Serotonin transporter gene polymorphisms and mental health

Current Opinion in Psychiatry

Volumn 16, Issue 2, 2003, Pages 215-220

  Melke, Jonas ^a  

^a UNIVERSITY OF GOTHENBURG   (Sweden)

Author keywords

Anxiety; Association study; Personality; Polymorphism; Psychiatry; Serotonin reuptake inhibitor; Serotonin transporter

Indexed keywords

ANTIDEPRESSANT AGENT; FLUVOXAMINE; PAROXETINE;

ALCOHOLISM; ANXIETY; ANXIETY DISORDER; ATTENTION DEFICIT DISORDER; AUTISM; BRAIN CIRCULATION; DEPRESSION; DNA POLYMORPHISM; DRUG RESPONSE; EATING DISORDER; FEAR; GENE; GENE FUNCTION; HUMAN; MEDICAL GENETICS; MENTAL DISEASE; MENTAL HEALTH; MOOD; MOOD DISORDER; OBSESSIVE COMPULSIVE DISORDER; PANIC; PERSONALITY; PHENOTYPE; POPULATION RESEARCH; PREMENSTRUAL DYSPHORIC DISORDER; REVIEW; SEROTONIN TRANSPORTER GENE; SEROTONINERGIC SYSTEM; SUICIDE;

EID: 0037335125     PISSN: 09517367     EISSN: None     Source Type: Journal    
DOI: 10.1097/00001504-200303000-00012     Document Type: Review

References (58)

1. Deeb SS, Fajas L, Nemoto M, et al. A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet 1998; 20:284-287.
2. Strittmatter WJ, Saunders AM, Schmechel D, et al. Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci U S A 1993; 90:1977-1981.
3. Bertina RM, Koeleman BP, Koster T, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369:64-67.
4. Lesch KP, Bengel D, Heils A, et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 1996; 274:1527-1531.
5. Ogilvie AD, Battersby S, Bubb VJ, et al. Polymorphism in serotonin transporter gene associated with susceptibility to major depression. Lancet 1996; 347:731-733.
6. Battersby S, Ogilvie AD, Blackwood DH, et al. Presence of multiple functional polyadenylation signals and a single nucleotide polymorphism in the 3′ untranslated region of the human serotonin transporter gene. J Neurochem 1999; 72:1384-1388.
7. Bennett AJ, Lesch KP, Heils A, et al. Early experience and serotonin transporter gene variation interact to influence primate CNS function. Mol Psychiatry 2002; 7:118-122. This was an interesting study of the 5-HTTLPR in non-human primates that demonstrated an effect of a gene-environment interaction on brain serotonergic function. The identification of an analogue to the 5-HTTLPR in non-human primates offers excellent opportunities for future studies of this polymorphism.
8. Melke J, Westberg L, Landén M, et al. Serotonin transporter gene polymorphisms and platelet [3H]paroxetine binding in premenstrual dysphoria. Psychoneuroendocrinology 2002 (in press).
9. Stoltenberg SF, Twitchell GR, Hanna GL, et al. Serotonin transporter promoter polymorphism, peripheral indexes of serotonin function, and personality measures in families with alcoholism. Am J Med Genet 2002; 114:230-234. Stoltenberg's study replicates previous findings of an association between the 5-HTTLPR and transporter density in human platelets. An interesting effect of gender on the relationship between this polymorphism and personality is also presented.
10. Anderson GM, Gutknecht L, Cohen DJ, et al. Serotonin transporter promoter variants in autism: functional effects and relationship to platelet hyperserotonemia. Mol Psychiatry 2002; 7:831-836. This is an interesting discussion about the genetic influence on the well-replicated platelet hyperserotonemia of autism.
11. Heinz A, Jones DW, Mazzanti C, et al. A relationship between serotonin transporter genotype and in vivo protein expression and alcohol neurotoxicity. Biol Psychiatry 2000; 47:643-649.
12. Willeit M, Stastny J, Pirker W, et al. No evidence for in vivo regulation of midbrain serotonin transporter availability by serotonin transporter promoter gene polymorphism. Biol Psychiatry 2001; 50:8-12. Willeit's elegant study aimed to investigate the role of the 5-HTTLPR in the in-vivo regulation of SERT availability as assessed with single photon emission-computed tomography.
13. Fiskerstrand CE, Lovejoy EA, Quinn JP. An intronic polymorphic domain often associated with susceptibility to affective disorders has allele dependent differential enhancer activity in embryonic stem cells. FEBS Lett 1999; 458:171-174.
14. Kaiser R, Muller-Oerlinghausen B, Filler D, et al. Correlation between serotonin uptake in human blood platelets with the 44-bp polymorphism and the 17-bp variable number of tandem repeat of the serotonin transporter. Am J Med Genet 2002; 114:323-328.
15. Bellivier F, Roy I, Leboyer M. Serotonin transporter gene polymorphisms and affective disorder-related phenotypes. Curr Opin Psychiatry 2002; 15:49-58. This thorough review covers recent studies investigating the SERT polymorphism in depression and bipolar disorder and gives an interesting discussion regarding the methodological problems in these studies.
16. Mann JJ. The neurobiology of suicide. Nat Med 1998; 4:25-30.
17. Courtet P, Baud P, Abbar M, et al. Association between violent suicidal behavior and the low activity allele of the serotonin transporter gene. Mol Psychiatry 2001; 6:338-341. This study showed that elements of violent behavior may be used to subdivide those who attempt suicide in genetic studies of suicide.
18. Baca-Garcia E, Vaquero C, Diaz-Sastre C, et al. A gender-specific association between the serotonin transporter gene and suicide attempts. Neuropsychopharmacology 2002; 26:692-695. In this study, the association between the 5-HTTLPR and suicide was more prominent in women than in men, emphasizing the importance of sex as a confounding factor in genetic studies of suicidal behavior.
19. Preuss UW, Koller G, Soyka M, et al. Association between suicide attempts and 5-HTTLPR-S-allele in alcohol-dependent and control subjects: further evidence from a German alcohol-dependent inpatient sample. Biol Psychiatry 2001; 50:636-639. This study replicates previous findings of an association between the 5-HTTLPR and suicidal behavior in alcohol dependent subjects.
20. Mann JJ, Huang YY, Underwood MD, et al. A serotonin transporter gene promoter polymorphism (5-HTTLPR) and prefrontal cortical binding in major depression and suicide. Arch Gen Psychiatry 2000; 57:729-738.
21. Rujescu D, Giegling I, Sato T, et al. A polymorphism in the promoter of the serotonin transporter gene is not associated with suicidal behavior. Psychiatr Genet 2001; 11:169-172.
22. Bengel D, Greenberg BD, Cora-Locatelli G, et al. Association of the serotonin transporter promoter regulatory region polymorphism and obsessive-compulsive disorder. Mol Psychiatry 1999; 4:463-466.
23. McDougle CJ, Epperson CN, Price LH, et al. Evidence for linkage disequilibrium between serotonin transporter protein gene (SLC6A4) and obsessive compulsive disorder. Mol Psychiatry 1998; 3:270-273.
24. Camarena B, Rinetti G, Cruz C, et al. Association study of the serotonin transporter gene polymorphism in obsessive-compulsive disorder. Int J Neuropsychopharmacol 2001; 4:269-272. Camarena's study fails to replicate previous reports of an association between the 5-HTTLPR and OCD in both an association study and in OCD trios.
25. Di Bella D, Erzegovesi S, Cavallini MC, et al. Obsessive-compulsive disorder, 5-HTTLPR polymorphism and treatment response. Pharmacogenomics J 2002; 2:176-181. This interesting study investigated the role of the 5-HTTLPR in antidepressant response of OCD patients. A reduction of compulsion symptoms seems to occur earlier in subjects carrying the s allele.
26. Cavallini MC, Di Bella D, Siliprandi F, et al. Exploratory factor analysis of obsessive-compulsive patients and association with 5-HTTLPR polymorphism. Am J Med Genet 2002; 114:347-353. A factor analysis using the Yale-Brown Obsessive-Compulsive Scale (YBOCS) was performed to refine phenotypic definition of OCD patients. This study identified several subtypes of importance for further genetic studies of OCD.
27. Rotondo A, Mazzanti C, Dell'Osso L, et al. Catechol o-methyltransferase, serotonin transporter, and tryptophan hydroxylase gene polymorphisms in bipolar disorder patients with and without comorbid panic disorder. Am J Psychiatry 2002; 159:23-29. This study exemplified the use of co-morbidity for phenotype definition in genetic studies of mental illness. Interaction effects between several serotonin-related polymorphisms were investigated using logistic regression.
28. Fumeron F, Betoulle D, Aubert R, et al. Association of a functional 5-HT transporter gene polymorphism with anorexia nervosa and food intake. Mol Psychiatry 2001; 6:9-10.
29. Matsushita S, Nakamura T, Nishiguchi N, et al. Association of serotonin transporter regulatory region polymorphism and abnormal eating behaviors. Mol Psychiatry 2002; 7:538-540. Using the Eating Attitudes Test (EAT-26), Matsushita's study showed an association between the 5-HTTLPR and eating behaviors in the normal population.
30. Serretti A, Lilli R, Lorenzi C, et al. Serotonin transporter gene (5-HTTLPR) and major psychoses. Mol Psychiatry 2002; 7:95-99. Serretti's study used a large sample to investigate the relationship between the 5-HTTLPR and symptoms of psychosis, both in schizophrenic patients and in patients with affective disorders.
31. Malhotra AK, Goldman D, Mazzanti C, et al. A functional serotonin transporter (5-HTT) polymorphism is associated with psychosis in neuroleptic-free schizophrenics. Mol Psychiatry 1998; 3:328-332.
32. Kaiser R, Tremblay PB, Schmider J, et al. Serotonin transporter polymorphisms: no association with response to antipsychotic treatment, but associations with the schizoparanoid and residual subtypes of schizophrenia. Mol Psychiatry 2001; 6:179-185. This large study subdivided patients using DSM IV-subtypes of schizophrenia.
33. Cook EH Jr, Courchesne R, Lord C, et al. Evidence of linkage between the serotonin transporter and autistic disorder. Mol Psychiatry 1997; 2:247-250.
34. Yirmiya N, Pilowsky T, Nemanov L, et al. Evidence for an association with the serotonin transporter promoter region polymorphism and autism. Am J Med Genet 2001; 105:381-386. Yirmiya's study replicates the previous association between the 5-HTTLPR and autism, both in a transmission/disequibrium test using trios and in an association study between patients and healthy controls.
35. Tordjman S, Gutknecht L, Carlier M, et al. Role of the serotonin transporter gene in the behavioral expression of autism. Mol Psychiatry 2001; 6:434-439.
36. Betancur C, Corbex M, Spielewoy C, et al. Serotonin transporter gene polymorphisms and hyperserotonemia in autistic disorder. Mol Psychiatry 2002; 7:67-71.
37. Kim SJ, Cox N, Courchesne R, et al. Transmission disequilibrium mapping at the serotonin transporter gene (SLC6A4) region in autistic disorder. Mol Psychiatry 2002; 7:278-288. This family-based study investigated the transmission of alleles (transmission/disequibrium test) of the 5-HTTLPR and several other polymorphisms within close vicinity of the SERT gene.
38. Zhong N, Ye L, Ju W, et al. 5-HTTLPR variants not associated with autistic spectrum disorders. Neurogenetics 1999; 2:129-131.
39. Manor I, Eisenberg J, Tyano S, et al. Family-based association study of the serotonin transporter promoter region polymorphism (5-HTTLPR) in attention deficit hyperactivity disorder. Am J Med Genet 2001; 105:91-95.
40. Zoroglu SS, Erdal ME, Alasehirli B, et al. Significance of serotonin transporter gene 5-HTTLPR and variable number of tandem repeat polymorphism in attention deficit hyperactivity disorder. Neuropsychobiology 2002; 45:176-181.
41. Seeger G, Schloss P, Schmidt MH. Functional polymorphism within the promotor of the serotonin transporter gene is associated with severe hyperkinetic disorders. Mol Psychiatry 2001; 6:235-238.
42. Retz W, Thome J, Blocher D, et al. Association of attention deficit hyperactivity disorder-related psychopathology and personality traits with the serotonin transporter promoter region polymorphism. Neurosci Lett 2002; 319:133-136.
43. Kent L, Doerry U, Hardy E, et al. Evidence that variation at the serotonin transporter gene influences susceptibility to attention deficit hyperactivity disorder (ADHD): analysis and pooled analysis. Mol Psychiatry 2002; 7:908-912. Kent's excellent family-based study performed a haplotype analysis combining all three polymorphisms of the SERT gene in a large sample of ADHD trios.
44. Hammoumi S, Payen A, Favre JD, et al. Does the short variant of the serotonin transporter linked polymorphic region constitute a marker of alcohol dependence? Alcohol 1999; 17:107-112.
45. Matsushita S, Yoshino A, Murayama M, et al. Association study of serotonin transporter gene regulatory region polymorphism and alcoholism. Am J Med Genet 2001; 105:446-450.
46. Praschak-Rieder N, Willeit M, Winkler D, et al. Role of family history and 5-HTTLPR polymorphism in female seasonal affective disorder patients with and without premenstrual dysphoric disorder. Eur Neuropsychopharmacol 2002; 12:129-134.
47. Smeraldi E, Zanardi R, Benedetti F, et al. Polymorphism within the promoter of the serotonin transporter gene and antidepressant efficacy of fluvoxamine. Mol Psychiatry 1998; 3:508-511.
48. Zanardi R, Serretti A, Rossini D, et al. Factors affecting fluvoxamine antidepressant activity: influence of pindolol and 5-HTTLPR in delusional and nondelusional depression. Biol Psychiatry 2001; 50:323-330.
49. Zanardi R, Benedetti F, Di Bella D, et al. Efficacy of paroxetine in depression is influenced by a functional polymorphism within the promoter of the serotonin transporter gene. J Clin Psychopharmacol 2000; 20:105-107.
50. Pollock BG, Ferrell RE, Mufsant BH, et al. Allelic variation in the serotonin transporter promoter affects onset of paroxetine treatment response in late-life depression. Neuropsychopharmacology 2000; 23:587-590.
51. Rausch JL, Johnson ME, Fei YJ, et al. Initial conditions of serotonin transporter kinetics and genotype: influence on SSRI treatment trial outcome. Biol Psychiatry 2002; 51:723-732. This study replicated previous reports of an association between the 5-HTTLPR and response to antidepressant treatment. Also, the influence of serotonin transport kinetics on this relationship was investigated.
52. Billett EA, Richter MA, King N, et al. Obsessive compulsive disorder, response to serotonin reuptake inhibitors and the serotonin transporter gene. Mol Psychiatry 1997; 2:403-406.
53. Melke J, Landen M, Baghei F, et al. Serotonin transporter gene polymorphisms are associated with anxiety-related personality traits in women. Am J Med Genet 2001; 105:458-463.
54. Greenberg BD, Li Q, Lucas FR, et al. Association between the serotonin transporter promoter polymorphism and personality traits in a primarily female population sample. Am J Med Genet 2000; 96:202-216
55. Van Gestel S, Forsgren T, Claes S, et al. Epistatic effect of genes from the dopamine and serotonin systems on the temperament traits of novelty seeking and harm avoidance. Mol Psychiatry 2002; 7:448-450. This study investigates gene-gene interactions between DAT, DRD4, and the 5-HTTLPR in subjects with extreme scores on harm avoidance and novelty seeking.
56. Tsai SJ, Hong CJ, Cheng CY. Serotonin transporter genetic polymorphisms and harm avoidance in the Chinese. Psychiatr Genet 2002; 12:165-168.
57. Auerbach JG, Faroy M, Ebstein R, et al. The association of the dopamine D4 receptor gene (DRD4) and the serotonin transporter promoter gene (5-HTTLPR) with temperament in 12-month-old infants. J Child Psychol Psychiatry 2001; 42:777-783. Auerbach's excellent study demonstrated that early human temperament dimensions are influenced by common polymorphisms. An interaction between the DRD4 and the 5-HTTLPR is investigated in this context.
58. Hariri AR, Mattay VS, Tessitore A, et al. Serotonin transporter genetic variation and the response of the human amygdala. Science 2002; 297:400-403. This elegant study shows that the 5-HTTLPR is associated with patterns of brain activity in response to fearful stimuli, suggesting that this polymorphism may contribute to how the brain reacts to its environment.