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C. To, G. Bagdy (1999)Anxiogenic effect of central CCK administration is attenuated by chronic fluoxetine or ipsapirone treatment 1 Parts of this data was presented at the 4th IUPHAR Satellite Meeting on Serotonin, Rotterdam, July 23–25, 1998. 1
R. Parsey, Ramin Hastings, M. Oquendo, Yung-yu Huang, N. Simpson, Julie Arcement, Yiyun Huang, R. Ogden, R. Heertum, V. Arango, J. Mann (2006)Lower serotonin transporter binding potential in the human brain during major depressive episodes.
The American journal of psychiatry, 163 1
F. Moreira, D. Aguiar, F. Guimarães (2007)Anxiolytic-like effect of cannabinoids injected into the rat dorsolateral periaqueductal gray
C. Mazzanti, J. Lappalainen, J. Long, D. Bengel, H. Naukkarinen, M. Eggert, M. Virkkunen, M. Linnoila, D. Goldman (1998)Role of the serotonin transporter promoter polymorphism in anxiety-related traits.
Archives of general psychiatry, 55 10
Xiaodong Zhang, R. Gainetdinov, J. Beaulieu, T. Sotnikova, L. Burch, Redford Williams, D. Schwartz, K. Krishnan, M. Caron (2005)Loss-of-Function Mutation in Tryptophan Hydroxylase-2 Identified in Unipolar Major Depression
X. Gonda, G. Juhász, A. Lászik, Z. Rihmer, G. Bagdy (2005)Subthreshold depression is linked to the functional polymorphism of the 5HT transporter gene.
Journal of affective disorders, 87 2-3
U. D'Souza, I. Craig (2008)Functional genetic polymorphisms in serotonin and dopamine gene systems and their significance in behavioural disorders.
Progress in brain research, 172
J. Carroll, Janel Boyce-Rustay, Rachel Millstein, R. Yang, Lisa Wiedholz, D. Murphy, A. Holmes (2007)Effects of Mild Early Life Stress on Abnormal Emotion-related Behaviors in 5-HTT Knockout Mice
Behavior Genetics, 37
Anthony Jorm, A. Henderson, P. Jacomb, H. Christensen, A. Korten, B. Rodgers, X. Tan, S. Easteal (1998)An association study of a functional polymorphism of the serotonin transporter gene with personality and psychiatric symptoms
Molecular Psychiatry, 3
R. Rodgers, J. Haller, J. Halasz, É. Mikics (2003)‘One‐trial sensitization’ to the anxiolytic‐like effects of cannabinoid receptor antagonist SR141716A in the mouse elevated plus‐maze
European Journal of Neuroscience, 17
M. Ricketts, R. Hamer, J. Sage, P. Manowitz, F. Feng, M. Menza (1998)Association of a serotonin transporter gene promoter polymorphism with harm avoidance behaviour in an elderly population
Psychiatric Genetics, 8
Gobbi (2005)Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis
Proc Natl Acad Sci USA, 102
D. Ball, L. Hill, B. Freeman, T. Eley, J. Strelau, R. Riemann, F. Spinath, A. Angleitner, R. Plomin (1997)The serotonin transporter gene and peer‐rated neuroticism
S. Gabriel, S. Schaffner, Huy Nguyen, Jamie Moore, J. Roy, B. Blumenstiel, J. Higgins, M. Defelice, Amy Lochner, M. Faggart, S. Liu-Cordero, C. Rotimi, A. Adeyemo, R. Cooper, R. Ward, E. Lander, M. Daly, D. Altshuler (2002)The Structure of Haplotype Blocks in the Human Genome
J. Barrett, B. Fry, J. Maller, M. Daly (2005)Haploview: analysis and visualization of LD and haplotype maps
Bioinformatics, 21 2
A. Ogborne, R. Smart, Timothy Weber, C. Birchmore-Timney (2000)Who is Using Cannabis as a Medicine and Why: An Exploratory Study
Journal of Psychoactive Drugs, 32
E. Tzavara, R. Davis, K. Perry, Xia Li, C. Salhoff, F. Bymaster, J. Witkin, G. Nomikos (2003)The CB1 receptor antagonist SR141716A selectively increases monoaminergic neurotransmission in the medial prefrontal cortex: implications for therapeutic actions
British Journal of Pharmacology, 138
Alessandro Serretti, C. Cusin, E. Lattuada, D. Bella, M. Catalano, Enrico Smeraldi (1999)Serotonin transporter gene (5-HTTLPR) is not associated with depressive symptomatology in mood disorders
Molecular Psychiatry, 4
S. Sen, M. Burmeister, D. Ghosh (2004)Meta‐analysis of the association between a serotonin transporter promoter polymorphism (5‐HTTLPR) and anxiety‐related personality traits
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 127B
G. Gobbi, F. Bambico, R. Mangieri, M. Bortolato, P. Campolongo, M. Solinas, T. Cassano, M. Morgese, G. Debonnel, A. Duranti, A. Tontini, G. Tarzia, M. Mor, V. Trezza, S. Goldberg, V. Cuomo, D. Piomelli (2005)Correction for Gobbi et al., Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis
Proceedings of the National Academy of Sciences of the United States of America, 103
S. Kathuria, S. Gaetani, D. Fegley, F. Valiño, A. Duranti, A. Tontini, M. Mor, G. Tarzia, G. Rana, A. Calignano, A. Giustino, M. Tattoli, M. Palmery, V. Cuomo, D. Piomelli (2003)Modulation of anxiety through blockade of anandamide hydrolysis
Nature Medicine, 9
J. Lazary, Á. Lazáry, X. Gonda, A. Benkő, E. Molnár, G. Juhász, G. Bagdy (2008)New Evidence for the Association of the Serotonin Transporter Gene (SLC6A4) Haplotypes, Threatening Life Events, and Depressive Phenotype
Biological Psychiatry, 64
J. Haller, B. Varga, C. Ledent, I. Barna, T. Freund (2004)Context‐dependent effects of CB1 cannabinoid gene disruption on anxiety‐like and social behaviour in mice
European Journal of Neuroscience, 19
M. Navarro, Elena Hernández, R. Muñoz, I. Arco, M. Villanúa, M. Carrera, F. Fonseca (1997)Acute administration of the CB1 cannabinoid receptor antagonist SR 141716A induces anxiety‐like responses in the rat
C. Spielberger, R. Gorsuch, R. Lushene (1970)Manual for the State-Trait Anxiety Inventory
M. Nakazi, U. Bauer, T. Nickel, M. Kathmann, E. Schlicker (1999)Inhibition of serotonin release in the mouse brain via presynaptic cannabinoid CB1 receptors
Naunyn-Schmiedeberg's Archives of Pharmacology, 361
S. Mato, E. Aso, E. Castro, Miquel Martin, O. Valverde, R. Maldonado, Á. Pazos (2007)CB1 knockout mice display impaired functionality of 5‐HT1A and 5‐HT2A/C receptors
Journal of Neurochemistry, 103
C. Wellman, A. Izquierdo, Joy Garrett, Kathryn Martin, J. Carroll, Rachel Millstein, K. Lesch, D. Murphy, Andrew Holmes (2007)Impaired Stress-Coping and Fear Extinction and Abnormal Corticolimbic Morphology in Serotonin Transporter Knock-Out Mice
The Journal of Neuroscience, 27
X. Messeguer, Ruth Escudero, Domènec Farré, Oscar Núñez, Javier Martínez, M. Albà (2002)PROMO: detection of known transcription regulatory elements using species-tailored searches
Bioinformatics, 18 2
Miquel Martin, C. Ledent, M. Parmentier, R. Maldonado, O. Valverde (2002)Involvement of CB1 cannabinoid receptors in emotional behaviour
A. Serretti, R. Calati, L. Mandelli, D. Ronchi (2006)Serotonin transporter gene variants and behavior: a comprehensive review.
Current drug targets, 7 12
M. Häring, G. Marsicano, B. Lutz, K. Monory (2007)Identification of the cannabinoid receptor type 1 in serotonergic cells of raphe nuclei in mice
S. Stewart, Julie Karp, R. Pihl, R. Peterson (1997)Anxiety sensitivity and self-reported reasons for drug use.
Journal of substance abuse, 9
E. Szádóczky, Z. Rihmer, Z. Papp, J. Füredi (1997)The prevalence of affective and anxiety disorders in primary care practice in Hungary.
Journal of affective disorders, 43 3
A. Goddard, D. Charney, M. Germine, S. Woods, G. Heninger, J. Krystal, W. Goodman, L. Price (1995)Effects of tryptophan depletion on responses to yohimbine in healthy human subjects
Biological Psychiatry, 38
N. Darmani, Jano Janoyan, N. Kumar, Jennifer Crim (2003)Behaviorally active doses of the CB1 receptor antagonist SR 141716A increase brain serotonin and dopamine levels and turnover
Pharmacology Biochemistry and Behavior, 75
T. Freund, I. Katona, D. Piomelli (2003)Role of endogenous cannabinoids in synaptic signaling.
Physiological reviews, 83 3
L. Derogatis, N. Melisaratos (1983)The Brief Symptom Inventory: an introductory report
Psychological Medicine, 13
B. Sethi, J. Trivedi, P. Kumar, A. Gulati, A. Agarwal, N. Sethi (1986)Antianxiety effect of cannabis: Involvement of central benzodiazepine receptors
Biological Psychiatry, 21
Gábor Turu, A. Simon, Pál Gyombolai, L. Szidonya, G. Bagdy, Z. Lenkei, L. Hunyady (2007)The Role of Diacylglycerol Lipase in Constitutive and Angiotensin AT1 Receptor-stimulated Cannabinoid CB1 Receptor Activity*
Journal of Biological Chemistry, 282
Ping Zhang, Hiroki Ishiguro, T. Ohtsuki, Judith Hess, F. Carillo, Donna Walther, E. Onaivi, E. Onaivi, T. Arinami, George Uhl (2004)Human cannabinoid receptor 1: 5′ exons, candidate regulatory regions, polymorphisms, haplotypes and association with polysubstance abuse
Molecular Psychiatry, 9
H. Hermann, G. Marsicano, B. Lutz (2002)Coexpression of the cannabinoid receptor type 1 with dopamine and serotonin receptors in distinct neuronal subpopulations of the adult mouse forebrain
J. Haller, N. Bakos, M. Szirmay, C. Ledent, T. Freund (2002)The effects of genetic and pharmacological blockade of the CB1 cannabinoid receptor on anxiety
European Journal of Neuroscience, 16
H. Akiskal, K. Akiskal, R. Haykal, J. Manning, Pamela Connor (2005)TEMPS-A: progress towards validation of a self-rated clinical version of the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Autoquestionnaire.
Journal of affective disorders, 85 1-2
Y. Osher, D. Hamer, J. Benjamin (2000)Association and linkage of anxiety-related traits with a functional polymorphism of the serotonin transporter gene regulatory region in Israeli sibling pairs
Molecular Psychiatry, 5
K. Lesch, D. Bengel, A. Heils, S. Sabol, B. Greenberg, S. Petri, J. Benjamin, C. Müller, D. Hamer, D. Murphy (1996)Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region
J. Flory, S. Manuck, R. Ferrell, K. Dent, D. Peters, M. Muldoon (1999)Neuroticism is not associated with the serotonin transporter (5-HTTLPR) polymorphism
Molecular Psychiatry, 4
Benjamin Greenberg, Qian Li, Frank Iv, Stella Hu, L. Sirota, J. Benjamin, K. Lesch, Dean Hamer, Dennis Murphy (2000)Association between the serotonin transporter promoter polymorphism and personality traits in a primarily female population sample.
American journal of medical genetics, 96 2
G. Bagdy, Márton Gráf, Z. Anheuer, Edit Modos, S. Kantor (2001)Anxiety-like effects induced by acute fluoxetine, sertraline or m-CPP treatment are reversed by pretreatment with the 5-HT2C receptor antagonist SB-242084 but not the 5-HT1A receptor antagonist WAY-100635.
The international journal of neuropsychopharmacology, 4 4
F. Murakami, T. Shimomura, K. Kotani, S. Ikawa, E. Nanba, K. Adachi (1999)Anxiety traits associated with a polymorphism in the serotonin transporter gene regulatory region in the Japanese
Journal of Human Genetics, 44
Cláudia Wachleski, C. Blaya, G. Salum, V. Vargas, G. Manfro (2008)Lack of association between the serotonin transporter promoter polymorphism (5-HTTLPR) and personality traits in asymptomatic patients with panic disorder
Neuroscience Letters, 431
J. Gelernter, H. Kranzler, E. Coccaro, L. Siever, A. New (1998)Serotonin transporter protein gene polymorphism and personality measures in African American and European American subjects.
The American journal of psychiatry, 155 10
G. Bagdy (1998)Serotonin, Anxiety, and Stress Hormones: Focus on 5‐HT Receptor Subtypes, Species and Gender Differences a
Annals of the New York Academy of Sciences, 851
D. Tregouet, V. Garelle (2007)A new JAVA interface implementation of THESIAS: testing haplotype effects in association studies
Bioinformatics, 23 8
Dong-kyu Kim, T. Tolliver, Su‐Jan Huang, B. Martin, A. Andrews, Christine Wichems, A. Holmes, K. Lesch, D. Murphy (2005)Altered serotonin synthesis, turnover and dynamic regulation in multiple brain regions of mice lacking the serotonin transporter
J. González, L. Armengol, X. Solé, E. Guinó, J. Mercader, X. Estivill, V. Moreno (2007)SNPassoc: an R package to perform whole genome association studies
Bioinformatics, 23 5
M. Bortolato, P. Campolongo, R. Mangieri, M. Scattoni, R. Frau, Viviana Trezza, G. Rana, R. Russo, A. Calignano, G. Gessa, V. Cuomo, D. Piomelli (2006)Anxiolytic-Like Properties of the Anandamide Transport Inhibitor AM404
R. Pertwee (2005)Inverse agonism and neutral antagonism at cannabinoid CB1 receptors.
Life sciences, 76 12
Gábor Turu, P. Várnai, Pál Gyombolai, L. Szidonya, László Offertáler, G. Bagdy, G. Kunos, L. Hunyady (2009)Paracrine Transactivation of the CB1 Cannabinoid Receptor by AT1 Angiotensin and Other Gq/11 Protein-coupled Receptors*
The Journal of Biological Chemistry, 284
Sen (2004)Meta-analysis of the association between a serotonin transporter promoter polymorphism (5-HTTLPR) and anxiety-related personality traits
Am J Med Genet B Neuropsychiatr Genet, 127
A. Lu, M. Ogdie, M. Järvelin, I. Moilanen, S. Loo, J. McCracken, J. McGough, May Yang, L. Peltonen, S. Nelson, R. Cantor, S. Smalley (2008)Association of the cannabinoid receptor gene (CNR1) with ADHD and post‐traumatic stress disorder
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 147B
T. Klaassen, Jurjen Klumperbeek, N. Deutz, H. Praag, E. Griez (1998)Effects of tryptophan depletion on anxiety and on panic provoked by carbon dioxide challenge
Psychiatry Research, 77
R. Ebstein, I. Gritsenko, L. Nemanov, A. Frisch, Y. Osher, R. Belmaker (1997)No association between the serotonin transporter gene regulatory region polymorphism and the Tridimensional Personality Questionnaire (TPQ) temperament of harm avoidance
Molecular Psychiatry, 2
C. Spielberger, R. Gorsuch, R. Lushene (1970)STAI manual for the State-trait anxiety inventory ("self-evaluation questionnaire")
Lu (2008)Association of the cannabinoid receptor gene (CNR1) with ADHD and post-traumatic stress disorder
Am J Med Genet B Neuropsychiatr Genet, 147B
X. Gonda, Z. Rihmer, G. Juhász, T. Zsombók, G. Bagdy (2007)High anxiety and migraine are associated with the s allele of the 5HTTLPR gene polymorphism
Psychiatry Research, 149
I. Deary, S. Battersby, M. Whiteman, J. Connor, F. Fowkes, A. Harmar (1999)Neuroticism and polymorphisms in the serotonin transporter gene
Psychological Medicine, 29
D. Murphy, M. Fox, K. Timpano, P. Moya, Renee Ren-Patterson, A. Andrews, A. Holmes, K. Lesch, J. Wendland (2008)How the serotonin story is being rewritten by new gene-based discoveries principally related to SLC6A4, the serotonin transporter gene, which functions to influence all cellular serotonin systems
X. Gonda, Z. Rihmer, T. Zsombók, G. Bagdy, K. Akiskal, H. Akiskal (2006)The 5HTTLPR polymorphism of the serotonin transporter gene is associated with affective temperaments as measured by TEMPS-A.
Journal of affective disorders, 91 2-3
Anxiety is a polygenic condition, and the recently discovered Endocannabinoid System (ECS) is one plausible candidate. Experimental data suggest that the ECS can modulate several neurotransmitter systems, including the serotonergic system, which itself plays a significant role in anxiety. However, to date there is no evidence of gene–gene interactions; indeed genetic studies focusing separately on the two systems provide conflicting data. Thus, the aim of our study was to analyze the interaction of the promoter regions of the serotonin transporter (SLC6A4) and cannabinoid receptor 1 (CNR1) genes on anxiety. We genotyped 706 individuals for the 5‐HTTLPR in the SLC6A4 promoter and 4 SNPs located in the CNR1 promoter region. Anxiety was measured by the State‐Trait Anxiety Inventory (STAI‐S, STAI‐T), the anxiety subscale of TEMPS‐A (TEMPS‐Anx), and the Brief Symptom Inventory (BSI‐Anx). Significant 5‐HTTLPR x CNR1 promoter‐promoter interaction was observed using STAI‐T (P = 0.0006) and TEMPS‐Anx (P = 0.0013). The risk of high anxiety scores on BSI‐Anx was 4.6‐fold greater in homozygous 'GG' rs2180619 in combination with homozygous ‘SS’ 5‐HTTLPR (P = 0.0005) compared to other genotypes. The effect of previously described “TGC” haplotype in the alternative promoter of CNR1 depended both on the conventional promoter polymorphism and the 5‐HTTLPR. Our haplotype and putative transcription binding profile analyses strongly suggest that certain constellations of CB1‐receptor and 5‐HTT promoters yield extremely high or low synaptic 5‐HT concentrations, and these are associated with an anxious phenotype. In conclusion, genetically determined serotonergic and endocannabinoid dysfunctions could lead to a vulnerability causing anxiety disorders and possibly depression. © 2009 Wiley‐Liss, Inc.
American Journal of Medical Genetics part B – Wiley
Published: Dec 5, 2009
Keywords: cannabinoid receptor; 5‐HTTLPR ; genetic interaction; anxiety; haplotype
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