- Movement Disorders Centre, Neurology Unit, Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy; (A.V.M.); (E.C.)
- PhD Program in Medical Sciences and Biotechnology, University of Piemonte Orientale, 28100 Novara, Italy
| | - Cristoforo Comi
- Movement Disorders Centre, Neurology Unit, Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy; (A.V.M.); (E.C.)
- Centre of Research in Medical Pharmacology, University of Insubria, 21100 Varese, Italy; (M.F.); (M.C.); (F.M.)
- Correspondence:
| | - Marco Cosentino
- Centre of Research in Medical Pharmacology, University of Insubria, 21100 Varese, Italy; (M.F.); (M.C.); (F.M.)
- Center of Research in Neuroscience, University of Insubria, 21100 Varese, Italy
| | - Franca Marino
- Centre of Research in Medical Pharmacology, University of Insubria, 21100 Varese, Italy; (M.F.); (M.C.); (F.M.)
- Center of Research in Neuroscience, University of Insubria, 21100 Varese, Italy
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48
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Ney LJ, Akhurst J, Bruno R, Laing PAF, Matthews A, Felmingham KL. Dopamine, endocannabinoids and their interaction in fear extinction and negative affect in PTSD. Prog Neuropsychopharmacol Biol Psychiatry 2021; 105:110118. [PMID: 32991952 DOI: 10.1016/j.pnpbp.2020.110118] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 09/03/2020] [Accepted: 09/22/2020] [Indexed: 12/13/2022]
Abstract
There currently exist few frameworks for common neurobiology between reexperiencing and negative cognitions and mood symptoms of PTSD. Adopting a dopaminergic framework for PTSD unites many aspects of unique symptom clusters, and this approach also links PTSD symptomology to common comorbidities with a common neurobiological deficiency. Here we review the dopamine literature and incorporate it with a growing field of research that describes both the contribution of endocannabinoids to fear extinction and PTSD, as well as the interactions between dopaminergic and endocannabinoid systems underlying this disorder. Based on current evidence, we outline an early, preliminary model that links re-experiencing and negative cognitions and mood in PTSD by invoking the interaction between endocannabinoid and dopaminergic signalling in the brain. These interactions between PTSD, dopamine and endocannabinoids may have implications for future therapies for treatment-resistant and comorbid PTSD patients.
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Affiliation(s)
- Luke J Ney
- School of Psychology, University of Tasmania, Australia.
| | - Jane Akhurst
- School of Psychology, University of Tasmania, Australia
| | | | - Patrick A F Laing
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne & Melbourne Health, Australia
| | | | - Kim L Felmingham
- School of Psychological Sciences, University of Melbourne, Australia
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Park S, Kwon J, Ahn C, Cho HS, Moon HY, Lee CG. The Role of Dopamine Receptor D2 in Bridging the Intention-Behavior Gap in Sport Participation. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18052379. [PMID: 33804403 PMCID: PMC7967739 DOI: 10.3390/ijerph18052379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 02/12/2021] [Accepted: 02/20/2021] [Indexed: 11/27/2022]
Abstract
Previous studies have identified that a behavior can occur through the strongest predictor intention, but there is a gap between intention and behavior. Dopamine receptor D2 (DRD2) is known to account for a variance in sporting behaviors in human and animal subjects. However, the relationship between DRD2 and sport participation has been poorly studied, and the limited available reports are inconsistent. The present study was performed to examine the impact of DRD2 on sport participation among Korean university students based on the integrated behavioral model (IBM). Data were collected from enrolled university students in Seoul (N = 45). Participants answered survey questions first, and then they gave investigators their hair to provide DNA information (i.e., the A1 allele of DRD2). DRD2 had a significant effect on sport participation, but only in male students. Male students who carried the A1 allele of DRD2 significantly participated in 105.10 min more sporting activities than male students who did not. Moreover, the effect of intention on sport participation was significantly decreased when considering DRD2. Despite the small sample size, the results of this study could be a preliminary case for a larger study and indicate the direction of future research. Our results suggest that DRD2 may have played an important role as the “actual skill” shown in the IBM.
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50
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Miranda GG, Rodrigue KM, Kennedy KM. Cortical thickness mediates the relationship between DRD2 C957T polymorphism and executive function across the adult lifespan. Brain Struct Funct 2021; 226:121-136. [PMID: 33179159 PMCID: PMC7855542 DOI: 10.1007/s00429-020-02169-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Accepted: 10/24/2020] [Indexed: 12/26/2022]
Abstract
Dopamine (DA) signaling is critical for optimal cognitive performance. Aging is accompanied by a change in the strength of this signaling, with a loss of striatal and extrastriatal D2 binding potential. The reduction in dopamine modulation with age negatively influences various aspects of cognition. DRD2 C957T (rs6277) impacts DA D2 receptor density and availability, with C homozygotes linked to lower striatal DA availability and reduced executive functioning (EF), but also high extrastriatal binding potential. Here, we investigated in 176 participants aged 20-94 years whether: (1) DRD2 C carriers differ from T carriers in cortical thickness or subcortical volume in areas of high concentrations of D2 receptors that receive projections from mesocortical or nigrostriatal dopaminergic pathways; (2) whether the DRD2*COMT relationship has any synergistic effects on cortical thickness; (3) whether the effect of DRD2 on brain structure depends upon age; and (4) whether DRD2-related regional thinning affects executive function performance. We show that DRD2 impacts cortical thickness in the superior parietal lobule, precuneus, and anterior cingulate (marginal after FDR correction), while statistically controlling sex, age, and COMT genotype. Specifically, C homozygotes demonstrated thinner cortices than both heterozygotes and/or T homozygotes in an age-invariant manner. Additionally, DRD2 predicted executive function performance via cortical thickness. The results highlight that genetic influences on dopamine availability impact cognitive performance via the contribution of brain structure in cortical regions influenced by DRD2.
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Affiliation(s)
- Giuseppe G Miranda
- Center for Vital Longevity, School of Behavioral and Brain Science, The University of Texas At Dallas, Dallas, TX, USA
| | - Karen M Rodrigue
- Center for Vital Longevity, School of Behavioral and Brain Science, The University of Texas At Dallas, Dallas, TX, USA
| | - Kristen M Kennedy
- Center for Vital Longevity, School of Behavioral and Brain Science, The University of Texas At Dallas, Dallas, TX, USA.
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