A Review on Experimental and Clinical Genetic Associations Studies on Fear Conditioning, Extinction and Cognitive-behavioral Treatment

Overview

Journal Transl Psychiatry

Specialties Psychiatry
Public Health

Date 2012 Jul 27

PMID 22832657

Citations 32

Authors

T B Lonsdorf

R Kalisch

Affiliations

Soon will be listed here.

Abstract

Fear conditioning and extinction represent basic forms of associative learning with considerable clinical relevance and have been implicated in the pathogenesis of anxiety disorders. There is considerable inter-individual variation in the ability to acquire and extinguish conditioned fear reactions and the study of genetic variants has recently become a focus of research. In this review, we give an overview of the existing genetic association studies on human fear conditioning and extinction in healthy individuals and of related studies on cognitive-behavioral treatment (CBT) and exposure, as well as pathology development after trauma. Variation in the serotonin transporter (5HTT) and the catechol-o-methyltransferase (COMT) genes has consistently been associated with effects in pre-clinical and clinical studies. Interesting new findings, which however require further replication, have been reported for genetic variation in the dopamine transporter (DAT1) and the pituitary adenylate cyclase 1 receptor (ADCYAP1R1) genes, whereas the current picture is inconsistent for variation in the brain-derived neurotrophic factor (BDNF) gene. We end with a discussion of the findings and their limitations, as well as future directions that we hope will aid the field to develop further.

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References

Garpenstrand H, Annas P, Ekblom J, Oreland L, Fredrikson M . Human fear conditioning is related to dopaminergic and serotonergic biological markers. Behav Neurosci. 2001; 115(2):358-64. View

Nordquist N, Oreland L . Serotonin, genetic variability, behaviour, and psychiatric disorders--a review. Ups J Med Sci. 2010; 115(1):2-10. PMC: 2853349. DOI: 10.3109/03009730903573246. View

Reimold M, Smolka M, Schumann G, Zimmer A, Wrase J, Mann K . Midbrain serotonin transporter binding potential measured with [11C]DASB is affected by serotonin transporter genotype. J Neural Transm (Vienna). 2007; 114(5):635-9. DOI: 10.1007/s00702-006-0609-0. View

Heinz A, Goldman D, Jones D, Palmour R, Hommer D, Gorey J . Genotype influences in vivo dopamine transporter availability in human striatum. Neuropsychopharmacology. 2000; 22(2):133-9. DOI: 10.1016/S0893-133X(99)00099-8. View

Domschke K, Reif A, Weber H, Richter J, Hohoff C, Ohrmann P . Neuropeptide S receptor gene -- converging evidence for a role in panic disorder. Mol Psychiatry. 2010; 16(9):938-48. DOI: 10.1038/mp.2010.81. View

Ressler K, Mercer K, Bradley B, Jovanovic T, Mahan A, Kerley K . Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor. Nature. 2011; 470(7335):492-7. PMC: 3046811. DOI: 10.1038/nature09856. View

Lonsdorf T, Ruck C, Bergstrom J, Andersson G, Ohman A, Schalling M . The symptomatic profile of panic disorder is shaped by the 5-HTTLPR polymorphism. Prog Neuropsychopharmacol Biol Psychiatry. 2009; 33(8):1479-83. DOI: 10.1016/j.pnpbp.2009.08.004. View

Fuke S, Suo S, Takahashi N, Koike H, Sasagawa N, Ishiura S . The VNTR polymorphism of the human dopamine transporter (DAT1) gene affects gene expression. Pharmacogenomics J. 2002; 1(2):152-6. DOI: 10.1038/sj.tpj.6500026. View

Anderson K, Insel T . The promise of extinction research for the prevention and treatment of anxiety disorders. Biol Psychiatry. 2006; 60(4):319-21. PMC: 1959510. DOI: 10.1016/j.biopsych.2006.06.022. View

10.

Koenen K, Aiello A, Bakshis E, Amstadter A, Ruggiero K, Acierno R . Modification of the association between serotonin transporter genotype and risk of posttraumatic stress disorder in adults by county-level social environment. Am J Epidemiol. 2009; 169(6):704-11. PMC: 2727213. DOI: 10.1093/aje/kwn397. View

11.

Olsson A, Nearing K, Phelps E . Learning fears by observing others: the neural systems of social fear transmission. Soc Cogn Affect Neurosci. 2008; 2(1):3-11. PMC: 2555428. DOI: 10.1093/scan/nsm005. View

12.

Sabol S, Hu S, Hamer D . A functional polymorphism in the monoamine oxidase A gene promoter. Hum Genet. 1998; 103(3):273-9. DOI: 10.1007/s004390050816. View

13.

Hu X, Lipsky R, Zhu G, Akhtar L, Taubman J, Greenberg B . Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. Am J Hum Genet. 2006; 78(5):815-826. PMC: 1474042. DOI: 10.1086/503850. View

14.

Mannisto P, Kaakkola S . Catechol-O-methyltransferase (COMT): biochemistry, molecular biology, pharmacology, and clinical efficacy of the new selective COMT inhibitors. Pharmacol Rev. 1999; 51(4):593-628. View

15.

Lonsdorf T, Weike A, Nikamo P, Schalling M, Hamm A, Ohman A . Genetic gating of human fear learning and extinction: possible implications for gene-environment interaction in anxiety disorder. Psychol Sci. 2009; 20(2):198-206. DOI: 10.1111/j.1467-9280.2009.02280.x. View

16.

Norrholm S, Vervliet B, Jovanovic T, Boshoven W, Myers K, Davis M . Timing of extinction relative to acquisition: a parametric analysis of fear extinction in humans. Behav Neurosci. 2008; 122(5):1016-30. PMC: 3731450. DOI: 10.1037/a0012604. View

17.

Mill J, Asherson P, Craig I, DSouza U . Transient expression analysis of allelic variants of a VNTR in the dopamine transporter gene (DAT1). BMC Genet. 2005; 6:3. PMC: 549191. DOI: 10.1186/1471-2156-6-3. View

18.

van Dyck C, Malison R, Staley J, Jacobsen L, Seibyl J, Laruelle M . Central serotonin transporter availability measured with [123I]beta-CIT SPECT in relation to serotonin transporter genotype. Am J Psychiatry. 2004; 161(3):525-31. DOI: 10.1176/appi.ajp.161.3.525. View

19.

Raczka K, Mechias M, Gartmann N, Reif A, Deckert J, Pessiglione M . Empirical support for an involvement of the mesostriatal dopamine system in human fear extinction. Transl Psychiatry. 2012; 1:e12. PMC: 3309464. DOI: 10.1038/tp.2011.10. View

20.

Kraft J, Slager S, McGrath P, Hamilton S . Sequence analysis of the serotonin transporter and associations with antidepressant response. Biol Psychiatry. 2005; 58(5):374-81. DOI: 10.1016/j.biopsych.2005.04.048. View