|
1
|
Lorek M, Kamiński P, Baszyński J, Tadrowski T, Gorzelańczyk EJ, Feit J, Kurhaluk N, Woźniak A, Tkaczenko H. Molecular and Environmental Determinants of Addictive Substances. Biomolecules 2024; 14:1406. [PMID: 39595582 PMCID: PMC11592269 DOI: 10.3390/biom14111406] [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: 09/11/2024] [Revised: 10/25/2024] [Accepted: 11/02/2024] [Indexed: 11/28/2024] Open
Abstract
Knowledge about determinants of addiction in people taking addictive substances is poor and needs to be supplemented. The novelty of this paper consists in the analysis of innovative aspects of current research about relationships between determinants of addiction in Polish patients taking addictive substances and rare available data regarding the relationships between these factors from studies from recent years from other environments, mainly in Europe, and on the development of genetic determinants of physiological responses. We try to explain the role of the microelements Mn, Fe, Cu, Co, Zn, Cr, Ni, Tl, Se, Al, B, Mo, V, Sn, Sb, Ag, Sr, and Ba, the toxic metals Cd, Hg, As, and Pb, and the rare earth elements Sc, La, Ce, Pr, Eu, Gd, and Nd as factors that may shape the development of addiction to addictive substances or drugs. The interactions between factors (gene polymorphism, especially ANKK1 (TaqI A), ANKK1 (Taq1 A-CT), DRD2 (TaqI B, DRD2 Taq1 B-GA, DRD2 Taq1 B-AA, DRD2-141C Ins/Del), and OPRM1 (A118G)) in patients addicted to addictive substances and consumption of vegetables, consumption of dairy products, exposure to harmful factors, and their relationships with physiological responses, which confirm the importance of internal factors as determinants of addiction, are analyzed, taking into account gender and region. The innovation of this review is to show that the homozygous TT mutant of the ANKK1 TaqI A polymorphism rs 1800497 may be a factor in increased risk of opioid dependence. We identify a variation in the functioning of the immune system in addicted patients from different environments as a result of the interaction of polymorphisms.
Collapse
Affiliation(s)
- Małgorzata Lorek
- Division of Ecology and Environmental Protection, Department of Medical Biology and Biochemistry, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, M. Skłodowska-Curie St. 9, PL 85-094 Bydgoszcz, Poland; (M.L.); (J.B.)
| | - Piotr Kamiński
- Division of Ecology and Environmental Protection, Department of Medical Biology and Biochemistry, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, M. Skłodowska-Curie St. 9, PL 85-094 Bydgoszcz, Poland; (M.L.); (J.B.)
- Department of Biotechnology, Institute of Biological Sciences, Faculty of Biological Sciences, University of Zielona Góra, Prof. Z. Szafran St. 1, PL 65-516 Zielona Góra, Poland
| | - Jędrzej Baszyński
- Division of Ecology and Environmental Protection, Department of Medical Biology and Biochemistry, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, M. Skłodowska-Curie St. 9, PL 85-094 Bydgoszcz, Poland; (M.L.); (J.B.)
| | - Tadeusz Tadrowski
- Department of Dermatology and Venereology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, M. Skłodowska-Curie St. 9, PL 85-094 Bydgoszcz, Poland;
| | - Edward Jacek Gorzelańczyk
- Institute of Philosophy, Kazimierz Wielki University in Bydgoszcz, M.K. Ogiński St. 16, PL 85-092 Bydgoszcz, Poland;
- Faculty of Mathematics and Computer Science, Adam Mickiewicz University in Poznań, Uniwersytet Poznański St., 4, PL 61-614 Poznań, Poland
- Primate Cardinal Stefan Wyszyński Provincial Hospital in Sieradz, Psychiatric Centre in Warta, Sieradzka St. 3, PL 98-290 Warta, Poland
- Department of Theoretical Foundations of Biomedical Sciences and Medical Computer Science, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Jagiellońska St. 15, PL 85-067 Bydgoszcz, Poland
| | - Julia Feit
- Pallmed sp. z o.o., W. Roentgen St. 3, PL 85-796 Bydgoszcz, Poland;
| | - Natalia Kurhaluk
- Department of Animal Physiology, Institute of Biology, Pomeranian University in Słupsk, Arciszewski St. 22 B, PL 76-200 Słupsk, Poland; (N.K.); (H.T.)
| | - Alina Woźniak
- Department of Medical Biology and Biochemistry, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, M. Karłowicz St. 24, PL 85-092 Bydgoszcz, Poland;
| | - Halina Tkaczenko
- Department of Animal Physiology, Institute of Biology, Pomeranian University in Słupsk, Arciszewski St. 22 B, PL 76-200 Słupsk, Poland; (N.K.); (H.T.)
| |
Collapse
|
|
2
|
Herzog N, Hartmann H, Janssen LK, Kanyamibwa A, Waltmann M, Kovacs P, Deserno L, Fallon S, Villringer A, Horstmann A. Working memory gating in obesity is moderated by striatal dopaminergic gene variants. eLife 2024; 13:RP93369. [PMID: 39431987 PMCID: PMC11493406 DOI: 10.7554/elife.93369] [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] [Indexed: 10/22/2024] Open
Abstract
Everyday life requires an adaptive balance between distraction-resistant maintenance of information and the flexibility to update this information when needed. These opposing mechanisms are proposed to be balanced through a working memory gating mechanism. Prior research indicates that obesity may elevate the risk of working memory deficits, yet the underlying mechanisms remain elusive. Dopaminergic alterations have emerged as a potential mediator. However, current models suggest these alterations should only shift the balance in working memory tasks, not produce overall deficits. The empirical support for this notion is currently lacking, however. To address this gap, we pooled data from three studies (N = 320) where participants performed a working memory gating task. Higher BMI was associated with overall poorer working memory, irrespective of whether there was a need to maintain or update information. However, when participants, in addition to BMI level, were categorized based on certain putative dopamine-signaling characteristics (single-nucleotide polymorphisms [SNPs]; specifically, Taq1A and DARPP-32), distinct working memory gating effects emerged. These SNPs, primarily associated with striatal dopamine transmission, appear to be linked with differences in updating, specifically, among high-BMI individuals. Moreover, blood amino acid ratio, which indicates central dopamine synthesis capacity, combined with BMI shifted the balance between distractor-resistant maintenance and updating. These findings suggest that both dopamine-dependent and dopamine-independent cognitive effects exist in obesity. Understanding these effects is crucial if we aim to modify maladaptive cognitive profiles in individuals with obesity.
Collapse
Affiliation(s)
- Nadine Herzog
- Department of Neurology, Max Planck Institute for Human Cognitive & Brain SciencesLeipzigGermany
- International Max Planck Research School NeuroComLeipzigGermany
| | - Hendrik Hartmann
- Department of Neurology, Max Planck Institute for Human Cognitive & Brain SciencesLeipzigGermany
- Collaborative Research Centre 1052, University of LeipzigLeipzigGermany
- Department of Psychology and Logopedics, Faculty of Medicine, University of HelsinkiHelsinkiFinland
| | - Lieneke Katharina Janssen
- Department of Neurology, Max Planck Institute for Human Cognitive & Brain SciencesLeipzigGermany
- Institute of Psychology, Otto von Guericke University MagdeburgMagdeburgGermany
| | - Arsene Kanyamibwa
- Department of Psychology and Logopedics, Faculty of Medicine, University of HelsinkiHelsinkiFinland
| | - Maria Waltmann
- Department of Neurology, Max Planck Institute for Human Cognitive & Brain SciencesLeipzigGermany
- Department of Child and Adolescent Psychiatry, University of WürzburgWürzburgGermany
| | - Peter Kovacs
- Medical Department III – Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical CenterLeipzigGermany
| | - Lorenz Deserno
- Department of Child and Adolescent Psychiatry, University of WürzburgWürzburgGermany
- Department of Psychiatry and Psychotherapy, Technische Universität DresdenDresdenGermany
| | - Sean Fallon
- School of Psychology, University of PlymouthPlymouthUnited Kingdom
| | - Arno Villringer
- Department of Neurology, Max Planck Institute for Human Cognitive & Brain SciencesLeipzigGermany
| | - Annette Horstmann
- Department of Neurology, Max Planck Institute for Human Cognitive & Brain SciencesLeipzigGermany
- Collaborative Research Centre 1052, University of LeipzigLeipzigGermany
- Department of Psychology and Logopedics, Faculty of Medicine, University of HelsinkiHelsinkiFinland
| |
Collapse
|
|
3
|
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.
Collapse
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
| |
Collapse
|
|
4
|
Oka M, Yoshino R, Kitanaka N, Hall FS, Uhl GR, Kitanaka J. Role of glycogen synthase kinase-3β in dependence and abuse liability of alcohol. Alcohol Alcohol 2024; 59:agad086. [PMID: 38145944 DOI: 10.1093/alcalc/agad086] [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: 07/30/2023] [Revised: 11/25/2023] [Accepted: 11/28/2023] [Indexed: 12/27/2023] Open
Abstract
BACKGROUND Alcohol is a major abused drug worldwide that contributes substantially to health and social problems. These problems result from acute alcohol overuse as well as chronic use, leading to alcohol use disorder (AUD). A major goal of this field is to establish a treatment for alcohol abuse and dependence in patients with AUD. The central molecular mechanisms of acute alcohol actions have been extensively investigated in rodent models. AIMS One of the central mechanisms that may be involved is glycogen synthase kinase-3β (GSK-3β) activity, a key enzyme involved in glycogen metabolism but which has crucial roles in numerous cellular processes. Although the exact mechanisms leading from acute alcohol actions to these chronic changes in GSK-3β function are not yet clear, GSK-3β nonetheless constitutes a potential therapeutic target for AUD by reducing its function using GSK-3β inhibitors. This review is focused on the correlation between GSK-3β activity and the degree of alcohol consumption. METHODS Research articles regarding investigation of effect of GSK-3β on alcohol consumption in rodents were searched on PubMed, Embase, and Scopus databases using keywords "glycogen synthase kinase," "alcohol (or ethanol)," "intake (or consumption)," and evaluated by changes in ratios of pGSK-3βSer9/pGSK-3β. RESULTS In animal experiments, GSK-3β activity decreases in the brain under forced and voluntary alcohol consumption while GSK-3β activity increases under alcohol-seeking behavior. CONCLUSIONS Several pieces of evidence suggest that alterations in GSK-3β function are important mediators of chronic ethanol actions, including those related to alcohol dependence and the adverse effects of chronic ethanol exposure.
Collapse
Affiliation(s)
- Masahiro Oka
- Laboratory of Drug Addiction and Experimental Therapeutics, Department of Pharmacy, School of Pharmacy, Hyogo Medical University, 1-3-6 Minatojima, Chuo-ku, Kobe, Hyogo 650-8530, Japan
| | - Rui Yoshino
- Laboratory of Drug Addiction and Experimental Therapeutics, Department of Pharmacy, School of Pharmacy, Hyogo Medical University, 1-3-6 Minatojima, Chuo-ku, Kobe, Hyogo 650-8530, Japan
| | - Nobue Kitanaka
- Department of Pharmacology, School of Medicine, Hyogo Medical University, Nishinomiya, Hyogo 663-8501, Japan
| | - F Scott Hall
- Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Frederic and Mary Wolfe Center HEB 282D, Mail Stop 1015, 3000 Arlington Avenue,Toledo, OH 43614, United States
| | - George R Uhl
- Neurology Service, VA Maryland Healthcare System, 10 North Greene Street, Baltimore, MD 21201, United States
- Departments of Neurology and Pharmacology, University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, United States
| | - Junichi Kitanaka
- Laboratory of Drug Addiction and Experimental Therapeutics, Department of Pharmacy, School of Pharmacy, Hyogo Medical University, 1-3-6 Minatojima, Chuo-ku, Kobe, Hyogo 650-8530, Japan
| |
Collapse
|
|
5
|
The molecular genetic basis of creativity: a mini review and perspectives. PSYCHOLOGICAL RESEARCH 2023; 87:1-16. [PMID: 35217895 DOI: 10.1007/s00426-022-01649-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 01/16/2022] [Indexed: 01/27/2023]
Abstract
Although creativity is one of the defining features of human species, it is just the beginning of an ambitious attempt for psychologists to understand its genetic basis. With ongoing efforts, great progress has been achieved in molecular genetic studies of creativity. In this mini review, we highlighted recent molecular genetic findings for both domain-general and domain-specific creativity, and provided some perspectives for future studies. It is expected that this work will provide an update on the knowledge regarding the molecular genetic basis of creativity, and contribute to the further development of this field.
Collapse
|
|
6
|
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.
Collapse
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
| |
Collapse
|
|
7
|
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.
Collapse
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.
| |
Collapse
|
|
8
|
Obregón AM, Oyarce K, García-Robles MA, Valladares M, Pettinelli P, Goldfield GS. Association of the dopamine D2 receptor rs1800497 polymorphism with food addiction, food reinforcement, and eating behavior in Chilean adults. Eat Weight Disord 2022; 27:215-224. [PMID: 33738781 DOI: 10.1007/s40519-021-01136-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Accepted: 01/28/2021] [Indexed: 12/22/2022] Open
Abstract
PURPOSE The regulation of food intake and body weight involves two interacting systems: (a) The homeostatic system (including biological regulators of hunger and satiety) and (b) the non-homeostatic system, (involving concepts of food reinforcement and food addiction). Studies have established a strong genetic component in eating behavior and obesity. The TaqI A1 polymorphism (rs1800497) has previously been associated with eating behavior, diminished dopamine D2 receptor (DRD2) density, higher body mass, and food reinforcement, but relations to food addiction remain unclear. AIM To evaluate the association between the polymorphism rs1800497 with eating behavior, food reinforcement and food addiction in Chilean adults. METHODS This cross-sectional study recruited a convenience sample of 97 obese, 25 overweight and 99 normal-weight adults (18-35 years). Anthropometric measurements were performed by standard procedures. Eating behavior was assessed using the: Yale Food Addiction Scale (YFAS), the Three Factor Eating Behavior Questionnaire and the Food Reinforcement Value Questionnaire (FRVQ). The DRD2 genotype (rs1800497) was determined by taqman assays. RESULTS Twenty-two percentage of the participants met the criteria for food addiction. Food addiction was higher in women than men (26% vs 10.7%) and in obese compared to non-obese (40% vs 6%). There was no relationship between food addiction and DRD2 genotype. However when stratified by sex and nutritional status, obese female carriers of the A1 allele reported greater scores on emotional eating and snack food reinforcement compared to non-carriers. CONCLUSIONS The DRD2 polymorphism is associated with some hedonic aspects of eating behavior, namely food reinforcement and emotional eating but not food addiction, and this association may be moderated by sex and obesity status, with obese women who are carriers of this genetic variant at higher risk. LEVEL OF EVIDENCE Level V: evidence obtained from a cross-sectional descriptive study.
Collapse
Affiliation(s)
- Ana M Obregón
- Escuela de Nutrición y Dietética, Facultad de Ciencias para el Cuidado de la Salud, Universidad San Sebastián, Lientur 1457, 4080871, Concepción, Chile.
| | - Karina Oyarce
- Escuela de Tecnología Medica, Facultad de Ciencias de la Salud, Universidad San Sebastián, Concepción, Chile
| | | | - Macarena Valladares
- Centro Integrativo de Biología y Química Aplicada (CIBQA), Universidad Bernardo O' Higgins, Santiago, Chile
| | - Paulina Pettinelli
- Departamento de Ciencias de la Salud, Carrera de Nutrición y Dietética, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Gary S Goldfield
- Children's Hospital of Eastern Ontario Research Institute, Ottawa, Canada
| |
Collapse
|
|
9
|
Boness CL, Watts AL, Moeller KN, Sher KJ. The Etiologic, Theory-Based, Ontogenetic Hierarchical Framework of Alcohol Use Disorder: A Translational Systematic Review of Reviews. Psychol Bull 2021; 147:1075-1123. [PMID: 35295672 PMCID: PMC8923643 DOI: 10.1037/bul0000333] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/24/2023]
Abstract
Modern nosologies (e.g., ICD-11, DSM-5) for alcohol use disorder (AUD) and dependence prioritize reliability and clinical presentation over etiology, resulting in a diagnosis that is not always strongly grounded in basic theory and research. Within these nosologies, DSM-5 AUD is treated as a discrete, largely categorical, but graded, phenomenon, which results in additional challenges (e.g., significant phenotypic heterogeneity). Efforts to increase the compatibility between AUD diagnosis and modern conceptualizations of alcohol dependence, which describe it as dimensional and partially overlapping with other psychopathology (e.g., other substance use disorders) will inspire a stronger scientific framework and strengthen AUD's validity. We conducted a systematic review of 144 reviews to integrate addiction constructs and theories into a comprehensive framework with the aim of identifying fundamental mechanisms implicated in AUD. The product of this effort was the Etiologic, Theory-Based, Ontogenetic Hierarchical Framework (ETOH Framework) of AUD mechanisms, which outlines superdomains of cognitive control, reward, as well as negative valence and emotionality, each of which subsume narrower, hierarchically-organized components. We also outline opponent processes and self-awareness as key moderators of AUD mechanisms. In contrast with other frameworks, we recommend an increased conceptual role for negative valence and compulsion in AUD. The ETOH framework serves as a critical step towards conceptualizations of AUD as dimensional and heterogeneous. It has the potential to improve AUD assessment and aid in the development of evidence-based diagnostic measures that focus on key mechanisms in AUD, consequently facilitating treatment matching.
Collapse
Affiliation(s)
| | - Ashley L Watts
- Department of Psychological Science, University of Missouri
| | | | - Kenneth J Sher
- Department of Psychological Science, University of Missouri
| |
Collapse
|
|
10
|
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]
|
|
11
|
Ossola P, Gerra MC, Gerra ML, Milano G, Zatti M, Zavan V, Volpi R, Marchesi C, Donnini C, Gerra G, Di Gennaro C. Alcohol use disorders among adult children of alcoholics (ACOAs): Gene-environment resilience factors. Prog Neuropsychopharmacol Biol Psychiatry 2021; 108:110167. [PMID: 33166669 DOI: 10.1016/j.pnpbp.2020.110167] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Revised: 10/03/2020] [Accepted: 11/02/2020] [Indexed: 11/17/2022]
Abstract
Both genetic and early environmental factors contribute to the pathogenesis of Alcohol Use Disorder (AUD). Gender and psychopathology symptoms might further moderate this association, resulting in an impairment of both the dopaminergic and serotoninergic pathways that sustain the binge, withdrawal and craving cycle. In a sample of of adult children of alcoholic parents (ACOAs) (n = 107) we compared those with and without an AUD, on socio-demographic variables, adverse childhood experiences, psychopathology symptoms and two polymorphisms associated with an impaired serotoninergic and dopaminergic neurotransmission (5HTTLPR and Taq1A/DRD2). A logistic regression revealed that an early caring environment might lower the risk of developing an AUD. When controlling for the actual psychopathology symptoms, being male and having the genotype associated with an impaired dopaminergic neurotransmission were still associated with AUD. Results were confirmed by an unsupervised approach that showed how the clusters characterised by being male and having the high risk genotypes were still associated with AUD compared to being female without the unfavourable dopamine genotype.Our results point to the need for implementing prevention strategies aimed at creating a caring environment especially in those families with an alcoholic parent. We further suggest that psycho-education as a symptom recognition and avoiding self-medication could improve the outcome in those subjects at higher risk, especially males.
Collapse
Affiliation(s)
- Paolo Ossola
- Department of Medicine and Surgery, University of Parma, Parma, Italy.
| | - Maria Carla Gerra
- Center for Neuroplasticity and Pain (CNAP), SMI®, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
| | - Maria Lidia Gerra
- Department of Mental Health, Local Health Agency Parma, Parma, Italy
| | - Giulia Milano
- Department of Laboratory Medicine, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Marta Zatti
- Department of Medicine and Surgery, University of Parma, Parma, Italy.
| | - Valeria Zavan
- Department of Addiction Pathology, Local Health Agency Alessandria, Alessandria, Italy
| | - Riccardo Volpi
- Department of Medicine and Surgery, University of Parma, Parma, Italy.
| | - Carlo Marchesi
- Department of Medicine and Surgery, University of Parma, Parma, Italy.
| | - Claudia Donnini
- Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy.
| | - Gilberto Gerra
- Drug Prevention and Health Branch, Division for Operations, United Nation Office on Drugs and Crime, Vienna, Austria.
| | | |
Collapse
|
|
12
|
Aliasghari F, Nazm SA, Yasari S, Mahdavi R, Bonyadi M. Associations of the ANKK1 and DRD2 gene polymorphisms with overweight, obesity and hedonic hunger among women from the Northwest of Iran. Eat Weight Disord 2021; 26:305-312. [PMID: 32020513 DOI: 10.1007/s40519-020-00851-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Accepted: 01/16/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Pleasure from palatable foods can stimulate hedonic eating and, therefore, might be a major culprit for obesity. Dopamine receptor polymorphisms, especially variants in the genes regulating the D2 receptor, including ANKK1 and DRD2, are the prime candidates for assessing the individual differences in hedonic eating. This study was carried out to investigate the possible associations of the T (rs1800497) and Del (rs1799732) alleles with body mass index (BMI) and hedonic hunger among Iranian Azeri women. METHODS A total of 372 healthy overweight/obese subjects (BMI ≥ 25 kg/m2) and 159 normal weight individuals (BMI 18.5-24.9 kg/m2) were genotyped for the polymorphisms of ANNK1 and DRD2 genes using PCR-RFLP. BMI and hedonic hunger were also evaluated. RESULTS Three hundred and sixty-three (68.36%), 152 (28.63%), and 16 (3.01%) of the participants had CC, CT, and TT genotypes for ANNK1 gene, respectively. Of 515 samples genotyped for DRD2 gene, 315 (60.51%), 173 (33.59%), and 27 (5.24%) had Ins/Ins, Ins/Del, and Del/Del genotypes, respectively. The genotype and genotype frequencies were significantly different between the groups (p = 0.04). Significant differences were observed between the T+ genotype (TT + TC) and the T- genotype (CC) regarding the BMI and hedonic hunger scores (p < 0.05). In addition, Del+ group (Del/Del + Ins/Del) had higher BMI and hedonic hunger scores compared to Del- group (Ins/Ins) (p < 0.05). CONCLUSIONS Our findings showed that the frequencies of T and Del alleles were greater in the overweight/obese individuals. Also, the polymorphism of ANKK1 (rs1800497) and polymorphism of the DRD2 gene (rs1799732) showed significant associations with BMI and hedonic hunger. LEVEL OF EVIDENCE Level III, case-control study.
Collapse
Affiliation(s)
- Fereshteh Aliasghari
- Nutrition Research Center, Student Research Committee, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Saba A Nazm
- Faculty of Natural Sciences, Center of Excellence for Biodiversity, University of Tabriz, Tabriz, Iran
| | - Sepideh Yasari
- Faculty of Natural Sciences, Center of Excellence for Biodiversity, University of Tabriz, Tabriz, Iran
| | - Reza Mahdavi
- Nutrition Research Center, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Morteza Bonyadi
- Faculty of Natural Sciences, Center of Excellence for Biodiversity, University of Tabriz, Tabriz, Iran.
| |
Collapse
|
|
13
|
Ikeda K, Ide S, Takahashi-Omoe H, Minami M, Miyata H, Kawato M, Okamoto H, Kikuchi T, Saito Y, Shirao T, Sekino Y, Murai T, Matsumoto T, Iseki M, Nishitani Y, Sumitani M, Takahashi H, Yamawaki S, Isa T, Kamio Y. Required research activities to overcome addiction problems in Japan. TAIWANESE JOURNAL OF PSYCHIATRY 2021. [DOI: 10.4103/tpsy.tpsy_3_21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
|
|
14
|
Sindermann C, Sariyska R, Elhai JD, Montag C. Molecular genetics of neurotransmitters and neuropeptides involved in Internet use disorders including first insights on a potential role of hypothalamus' oxytocin hormone. HANDBOOK OF CLINICAL NEUROLOGY 2021; 182:389-400. [PMID: 34266607 DOI: 10.1016/b978-0-12-819973-2.00026-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
This chapter covers the phenomenon of Internet use disorders (IUDs) and putative associations with different neurotransmitter and neuropeptide systems. Genes coding for such messengers can be seen as an important starting point in the complicated quest to understand human behavior including new phenomena such as IUDs. Therefore, a special focus of this chapter will lie on individual differences in molecular genetic underpinnings of neurotransmitter and neuropeptide systems and their associations with individual differences in tendencies towards IUDs. By shedding light on these associations, putative predisposing molecular genetic factors for the emergence and maintenance of IUDs can be carved out. Therefore, first an introduction to IUDs and a model that can guide research on putative associations of IUDs with different specific neurotransmitters and neuropeptides will be presented. Subsequently, twin studies on the heritability of IUDs are reviewed. Finally, studies on differences in molecular genetic predispositions and their associations with differences in IUDs will be presented and discussed, including targets related to the dopaminergic and serotonergic system as well as the hypothalamic neuropeptide oxytocin. The chapter closes with a conclusion about what is already known and what needs to be investigated in future studies to gain further insights into putative associations between molecular genetic markers and IUDs.
Collapse
Affiliation(s)
| | - Rayna Sariyska
- Department of Molecular Psychology, Ulm University, Ulm, Germany
| | - Jon D Elhai
- Departments of Psychology and of Psychiatry, University of Toledo, Toledo, OH, United States
| | - Christian Montag
- Department of Molecular Psychology, Ulm University, Ulm, Germany
| |
Collapse
|
|
15
|
Lack of Association between rs4680 Polymorphism in Catechol-O-Methyltransferase Gene and Alcohol Use Disorder: A Meta-Analysis. DISEASE MARKERS 2020; 2020:8850859. [PMID: 33282008 PMCID: PMC7685839 DOI: 10.1155/2020/8850859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 10/08/2020] [Accepted: 10/23/2020] [Indexed: 11/17/2022]
Abstract
Background The underlying mechanisms of alcohol use disorder (AUD) are regarded to be strongly associated with genetic factors. Although great efforts have been made to identify the association of rs4680 polymorphism in the catechol-o-methyltransferase gene and risk to AUD, the outcomes were still inconsistent. This study is aimed at exploring the association of rs4680 polymorphism and AUD by using a meta-analysis approach. Methods Literature searching was undertaken across PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases. We set the search period before February 20, 2020. We used the Review Manager 5.3 (RevMan 5.3) software to estimate the effect sizes in five genetic models. Results In total, eighteen case-control studies and two cohort studies were included in this study. The merged results of overall population indicated there was no significant association between rs4680 polymorphism and AUD: V vs. M, OR = 1.02, 95% CI 0.93-1.12, P = 0.70; VV vs. MM, OR = 0.99, 95% CI 0.79-1.23, P = 0.92; VM vs. MM, OR = 0.91, 95% CI 0.81-1.03, P = 0.15; VV+VM vs. MM, OR = 0.95, 95% CI 0.80-1.13, P = 0.65; VV vs. VM+MM, OR = 1.04, 95% CI 0.91-1.18, P = 0.57. Subgroup analysis by gender suggested rs4680 polymorphism was marginally associated with an elevated risk to AUD among males (VM vs. MM, OR = 0.81, 95% CI 0.67-0.98, P = 0.03). However, subgroup analysis by race and diagnosis did not support any significant association. Conclusions The present study suggests that rs4680 polymorphism has no association with AUD in the overall population, but it has a weak association with AUD in males. Carriers of VM genotype in males appear to have an increased risk to AUD.
Collapse
|
|
16
|
Chiang TI, Lane HY, Lin CH. D2 dopamine receptor gene (DRD2) Taq1A (rs1800497) affects bone density. Sci Rep 2020; 10:13236. [PMID: 32764574 PMCID: PMC7414035 DOI: 10.1038/s41598-020-70262-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Accepted: 07/22/2020] [Indexed: 11/17/2022] Open
Abstract
Schizophrenia patients are susceptible to lower bone mineral density (BMD). However, studies exploring the genetic effects are lacking. Genes that affect the activity of antipsychotics may be associated with BMD, particularly in patients receiving long-term antipsychotic treatment. We aimed to explore the relationship between the dopamine receptor D2 (DRD2) gene Taq1A (rs1800497) polymorphism and BMD in chronic schizophrenia patients. We recruited schizophrenia patients (n = 47) and healthy controls (n = 39) from a medical center in Taiwan and collected data that may affect BMD. Patients' BMD was measured by dual-energy X-ray absorptiometer (DEXA). DRD2 rs1800497 was genotyped through polymerase chain reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Among all participants, subjects with DRD2 rs1800497(T;T) allele had lower DEXA T score and DEXA Z score compared to those with rs1800497(C;T) and rs1800497(C;C) alleles (p = 0.008, 0.003, respectively). In schizophrenia patients, subjects with rs1800497(T;T) allele also had lower DEXA Z score compared to the other two alleles (p = 0.045). Our findings suggest that individuals with the DRD2 rs1800497(T;T) had lower BMD than those with the rs1800497(C;T) and rs1800497(C;C) genotypes. Therefore, genes should be considered as one of the risk factors of lower BMD.
Collapse
Affiliation(s)
- Ting-I Chiang
- Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No. 123, Dapi Rd., Niaosong District, Kaohsiung City, 833, Taiwan
| | - Hsien-Yuan Lane
- Graduate Institute of Biomedical Sciences, China Medical University, No. 91, Hsueh-Shih Rd., North Dist., Taichung City, 404, Taiwan.
- Department of Psychiatry and Brain Disease Research Center, China Medical University Hospital, Taichung, Taiwan.
- Department of Psychology, College of Medical and Health Sciences, Asia University, Taichung, Taiwan.
| | - Chieh-Hsin Lin
- Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No. 123, Dapi Rd., Niaosong District, Kaohsiung City, 833, Taiwan.
- Graduate Institute of Biomedical Sciences, China Medical University, No. 91, Hsueh-Shih Rd., North Dist., Taichung City, 404, Taiwan.
- School of Medicine, Chang Gung University, Taoyuan, Taiwan.
| |
Collapse
|
|
17
|
Koeneke A, Ponce G, Troya-Balseca J, Palomo T, Hoenicka J. Ankyrin Repeat and Kinase Domain Containing 1 Gene, and Addiction Vulnerability. Int J Mol Sci 2020; 21:ijms21072516. [PMID: 32260442 PMCID: PMC7177674 DOI: 10.3390/ijms21072516] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 04/01/2020] [Accepted: 04/02/2020] [Indexed: 01/13/2023] Open
Abstract
The TaqIA single nucleotide variant (SNV) has been tested for association with addictions in a huge number of studies. TaqIA is located in the ankyrin repeat and kinase domain containing 1 gene (ANKK1) that codes for a receptor interacting protein kinase. ANKK1 maps on the NTAD cluster along with the dopamine receptor D2 (DRD2), the tetratricopeptide repeat domain 12 (TTC12) and the neural cell adhesion molecule 1 (NCAM1) genes. The four genes have been associated with addictions, although TTC12 and ANKK1 showed the strongest associations. In silico and in vitro studies revealed that ANKK1 is functionally related to the dopaminergic system, in particular with DRD2. In antisocial alcoholism, epistasis between ANKK1 TaqIA and DRD2 C957T SNVs has been described. This clinical finding has been supported by the study of ANKK1 expression in peripheral blood mononuclear cells of alcoholic patients and controls. Regarding the ANKK1 protein, there is direct evidence of its location in adult and developing central nervous system. Together, these findings of the ANKK1 gene and its protein suggest that the TaqIA SNV is a marker of brain differences, both in structure and in dopaminergic function, that increase individual risk to addiction development.
Collapse
Affiliation(s)
- Alejandra Koeneke
- Departamento de Psicología, Facultad de Ciencias Biomédicas, Universidad Europea Madrid, Villaviciosa de Odón, 28670 Madrid, Spain;
- Departamento de Medicina Legal, Psiquiatría y Patología, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain;
| | - Guillermo Ponce
- Servicio de Psiquiatría, Hospital Universitario 12 de Octubre, Av. de Córdoba s/n, 28041 Madrid, Spain;
| | - Johanna Troya-Balseca
- Laboratory of Neurogenetics and Molecular Medicine - IPER, Institut de Recerca Sant Joan de Déu, 08950 Barcelona, Spain;
| | - Tomás Palomo
- Departamento de Medicina Legal, Psiquiatría y Patología, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain;
- CIBER de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Janet Hoenicka
- Laboratory of Neurogenetics and Molecular Medicine - IPER, Institut de Recerca Sant Joan de Déu, 08950 Barcelona, Spain;
- CIBER de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Correspondence: ; Tel.: +34-936009751 (ext. 77833)
| |
Collapse
|
|
18
|
Chung P, Logge WB, Riordan BC, Haber PS, Merriman ME, Phipps-Green A, Topless RK, Merriman TR, Conner T, Morley KC. Genetic Polymorphisms on OPRM1, DRD2, DRD4, and COMT in Young Adults: Lack of Association With Alcohol Consumption. Front Psychiatry 2020; 11:549429. [PMID: 33364985 PMCID: PMC7750453 DOI: 10.3389/fpsyt.2020.549429] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Accepted: 11/17/2020] [Indexed: 12/05/2022] Open
Abstract
Background: Risk behaviors for young adults such as alcohol use are associated with increased risk of morbidity and mortality. Patterns of risk behavior may be genetically determined and vary between genders. Previous studies in both young adults and heavy drinking adult samples have demonstrated that some genotypes, such as OPRM1 A118G, COMT Val158Met and DRD2 Taq1A and DRD4 C52IT, may predict addictive behaviors including alcohol consumption and impulsivity, although results have been mixed. Methods: This study aimed to investigate the predictive relationship of these four single nucleotide polymorphisms (SNPs) prospectively on student patterns of drinking using a micro-longitudinal daily diary design in a sample of 628 young adults ages 18-25 of predominantly of European ethnicity. Linear mixed models were used to examine the effect of SNPs on the number of drinks per drinking session with gender as a moderating variable. Results: There were no main effects for genotype on alcohol consumption, nor for gender × genotype for any of the SNPs. There was a trend for an effect of the DRD2 Taq1A on the number of drinks per drinking day and for the interaction of gender and DRD2 Taq1A on the number of drinks per drinking day. Conclusion: These findings suggest that the DRD2 Taq1A, OPRM1 A118G, DRD4 C521T, or COMT Val158Met polymorphisms, are not associated with alcohol consumption in young adults, although there may be a relationship between DRD2 Taq1A and alcohol consumption in young adult males.
Collapse
Affiliation(s)
- Patrick Chung
- Discipline of Addiction Medicine, Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Warren B Logge
- Discipline of Addiction Medicine, Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Benjamin C Riordan
- Psychological Medicine, Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Paul S Haber
- Discipline of Addiction Medicine, Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.,Drug Health Services, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
| | | | | | - Ruth K Topless
- Department of Biochemistry, University of Otago, Dunedin, New Zealand
| | - Tony R Merriman
- Department of Biochemistry, University of Otago, Dunedin, New Zealand
| | - Tamlin Conner
- Department of Psychology, University of Otago, Dunedin, New Zealand
| | - Kirsten C Morley
- Discipline of Addiction Medicine, Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| |
Collapse
|
|
19
|
Effects of the monoamine stabilizer (-)OSU6162 on cognitive function in alcohol dependence. Psychopharmacology (Berl) 2020; 237:69-82. [PMID: 31628507 PMCID: PMC6952337 DOI: 10.1007/s00213-019-05345-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Accepted: 08/09/2019] [Indexed: 12/21/2022]
Abstract
INTRODUCTION Alcohol dependence (AD) is associated with a dysregulated mesolimbocortical dopamine system-a pathway which is also implicated in both reward and cognition. The monoamine stabilizer (-)-OSU6162 (OSU) is a novel pharmacological compound with the ability to reduce ethanol intake and ethanol seeking in long-term drinking rats as well as reducing alcohol craving in AD patients. Dopaminergic drugs can both impair and improve cognitive functions, and the aim of the current study was to investigate the effect of OSU treatment on cognitive functioning in AD patients. METHOD In a randomized double-blind placebo-controlled study, 56 individuals with AD received 14 days of OSU or placebo treatment. Neuropsychological tasks from the Cambridge Automated Neuropsychological Test Battery (CANTAB®) and other tasks were used to evaluate treatment effect on executive function/impulsivity, working memory, attention, emotional recognition, and divergent thinking. RESULTS Treatment with OSU did not impair neuropsychological function in any of the cognitive domains investigated (all p > 0.1). In fact, OSU treatment did, compared to placebo, improve future planning ability (F(1,46) = 6.9; p = 0.012; Cohen's d = 0.54), verbal divergent thinking (F(1,44) = 10.1; p = 0.003; d = 0.96), and response time for emotional recognition (F(1,47) = 6.7; p = 0.013; d = 0.44). CONCLUSION OSU treatment did not cause short-term cognitive side effects, further supporting the potential of OSU as a clinically feasible pharmacological treatment in AD patients. OSU treatment might improve future planning, verbal divergent thinking, and emotional recognition latency, which in turn may have a beneficial impact on alcohol use outcomes. Future studies are needed to confirm these preliminary findings.
Collapse
|
|
20
|
Farruggia MC, Small DM. Effects of adiposity and metabolic dysfunction on cognition: A review. Physiol Behav 2019; 208:112578. [PMID: 31194997 PMCID: PMC6625347 DOI: 10.1016/j.physbeh.2019.112578] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Revised: 05/29/2019] [Accepted: 06/09/2019] [Indexed: 12/31/2022]
Abstract
Obesity and metabolic dysfunction are both correlated with increased rates of cognitive decline. However, because these two conditions often co-occur, it remains unclear whether their cognitive consequences are independent. In this review, we carefully consider literature examining the effects of metabolic dysfunction and increased adiposity on cognition across the lifespan, including only well-controlled studies that attempt to dissociate their effects. We found a total of 36 studies, 17 examining metabolic dysfunction and 19 examining the effects of adiposity. We found evidence from the literature suggesting that increased adiposity and metabolic dysfunction may contribute to deficits in executive function, memory, and medial temporal lobe structures largely independent of one another. These deficits are thought to arise principally from physiological changes associated with inflammation, vascularization, and oxidative stress, among others. Such processes may result from excess adipose tissue and insulin resistance that occur independently and can further exacerbate when the two conditions co-occur. However, we also find it likely that impaired cognition plays a role in behavioral and lifestyle choices that lead to increased adiposity and metabolic dysfunction, which can then perpetuate and augment cognitive decline. We recommend additional prospective and longitudinal studies to examine whether impaired cognition is a cause and/or consequence of these factors.
Collapse
Affiliation(s)
- Michael C Farruggia
- Interdepartmental Neuroscience Program, Yale University, 333 Cedar Street, New Haven, CT, USA; Department of Psychiatry, Yale University School of Medicine, 300 George Street, New Haven, CT 06511, USA.
| | - Dana M Small
- Interdepartmental Neuroscience Program, Yale University, 333 Cedar Street, New Haven, CT, USA; Department of Psychiatry, Yale University School of Medicine, 300 George Street, New Haven, CT 06511, USA; Department of Psychology, Yale University, New Haven, CT, USA; fMEG Center, University of Tubingen, Tubingen, Germany.
| |
Collapse
|
|
21
|
Kozak K, Lucatch AM, Lowe DJ, Balodis IM, MacKillop J, George TP. The neurobiology of impulsivity and substance use disorders: implications for treatment. Ann N Y Acad Sci 2019; 1451:71-91. [PMID: 30291624 PMCID: PMC6450787 DOI: 10.1111/nyas.13977] [Citation(s) in RCA: 134] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Revised: 09/11/2018] [Accepted: 09/13/2018] [Indexed: 12/20/2022]
Abstract
Impulsivity is strongly associated with substance use disorders (SUDs). Our review discusses impulsivity as an underlying vulnerability marker for SUDs, and treatment of co-occurring impulsivity in SUDs. Three factors should be considered for the complex relationship between impulsivity and a SUD: (1) the trait effect of impulsivity, centering on decreased cognitive and response inhibition, (2) the state effect resulting from either acute or chronic substance use on brain structure and function, and (3) the genetic and environmental factors (e.g., age and sex) may influence impulsive behavior associated with SUDs. Both subjective and objective measures are used to assess impulsivity. Together, treatment developments (pharmacological, behavioral, and neurophysiological) should consider these clinically relevant dimensions assessed by a variety of measures, which have implications for treatment matching in individuals with SUD. Despite its heterogeneity, impulsivity is a marker associated with SUDs and may be understood as an imbalance of bottom-up and top-down neural systems. Further investigation of these relationships may lead to more effective SUD treatments.
Collapse
Affiliation(s)
- Karolina Kozak
- Addictions Division, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto,
Canada
- Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, Toronto, Canada
- Institute of Medical Sciences, University of Toronto, Toronto, Canada
| | - Aliya M. Lucatch
- Addictions Division, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto,
Canada
| | - Darby J.E. Lowe
- Addictions Division, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto,
Canada
| | - Iris M. Balodis
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Canada
| | - James MacKillop
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Canada
| | - Tony P. George
- Addictions Division, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto,
Canada
- Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, Toronto, Canada
- Institute of Medical Sciences, University of Toronto, Toronto, Canada
| |
Collapse
|
|
22
|
Baker TE, Castellanos-Ryan N, Schumann G, Cattrell A, Flor H, Nees F, Banaschewski T, Bokde A, Whelan R, Buechel C, Bromberg U, Papadopoulos Orfanos D, Gallinat J, Garavan H, Heinz A, Walter H, Brühl R, Gowland P, Paus T, Poustka L, Martinot JL, Lemaitre H, Artiges E, Paillère Martinot ML, Smolka MN, Conrod P. Modulation of orbitofrontal-striatal reward activity by dopaminergic functional polymorphisms contributes to a predisposition to alcohol misuse in early adolescence. Psychol Med 2019; 49:801-810. [PMID: 29909784 DOI: 10.1017/s0033291718001459] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
BACKGROUND Abnormalities in reward circuit function are considered a core feature of addiction. Yet, it is still largely unknown whether these abnormalities stem from chronic drug use, a genetic predisposition, or both. METHODS In the present study, we investigated this issue using a large sample of adolescent children by applying structural equation modeling to examine the effects of several dopaminergic polymorphisms of the D1 and D2 receptor type on the reward function of the ventral striatum (VS) and orbital frontal cortex (OFC), and whether this relationship predicted the propensity to engage in early alcohol misuse behaviors at 14 years of age and again at 16 years of age. RESULTS The results demonstrated a regional specificity with which the functional polymorphism rs686 of the D1 dopamine receptor (DRD1) gene and Taq1A of the ANKK1 gene influenced medial and lateral OFC activation during reward anticipation, respectively. Importantly, our path model revealed a significant indirect relationship between the rs686 of the DRD1 gene and early onset of alcohol misuse through a medial OFC × VS interaction. CONCLUSIONS These findings highlight the role of D1 and D2 in adjusting reward-related activations within the mesocorticolimbic circuitry, as well as in the susceptibility to early onset of alcohol misuse.
Collapse
Affiliation(s)
- Travis E Baker
- Department of Psychiatry,Universite de Montreal, CHU Ste Justine Hospital,Montreal,Canada
| | | | | | - Anna Cattrell
- Institute of Psychiatry, King's College London,London,UK
| | - Herta Flor
- Department of Cognitive and Clinical Neuroscience,Central Institute of Mental Health,Medical Faculty Mannheim,Heidelberg University,Square J5, Mannheim,Germany
| | - Frauke Nees
- Department of Cognitive and Clinical Neuroscience,Central Institute of Mental Health,Medical Faculty Mannheim,Heidelberg University,Square J5, Mannheim,Germany
| | - Tobias Banaschewski
- Department of Child and Adolescent Psychiatry,Central Institute of Mental Health,Faculty of Clinical Medicine Mannheim,Medical Faculty Mannheim,Heidelberg University,Square J5, 68159 Mannheim,Germany
| | - Arun Bokde
- Discipline of Psychiatry,School of Medicine and Trinity College Institute of Neurosciences, Trinity College,Dublin,Ireland
| | - Rob Whelan
- Discipline of Psychiatry,School of Medicine and Trinity College Institute of Neurosciences, Trinity College,Dublin,Ireland
| | - Christian Buechel
- University Medical Centre Hamburg-Eppendorf,Haus S10, Martinistr. 52, Hamburg,Germany
| | - Uli Bromberg
- University Medical Centre Hamburg-Eppendorf,Haus S10, Martinistr. 52, Hamburg,Germany
| | | | - Juergen Gallinat
- Department of Psychiatry and Psychotherapy,Campus Charité Mitte, Charité,Universitätsmedizin Berlin,Charitéplatz 1, Berlin,Germany
| | - Hugh Garavan
- Departments of Psychiatry and Psychology,University of Vermont,05405 Burlington, Vermont,USA
| | - Andreas Heinz
- Department of Psychiatry and Psychotherapy,Campus Charité Mitte, Charité,Universitätsmedizin Berlin,Charitéplatz 1, Berlin,Germany
| | - Henrik Walter
- Department of Psychiatry and Psychotherapy,Campus Charité Mitte, Charité,Universitätsmedizin Berlin,Charitéplatz 1, Berlin,Germany
| | - Rüdiger Brühl
- Physikalisch-Technische Bundesanstalt,Abbestr. 2 - 12, Berlin,Germany
| | - Penny Gowland
- School of Psychology, University of Nottingham, University Park,Nottingham,UK
| | - Tomáš Paus
- Rotman Research Institute, University of Toronto,Toronto,Canada
| | - Luise Poustka
- Department of Child and Adolescent Psychiatry,Central Institute of Mental Health,Faculty of Clinical Medicine Mannheim,Medical Faculty Mannheim,Heidelberg University,Square J5, 68159 Mannheim,Germany
| | | | - Herve Lemaitre
- Institut National de la Sante et de la Recherche Medicale, INSERM CEAUnit1000, Imaging & Psychiatry, University Paris Sud,91400 Orsay,France
| | - Eric Artiges
- Department of Psychiatry,Universite de Montreal, CHU Ste Justine Hospital,Montreal,Canada
| | | | - Michael N Smolka
- Department of Psychiatry and Neuroimaging Center,Technische Universität Dresden,Dresden,Germany
| | - Patricia Conrod
- Department of Psychiatry,Universite de Montreal, CHU Ste Justine Hospital,Montreal,Canada
| |
Collapse
|
|
23
|
Klaus K, Butler K, Curtis F, Bridle C, Pennington K. The effect of ANKK1 Taq1A and DRD2 C957T polymorphisms on executive function: A systematic review and meta-analysis. Neurosci Biobehav Rev 2019; 100:224-236. [PMID: 30836122 DOI: 10.1016/j.neubiorev.2019.01.021] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Revised: 01/14/2019] [Accepted: 01/21/2019] [Indexed: 12/25/2022]
Abstract
Research in healthy adults suggests that C957T polymorphism of the dopamine D2 receptor encoding DRD2 and the Taq1A polymorphism of the neighbouring gene ankyrin repeat and kinase domain containing 1 (ANKK1) alter dopaminergic signalling and may influence prefrontally-mediated executive functions. A systematic review and meta-analysis was carried out on the evidence for the association of DRD2 C957T and ANKK1 Taq1A polymorphisms in performance on tasks relating to the three core domains of executive function: working memory, response inhibition and cognitive flexibility in healthy adults. CINAHL, MEDLINE, PsycARTICLES and PsychINFO databases were searched for predefined key search terms associated with the two polymorphisms and executive function. Studies were included if they investigated a healthy adult population with the mean age of 18-65 years, no psychiatric or neurological disorder and only the healthy adult arm were included in studies with any case-control design. Data from 17 independent studies were included in meta-analysis, separated by the Taq1A and C957T polymorphisms and by executive function tests: working memory (Taq1A, 6 samples, n = 1270; C957 T, 6 samples, n = 977), cognitive flexibility (C957 T, 3 samples, n = 620), and response inhibition (C957 T, 3 samples, n = 598). The meta-analyses did not establish significant associations between these gene polymorphisms of interest and any of the executive function domains. Theoretical implications and methodological considerations of these findings are discussed.
Collapse
Affiliation(s)
- Kristel Klaus
- School of Psychology, University of Lincoln, Brayford Wharf, Lincoln, LN5 7AT, UK
| | - Kevin Butler
- School of Psychology, University of Lincoln, Brayford Wharf, Lincoln, LN5 7AT, UK
| | - Ffion Curtis
- Lincoln Institute for Health, University of Lincoln, Brayford Pool, Lincoln, LN6 7TS, UK
| | - Chris Bridle
- Lincoln Institute for Health, University of Lincoln, Brayford Pool, Lincoln, LN6 7TS, UK
| | - Kyla Pennington
- School of Psychology, University of Lincoln, Brayford Wharf, Lincoln, LN5 7AT, UK.
| |
Collapse
|
|
24
|
Fletcher PC, Kenny PJ. Food addiction: a valid concept? Neuropsychopharmacology 2018; 43:2506-2513. [PMID: 30188514 PMCID: PMC6224546 DOI: 10.1038/s41386-018-0203-9] [Citation(s) in RCA: 106] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Revised: 08/12/2018] [Accepted: 08/15/2018] [Indexed: 12/24/2022]
Abstract
Can food be addictive? What does it mean to be a food addict? Do common underlying neurobiological mechanisms contribute to drug and food addiction? These vexing questions have been the subject of considerable interest and debate in recent years, driven in large part by the major health concerns associated with dramatically increasing body weights and rates of obesity in the United States, Europe, and other regions with developed economies. No clear consensus has yet emerged on the validity of the concept of food addiction and whether some individuals who struggle to control their food intake can be considered food addicts. Some, including Fletcher, have argued that the concept of food addiction is unsupported, as many of the defining features of drug addiction are not seen in the context of feeding behaviors. Others, Kenny included, have argued that food and drug addiction share similar features that may reflect common underlying neural mechanisms. Here, Fletcher and Kenny argue the merits of these opposing positions on the concept of food addiction.
Collapse
Affiliation(s)
- Paul C Fletcher
- Department of Psychiatry, University of Cambridge, Cambridge, CB2 8AH, UK.
- Cambridgeshire and Peterborough NHS Foundation Trust, Cambrdge, CB21 5EF, UK.
| | - Paul J Kenny
- Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
| |
Collapse
|
|
25
|
Fineberg NA, Demetrovics Z, Stein DJ, Ioannidis K, Potenza MN, Grünblatt E, Brand M, Billieux J, Carmi L, King DL, Grant JE, Yücel M, Dell'Osso B, Rumpf HJ, Hall N, Hollander E, Goudriaan A, Menchon J, Zohar J, Burkauskas J, Martinotti G, Van Ameringen M, Corazza O, Pallanti S, Chamberlain SR. Manifesto for a European research network into Problematic Usage of the Internet. Eur Neuropsychopharmacol 2018; 28:1232-1246. [PMID: 30509450 PMCID: PMC6276981 DOI: 10.1016/j.euroneuro.2018.08.004] [Citation(s) in RCA: 177] [Impact Index Per Article: 25.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Revised: 07/18/2018] [Accepted: 08/07/2018] [Indexed: 12/24/2022]
Abstract
The Internet is now all-pervasive across much of the globe. While it has positive uses (e.g. prompt access to information, rapid news dissemination), many individuals develop Problematic Use of the Internet (PUI), an umbrella term incorporating a range of repetitive impairing behaviours. The Internet can act as a conduit for, and may contribute to, functionally impairing behaviours including excessive and compulsive video gaming, compulsive sexual behaviour, buying, gambling, streaming or social networks use. There is growing public and National health authority concern about the health and societal costs of PUI across the lifespan. Gaming Disorder is being considered for inclusion as a mental disorder in diagnostic classification systems, and was listed in the ICD-11 version released for consideration by Member States (http://www.who.int/classifications/icd/revision/timeline/en/). More research is needed into disorder definitions, validation of clinical tools, prevalence, clinical parameters, brain-based biology, socio-health-economic impact, and empirically validated intervention and policy approaches. Potential cultural differences in the magnitudes and natures of types and patterns of PUI need to be better understood, to inform optimal health policy and service development. To this end, the EU under Horizon 2020 has launched a new four-year European Cooperation in Science and Technology (COST) Action Programme (CA 16207), bringing together scientists and clinicians from across the fields of impulsive, compulsive, and addictive disorders, to advance networked interdisciplinary research into PUI across Europe and beyond, ultimately seeking to inform regulatory policies and clinical practice. This paper describes nine critical and achievable research priorities identified by the Network, needed in order to advance understanding of PUI, with a view towards identifying vulnerable individuals for early intervention. The network shall enable collaborative research networks, shared multinational databases, multicentre studies and joint publications.
Collapse
Affiliation(s)
- N A Fineberg
- Hertfordshire Partnership University NHS Foundation Trust, Rosanne House, Welwyn Garden City, Hertfordshire AL8 6HG, UK; Center for Clinical & Health Research Services, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK; School of Clinical Medicine, University of Cambridge, Cambridge, UK.
| | - Z Demetrovics
- Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary
| | - D J Stein
- Department of Psychiatry and Mental Health at the University of Cape Town and South African MRC Unit on Risk & Resilience in Mental Disorders, Cape Town, South Africa
| | - K Ioannidis
- Department of Psychiatry, University of Cambridge, Cambridge, UK; Cambridge & Peterborough NHS Foundation Trust, Cambridge, UK
| | - M N Potenza
- Connecticut Mental Health Center and Departments of Psychiatry, Neuroscience and Child Study Center, Yale School of Medicine, New Haven, USA; Connecticut Council on Problem Gambling, Wethersfield, CT, USA
| | - E Grünblatt
- Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital Zurich, University of Zurich, Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland; Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
| | - M Brand
- General Psychology: Cognition and Center for Behavioral Addiction Research (CeBAR), Department of Computer Science and Applied Cognitive Science Faculty of Engineering, University of Duisburg-Essen, Duisburg, Germany; Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen, Germany
| | - J Billieux
- Addictive and Compulsive Behaviours Lab, Institute for Health and Behaviour, University of Luxembourg, Esch-sur-Alzette, Luxembourg; Addiction Division, Department of Mental Health and Psychiatry, University Hospitals of Geneva, Switzerland; Centre for Excessive Gambling, Lausanne University Hospitals (CHUV), Lausanne, Switzerland
| | - L Carmi
- School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel
| | - D L King
- School of Psychology, University of Adelaide, Adelaide, Australia
| | - J E Grant
- Department of Psychiatry, University of Chicago, Chicago, USA
| | - M Yücel
- Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences, Monash University, Melbourne, Australia
| | - B Dell'Osso
- Department of Pathophysiology and Transplantation, University of Milan, Fondazione IRCCS Ca' Granda and CRC "Aldo Ravelli" for neurotechnology and experimental brain therapeutics, Milan, Italy; Department of Psychiatry, University of Milan, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA; CRC "Aldo Ravelli" for Neurotechnology and Experimental Brain Therapeutics, University of Milan, Milan, Italy
| | - H J Rumpf
- University of Lübeck, Department of Psychiatry and Psychotherapy, Centre for Integrative Psychiatry, Lübeck, Germany
| | - N Hall
- Center for Clinical & Health Research Services, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK
| | - E Hollander
- Department of Psychiatry and Compulsive, Impulsive and Autism Spectrum Program, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA
| | - A Goudriaan
- Department of Psychiatry, Academisch Medisch Centrum (AMC), University of Amsterdam, Amsterdam, Netherlands; Amsterdam UMC, University of Amsterdam, Department of Psychiatry, Amsterdam Institute for Addiction Research, Meibergdreef 9, Amsterdam, Netherlands; Arkin, Amsterdam, The Netherlands
| | - J Menchon
- Department of Psychiatry, Bellvitge University, Hospital-IDIBELL, University of Barcelona, Cibersam, Barcelona, Spain
| | - J Zohar
- Sackler Medical School, Tel Aviv University, and Chaim Sheba Medical Center Tel Hashomer, Tel Aviv, Israel
| | - J Burkauskas
- Laboratory of Behavioral Medicine, Neuroscience Institute, Lithuanian University of Health Sciences, Palanga, Lithuania
| | - G Martinotti
- Department of Neuroscience, Imaging, Clinical Science, University G.d'Annunzio of Chieti-Pescara, Chieti, Italy
| | - M Van Ameringen
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Ontario, Canada
| | - O Corazza
- Center for Clinical & Health Research Services, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK
| | - S Pallanti
- Albert Einstein College of Medicine, New York, USA; University of Florence, Italy
| | - S R Chamberlain
- Department of Psychiatry, University of Cambridge, Cambridge, UK; Cambridge & Peterborough NHS Foundation Trust, Cambridge, UK
| |
Collapse
|
|
26
|
White R, Gatzke-Kopp LM, Ryan PJ, Lydon-Staley DM. The association between perinatal hypoxia exposure and externalizing symptoms and children's decision making in conditions of uncertainty is moderated by DRD2 genotype. Dev Psychobiol 2018; 61:56-68. [PMID: 30264459 DOI: 10.1002/dev.21785] [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: 02/06/2018] [Revised: 08/14/2018] [Accepted: 08/26/2018] [Indexed: 11/10/2022]
Abstract
Variants of the DRD2 Taq1A polymorphism, which have been shown to result in functional differences in dopamine D2 receptors (D2R), have been linked to various externalizing outcomes in adults. However, the neurobiological processes that contribute to these associations are not well understood. The current study investigates gene × environment effects on teacher-rated externalizing behaviors and probabilistic decision making in a sample of 333 children (age 9) enrolled in an ongoing longitudinal study. Findings indicate that externalizing behaviors increased as a function of hypoxic exposure only among individuals carrying the A1 (A1+) allele. Results also indicate that willingness to pursue reward under conditions of maximum uncertainty (50% probability) decreased as a function of hypoxic exposure only among A1- individuals. Among A1 carriers, no association between probability decision making and hypoxic exposure emerged. These findings suggest that hypoxia could influence neural development through different biological pathways depending on D2 receptor genotype, and provide insight into the development of individual differences in behavior and decision making.
Collapse
Affiliation(s)
- Roisin White
- Department of Human Development and Family Studies, The Pennsylvania State University, University Park, Pennsylvania
| | - Lisa M Gatzke-Kopp
- Department of Human Development and Family Studies, The Pennsylvania State University, University Park, Pennsylvania
| | - Patrick J Ryan
- Department of Human Development and Family Studies, The Pennsylvania State University, University Park, Pennsylvania
| | - David M Lydon-Staley
- Department of Bioengineering, The University of Pennsylvania, University Park, Pennsylvania
| |
Collapse
|
|
27
|
Bellamy KK, Storengen LM, Handegård KW, Arnet EF, Prestrud KW, Overall KL, Lingaas F. DRD2 is associated with fear in some dog breeds. J Vet Behav 2018. [DOI: 10.1016/j.jveb.2018.07.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
|
|
28
|
Palacios A, Canto P, Tejeda ME, Stephano S, Luján H, García-García E, Rojano-Mejía D, Méndez JP. Complete sequence of the ANKK1 gene in Mexican-Mestizo individuals with obesity, with or without binge eating disorder. Eur Psychiatry 2018; 54:59-64. [PMID: 30121507 DOI: 10.1016/j.eurpsy.2018.07.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Revised: 07/26/2018] [Accepted: 07/27/2018] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND The aim of this study was to investigate if Mexican-Mestizo individuals with obesity, with or without binge eating disorder (BED), exhibited mutations or other type of genetic variants in the sequence of ANKK1. SUBJECTS AND METHODS Fifty unrelated individuals (21-53 years of age) with obesity, of Mexican-Mestizo ethnic origin were included; 25 of them had BED and 25 presented obesity without BED. The diagnosis of BED was based on criteria proposed in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Besides, we also analyzed 100 individuals with normal body mass index. DNA from blood leukocytes was amplified by the polymerase chain reaction and all exons of ANKK1 were sequenced. RESULTS After ANKK1 sequencing we did not find any mutations; however, we observed various polymorphisms. One polymorphism, rs4938013 in exon 2 showed an association with obesity, whilst rs1800497 (also known as Taq1A) in exon 8, showed an association with BED (P = 0.020). Remarkable, for this study, the number of individuals for both polymorphisms for and additive model was sufficient to derive strong statistical power (80%, with a P < 0.05). CONCLUSIONS To our knowledge, this constitutes the first report where the complete sequences of ANKK1 has been analyzed in individuals with obesity, with or without BED. No mutations were found; however, one polymorphism was associated with obesity, with or without BED, and another one was associated with BED.
Collapse
Affiliation(s)
- Adriana Palacios
- Unidad de Investigación en Obesidad, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
| | - Patricia Canto
- Unidad de Investigación en Obesidad, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, Mexico; Clínica de Obesidad, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Ciudad de México, Mexico
| | - María Elena Tejeda
- Unidad de Investigación en Obesidad, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
| | - Sylvana Stephano
- Clínica de Obesidad, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Ciudad de México, Mexico
| | - Hassell Luján
- Unidad de Investigación en Obesidad, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
| | - Eduardo García-García
- Clínica de Obesidad, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Ciudad de México, Mexico
| | - David Rojano-Mejía
- Unidad de Medicina Física y Rehabilitación Centro, UMAE, Hospital de Traumatología y Ortopedia "Lomas Verdes", Instituto Mexicano del Seguro Social, México, D.F., Mexico
| | - Juan Pablo Méndez
- Unidad de Investigación en Obesidad, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, Mexico; Clínica de Obesidad, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Ciudad de México, Mexico.
| |
Collapse
|
|
29
|
Potential Role of Brain-Derived Neurotrophic Factor and Dopamine Receptor D2 Gene Variants as Modifiers for the Susceptibility and Clinical Course of Wilson's Disease. Neuromolecular Med 2018; 20:401-408. [PMID: 29992511 DOI: 10.1007/s12017-018-8501-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2018] [Accepted: 07/07/2018] [Indexed: 01/10/2023]
Abstract
Wilson's disease (WD), an inborn error of copper metabolism caused by mutations in the ATPase copper transporting beta (ATP7B) gene, manifests variable age of onset and different degrees of hepatic and neurological disturbances. This complex phenotypical outcome of a classical monogenic disease can possibly be explained by modifier loci regulating the clinical course of the disease. The brain-derived neurotropic factor (BDNF), critical for the survival, morphogenesis, and plasticity of the neurons, and the dopamine receptor D2 (DRD2), one of the most abundant dopamine receptors in the brain, have been highlighted in the pathophysiology of various neuropsychiatric diseases. This study aims to identify the potential association between BDNF and DRD2 gene polymorphisms and WD and its clinical characteristics. A total of 164 WD patients and 270 controls from India were included in this study. Two BDNF polymorphisms [p.Val66Met (c.G196A) and c.C270T] and the DRD2 Taq1A (A2/A1 or C/T) polymorphism were examined for their association with WD and some of its clinical attributes, using polymerase chain reaction, restriction fragment length digestion, and bidirectional sequencing. The C allele and CC genotype of BDNF C270T were significantly overrepresented among controls compared to WD patients. In addition, a significantly higher proportion of the allele coding for Val and the corresponding homozygous genotype of BDNF Val66Met polymorphism was found among WD patients with age of onset later than 10 years. Furthermore, the A1A1 genotype of DRD2 Taq1A polymorphism was significantly more common among WD patients with rigidity. Our data suggest that both BDNF and DRD2 may act as potential modifiers of WD phenotype in the Indian context.
Collapse
|
|
30
|
Lacroix E, Tavares H, von Ranson KM. Moving beyond the "eating addiction" versus "food addiction" debate: Comment on Schulte et al. (2017). Appetite 2018; 130:286-292. [PMID: 29936021 DOI: 10.1016/j.appet.2018.06.025] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Revised: 06/19/2018] [Accepted: 06/19/2018] [Indexed: 12/21/2022]
Abstract
In a recent commentary, Schulte et al. (2017) argued that addictive-like eating should be conceptualized as a substance use disorder rather than a behavioural addiction, and noted that many parallels that Hebebrand et al. (2014) drew between addictive-like eating and behavioural addictions apply likewise to substance use disorders. However, we argue that many of the arguments advanced by Schulte et al. (2017) in support of a substance-based food addiction model, including the important role played by ingested substances, are nonspecific. That is, these arguments apply equally well to behavioural addictions and other mental disorders, notably eating disorders, which raises the question of whether the phenomenon of addictive-like eating is encompassed by existing eating disorder diagnoses. Similarities between addictive-like eating and substance use, no matter how compelling, do not ensure the validity or clinical utility of a substance-based food addiction model and should not drive the conceptualization of addictive-like eating. The present commentary discusses problems with Schulte et al.'s (2017) arguments for substance-based food addiction, and draws attention to alternative conceptualizations of addictive-like eating which risk being overlooked when this conversation is framed as a dichotomous debate between the food and eating addiction models.
Collapse
Affiliation(s)
- Emilie Lacroix
- Department of Psychology, University of Calgary, 2500 University Dr. NW, Calgary, AB, T2N 1N4, Canada.
| | - Hermano Tavares
- Department of Psychiatry, University of São Paulo, Rua Dr. Ovídio Pires de Campos, 785, Cerqueira César, Sao Paulo, SP, CEP 05403-010, Brazil.
| | - Kristin M von Ranson
- Department of Psychology, University of Calgary, 2500 University Dr. NW, Calgary, AB, T2N 1N4, Canada.
| |
Collapse
|
|
31
|
Identification of rs7350481 at chromosome 11q23.3 as a novel susceptibility locus for metabolic syndrome in Japanese individuals by an exome-wide association study. Oncotarget 2018; 8:39296-39308. [PMID: 28445147 PMCID: PMC5503614 DOI: 10.18632/oncotarget.16945] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Accepted: 03/14/2017] [Indexed: 12/12/2022] Open
Abstract
We have performed exome-wide association studies to identify genetic variants that influence body mass index or confer susceptibility to obesity or metabolic syndrome in Japanese. The exome-wide association study for body mass index included 12,890 subjects, and those for obesity and metabolic syndrome included 12,968 subjects (3954 individuals with obesity, 9014 controls) and 6817 subjects (3998 individuals with MetS, 2819 controls), respectively. Exome-wide association studies were performed with Illumina HumanExome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays. The relation of genotypes of single nucleotide polymorphisms to body mass index was examined by linear regression analysis, and that of allele frequencies of single nucleotide polymorphisms to obesity or metabolic syndrome was evaluated with Fisher's exact test. The exome-wide association studies identified six, 11, and 40 single nucleotide polymorphisms as being significantly associated with body mass index, obesity (P <1.21 × 10−6), or metabolic syndrome (P <1.20 × 10−6), respectively. Subsequent multivariable logistic regression analysis with adjustment for age and sex revealed that three and five single nucleotide polymorphisms were related (P < 0.05) to obesity or metabolic syndrome, respectively, with one of these latter polymorphisms—rs7350481 (C/T) at chromosome 11q23.3—also being significantly (P < 3.13 × 10−4) associated with metabolic syndrome. The polymorphism rs7350481 may thus be a novel susceptibility locus for metabolic syndrome in Japanese. In addition, single nucleotide polymorphisms in three genes (CROT, TSC1, RIN3) and at four loci (ANKK1, ZNF804B, CSRNP3, 17p11.2) were implicated as candidate determinants of obesity and metabolic syndrome, respectively.
Collapse
|
|
32
|
Balldin J, Berglund KJ, Berggren U, Wennberg P, Fahlke C. TAQ1A1 Allele of the DRD2 Gene Region Contribute to Shorter Survival Time in Alcohol Dependent Individuals When Controlling for the Influence of Age and Gender. A Follow-up Study of 18 Years. Alcohol Alcohol 2018; 53:216-220. [PMID: 29236941 DOI: 10.1093/alcalc/agx089] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Accepted: 10/10/2017] [Indexed: 11/13/2022] Open
Abstract
Aims To investigate the influence of the A1 allele of the TAQ1A polymorphism in the dopamine D2 receptor (DRD2) gene region on mortality in adult individuals with alcohol dependence. Methods The study sample consisted of 359 alcohol-dependent individuals treated for severe alcohol withdrawal symptoms in 1997. Years of survival was studied in an 18-year follow-up. In the analyses, gender and age were controlled for. Results At the 18-year follow-up, 53% individuals had deceased. The analyses showed that older age (P < 0.001), male gender (P < 0.05) and carrying the A1 allele (P < 0.01) all significantly and independently contributed to shorten years of survival. Among the deceased individuals, the genotype A1+ was the only significant contributor to shorten years of survival. Conclusions An important contribution of the present study is that in alcohol dependence the Taq1A1 allele of the DRD2 gene region is a risk factor for premature death of similar importance as the well-known risk factors of age and gender. Short Summary We investigated the influence of A1 allele of the TAQ1A polymorphism in DRD2 receptor gene region on mortality in alcohol-dependent individuals in an 18-year follow-up. Age, gender and the A1 allele contributed to shorten years of survival. Among the deceased, the A1+ was the only contributor to shorten years of survival.
Collapse
Affiliation(s)
- Jan Balldin
- Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, PO Box 430, SE-405 30 Göteborg, Sweden
| | - Kristina J Berglund
- Department of Psychology, University of Gothenburg, PO Box 500, SE-405 30 Göteborg, Sweden
| | - Ulf Berggren
- Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, PO Box 430, SE-405 30 Göteborg, Sweden
| | - Peter Wennberg
- Centre for Social Research on Alcohol and Drugs, Stockholm University, SE-106 91 Stockholm, Sweden
| | - Claudia Fahlke
- Department of Psychology, University of Gothenburg, PO Box 500, SE-405 30 Göteborg, Sweden
| |
Collapse
|
|
33
|
Matsusue A, Ishikawa T, Ikeda T, Tani N, Arima H, Waters B, Hara K, Kashiwagi M, Takayama M, Ikematsu N, Kubo SI. DRD2/ANKK1 gene polymorphisms in forensic autopsies of methamphetamine intoxication fatalities. Leg Med (Tokyo) 2018; 33:6-9. [PMID: 29702335 DOI: 10.1016/j.legalmed.2018.04.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2017] [Revised: 03/20/2018] [Accepted: 04/20/2018] [Indexed: 10/17/2022]
Abstract
Dopamine D2 receptor/ankyrin repeat and kinase domain containing 1 (DRD2/ANKK1) gene polymorphisms have been associated with responses to psychotropic drugs and addiction. We analyzed two DRD2/ANKK1 polymorphisms, Taq1A and -141C Ins/Del, in 37 fatal methamphetamine (MA) intoxication cases and 235 control cases in which MA and psychotropic drugs were not detected. The association among polymorphism, cause of death, and cerebrospinal fluid (CSF) dopamine concentration was evaluated. The Taq1A polymorphism distribution in the fatal MA intoxication cases differed from in the controls (P = 0.030) with a significantly high A1/A1 + A1/A2 genotype frequency. No significant associations were observed between -141C Ins/Del polymorphisms and MA intoxication cases or between DRD2/ANKK1 polymorphisms and CSF dopamine concentrations. Our findings suggest that the DRD2/ANKK1 Taq1A polymorphism is associated with susceptibility to fatal MA intoxication.
Collapse
Affiliation(s)
- Aya Matsusue
- Department of Forensic Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
| | - Takaki Ishikawa
- Department of Legal Medicine, Osaka City University Medical School, Asahi-machi 1-4-3, Abeno, Osaka 545-8585, Japan
| | - Tomoya Ikeda
- Department of Legal Medicine, Osaka City University Medical School, Asahi-machi 1-4-3, Abeno, Osaka 545-8585, Japan
| | - Naoto Tani
- Department of Legal Medicine, Osaka City University Medical School, Asahi-machi 1-4-3, Abeno, Osaka 545-8585, Japan
| | - Hisatomi Arima
- Department of Preventive Medicine and Public Health, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
| | - Brian Waters
- Department of Forensic Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
| | - Kenji Hara
- Department of Forensic Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
| | - Masayuki Kashiwagi
- Department of Forensic Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
| | - Mio Takayama
- Department of Forensic Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
| | - Natsuki Ikematsu
- Department of Forensic Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
| | - Shin-Ichi Kubo
- Department of Forensic Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
| |
Collapse
|
|
34
|
Jeong JE, Rhee JK, Kim TM, Kwak SM, Bang SH, Cho H, Cheon YH, Min JA, Yoo GS, Kim K, Choi JS, Choi SW, Kim DJ. The association between the nicotinic acetylcholine receptor α4 subunit gene (CHRNA4) rs1044396 and Internet gaming disorder in Korean male adults. PLoS One 2017; 12:e0188358. [PMID: 29240768 PMCID: PMC5730169 DOI: 10.1371/journal.pone.0188358] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2017] [Accepted: 11/06/2017] [Indexed: 11/18/2022] Open
Abstract
The primary aim of this study was to investigate the genetic predisposition of Internet gaming disorder (IGD), and the secondary aim was to compare the results to those of alcohol dependence (AD). Two independent case-control studies were conducted. A total of 30 male participants with IGD, diagnosed according to the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, and 30 sex-matched controls participated in study 1. We designed targeted exome sequencing (TES) to test for 72 candidate genes that have been implicated in the pathogenesis of addiction. The genes included seven neurotransmitter (dopamine, serotonin, glutamate, r-aminobutyric acid (GABA), norepinephrine, acetylcholine, and opioid) system genes. A total of 31 male in-patients with AD and 29 normal male controls (NC) were enrolled in study 2. The same 72 genes included in study 1 and ten additional genes related to alcohol-metabolic enzyme were selected as the target genes, and we identified the genetic variants using the same method (TES). The IGD group had a lower frequency of the T allele of rs1044396 in the nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4), and this variant represents a protective allele against IGD. However, we did not find a significant difference in the polymorphisms of the 72 genes that encode neurotransmitter systems between the AD and NC groups. This study demonstrated that rs1044396 of CHRNA4 was significantly associated with IGD.
Collapse
Affiliation(s)
- Jo-Eun Jeong
- Department of Psychiatry, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Je-Keun Rhee
- Catholic Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Tae-Min Kim
- Catholic Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Su-Min Kwak
- Department of Psychiatry, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sol-hee Bang
- Department of Psychiatry, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Hyun Cho
- Department of Psychiatry, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Young-Hoon Cheon
- Department of Psychiatry, Incheon Chamsarang Hospital, Incheon, Republic of Korea
| | - Jung Ah Min
- Department of Psychiatry, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Gil Sang Yoo
- Department of Psychiatry, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Kyudong Kim
- Department of Psychiatry, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jung-Seok Choi
- Department of Psychiatry, SMU-SNU Boramae Medical Center, Seoul, Republic of Korea
- Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sam-Wook Choi
- Department of Psychiatry, True Mind Mental Health Clinic, Seoul, Republic of Korea
| | - Dai-Jin Kim
- Department of Psychiatry, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- * E-mail:
| |
Collapse
|
|
35
|
Ragia G, Veresies I, Veresie L, Veresies K, Manolopoulos VG. Association study of DRD2 A2/A1, DRD3 Ser9Gly, DβH -1021C>T, OPRM1 A118G and GRIK1 rs2832407C>A polymorphisms with alcohol dependence. Drug Metab Pers Ther 2017; 31:143-50. [PMID: 27447243 DOI: 10.1515/dmpt-2016-0015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2016] [Accepted: 06/24/2016] [Indexed: 01/05/2023]
Abstract
BACKGROUND The reinforcing effects of alcohol are mediated through complex interactions between multiple neurochemical systems. Genes of dopaminergic (DRD2, DRD3 and DβH), opioid (OPRM1) and glutaminergic (GRIK1) systems mediate the dependent behavior via different mechanisms; however, they all target the serotonergic and dopaminergic pathways in the ventral tegmental area. METHODS In the present study, DRD2 A2/A1, DRD3 Ser9Gly, DβH -1021C>T, OPRM1 A118G and GRIK1 rs2832407C>A polymorphisms and their interactions were analyzed in 72 alcohol-dependent patients and 74 controls of Greek-Cypriot origin, using the PCR-RFLP method. RESULTS No differences were found in the genotype or allele distribution of DRD2 A2/A1, DRD3 Ser9Gly, DβH -1021C>T, OPRM1 A118G and GRIK1 rs2832407C>A between alcohol-dependent patients and controls. Additionally, we did not find any gene×gene interactions in association with alcohol dependence in the studied population. CONCLUSIONS Alcohol dependence is a complex interaction of genetic and environmental factors. In the present study, we have shown that DRD2 A2/A1, DRD3 Ser9Gly, DβH -1021C>T, OPRM1 A118G and GRIK1 rs2832407C>A are not associated with this dependent behavior alone or in interaction.
Collapse
|
|
36
|
Yeung EW, Craggs JG, Gizer IR. Comorbidity of Alcohol Use Disorder and Chronic Pain: Genetic Influences on Brain Reward and Stress Systems. Alcohol Clin Exp Res 2017; 41:1831-1848. [PMID: 29048744 DOI: 10.1111/acer.13491] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2017] [Accepted: 08/25/2017] [Indexed: 01/10/2023]
Abstract
Alcohol use disorder (AUD) is highly comorbid with chronic pain (CP). Evidence has suggested that neuroadaptive processes characterized by reward deficit and stress surfeit are involved in the development of AUD and pain chronification. Neurological data suggest that shared genetic architecture associated with the reward and stress systems may contribute to the comorbidity of AUD and CP. This monograph first delineates the prevailing theories of the development of AUD and pain chronification focusing on the reward and stress systems. It then provides a brief summary of relevant neurological findings followed by an evaluation of evidence documented by molecular genetic studies. Candidate gene association studies have provided some initial support for the genetic overlap between AUD and CP; however, these results must be interpreted with caution until studies with sufficient statistical power are conducted and replications obtained. Genomewide association studies have suggested a number of genes (e.g., TBX19, HTR7, and ADRA1A) that are either directly or indirectly related to the reward and stress systems in the AUD and CP literature. Evidence reviewed in this monograph suggests that shared genetic liability underlying the comorbidity between AUD and CP, if present, is likely to be complex. As the advancement in molecular genetic methods continues, future studies may show broader central nervous system involvement in AUD-CP comorbidity.
Collapse
Affiliation(s)
- Ellen W Yeung
- Department of Psychological Sciences, University of Missouri, Columbia, Missouri.,Institute for Interdisciplinary Salivary Bioscience Research, University of California at Irvine, Irvine, California
| | - Jason G Craggs
- Department of Psychological Sciences, University of Missouri, Columbia, Missouri.,School of Health Professions, University of Missouri, Columbia, Missouri
| | - Ian R Gizer
- Department of Psychological Sciences, University of Missouri, Columbia, Missouri
| |
Collapse
|
|
37
|
Elam KK, Chassin L, Lemery-Chalfant K, Pandika D, Wang FL, Bountress K, Dick D, Agrawal A. Affiliation with substance-using peers: Examining gene-environment correlations among parent monitoring, polygenic risk, and children's impulsivity. Dev Psychobiol 2017; 59:561-573. [PMID: 28561888 PMCID: PMC6035731 DOI: 10.1002/dev.21529] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Accepted: 05/05/2017] [Indexed: 02/05/2023]
Abstract
Parental monitoring can buffer the effect of deviant peers on adolescents' substance use by reducing affiliation with substance-using peers. However, children's genetic predispositions may evoke poorer monitoring, contributing to negative child outcomes. We examined evocative genotype-environment correlations underlying children's genetic predisposition for behavioral undercontrol and parental monitoring in early adolescence via children's impulsivity in middle childhood, and the influence of parental monitoring on affiliation with substance-using peers a year and a half later (n = 359). Genetic predisposition for behavioral undercontrol was captured using a polygenic risk score, and a portion of passive rGE was controlled by including parents' polygenic risk scores. Children's polygenic risk predicted poorer parental monitoring via greater children's impulsivity, indicating evocative rGE, controlling for a portion of passive rGE. Poorer parental monitoring predicted greater children's affiliation with substance-using peers a year and a half later. Results are discussed with respect to gene-environment correlations within developmental cascades.
Collapse
Affiliation(s)
- Kit K. Elam
- T. Denny Sanford School of Social and Family Dynamics, Arizona State University, Tempe, Arizona
| | - Laurie Chassin
- Department of Psychology, Arizona State University, Tempe, Arizona
| | | | - Danielle Pandika
- Department of Psychology, Arizona State University, Tempe, Arizona
| | - Frances L. Wang
- Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Kaitlin Bountress
- National Crime Victims Research & Treatment Center, Medical University of South Carolina, Charleston, South Carolina
| | - Danielle Dick
- Department of Psychology, Virginia Commonwealth University, Richmond, Virginia
| | - Arpana Agrawal
- Department of Psychological & Brain Sciences, Washington University in St. Louis, Saint Louis, Missouri
| |
Collapse
|
|
38
|
Katsarou MS, Karakonstantis K, Demertzis N, Vourakis E, Skarpathioti A, Nosyrev AE, Tsatsakis A, Kalogridis T, Drakoulis N. Effect of single-nucleotide polymorphisms in ADH1B, ADH4, ADH1C, OPRM1, DRD2, BDNF, and ALDH2 genes on alcohol dependence in a Caucasian population. Pharmacol Res Perspect 2017; 5. [PMID: 28805974 PMCID: PMC5684860 DOI: 10.1002/prp2.326] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2017] [Accepted: 04/22/2017] [Indexed: 01/12/2023] Open
Abstract
Alcohol is a frequently used addictive substance worldwide. Aim of this study is to determine the frequency distribution of SNPs within ADH1B,ADH4,ADH1C,ALDH2, BDNF,OPRM1, and DRD2 genes in a southeastern European Caucasian population from Greece. For this purpose samples of 1276 volunteers were analyzed after deidentification and anonymization. The allele distribution of the examined polymorphisms in the present Greek population cohort was as follows: rs1229984 (ADH1B): GG(wt) = 64.14%, GA = 29.86%, AA = 4.00%; rs1693482 (ADH1C): CC(wt) = 57.45%, CT = 36.76%, TT = 5.80%; rs1799971 (OPRM1): AA(wt) = 72.43%, AG = 28.72%, GG = 1.89%; rs1800497 (DRD2): CC(wt) = 70.84%, CT = 27.18%, TT = 1.98%; rs1800759 (ADH4): CC(wt) = 34.25%, CA = 48.12%, AA = 17.63%; rs6265 (BDNF): GG(wt) = 65.99%, GA = 31.02%, AA = 2.99%; and rs671 (ALDH2): GG(wt) = 99.84% GA = 0.16%, AA = 0.00%. Mutant rs1229984 allele A was ~6.5× more frequent in the Greek than in the European population. Mutant rs1693482 allele T was ~1.7× more frequent in the European than in the Greek population. Mutant alleles for polymorphisms rs1800759 and rs1799971 show similar frequencies in both northern and southern Europeans. One rs671 mutant A allele was detected in the Greek population (0.08%). The mutant rs1800497 allele T was ~1.2× more frequent in the European than in the Greek population and the mutant rs6265 allele A was ~1.1× more frequent in the European than in the Greek population. An alcohol addiction‐specific algorithm was generated (TGS) that may predict alcohol addiction prevalence in a population. According to our findings, the analyzed Southeastern population may differ genetically from north Europeans due to influences from neighboring Asian and African populations and a calculated TGS score >50 indicates individuals with low susceptibility to develop alcohol addiction.
Collapse
Affiliation(s)
- Martha-Spyridoula Katsarou
- Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, 15771, Greece
| | - Konstantinos Karakonstantis
- Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, 15771, Greece
| | - Nikolaos Demertzis
- Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, 15771, Greece
| | - Emmanouil Vourakis
- Department of Biochemistry and Molecular Biology, Faculty of Biology, School of Health Sciences, National and Kapodistrian University of Athens, Athens, 15771, Greece
| | - Aspasia Skarpathioti
- Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, 15771, Greece
| | - Aleksandr E Nosyrev
- Central Chemical Laboratory of Toxicology, I. M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
| | - Aristidis Tsatsakis
- Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, Heraklion, 71003, Greece
| | - Theodoris Kalogridis
- Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, 15771, Greece
| | - Nikolaos Drakoulis
- Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, 15771, Greece
| |
Collapse
|
|
39
|
Say YH. The association of insertions/deletions (INDELs) and variable number tandem repeats (VNTRs) with obesity and its related traits and complications. J Physiol Anthropol 2017; 36:25. [PMID: 28615046 PMCID: PMC5471687 DOI: 10.1186/s40101-017-0142-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Accepted: 06/01/2017] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Despite the fact that insertions/deletions (INDELs) are the second most common type of genetic variations and variable number tandem repeats (VNTRs) represent a large portion of the human genome, they have received far less attention than single nucleotide polymorphisms (SNPs) and larger forms of structural variation like copy number variations (CNVs), especially in genome-wide association studies (GWAS) of complex diseases like polygenic obesity. This is exemplified by the vast amount of review papers on the role of SNPs and CNVs in obesity, its related traits (like anthropometric measurements, biochemical variables, and eating behavior), and its related complications (like hypertension, hypertriglyceridemia, hypercholesterolemia, and insulin resistance-collectively known as metabolic syndrome). Hence, this paper reviews the types of INDELs and VNTRs that have been studied for association with obesity and its related traits and complications. These INDELs and VNTRs could be found in the obesity loci or genes from the earliest GWAS and candidate gene association studies, like FTO, genes in the leptin-proopiomelanocortin pathway, and UCP2/3. Given the important role of the brain serotonergic and dopaminergic reward system in obesity susceptibility, the association of INDELs and VNTRs in these neurotransmitters' metabolism and transport genes with obesity is also reviewed. Next, the role of INS VNTR in obesity and its related traits is questionable, since recent large-scale studies failed to replicate the earlier positive associations. As obesity results in chronic low-grade inflammation of the adipose tissue, the proinflammatory cytokine gene IL1RA and anti-inflammatory cytokine gene IL4 have VNTRs that are implicated in obesity. A systemic proinflammatory state in combination with activation of the renin-angiotensin system and decreased nitric oxide bioavailability as found in obesity leads to endothelial dysfunction. This explains why VNTR and INDEL in eNOS and ACE, respectively, could be predisposing factors of obesity. Finally, two novel genes, DOCK5 and PER3, which are involved in the regulation of the Akt/MAPK pathway and circadian rhythm, respectively, have VNTRs and INDEL that might be associated with obesity. SHORT CONCLUSION In conclusion, INDELs and VNTRs could have important functional consequences in the pathophysiology of obesity, and research on them should be continued to facilitate obesity prediction, prevention, and treatment.
Collapse
Affiliation(s)
- Yee-How Say
- Department of Biomedical Science, Faculty of Science, Universiti Tunku Abdul Rahman (UTAR) Kampar Campus, Jalan Universiti, Bandar Barat, 31900, Kampar, Perak, Malaysia.
| |
Collapse
|
|
40
|
Coley RL, Sims J, Carrano J. Environmental risks outweigh dopaminergic genetic risks for alcohol use and abuse from adolescence through early adulthood. Drug Alcohol Depend 2017; 175:106-118. [PMID: 28412301 DOI: 10.1016/j.drugalcdep.2017.01.042] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2016] [Revised: 12/16/2016] [Accepted: 01/24/2017] [Indexed: 10/19/2022]
Abstract
BACKGROUND Alcohol use is a primary public health concern, particularly among adolescents and young adults. Based on the rapidly growing field of gene-environment models, this study assessed the combined role of environmental and dopamine-related genetic correlates of early alcohol use and abuse. METHODS Multilevel growth models assessed trajectories of alcohol use and intoxication and ordered logistic regressions assessed alcohol use disorder among a sample of 12,437 youth from the nationally representative Add Health study who were followed from mid-adolescence through early adulthood. RESULTS Endogenous and exogenous stressful life events and social norms supportive of alcohol use from parents and peers were significant predictors of alcohol use, intoxication, and alcohol use disorder, with consistent patterns across males and females. In contrast, a dopamine-system genetic risk score (GRS) was not associated with alcohol use trajectories nor alcohol use disorder in early adulthood, although weak connections emerged between the GRS and growth trajectories of intoxication, indicating that higher GRS predicted more frequent episodes of intoxication during the transition to adulthood but not during adolescence or later 20s. No evidence of gene-environment interactions emerged. CONCLUSIONS Results extend a substantial body of prior research primarily assessing single genetic polymorphisms in the dopamine system, suggesting that dopaminergic GRSs may be associated with more problematic alcohol behaviors at some developmental periods, but further, that social norms and stressful life experiences are more consistent correlates of early and problematic alcohol use among youth. These environmental factors present potential targets for research manipulating contexts to identify causal pathways.
Collapse
Affiliation(s)
- Rebekah Levine Coley
- Boston College, Lynch School of Education, Department of Counseling, Developmental, and Educational Psychology, United States.
| | - Jacqueline Sims
- Boston College, Lynch School of Education, Department of Counseling, Developmental, and Educational Psychology, United States
| | - Jennifer Carrano
- University of Delaware, Department of Human Development and Family Studies, United States
| |
Collapse
|
|
41
|
Panduro A, Ramos-Lopez O, Campollo O, Zepeda-Carrillo EA, Gonzalez-Aldaco K, Torres-Valadez R, Roman S. High frequency of the DRD2/ANKK1 A1 allele in Mexican Native Amerindians and Mestizos and its association with alcohol consumption. Drug Alcohol Depend 2017; 172:66-72. [PMID: 28152448 DOI: 10.1016/j.drugalcdep.2016.12.006] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Revised: 11/28/2016] [Accepted: 12/01/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND Mexico has an ancient tradition of alcohol drinking influenced by genetic and sociocultural factors. This study aimed to determine the distribution of the DRD2/ANKK1 TaqIA polymorphism in Mexican populations and to analyze its association with heavy drinking. METHODS In a cross-sectional and analytical study, 680 unrelated subjects including two Native Amerindians groups (87 Nahuas and 139 Huicholes), and two Mestizos groups (158 subjects from Tepic, Nayarit and 296 subjects from Guadalajara, Jalisco) were enrolled. DRD2/ANKK1 genotyping was performed by PCR-RFLP and allelic discrimination assays. Genetic analyses were conducted by Arlequin and Structure software. Heavy drinking was defined as ≥300g alcohol/week. The association of the DRD2/ANKK1 TaqIA polymorphism with heavy drinking was estimated. RESULTS Heavy drinking was prevalent in 64.7% of the study population. The DRD2/ANKK1 A1 allele prevailed in 67% and 65% of Nahuas and Huicholes, respectively and 51% and 47.3% in Mestizos from Tepic and Guadalajara, respectively. Heavy drinking was associated with the A1A1 genotype in the Mestizos of Guadalajara (A1A1 vs. A1A2 OR=4.79, 95%CI 1.81-12.68, p=0.0006; A1A1 vs. A1A2+A2A2, OR=4.09, 95%CI 1.56-10.68, p=0.0021) and in the Mestizos from Tepic (A1A1 vs. A1A2, OR=5.92, 95%CI 2.12-16.49, p=0.0002); A2A2, OR=14.56, 95%CI 3.57-59.24, p=0.00004); A1A2+A2A2, OR=6.68, 95%CI 2.42-18.42, p=0.00005). In Native Amerindians, a lack of association was found. CONCLUSIONS High frequencies of the DRD2/ANKK1 A1 allele were present in Mexican populations. Native Amerindians exhibited the highest frequencies of the A1 allele documented worldwide to date. The A1A1 genotype was associated with heavy drinking in Mestizos.
Collapse
Affiliation(s)
- Arturo Panduro
- Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, "Fray Antonio Alcalde," Guadalajara, Jalisco, Mexico; Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico.
| | - Omar Ramos-Lopez
- Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, "Fray Antonio Alcalde," Guadalajara, Jalisco, Mexico; Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico
| | - Octavio Campollo
- Center for the Study of Alcoholism and Addictions, Guadalajara, Jalisco, Mexico; Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico
| | - Eloy Alfonso Zepeda-Carrillo
- Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, "Fray Antonio Alcalde," Guadalajara, Jalisco, Mexico; Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico
| | - Karina Gonzalez-Aldaco
- Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, "Fray Antonio Alcalde," Guadalajara, Jalisco, Mexico; Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico
| | - Rafael Torres-Valadez
- Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, "Fray Antonio Alcalde," Guadalajara, Jalisco, Mexico; Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico
| | - Sonia Roman
- Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, "Fray Antonio Alcalde," Guadalajara, Jalisco, Mexico; Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico
| |
Collapse
|
|
42
|
Anderson MR, Miller L, Wickramaratne P, Svob C, Odgerel Z, Zhao R, Weissman MM. Genetic Correlates of Spirituality/Religion and Depression: A Study in Offspring and Grandchildren at High and Low Familial Risk for Depression. ACTA ACUST UNITED AC 2017; 4:43-63. [PMID: 29057276 DOI: 10.1037/scp0000125] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
RATIONALE Possible genetic correlates of spirituality and depression have been identified in community samples. We investigate some of the previously identified candidates in a sample of families at both high and low-risk for depression. METHOD Offspring and grandchildren of individuals at high and low-risk for depression, participating in a multi-wave thirty-year longitudinal study, were assessed for seven SNPS drawn from four single gene candidates associated with systems implicated in both depression and spirituality: Serotonin (5-HT1B and 5-HT2A), Dopamine (DRD2), Oxytocin (OT) and Monoamine Vesicular Transporter (VMAT1). RESULTS Dopamine (DRD2) Serotonin (5-HT1B), their Transporter (VMAT1) and Oxytocin (OXTR) were positively associated with a high level of importance of spirituality or religion (S/R) in the group at low familial risk for depression. DRD2 minor allele was associated with both lifetime major depressive disorder (MDD) and spirituality in the low-risk group for depression. No SNPs were related to S/R in the group at high familial risk for depression. OXTR was associated with lifetime MDD in the full sample. CONCLUSION Genes for dopamine, serotonin, their vesicular transporter, and oxytocin may be associated with S/R in people at low familial risk for depression. Genes for dopamine may be associated both with S/R and increased risk for depression in people at low-risk for depression, suggesting a common pathway or physiology to mild to moderate depression. MDD is associated with oxytocin across risk groups. In the high-risk group, phenotypic expression of S/R may be suppressed. IMPLICATIONS The shared association of DRD2 by S/R and depression, generally found to be inversely related, calls for further research on their common physiological pathways, and the phenotypic expression of these pathways based upon use and environment. Prevention for offspring at high familial risk for depression might include support for the development of child spirituality.
Collapse
Affiliation(s)
| | - Lisa Miller
- Teachers College, Columbia University, New York, NY
| | - Priya Wickramaratne
- Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA.,Division of Epidemiology, New York State Psychiatric Institute, New York, NY, USA.,Mailman School of Public Health, Columbia University, New York, NY, USA
| | - Connie Svob
- Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA.,Division of Epidemiology, New York State Psychiatric Institute, New York, NY, USA
| | - Zagaa Odgerel
- Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA.,Division of Epidemiology, New York State Psychiatric Institute, New York, NY, USA
| | - Ruixin Zhao
- Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA.,Division of Epidemiology, New York State Psychiatric Institute, New York, NY, USA
| | - Myrna M Weissman
- Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA.,Division of Epidemiology, New York State Psychiatric Institute, New York, NY, USA.,Mailman School of Public Health, Columbia University, New York, NY, USA
| |
Collapse
|
|
43
|
Rogers PJ. Food and drug addictions: Similarities and differences. Pharmacol Biochem Behav 2017; 153:182-190. [PMID: 28063947 DOI: 10.1016/j.pbb.2017.01.001] [Citation(s) in RCA: 74] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2016] [Revised: 12/23/2016] [Accepted: 01/03/2017] [Indexed: 11/18/2022]
Abstract
This review examines the merits of 'food addiction' as an explanation of excessive eating (i.e., eating in excess of what is required to maintain a healthy body weight). It describes various apparent similarities in appetites for foods and drugs. For example, conditioned environmental cues can arouse food and drug-seeking behaviour, 'craving' is an experience reported to precede eating and drug taking, 'bingeing' is associated with both eating and drug use, and conditioned and unconditioned tolerance occurs to food and drug ingestion. This is to be expected, as addictive drugs tap into the same processes and systems that evolved to motivate and control adaptive behaviours, including eating. The evidence, however, shows that drugs of abuse have more potent effects than foods, particularly in respect of their neuroadaptive effects that make them 'wanted.' While binge eating has been conceptualised as form of addictive behaviour, it is not a major cause of excessive eating, because binge eating has a far lower prevalence than obesity. Rather, it is proposed that obesity results from recurrent overconsumption of energy dense foods. Such foods are, relatedly, both attractive and (calorie for calorie) weakly satiating. Limiting their availability could partially decrease excessive eating and consequently decrease obesity. Arguably, persuading policy makers that these foods are addictive could support such action. However, blaming excessive eating on food addiction could be counterproductive, because it risks trivialising serious addictions, and because the attribution of excessive eating to food addiction implies an inability to control one's eating. Therefore, attributing everyday excessive eating to food addiction may neither explain nor significantly help reduce this problem.
Collapse
Affiliation(s)
- Peter J Rogers
- Nutrition and Behaviour Unit, School of Experimental Psychology, University of Bristol, Bristol, UK.
| |
Collapse
|
|
44
|
Hodgson K, Almasy L, Knowles EEM, Kent JW, Curran JE, Dyer TD, Göring HHH, Olvera RL, Woolsey MD, Duggirala R, Fox PT, Blangero J, Glahn DC. The genetic basis of the comorbidity between cannabis use and major depression. Addiction 2017; 112:113-123. [PMID: 27517884 PMCID: PMC5148647 DOI: 10.1111/add.13558] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2015] [Revised: 04/06/2016] [Accepted: 08/09/2016] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIMS While the prevalence of major depression is elevated among cannabis users, the role of genetics in this pattern of comorbidity is not clear. This study aimed to estimate the heritability of cannabis use and major depression, quantify the genetic overlap between these two traits and localize regions of the genome that segregate in families with cannabis use and major depression. DESIGN Family-based univariate and bivariate genetic analysis. SETTING San Antonio, Texas, USA. PARTICIPANTS Genetics of Brain Structure and Function study (GOBS) participants: 1284 Mexican Americans from 75 large multi-generation families and an additional 57 genetically unrelated spouses. MEASUREMENTS Phenotypes of life-time history of cannabis use and major depression, measured using the semistructured MINI-Plus interview. Genotypes measured using ~1 M single nucleotide polymorphisms (SNPs) on Illumina BeadChips. A subselection of these SNPs were used to build multi-point identity-by-descent matrices for linkage analysis. FINDINGS Both cannabis use [h2 = 0.614, P = 1.00 × 10-6 , standard error (SE) = 0.151] and major depression (h2 = 0.349, P = 1.06 × 10-5 , SE = 0.100) are heritable traits, and there is significant genetic correlation between the two (ρg = 0.424, P = 0.0364, SE = 0.195). Genome-wide linkage scans identify a significant univariate linkage peak for major depression on chromosome 22 [logarithm of the odds (LOD) = 3.144 at 2 centimorgans (cM)], with a suggestive peak for cannabis use on chromosome 21 (LOD = 2.123 at 37 cM). A significant pleiotropic linkage peak influencing both cannabis use and major depression was identified on chromosome 11 using a bivariate model (LOD = 3.229 at 112 cM). Follow-up of this pleiotropic signal identified a SNP 20 kb upstream of NCAM1 (rs7932341) that shows significant bivariate association (P = 3.10 × 10-5 ). However, this SNP is rare (seven minor allele carriers) and does not drive the linkage signal observed. CONCLUSIONS There appears to be a significant genetic overlap between cannabis use and major depression among Mexican Americans, a pleiotropy that appears to be localized to a region on chromosome 11q23 that has been linked previously to these phenotypes.
Collapse
Affiliation(s)
- Karen Hodgson
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT,Correspondence to Karen Hodgson Ph.D., Department of Psychiatry, Yale School of Medicine, New Haven, CT
| | - Laura Almasy
- South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio & University of Texas of the Rio Grande Valley, Brownsville, TX
| | - Emma E. M. Knowles
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT
| | - Jack W. Kent
- Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX
| | - Joanne E. Curran
- South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio & University of Texas of the Rio Grande Valley, Brownsville, TX
| | - Thomas D. Dyer
- South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio & University of Texas of the Rio Grande Valley, Brownsville, TX
| | - Harald H. H. Göring
- South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio & University of Texas of the Rio Grande Valley, Brownsville, TX
| | - Rene L. Olvera
- Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX
| | - Mary D. Woolsey
- Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX
| | - Ravi Duggirala
- South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio & University of Texas of the Rio Grande Valley, Brownsville, TX
| | - Peter T. Fox
- Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, South Texas Veterans Health System, 7400 Merton Minter, San Antonio, TX
| | - John Blangero
- South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio & University of Texas of the Rio Grande Valley, Brownsville, TX
| | - David C. Glahn
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT, Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, CT
| |
Collapse
|
|
45
|
Alvanzo AAH, Wand GS, Kuwabara H, Wong DF, Xu X, McCaul ME. Family history of alcoholism is related to increased D 2 /D 3 receptor binding potential: a marker of resilience or risk? Addict Biol 2017; 22:218-228. [PMID: 26416591 DOI: 10.1111/adb.12300] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2015] [Revised: 06/21/2015] [Accepted: 08/08/2015] [Indexed: 12/01/2022]
Abstract
The aim of this study was to examine the relationship between family history of alcohol use disorder and striatal dopamine using positron emission tomography imaging. Participants were 84 healthy, 18- to 30-year-old, social drinkers recruited via fliers and newspaper advertisements. At assessment, participants completed measures of lifetime personal and family substance use and psychiatric symptoms. Participants underwent two consecutive positron emission tomography scans using the D2 /D3 dopamine receptor radioligand [11 C]raclopride. Scans were preceded by intravenous saline and amphetamine 0.3 mg/kg, providing measures of baseline [11 C]raclopride binding potential (BPND ) and change in [11 C]raclopride (ΔBPND ). Subjective ratings of stimulant drug effects were collected during scans. Subjects were classified as family history positive (FHP) if they reported any first-degree relative with alcohol use disorder (AUD) and family history negative (FHN) if no first-degree relatives had history of AUD. Participants were predominantly White (69.0 percent) and male (62.1 percent). Baseline [11 C]raclopride BPND was generally higher in FHP compared with FHN subjects across striatal subdivisions. There were no differences in ΔBPND across regions. Negative subjective drug effects were more pronounced in FHP than in FHN subjects. While FHN subjects evidenced the expected positive relationship between ΔBPND and positive subjective drug effects, this relationship was disrupted in FHP subjects. There are key differences in dopamine status and subjective stimulant drug experiences as a function of family AUD history. These findings have important implications for understanding risk for AUD development in FHP offspring.
Collapse
Affiliation(s)
- Anika A. H. Alvanzo
- Division of General Internal Medicine; Johns Hopkins University School of Medicine; Baltimore MD USA
| | - Gary S. Wand
- Department of Medicine; Johns Hopkins University School of Medicine; Baltimore MD USA
| | - Hiroto Kuwabara
- Department of Radiology and Radiological Sciences; Johns Hopkins University School of Medicine; Baltimore MD USA
| | - Dean F. Wong
- Department of Radiology and Radiological Sciences; Johns Hopkins University School of Medicine; Baltimore MD USA
- Department of Psychiatry and Behavioral Sciences; Johns Hopkins School of Medicine; Baltimore MD USA
- Solomon H. Snyder Department of Neuroscience; Johns Hopkins University School of Medicine; Baltimore MD USA
| | - Xiaoqiang Xu
- Department of Psychiatry and Behavioral Sciences; Johns Hopkins School of Medicine; Baltimore MD USA
| | - Mary E. McCaul
- Department of Psychiatry and Behavioral Sciences; Johns Hopkins School of Medicine; Baltimore MD USA
| |
Collapse
|
|
46
|
A meta-analysis of the relationship between brain dopamine receptors and obesity: a matter of changes in behavior rather than food addiction? Int J Obes (Lond) 2016; 40 Suppl 1:S12-21. [PMID: 27001642 PMCID: PMC4819757 DOI: 10.1038/ijo.2016.9] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Addiction to a wide range of substances of abuse has been suggested to reflect a ‘Reward Deficiency Syndrome'. That is, drugs are said to stimulate the reward mechanisms so intensely that, to compensate, the population of dopamine D2 receptors (DD2R) declines. The result is that an increased intake is necessary to experience the same degree of reward. Without an additional intake, cravings and withdrawal symptoms result. A suggestion is that food addiction, in a similar manner to drugs of abuse, decrease DD2R. The role of DD2R in obesity was therefore examined by examining the association between body mass index (BMI) and the Taq1A polymorphism, as the A1 allele is associated with a 30–40% lower number of DD2R, and is a risk factor for drug addiction. If a lower density of DD2R is indicative of physical addiction, it was argued that if food addiction occurs, those with the A1 allele should have a higher BMI. A systematic review found 33 studies that compared the BMI of those who did and did not have the A1 allele. A meta-analysis of the studies compared those with (A1/A1 and A1/A2) or without (A2/A2) the A1 allele; no difference in BMI was found (standardized mean difference 0.004 (s.e. 0.021), variance 0.000, Z=0.196, P<0.845). It was concluded that there was no support for a reward deficiency theory of food addiction. In contrast, there are several reports that those with the A1 allele are less able to benefit from an intervention that aimed to reduce weight, possibly a reflection of increased impulsivity.
Collapse
|
|
47
|
Carlson MD, Harden KP, Kretsch N, Corbin WR, Fromme K. Interactions between DRD4 and developmentally specific environments in alcohol-dependence symptoms. JOURNAL OF ABNORMAL PSYCHOLOGY 2016; 124:1043-9. [PMID: 26595480 DOI: 10.1037/abn0000120] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Social experiences may moderate genetic influences on alcohol dependence (AD) symptoms. Consistent with this hypothesis, Park, Sher, Todorov, and Heath (2011) previously reported interactions between the dopamine D4 receptor gene (DRD4) and developmentally specific environments in the etiology of AD symptoms during emerging and young adulthood. Using a longitudinal cohort of n = 367 White participants followed from ages 18 to 27 years, we examine a series of similar interactions between DRD4 and developmentally sensitive contexts including childhood adversity and work and family roles. In contrast to previous results, we observed no significant interactions between DRD4 and childhood adversity. Overall, results further highlight the need for longitudinal studies of Gene × Environment interaction in the behavioral sciences and the difficulty of identifying candidate Gene × Environment interaction effects that are consistent across studies.
Collapse
Affiliation(s)
| | | | | | | | - Kim Fromme
- Department of Psychology, University of Texas at Austin
| |
Collapse
|
|
48
|
Association of the dopamine D2 receptor rs1800497 polymorphism and eating behavior in Chilean children. Nutrition 2016; 35:139-145. [PMID: 28241982 DOI: 10.1016/j.nut.2016.11.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2015] [Revised: 08/04/2016] [Accepted: 11/19/2016] [Indexed: 02/02/2023]
Abstract
OBJECTIVES Studies have established a strong genetic component in eating behavior. The TaqI A1 polymorphism (rs1800497) has previously been associated with obesity and eating behavior. Additionally, this polymorphism has been associated with diminished dopamine D2 receptor (DRD2) density, higher body mass, and food reinforcement. The aim of this study was to evaluate the association between the DRD2 rs1800497 polymorphism and eating behavior in Chilean children. METHODS This was a cross-sectional study in which we selected 258 children (44% girls, 56% boys; ages 8-14 y) with a wide variation in body mass index. Anthropometric measurements were performed by standard procedures. Eating behavior was assessed using the Eating in Absence of Hunger Questionnaire (EAHQ), Child Eating Behavior Questionnaire, and the Food Reinforcement Value Questionnaire. Genotype of the rs1800497 was determined by polymerase chain reaction-restriction fragment length polymorphism. Association of the TaqI A1 variant (T allele) with eating behavior was assessed using nonparametric tests. RESULTS Compared with normal-weight children, the obese group demonstrated higher scores on the External Eating and Fatigue/Boredom subscales of the EAHQ. Higher scores were assessed in Food Responsiveness, Emotional Overeating, Enjoyment to Food and Desire to Drink subscales (P < 0.001) and lower scores of the Satiety Responsiveness and Slowness in Eating (P < 0.05). In the sex-specific analysis, the TaqI A1 allele was associated with higher scores on Satiety Responsiveness and Emotional Undereating subscales in obese girls, and higher scores of Enjoyment of Food subscale in boys. CONCLUSION The TaqI A1 polymorphism may be a risk factor for eating behavior traits that may predispose children to greater energy intake and obesity.
Collapse
|
|
49
|
Alcohol misuse in emerging adulthood: Association of dopamine and serotonin receptor genes with impulsivity-related cognition. Addict Behav 2016; 63:29-36. [PMID: 27399274 DOI: 10.1016/j.addbeh.2016.05.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Revised: 03/29/2016] [Accepted: 05/05/2016] [Indexed: 12/25/2022]
Abstract
Impulsivity predicts alcohol misuse and risk for alcohol use disorder. Cognition mediates much of this association. Genes also account for a large amount of variance in alcohol misuse, with dopamine and serotonin receptor genes of particular interest, because of their role in motivated behavior. The precise psychological mechanisms through which such genes confer risk is unclear. Trait impulsivity conveys risk for alcohol misuse by influencing two distinct domains of cognition: beliefs about the reinforcing effects of alcohol consumption (positive alcohol expectancy) and the perceived ability to resist it (drinking refusal self-efficacy). This study investigated the effect of the dopamine-related polymorphism in the DRD2/ANKK1 gene (rs1800497) and a serotonin-related polymorphism in the HTR2A gene (rs6313) on associations between impulsivity, cognition, and alcohol misuse in 120 emerging adults (18-21years). HTR2A predicted lower positive alcohol expectancy, higher refusal self-efficacy, and lower alcohol misuse. However, neither polymorphism moderated the linkages between impulsivity, cognition, and alcohol misuse. This is the first report of an association between HTR2A and alcohol-related cognition. Theoretically-driven biopsychosocial models have potential to elucidate the specific cognitive mechanisms through which distal risk factors like genes and temperament affect alcohol misuse in emerging adulthood.
Collapse
|
|
50
|
Zhang S, Zhang J. The Association of DRD2 with Insight Problem Solving. Front Psychol 2016; 7:1865. [PMID: 27933030 PMCID: PMC5121534 DOI: 10.3389/fpsyg.2016.01865] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2016] [Accepted: 11/10/2016] [Indexed: 11/15/2022] Open
Abstract
Although the insight phenomenon has attracted great attention from psychologists, it is still largely unknown whether its variation in well-functioning human adults has a genetic basis. Several lines of evidence suggest that genes involved in dopamine (DA) transmission might be potential candidates. The present study explored for the first time the association of dopamine D2 receptor gene (DRD2) with insight problem solving. Fifteen single-nucleotide polymorphisms (SNPs) covering DRD2 were genotyped in 425 unrelated healthy Chinese undergraduates, and were further tested for association with insight problem solving. Both single SNP and haplotype analysis revealed several associations of DRD2 SNPs and haplotypes with insight problem solving. In conclusion, the present study provides the first evidence for the involvement of DRD2 in insight problem solving, future studies are necessary to validate these findings.
Collapse
Affiliation(s)
- Shun Zhang
- Department of Psychology, Shandong Normal University Jinan, China
| | - Jinghuan Zhang
- Department of Psychology, Shandong Normal University Jinan, China
| |
Collapse
|