Depressive disorders are a heterogeneous group of diseases. The etiology, precise pathophysiological mechanisms, response to treatment, and outcome of depressive disorders are still poorly understood. The cytokine hypothesis of depression proposes that pro-inflammatory cytokines acting as neuromodulators are a key factor mediating behavioral, neuroendocrine, and neurochemical changes in this disease.
Research | Analyzed Polymorphisms | Sample | Results |
---|---|---|---|
Kim et al. (2017) [27] | TNFA: rs1799724 (−850C/T; −308G/A); IL1B: rs16944 (−511C/T), +3953C/T |
286 patients with PSD | −511C/T polymorphism was associated with primary depression and PSD at 2 weeks; higher TNF-α levels were associated with PSD at 2 weeks in in patients carried −850T allele. |
Tartter et al. (2015) [28] | IL6: rs1800795 (−174G/C); IL1B: rs16944 (−511C/T); TNF: rs1800629 (−308G/A) |
444 young adults whose exposure to chronic stress in the past 6 months; Australian cohort | Patients with the −174G allele had fewer depressive symptoms after interpersonal stress compared with CC homozygotes with equal exposure to interpersonal stress. The −511C allele in IL1B was associated with more severe depression after chronic interpersonal stress compared with TT homozygotes. |
Lezheiko et al. (2018) [29] | IL1B: rs16944 (−511T/C); TNFA: rs1800629 (−308A/G) |
139 patients with depression vs. 530 HS; Russian cohort | The −511T/C and −308A/G polymorphisms were associated with depression; CC genotype and GG genotype are the risk factors of depression. |
McQuaid et al. (2019) [30] | IL1B: rs16944; IL6: rs1800795; TNFA: rs1800629 |
475 university students | Depressive symptoms were higher among individuals who experienced childhood adversity with the GG genotype of the IL1B rs16944. |
Kovacs et al. (2016) [31] | IL1B: rs16944, rs1143643 | 1053 persons; Hungarian cohort | The rs16944*A allele was associated with childhood adversity increasing anxiety and depressive symptoms. The A allele of rs1143643 demonstrated protective effect against depressive symptoms after recent life stress. |
Bialek et al. (2020) [18] | IL1B: rs1143623 (−1560G/C), rs1143627 (−118C/T); IL1A: rs17561 (c.340G/T); TNFA: rs1799964 (−1211T/C), rs1800629 (−488G/A) |
270 patients with depression vs. 231 HS; Polish cohort | It was shown an association between the T allele and the TT genotype of rs1799964 TNFA and low effectiveness of pharmacotherapy; the C allele and CT genotype were associated with good response to therapy. Carryer of GC and CC genotypes of rs1143623 IL1B showed varying levels of disease severity ccording to the HDRS. The combined genotypes of rs1143627–rs17561, rs1143627–rs1799964 and rs1143623–rs1799964, decreased the risk of depression occurrence, rs1143627–rs1800629 increased the risk. |
Kang et al. (2017) [32] | IL1B: rs16944 (−511C/T), +3953C/T | 969 patients at 2 weeks after ACS, 711—at 1 year later | Depression during the acute ACS was associated with the −511T allele and the IL-1β levels. There was no association with depression in chronic ACS. There was no association with depression in the acute or chronic phase and the +3953C/T genotype. |
Draganov et al. (2019) [33] | 41 SNPs in IL1B, IL2, IL6, IL6R, IL10, IL18, TNFA, IFNG | 153 patients with MDD | Polymorphic variant rs1143643 of IL1B was associated with MSM scores. Allelic distribution of rs57569414 IL6R demonstrates a trend to significance with MSM scores. Combinations of alleles of IL1B and IL10 were associated with response to treatment. |
Kim et al. (2013) [34] | TNFA: rs1800629 (−308G/A); IL10: rs1800896 (−1082A/G); IFNG: rs2430561 (+874T/A) |
301 patients with MDD (204 attempted suicide, 97 not attempted suicide); Korean cohort | Among patients with MDD the TNFA −308GG genotype was associated with an increased risk of suicide; IL10-1082A/G were not associated with that risk. |
Tsai et al. (2023) [35] | GWAS involving 684,616 SNPs | 65 patients with TRD; Chinese cohort | Two SNPs (rs2540315 and rs75746675) in IL1R1 were associated with a rapid (within 240 min) antidepressant effect of ketamine infusion in patients with TRD. |
Kim et al. (2013) [36] | TNFA: rs1799724 (−850C/T); IL1B: rs16944 (−511C/T), +3953C/T; IL6: rs1800795 (−174G/C); IL8: −251T/A; IL4: +33T/C; IL10: rs1800896 (−1082A/G) |
309 women with breast cancer at one week after surgery, 244 (79%)—at one year later. | IL1B-511TT was associated with depression at one week after surgery with breast cancer and persistent depression at one year follow-up. |
Luckhoff et al. (2016) [37] | TNFA: rs1800629 (−308G/A) | 94 patients with MDD vs. 97 HS; South African cohort | The rs1800629*A-allele in TNFA was associated with early-onset of MDD. |
Lu et al. (2023) [38] | IL6: rs1800795; rs1800796 | 114 patients with depression vs. 110 HS; Han Chinese cohort | The CC genotype and the C allele of rs1800796 were associated with depression. |
Golimbet et al. (2017) [39] | IL4: −589C/T; IL6: rs1800795 (−174G/C); TNFA: rs1800629 (−308G/A); CRP: −717A/G |
78 male CHD patients with depression; 91—without depression; 127 HS; Russian cohort | The IL6-174G/C was associated with depression comorbid to CHD. The IL4-589C/T was associated with CHD. No association between the TNFA-308G/A and the CRP-717A/G with depression in CHD. |
Kovacs et al. (2016) [40] | IL6 : rs1800795 | 1053 volunteers; Hungarian cohort | The IL6 rs1800795 in common with various stressors increases the risk of depression and has a greater impact measured by the ZSDS symptoms. |
Gal et al (2023) [41] | IL6 : rs1800795 | UK Biobank, n = 277 501 |
The rs1800795 was associated with recent stress on current depressive symptoms and lifetime depression. |
Udina et al. (2013) [42] | IL6 : rs1800795 | 385 patients with chronic hepatitis; Caucasian cohort | The rs1800795 IL6 increases the risk of induced by IFN depression and anxiety. It was associated with fatigue rates in patients with chronic hepatitis C before treatment. |
Zhang et al. (2016) [43] | IL6 : 1800797 | 772 patients with MDD vs. 759 HS; Han Chinese cohort | Association between rs1800797 and the risk of MDD. |
Maciukiewicz et al. (2015) [44] | Twenty SNPs in IL1B, IL2, IL6, TSPO and BDNF | MDD patients treated with duloxetine (n = 215) or placebo (n = 235) | Association IL6 (−63G/A, rs2066992; +1984T/G, rs10242595) with response to duloxetine therapy in MDD patients. IL6 rs2066992 and rs10242595 were associated with duloxetine response. The rs2066992 was associated with placebo response. |
Khandaker at al. (2018) [45] | IL6R: rs2228145 (Asp358Ala) | 9912 unselected participants from the ALSPAC birth cohort | Asp358Ala was associated with a reduced risk of severe depression and/or psychosis. Asp358Ala was not associated with total depression score and with the risk factors related with inflammation, depression or psychosis. |
Dunn et al. (2013) [46] | 104 SNPs and haplotypes in 15 cytokine genes | 167 oncology patients with prostate, breast, lung, or brain cancer and 85 of their FCs | Significant associations of cytokine gene variants with trajectories of depressive symptoms in cancer patients and their FC have been identified. Two of these associations were in genes with anti-inflammatory functions (IL1R2, IL10), and one was with a gene with proinflammatory functions (TNFA). |
Doong et al. (2015) [47] | 82 SNPs in 15 genes of cytokine | 398 breast cancer patients | Significant associations between IL6 rs2069845, IL13 rs1295686, and TNFA rs18800610 with a symptom cluster of pain, sleep disturbance, fatigue and depression. |
Santos et al. (2016) [48] | IL18: rs1946518 (-607A/C), rs187238 (-137C/G) | 80 MDD patients; Portuguese cohort | IL18-607A/C and IL18-137C/G were associated with the effect of the AD therapy. Patients carrying CA or AA genotypes of -607A/C and patients carrying GC or CC genotypes of -137C/G were significantly more prone to relapse after therapy and present a significantly lower time to relapse. |
Sandoval-Carrillo et al. (2018) [49] | TNFA: rs1799724 (-857C/T), rs1800629 (-308G/A), rs361525 (-238G/A) | 153 pregnant women with depression vs. 177 HS | The −857CT genotype increased the risk for depression. The −238GA genotype reduced the risk. No association between the −308G/A polymorphism and depression risk. The C857-G308-A238 haplotype was associated with a decrease of depression risk. |
Saad et al. (2014) [50] | 82 SNPs in 15 cytokine genes | 155 patients with resilient and 180 patients with subsyndromal depressive symptom classes | In patients with breast cancer variation in three cytokine genes IFNGR1 rs937626, IL6 rs2069840, TNFA rs1799964, predicted membership in the Subsyndromal versus the Resilient class as well as age and functional status. |
Bialek et al. (2020) [51] | TGFB1: rs1800469 (g.41354391A/G); IRF: rs2070729 (g.132484229C/A); PTGS2: rs5275 (186643058A/G); PTGS2: rs4648308 (g.186640617C/T); TGF-α: rs2166975 (g.70677994G/A); IKBKB: rs5029748 (g.42140549G/T). |
80 patients with depression vs. 180 HS | The AG genotype of rs2166975 TGFA was associated with an increased risk of depression, the GG genotype reduced the risk. The AG genotype and G allele of the rs2166975 TGFA was associated with increased risk of depression development in men. Genotype rs1800469*AA of TGFB1 was associated with earlier age of onset of the disease, GG genotype increased severity of the depressive episode. |
Mihailova et al. (2016) [52] | TNFA , TGFB , IL10 , IL6 , IFNG | 80 patients with depression vs. 50 HS; Bulgarian cohort | The TGFB + 869TT genotype (rs1800470) prevailed in patients compared with HS. The TT-GC combined genotype (+869T/C, +915G/C) was associated with disease recurrence. |
This entry is adapted from the peer-reviewed paper 10.3390/genes14071460