Table 1.
Serotonergic gene polymorphisms in MDD.
| Reference | Candidate gene | Sample size | Main findings |
|---|---|---|---|
| (40) | serotonin transporter (SERT) | 30 (15 healthy controls) | Compared to controls, MDD patents showed reduced SERT in brain. |
| (41) | 5-hydroxyindoleacetic acid (5-HIAA) | 68 depressed subjects | Lower 5-HIAA predicted suicide attempt in MDD. |
| (42) | 5-HIAA, SERT | 10 matched pairs | 5-HIAA and SERT deficiency in depression. |
| (43) | serotonin transporter (5-HTT) and the serotonin-transporter-linked polymorphic region (5-HTTLPR) | 220 subjects | Lower 5-HTT binding related to suicide and MDD. 5-HTTLPR related to MDD but not to suicide or 5-HTT binding. |
| (11) | 5-HTT | 1,037 subjects | Short allele of the 5-HTT promoter related to depressive symptoms, diagnosable depression, suicide, and stressful life events. |
| (44) | 5-HTT | 549 twins | Individuals expressing 2 short (S) alleles most sensitive to the depressogenic effects of stressful life events. |
| (45) | The intron 2 (STin2) polymorphism of the serotonin transporter | 258 (152 controls) | The STin2 variant predicts suicide in MDD. |
| (46) | STin2 polymorphism of the serotonin transporter | 170 (99 healthy controls) | Significant difference in the genotype frequency of STin2.10/10 in MDD. |
| (47) | 5-HTT | 66 (43 healthy controls) | Lower 5-HTT binding potential proportional to the number of available transporters in individuals with childhood abuse. |
| (48) | the serotonin transporter gene (SLC6A4) | 98 subjects | Depressed mood during the 2nd trimester of pregnancy negatively correlated with maternal SLC6A4 promoter methylation status. |
| (49) | SLC6A4 | 108 depressed subjects | SLC6A4 methylation status related to childhood adversities and MDD. |
| (50) | SLC6A4 | 84 twins | Serotonin transporter receptor gene methylation variation in peripheral blood leukocytes positively related to depressive symptom severity. |
| (51) | SLC6A4 | 100 (50 healthy controls) | Compared with healthy controls, no significantly differed with MDD. |
| (52) | SLC6A4 | 94 depressed subjects | Reduced SLC6A4 expression related to impaired antidepressant treatment response after 6 weeks. |
| (53) | SLC6A4, and Serotonin 2A receptor (5-HT2AR) | 137 depressed subjects | SLC6A4 AA genotype and A-allele related to antidepressant response. |
| (54) | SLC6A4 | 43 (24 healthy controls) | No significant associations with MDD. |
| (55) | SLC6A4 | 36 depressed subjects | Three candidate genes, including SLC6A4 related to the etiology of MDD and suicide attempts in Chinese. |
| (56) | SLC6A4 | 224 (150 healthy controls) | SLC6A4 allelic variations related to suicidal ideation in MDD. |
| (57) | SLC6A4 | 370 Parkinson's Disease patients | SS genotype predicts higher depression risk in Parkinson's disease. |
| (58) | 5-HTTLPR | 150 depressed subjects | No significant associations with MDD. |
| (59) | 5-HTTLPR | 136 (68 healthy controls) | SS genotype and S allele of 5-HTTLPR related to MDD in children. |
| (60) | 5-HTTLPR | 1,206 twins | No association between 5-HTTLPR and MDD. |
| (61) | 5-HTTLPR | 316 (125 healthy controls) | LG and S allele positively correlated with MDD in patients experiencing moderate to severe life events. |
| (62) | 5-HTTLPR | 4,175 depressed subjects | Significant association between social adversity and MDD prevalence. |
| (63) | 5-HTTLPR | 306 males | The 34-item Childhood Trauma Questionnaire (CTQ) score and 5-HTTLPR level are independent risk factors predicting suicide attempt. |
| (64) | 5-HTTLPR | 233 depressed subjects | Associations among 5-HTTLPR polymorphisms, comorbid disorders, and sex in MDD. |
| (65) | 5-HTTLPR | 103 depressed subjects | 5-HTTLPR SS genotype related to poor antidepressant response in females. |
| (66) | 5-HTTLPR | 984 subjects | Trauma was a risk factor for depressive symptoms who carries S/S or S/L genotype. |
| (67) | 5-HTTLPR and Serotonin 2A receptor (5-HT2AR) | 132 depressed subjects | 5-HT2A A-allele associated with MDD, 5-HTTLPR S allele associated with higher irritability score. |
| (68) | 5-HTTLPR | 104 depressed subjects | Statistical association between MDD and 5-HTTLPR L allele. |
| (69) | 5-HTTLPR | 121 (66 healthy controls) | No significant associations with MDD. |
| (70) | 5-HTTLPR | 1,111 subjects | Limited role of 5-HTTLPR in mediating effects of adolescent/parent relationship on depressive symptoms. |
| (71) | 5-HTTLPR | 73 (18 healthy controls) | Decreased fractional anisotropy (FA) related to 5-HTTLPR-S′L′in MDD. |
| (72) | 5-HTTLPR | 57 (29 healthy controls) | 5-HTTLPR genotype related to mean methylation levels in MDD. |
| (73) | 5-HTTLPR | 160 depressed subjects | 5-HTTLPR polymorphisms related to dysphoria score on Montgomery-Åsberg Depression Rating Scale (MADRS). |
| (74) | 5-HTTLPR | 178 depressed subjects | 5-HTTLPR genotype predictive of resistance to SSRI treatment. |
| (75) | Serotonin 2A receptor (5-HT2AR) and 5-HTTLPR | 136 (69 healthy controls) | 5-HT2A promoter -1438A variant associated with depressive symptoms of seasonal affective disorder. |
| (76) | Serotonin 1A receptor (5-HT1AR) | 263 (134 healthy controls) | Compared to the healthy controls, depressed individuals twice as likely to carry -1019G genotype. |
| (77) | 5-HT2AR | 251 (131 healthy controls) | 5-HT2AR 102C allele significantly associated with MDD, particularly in patients with suicidal ideation. |
| (78) | 5-HT1AR | 24 (8 healthy controls) | Decreased 5-HT1AR binding potential in MDD compared to controls. |
| (79) | HTR1A, HTR2A, HTR6, TPH1 and TPH2 | 481 (395 healthy controls) | No significant associations with MDD. |
| (80) | 5-HT2AR | 56 depressed subjects | AA genotype of 5-HT2AR -1438 G/A polymorphism related to sexual dysfunction in male MDD patients. |
| (81) | 5-HT2AR and Serotonin 3A receptor (5-HT3AR) | 50 (25 healthy controls) | Increased 5-HT2AR mRNA expression in peripheral blood mononuclear cells of MDD patients. |
| (82) | SERT, 5-HT1AR, and 5-HT2AR | 167 depressed subjects | Lower SERT binding associated with MDD. Both greater 5-HT1A binding and 5-HT2A binding associated with MDD. |
| (33) | 5-HT1AR | 25 depressed subjects | Reduced 5-HT1AR binding potential in MDD. |
| (83) | 5-HT1AR, 5-HT2AR and SERT | 76 brain samples | Lower 5-HT2A receptor binding in Brodmann areas 41/42 of MDD patients. |
| (84) | HTR1A | 800 (400 healthy controls) | 5-HTR1A C (−1,019) G polymorphism significantly related to MDD. |
| (85) | HTR2A | 1,282 (325 MDD patients, 155 BP patients and 802 healthy controls) | No significant associations. |
| (86) | HTR1A | 1,135 (804 healthy controls) | No significant associations. |
| (87) | HTR1A, HTR2A | 2,023 depressed subjects | No significantly associated SNP at genome-wide level. |
| (88) | HTR1A | 81 (62 healthy controls) | HTR1A rs6295 genotype related to MDD. |
| (89) | Tryptophan hydroxylase-2 (TPH2) and 5-HT2A | 564 (287 healthy controls) | TPH2/5-HT2A interaction influences MDD susceptibility. |
| (90) | Serotonin 4 (5-HT4) receptor | 96 (48 depressed subjects, 48 schizophrenia subjects) | Associations between HTR4 polymorphisms and mood disorder. |
| (91) | 5-HT4 | 57 healthy subjects, including 26 subjects had a family history of MDD | Association between the family history of MDD and lower striatal 5-HT4 receptor binding. |