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Serotonin Transporter (SLC6A4)
| Variant | Association | Phenotype | Sample Information | Author |
|---|---|---|---|---|
| 5HTTLPR | Genoytpic; ns |
Depression and suicidality | Cases: 4062 suicidality | Coventry, 2010 |
Control:4241 SelfRepDep 3243 ClinDep (F: 60% 32.3 ± 13.6) |
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| Notes: Could not replicate experiment by Caspi et al. (2003). There was no significant relationship between stress and S,L alleles despite strong relationship between suicide and PLE. | ||||
| LPR | Allelic:+, S, S allèle among violent suicide attempt; χ2 =16.969;p=0.0001 | Suicide attemps among bipolar patients | Controls: 103 healthy persons | Neves, 2010 |
| Cases: 198 bipolar patients, No suicide attempters: N=112 (F=73), mean age 44.6 ±13, Suicide attempters: N=86 (F=66) 38.8 ±12.3, Non violent suicide attempt: 53, Violent suicide attempt33 | ||||
LPR STin2 |
Genotypic: ns |
Suicide attempts | Cases: 9 males admitted for suicide attempts |
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| 9 age-matched male controls | ||||
Notes: in suicide attempters, serotonin availability negatively associated with LPR's S allele and STin2's 12 allele mainly in the cortical regions |
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LPR |
Allelic: ns Genotypic: ns |
Suicide attempts | Ethnicity: Chinese |
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| Cases: 439 (F: 162;mean age: 27.3±7.0) metamphetamine abusers (MAP) including 94 suicide attempters | ||||
Notes: tested all there alleles [(S, L(G), L(A)]; no association with MAP-induced depressive disorder or MAP-induced psychotic disorder |
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| LPR |
Genotypic: +,S-, OR: 6.3 CI 95% 12.1-18.9 |
Violent suicide attempts |
Geographical region: Brazil | Neves, 2008 |
| Cases: 167 (77 with suicide attempts) bipolar patients | ||||
| Controls: 184 non psychiatric, nonsuicidal individuals | ||||
Genotypic: +,S-, p=.008 |
Repeated suicide attempts | Notes: no association with bipolar disorder | ||
| LPR | Genotypic: +,SS, p=.0026 | High lethality suicide attempts |
Ethnicity: Caucasian, Ukranian/ Russian/Eastern European | Wasserman, 2007 |
| Cases: suicide attempters: N: 85 (F: 31; high lethality: N:28), mean age: 20.1 ±1.7 | ||||
| LPR | Genotypic:+,SS, SLg or LgLg,victis of childhood physical abuse or emotional neglect |
Suicide attempts | Ethnicity: African-American | |
| Cases: 306 substance-dependent males (>18 years of age; 30.7% attempted suicide) | ||||
Controls: N:132 (1.5% attempted suicide) |
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rs2066713 rs6354 rs140701 rs4325622 |
Allelic: ns Genotypic: ns Haplotypic: ns |
Suicide attempts | Ethnicity: Han Chinese |
Zhang, 2007 |
Cases: 297 (F: 126; mean age 46.10 ± 12.76 ) patients who attempted suicide |
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| Controls: 329 (F:112; mean age 43.22 ± 12.77) psychiatric patients who had never attempted suicide | ||||
VNTR-2 rs25531 LPR |
Allelic: ns | Suicidal behaviour severity | Cases: 336 (F:62%) bipolar patients from 305 nuclear families (mean age: 35.36± 10.37 SD), including 267 patients with histories of suicide ideas or attempts | De Luca, 2007 |
| Notes: suicidality assessed quantitatively and coded as follows: 0 = absence of suicide/death thoughts, 1 = thoughts of death, 2 = suicide ideation, 3 = suicide plan, 4 = suicide attempt | ||||
| LPR | Genotypic: +, ss/sl, p=.008, in sexually abused in childhood |
Suicide attempts | SS/SL carriers: n:16 (F:50%,93.8% Caucasian) mean age: 37.31 ±10.74 |
Gibb, 2006 |
| LL carriers: n:14 (F:57.1%, 71/4% Caucasian) mean age: 34.93 ± 12.26 | ||||
| Notes: moderation not seen with emotional abuse histories | ||||
| LPR | Genotypic:+,LL, OR=2.09 CI 95% 1.11-3.95 in women |
Suicide attempts | Ethnicity: Russian |
|
| Cases: suicide attempters: N:150 (F:98), mean age: 33.80±15.68 (men); mean age: 33.42±15.19 (women) | ||||
244(F: 112) nonsuicidal volunteer controls: mean age:35.24±10.58 (men) and mean age:39.24±12.20 (women) |
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| STin2VNTR | Allelic: ns Genotypic: ns |
Notes: Bonferroni-adjusted | ||
Haplotypic: -,S12, OR=.62 & OR=. 67, in women and total sample, respectively |
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| LPR | Allelic: ns Genotypic:ns |
(Violent) suicide attempts | Ethnicity: Brazilian | Segal, 2006 |
| Cases: suicide attempters: N: 84 (F: 36), mean age:35.39±13; violent attempts seen in 44 | ||||
| Controls: N: 152 (F: 43), mean age: 35.65±10.0 | ||||
| Notes: no association with the degree of violence or suicidal intent. S allele carriers at higher risk of sucidal behavior in depressed cases only | ||||
| LPR | Allelic: ns Genotypic: ns |
Suicide attempts | Ethnicity: Caucasian, Europe | Zalsman, 2006 |
| Cases: mood-disorder subjects: N: 191(F: 136), mean age:39.8±15 | ||||
| Healthy volunteers:N: 125 (F: 63), mean age: 34.6±16.8 | ||||
| Notes: lower expressing alleles (S, Lg) predicted greater depression severity in interaction with stress | ||||
| LPR | Allelic: ns | Suicide attempts | Sample: schizophrenic patients: N: 290 (F: 25%), mean age:41±11, including 92 suicide attempters | De Luca, 2006 |
| Intron 2 VNTR | Allelic:-,10,p=.05 | |||
Haplotypic: +,long A/12, p=.031 |
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LPR VNTR |
Allelic: ns | Suicide attempts or suicidality | Sample: bipolar patients: N: 290 (F: 62%; 86 suicide attempters); mean age: 35±10 | De Luca, 2005 |
| Haplotypic: ns | Notes: considered 3 alleles at the LPR | |||
| LPR | Genotypic: +, SS/SL, p=.003 | Impulsive suicide attempts | Ethnicity: Spanish Caucasians | Baca-Garcia, 2005 |
| Cases: female obssessive-compulsive patients [n:24, mean age:38 .9±12.31]; impulsive patients who had attempted suicide [n:118, mean age: 34.1±13.34] | ||||
| Non-impulsive female controls [n:112, mean age: 36.5±12.39] | ||||
| Notes: postulated a continuum between compulsivity & impulsivity | ||||
| LPR | Allelic: +, S allele, OR=4.80 95% CI 1.03-24.71, males |
Suicide attempts | Ethnicity: French-Canadian | Limosin, 2005 |
| Cases: alcohol-dependent inpatients (M: 48,mean age:44.15±10.17; F: 52, mean age:46.17±9.9), including 45 suicide attempters (F:30, M: 52) | ||||
| Genotypic: ns | ||||
| LPR | Allelic:+,S, OR=2.83, 95% CI 1.29-6.22 | Suicide reattempts | Ethnicity: West European, Caucasian | Courtet, 2004 |
| Cases: suicide attempters: 103 (repeaters: F: 17(85%), mean age: 34.05 ±11.71 ; nonrepeaters: F:47 (84%), mean age: 37.89±14.42) | ||||
Genotypic: +,SS, OR=6.5 95% 1.2-35.8 |
Notes: SS genotypes were more impulsive | |||
| LPR | Allelic: ns Genotypic:ns |
Suicide attempts | Ethnicity: multicenter study that included 8 countries | Mendlewicz, 2004 |
| Cases: unipolar disorder: n:539, mean age: 53.8, F: 349; suicide attempters: n:63; bipolar disorder: n:572, mean age: 49.7, F:328; suicide attempters: n: 104 | ||||
| Controls: n: 821, mean age: 47.3, F:441 | ||||
| Notes: confounders: sex; Bonferroni-adjusted, as necessary; no association with depressive disorders | ||||
Intron 2 VNTRLPR |
Allelic: ns Genotypic:ns Haplotypic: ns |
Suicide attempts | Ethnicity: Han Chinese | Shen, 2004 |
| Cases: psychotic inpatient suicide attempters: F:122;M:150 mean age: 46.5±13.1; one-time attempters n:169 | ||||
| Controls: nonsuicidal psychotic patients: F:99, M:176; mean age: 43.2±12.3; Nonpsychiatric controls: F: 265, M:363; mean age: 33.3±10.1 | ||||
| Notes: significant difference in LPR polymorphism between first and repeated attempters after confounders controlled | ||||
| LPR | Genotypic: +, LS or SS, 2.34 95% CI 1.32-4.15 , p=.002 |
Suicide attempts | Ethnicity: African- & Caucasian-Brazilian | Correa, 2004 |
| Cases: probands with recurrent major depression (n:106) or schizophrenia (n:131), with 93 suicide attempters | ||||
| Healthy controls: n:75 (hospital staff & students) | ||||
| Notes: the three groups were not in Hardy-Weinberg equilibrium | ||||
| LPR | Genotypic: ns | Suicide attempts | Ethnicity: white Italian | Gerra, 2004 |
| Cases: heroin-dependent males (n: 101, mean age: 34.6±11.7) | ||||
| Age-matched healthy male volunteers (n: 101; mean age: 35.8±13.2) | ||||
| Notes: SS associated with heroin addiction | ||||
| Intron 2 VNTR | Allelic: ns Genotypic:ns |
Suicide attempts | Ethnicity: Chinese | Yen, 2003 |
| Cases: inpatients with unipolar or bipolar depressive disorder: F:95,M:65; mean age: 41.5±15.3 | ||||
| Healthy controls: F:108, M:61 mean age: 39.4±10.5 | ||||
| Notes: no association with mood disorders | ||||
| LPR | Genotypic:+, SL/SS, p=.002 | Suicide attempts | Ethnicity: African-& Caucasian-Brazilian | Campi-Azevedo, 2003 |
| Cases: Patients with recurrent major depression (n:106) or schizophrenia (n:131) | ||||
| Nonpsychiatric/nonsuicidal healthy controls (staff or faculty): n:75 | ||||
| Notes: S carriers attempted suicide more frequently OR:2.34 (95% CI 1.32-4.15), had greater lethality scores and suicidal intent OR: 2.44 (95% CI .93-6.53) , and used more violent means OR:3.97 (95% CI 1.37-11.91) | ||||
| LPR | Allelic: ns Genotypic: ns |
Nonviolent suicide attempts | Ethnicity: Caucasian, Western Europe | Courtet, 2003 |
| Cases: suicide attempters: F:104, M:62; mean age: 35.57±13.45 | ||||
| Non-attempting controls:F: 49, M:90; mean age:45.2±13.2 | ||||
| Notes: no differences in LPR in non-violent attempters stratified by mood disorder | ||||
| LPR | Genotypic: +, S-, p=.026
|
Violent suicide attempts |
Ethnicity: Mostly Caucasian, French | Bayle, 2003 |
| Cases: patients with schizophrenia (F:56,M:129; mean age:32±9) or schizoaffective disorder (n:8), including 70 attempters, 18 of whom used violent methods | ||||
| Nonpsychiatric controls (hospital staff or students) matched for gender and ethnicity: F:55, M:104; mean age: 35±10 | ||||
Allelic: ns Genotypic: ns |
Suicide attempts | Notes: no association with impulsivity or schizophrenia; S allele more frequent in when violent than nonviolent attempters | ||
| LPR | Genotypic:+,SS/SL, OR:2.0 95% 1.1-3.6, women | Suicide attempts | Ethnicity: Caucasian | Baca-Garcia, 2002 |
| Cases: suicide attempters: F:121,M:59; mean age:43±20; 81% made lethal attempts | ||||
| Nonpsychiatric/nonsuicidal controls: F:93,M:119; mean age:43±20 | ||||
| Notes: female s carriers more prone to non-lethal attempts | ||||
| LPR | Allelic: +,S, p=.019 | Suicide attempts | Ethnicity: Caucasian, South Germany | Preuss, 2001 |
| Cases: alcohol-dependent patients: n:163 (F:32), mean age:41.7±8.3, including 52 suicide attempters | ||||
| General population controls without physical or axis I/II diagnoses: n:117 (F:61), mean age: 46±8.1 | ||||
| Genotypic:+, LS/SS, p=.04 | Notes: no association with depressive disorders | |||
| LPR | Allelic: ns Genotypic: ns |
Suicide attempts | Ethnicity: German | Rujescu, 2001 |
| Cases: Suicide attempters: F:85, M:39; mean age: 39.2±14.8; | ||||
| Healthy community-based volunteers: F:102, M: 83; mean age: 47.7 | ||||
| Notes: no association when stratified by method violence or psychiatric disorders | ||||
| LPR | Allelic:+, S, OR:1.72 95%CI 1.09-2.71 | Violent suicide attempts |
Ethnicity: West European Caucasian | Courtet, 2001 |
| Cases: violent attempters: F:16, M:35; mean age:38.6±13.2 | ||||
| Nonsuicidal controls: F:49, M:90; mean age:45.2±13.2 | ||||
Genotypic: +, SS, OR:3.63, 95% CI 1.27-10.40 |
Notes: L allele may be associated with a psychobiological trait that is more common in subjects with major depression and violent suicide attempts | |||
| LPR | Allelic: ns | Suicide attempts | Cases: recent attempting adolescents [F:32, M:16; mean age: 18.9±2.5; 51% Ashkenazi and 49% North African, Iraqi or Muslim or Yemenite origin] | Zalsman, 2001 |
| Controls: one (n:9) or both parents of probands (n:78) | ||||
| Notes: used the haplotype relative risk method to control for population stratification; LL and LS genotypes differed on past acts of violence | ||||
| LPR | Allelic: +,S, OR 2.0 95% CI 1.1-3.6 |
Violent suicide attempts |
Ethnicity: Caucasian, French | Bellivier, 2000 |
| Cases: unipolar (M:78; F: 116) and bipolar depressive patients (M:11; F:32) including 99 attempters (18 had unipolar depression and 26 used violent means) | ||||
| Healthy volunteer controls: F:77, M:110 | ||||
| Genotypic: ns | Notes: the more severe the suicide attempt the higher the s allele frequency | |||
| LPR | Allelic: ns Genotypic: ns |
Suicide attempts | Ethnicity: Han Chinese | Chong, 2000 |
| Cases: patients (F:43,M:33; mean age:41.2±10.6) with schizophrenia with and without suicide attempts (F:79, M:183; mean age:48.8±10.8) | ||||
| LPR | Genotypic: ns
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Suicide attempts | Ethnicity: English, Caucasian | Ho, 2000 |
Cases: bipolar (M:58, F: 73 female) and unipolar patients (M:53, F: 86) |
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| VNTR | Notes: SERT polymorphisms associated with the number of manic episodes, psychotic symptoms in the bipolar sample; uncorrected for multiple testing |
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| LPR | Allelic: +, S,p=.01 | Suicide attempts | Ethnicity: French | Gorwood, 2000 |
| Cases: 110 male alcoholics including 55 suicide attempters: mean age:43.6±10.5 | ||||
| 61 male controls over 35 | ||||
| Notes: increase in number of attempts and lethality paralles the number of S alleles; no association with comorbid depression or alcohol dependence | ||||
Genotypic: +, SS or SL, in suicidal alcoholic subjects relative to nonsuicidal peers & controls, p=.04 |
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| LPR | Allelic: ns Genotypic: ns |
Suicide attempts | Ethnicity: European Caucasians , mostly Swedish | Geijer, 2000 |
| Cases: suicide attempters: F:108; M:57; mean age: 41±17 | ||||
| Nonpsychiatric controls: n:99, mean age: 38±6, F:95 | ||||
| Notes: no association when stratified by diagnosis or ethnicity | ||||
| LPR | Allelic: ns Genotypic: ns |
Suicide attempts | Ethnicity: Japanese | Ohara, 1998 |
| Cases: 80 mood disordered patients: mean age (46.6±16.4), F:42, including 13 suicide attempters | ||||
| 92 (F:55) healthy volunteers: mean age: 35.2±14.5 | ||||
| Notes: no association with mood disorders | ||||
| VNTR-2 | Allelic: ns Genotypic: ns |
Suicide attempts | Ethnicity: Caucasian, French | Bellivier, 1997 |
| Cases: bipolar disorder patients: M:47, F:62 | ||||
| Healthy controls with no personal or family history of mood disorder: F:34,M:52, age>35 | ||||
| Notes: no difference in f the violence of means used or bipolar diagnosis | ||||
| LPR |
Genotypic: +,SS, p=.04 |
Suicidal ideation | Ethnicity: Askhenazi grandparents (63.5%) | Kronenberg, 2007 |
| Cases: 74 (49.5% male; 35% under the age fo 13) children or adolescents with depression or anxiety disorders | ||||
| Notes: no gene-environment interaction for suicidal ideas; ss genotype associated with a poorer clinical response to citalopram and fewer reports of agitation | ||||
| LPR |
Gene-Environment interaction: +, SS,p= 0.09 or SL, p= 0.001
|
Suicide attempts or ideation | Ethnicity: Caucasian, non-Maori | Caspi, 2003 |
| Cases: 847 (F: 48%; age: around 26), including 3% who reported suicide attempts in the past year or recurrent suicidal ideas | ||||
| Notes: S allele predicted depression symptoms and diagnosis in individuals reporting stressful life events | ||||
| LPR |
Genotypic: ns |
Suicide risk | Cases: patients at high risk for suicide: F:32,M:19; mean age:38±15; Caucasian (n:41), African-American (n:6), and Hispanic, Indian, and Asian (n:4)] | Russ, 2001 |
| Race-matched controls: F:28,M:23; mean age: 41±13 | ||||
| Notes: LL genotype within the case group associated with suicidal ideation and hopelessness; Bonferroni corrected | ||||
| LPR | Genotypic:+, SS, p<.0002 | Family history of suicide & repeated suicide attempts | Healthy volunteers: F: 26, M:21; 9 had family history of suicide attempts or completions; mean age: 30.2±7.8 | Joiner, 2002 |
| LPR | Allelic: ns Genotypic: ns |
Suicide | Ethnicity: Slovenian | Pungercic, 2006 |
| Cases: n:235 (F:64; mean age: 49.31±17.27) | ||||
| Nonpsychiatric controls: n:233 | ||||
| VNTR-2 | Allelic: ns Genotypic: ns |
Notes: No association if stratified by violence of method | ||
| Haplotypic: ns | ||||
| LPR | Allelic: ns Genotypic: ns |
Suicide | Ethnicity: French Canadian (98%) | Lopez de Lara, 2006 |
| Cases: suicide completers with major depressive disorder, including not-otherwise-specified diagnoses: F:14,M:92; mean age: 41.8±14.7 | ||||
| Depressed controls: F:21, M:131; mean age: 41.7±10.2 | ||||
| Intron 2 STin2 | Allelic: +, 10, p=.025 Genotypic: +,12/10 & 10/10, p=.021 |
Notes: interaction of Stin2 and family history of suicide significantly predicts completions (OR=5.56 95% CI 1.06-29.25); carriers of at least one copy of allele 10 more likley to use violent mean;Bonferroni corrected | ||
| Haplotypic: ns | ||||
| LPR | Genotypic: ns | Suicide | Ethnicity: 92.5% white, 7.5% black, American | Helbecque, 2006 |
| Cases: 62 suicide completers: F: 11; mean age: 41±16 | ||||
| Matched unrelated controls: N: 72 (F: 21), mean age: 49±16 | ||||
| VNTR2 | Combined CC & 1010 genotypes (SLC6A4's VNTR2): +, p=.00156 | Suicide | Ethnicity: Croatian | Jernej, 2004 |
| Cases: 192 suicides: F: 25%; mean age:52±19 | ||||
| Nonpsychiatric controls: n:377, F:21%,mean age:43±12 | ||||
| Notes: looked at combinations of suspected risk genotypes (SLC6A4-VNTR2's 1010 & TPH's CC): Found a dose effect: carriers of either CC or 1010 genotypes [OR:1.45 95%CI:1.0-2.1] & carriers of both CC & 1010 genotypes [OR:2.57 95%CI:1.2-5.4] | ||||
LPR Intron2 VNTR |
Allelic: ns Genotypic: ns
|
Suicide | Ethnicity: Croatian | Hranilovic, 2003 |
| Cases: 135 (F:33)suicide completers (violent suicides: 98%); mean age: 51±19 | ||||
| Nonpsychiatric controls: n:299 (F:16), mean age: 41±12 | ||||
| Notes: Bonferroni-corrected analyses; linkage disequilibrium beween 2 loci | ||||
Haplotypic: +,L10, OR 1.5, 95% CI 1.1-2.1, p=.0112 |
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| LPR | Allelic: ns Genotypic: ns |
Suicide | Ethnicity: French-Canadian | Fitch, 2001 |
| Cases: 95 suicide completers | ||||
| Healthy living controls: n:120 | ||||
| Notes: trend for L allele to be more frequent in completers | ||||
| LPR | Allelic: ns Genotypic: ns |
Suicide | Ethnicity: Swedish | Roy, 2001 |
| Cases: surviving MZ co-twins of suicide completers: F:9, M:15; mean age:68.8±8.8 | ||||
| General population controls: F:81, M:77; mean age:56.7±15.8 | ||||
| LPR | Allelic: ns Genotypic: ns |
Suicide | Cases: suicides: F:21,M:61; mean age:43±20; 43 had major depression; Ethnicity: White: Hispanic: Black: Asian-59:11:9:3 | Mann, 2000 |
| Non-suicidal controls: F:31, M:107; mean age:42±16; 10 had major depression; Ethnicity: White:Hispanic: Black: Asian-77:17:40:4 | ||||
| Notes: race composition differences between cases and controls; no binding diferences between LL and non-LL genotypes; Suicides had lower 5-HTT binding in Brodmann area 47; women had less 5-HTT binding in the PFC depressed subjects had lower binding throughout the PFC | ||||
| LPR | Allelic: +,L, p=.009 | Suicide | Geographic origin: Budapest | Faludi, 2000 |
| Cases: Postmortem: depressed suicide completers: N:32, mean age: 41±17 | ||||
| Controls dying of causes unrelated to central nervous system: N:57, mean age: 38±6 | ||||
Genotypic:+, LL, p=.048 |
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| LPR | Allelic:-, L, OR:.59 95% CI .30-.76 |
Violent suicide |
Ethnicity: Caucasian, Southern Germany | Bondy, 2000 |
| Cases: suicide victims: F:18, M:40;mean age: 46±16 | ||||
| General population controls: F: 56, M:54; mean age: 47±12 | ||||
| Genotypic:+, LS & SS, p=.0014 | Notes: no difference in method or age | |||
| LPR | Allelic:+,L , OR:2.2 95% CI 95%4.8 |
Suicide | Location: Budapest | Du, 1999 |
| Cases: 24 depressed suicide completers (mean age: 50.7 ± 30.2) | ||||
| Controls who died from nonsuicide-related causes and with no evidence of psychiatric illness were matched for age, sex, and postmortem delay (n:31, mean age: 45.5 ± 2.8) | ||||
| Genotypic: ns | Notes: SS genotype associated with greater serotonin transporter binding site density than other genotypes |
Notes: += positive, significant; - =negative,significant; ns= nonsignificant; F=females; M=males