Genetic Variants in Oxytocinergic System Genes and Their Association with Postpartum Depression Susceptibility
Abstract
1. Introduction
2. Results
2.1. OXT_rs2740210 Genotyping
2.2. OXT_rs4813627 Genotyping
2.3. OXTR_rs237885 Genotyping
3. Discussion
4. Materials and Methods
4.1. Participants
4.2. Ethics Declarations
4.3. Procedure
- Participants were included in the study if they met the following inclusion criteria:
- Postpartum mothers within the age range of 18–50 years.
- Postpartum mothers at the consultation scheduled 6 weeks after childbirth.
- No history of high-risk obstetrical pregnancy in the case of the last pregnancy (gestational diabetes, pregnancy induced hypertension, preeclampsia, intrahepatic cholestasis of pregnancy, fetal anomalies, chromosomal aberrations, intrauterine growth restriction).
- No antepartum/postpartum dead fetus.
- Postpartum mothers who expressed an interest in this subject and who also have provided informed consent to be enrolled in the study.
- Mothers with current or past use of any sort of psychotropic medication.
- Mothers with high-risk obstetrical pregnancy in the case of the last one (gestational diabetes, pregnancy induced hypertension, preeclampsia, intrahepatic cholestasis of pregnancy, fetal anomalies, chromosomal aberrations, intrauterine growth restriction).
- Mothers with a history of psychiatric disorders or any mental health issues.
- Patients with twin, triplet, or higher-order multifetal gestations.
4.4. Edinburgh Postnatal Depression Scale Questionnaire
4.5. DNA Genotyping and Allelic Discrimination
4.6. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
PPD | Postpartum depression |
EPDS | Edinburgh Postnatal Depression Scale |
OXT | Oxytocin |
OXTR | Oxytocin receptor |
SNPs | Single nucleotide polymorphisms |
DNA | Deoxyribonucleic acid |
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Variable | OXT_rs2740210 Genotype | p Test | ||
---|---|---|---|---|
AA (13) | AC (41) | CC (44) | ||
Presence of PPD | ||||
No | 13 (15.500%) | 41 (48.800%) | 30 (35.700%) | <0.001 (C) * |
Yes | 0 (0.000%) | 0 (0.000%) | 14 (87.500%) | |
EPDS score | 8.462 ± 4.054 11 (5–11) | 9.317 ± 3.365 11 (8–11) | 10.455 ± 4.547 11 (6–13) | 0.213 (K-W) |
Marital status | ||||
Cohabiting | 2 (18.182%) | 6 (54.545%) | 3 (27.273%) | 0.312 (C) |
Divorced | 0 (0.000%) | 2 (66.667%) | 1 (33.333%) | |
Married | 9 (11.842%) | 28 (36.842%) | 39 (51.316%) | |
Single | 2 (25.000%) | 5 (62.500%) | 1 (12.500%) | |
Residence | ||||
Rural | 7 (11.864%) | 24 (40.678%) | 28 (47.458%) | 0.785 (C) |
Urban | 6 (15.385%) | 17 (43.590%) | 16 (41.026%) | |
Education | ||||
High school | 3 (10.000%) | 11 (36.667%) | 16 (53.333%) | 0.541 (C) |
Higher education | 5 (10.417%) | 21 (43.750%) | 22 (45.833%) | |
Middle school | 3 (25.000%) | 6 (50.000%) | 3 (25.000%) | |
Primary education | 1 (50.000%) | 0 (0.000%) | 1 (50.000%) | |
Vocational school | 1 (16.667%) | 3 (50.000%) | 2 (33.333%) | |
Socio-economic conditions | ||||
Good standard of living | 8 (14.286%) | 24 (42.857%) | 24 (42.857%) | 0.112 (C) |
Poor living conditions | 0 (0.000%) | 0 (0.000%) | 1 (100.000%) | |
Satisfactory conditions | 4 (19.048%) | 12 (57.143%) | 5 (23.810%) | |
Very good standard of living | 1 (5.000%) | 5 (25.000%) | 14 (70.000%) | |
Health status | ||||
Good | 11 (11.957%) | 39 (42.391%) | 42 (45.652%) | 0.326 (C) |
Satisfactory | 2 (33.333%) | 2 (33.333%) | 2 (33.333%) | |
Type of birth | ||||
Caesarean section | 7 (11.475%) | 24 (39.344%) | 30 (49.180%) | 0.525 (C) |
Vaginal delivery | 6 (16.216%) | 17 (45.946%) | 14 (37.838%) | |
Preterm birth | ||||
No | 12 (14.634%) | 32 (39.024%) | 38 (46.341%) | 0.388 (C) |
Yes | 1 (6.250%) | 9 (56.250%) | 6 (37.500%) | |
History of depressive disorder | ||||
No | 11 (11.702%) | 40 (42.553%) | 43 (45.745%) | 0.087 (C) |
Yes | 2 (50.000%) | 1 (25.000%) | 1 (25.000%) | |
History of postpartum depressive disorder | ||||
No | 12 (12.903%) | 40 (43.011%) | 41 (44.086%) | 0.592 (C) |
Yes | 1 (20.000%) | 1 (20.000%) | 3 (60.000%) | |
Insomnia | ||||
No | 9 (12.000%) | 33 (44.000%) | 33 (44.000%) | 0.670 (C) |
Yes | 4 (17.391%) | 8 (34.783%) | 11 (47.826%) | |
Anxiety | ||||
No | 11 (14.474%) | 35 (46.053%) | 30 (39.474%) | 0.133 (C) |
Yes | 2 (9.091%) | 6 (27.273%) | 14 (63.636%) | |
Family history of psychiatric disorders | ||||
No | 13 (13.542%) | 40 (41.667%) | 43 (44.792%) | 0.854 (C) |
Yes | 0 (0.000%) | 1 (50.000%) | 1 (50.000%) | |
History of psychotherapy | ||||
No | 12 (12.500%) | 41 (42.708%) | 43 (44.792%) | 0.230 (C) |
Yes | 1 (50.000%) | 0 (0.000%) | 1 (50.000%) |
PPD | Presence of A Allele in the OXT_rs2740210 Genotype | Total | Presence of C Allele in the OXT_rs2740210 Genotype | Total | |||||
---|---|---|---|---|---|---|---|---|---|
NA = No Results | No | Yes | NA = No Results | No | Yes | ||||
With PPD | Count | 2 | 14 | 0 | 16 | 2 | 0 | 14 | 16 |
% within PPD | 12.5% | 87.5% | 0.0% | 100.0% | 12.5% | 0.0% | 87.5% | 100.0% | |
Without PPD | Count | 0 | 30 | 54 | 84 | 0 | 13 | 71 | 84 |
% within PPD | 0.0% | 35.7% | 64.3% | 100.0% | 0.0% | 15.5% | 84.5% | 100.0% | |
Total | Count | 2 | 44 | 54 | 100 | 2 | 13 | 85 | 100 |
% within PPD | 2.0% | 44.0% | 54.0% | 100.0% | 2.0% | 13.0% | 85.0% | 100.0% |
Group | N | Mean EPDS SCORE | SD | SE | Coefficient of Variation | |
---|---|---|---|---|---|---|
Presence of A allele in OXT_rs2740210 genotype | No | 44 | 10.455 | 4.547 | 0.685 | 0.435 |
Yes | 54 | 9.111 | 3.522 | 0.479 | 0.387 | |
Presence of C allele in OXT_rs2740210 genotype | No | 13 | 8.462 | 4.054 | 1.124 | 0.479 |
Yes | 85 | 9.906 | 4.037 | 0.438 | 0.408 |
Variable | OXT_rs4813627 Genotype | p Test | ||
---|---|---|---|---|
AA (24) | AG (52) | GG (23) | ||
Presence of PPD | ||||
No | 22 (26.200%) | 45 (53.600%) | 17 (20.200%) | 0.050 (C) |
Yes | 2 (12.500%) | 7 (43.800%) | 6 (37.500%) | |
EPDS Score | 9.208 ± 4.139 11 (6–11) | 9.788 ± 3.455 11 (8–11) | 10.217 ± 5.161 11 (6.5–12.5) | 0.694 (K-W) |
Marital status | ||||
Cohabiting | 1 (9.091%) | 7 (63.636%) | 3 (27.273%) | 0.520 (C) |
Divorced | 2 (66.667%) | 1 (33.333%) | 0 (0.000%) | |
Married | 19 (24.675%) | 39 (50.649%) | 19 (24.675%) | |
Single | 2 (25.000%) | 5 (62.500%) | 1 (12.500%) | |
Residence | ||||
Rural | 15 (25.424%) | 29 (49.153%) | 15 (25.424%) | 0.704 (C) |
Urban | 9 (22.500%) | 23 (57.500%) | 8 (20.000%) | |
Education | ||||
High school | 8 (26.667%) | 13 (43.333%) | 9 (30.000%) | 0.914 (C) |
Higher education | 11 (22.449%) | 28 (57.143%) | 10 (20.408%) | |
Middle school | 3 (25.000%) | 7 (58.333%) | 2 (16.667%) | |
Primary education | 0 (0.000%) | 1 (50.000%) | 1 (50.000%) | |
Vocational school | 2 (33.333%) | 3 (50.000%) | 1 (16.667%) | |
Socio-economic conditions | ||||
Good standard of living | 15 (26.316%) | 30 (52.632%) | 12 (21.053%) | 0.559 (C) |
Poor living conditions | 0 (0.000%) | 0 (0.000%) | 1 (100.000%) | |
Satisfactory conditions | 4 (19.048%) | 13 (61.905%) | 4 (19.048%) | |
Very good standard of living | 5 (25.000%) | 9 (45.000%) | 6 (30.000%) | |
Health status | ||||
Good | 22 (23.656%) | 48 (51.613%) | 23 (24.731%) | 0.378 (C) |
Satisfactory | 2 (33.333%) | 4 (66.667%) | 0 (0.000%) | |
Type of birth | ||||
Caesarean section | 12 (19.355%) | 35 (56.452%) | 15 (24.194%) | 0.335 (C) |
Vaginal delivery | 12 (32.432%) | 17 (45.946%) | 8 (21.622%) | |
Preterm birth | ||||
No | 22 (26.506%) | 42 (50.602%) | 19 (22.892%) | 0.479 (C) |
Yes | 2 (12.500%) | 10 (62.500%) | 4 (25.000%) | |
History of depressive disorder | ||||
No | 22 (23.158%) | 51 (53.684%) | 22 (23.158%) | 0.417 (C) |
Yes | 2 (50.000%) | 1 (25.000%) | 1 (25.000%) | |
History of postpartum depressive disorder | ||||
No | 22 (23.404%) | 52 (55.319%) | 20 (21.277%) | 0.041 (C) * |
Yes | 2 (40.000%) | 0 (0.000%) | 3 (60.000%) | |
Insomnia | ||||
No | 18 (24.000%) | 38 (50.667%) | 19 (25.333%) | 0.671 (C) |
Yes | 6 (25.000%) | 14 (58.333%) | 4 (16.667%) | |
Anxiety | ||||
No | 17 (22.368%) | 42 (55.263%) | 17 (22.368%) | 0.593 (C) |
Yes | 7 (30.435%) | 10 (43.478%) | 6 (26.087%) | |
Family history of psychiatric disorders | ||||
No | 24 (24.742%) | 50 (51.546%) | 23 (23.711%) | 0.398 (C) |
Yes | 0 (0.000%) | 2 (100.000%) | 0 (0.000%) | |
History of psychotherapy | ||||
No | 23 (23.711%) | 52 (53.608%) | 22 (22.680%) | 0.323 (C) |
Yes | 1 (50.000%) | 0 (0.000%) | 1 (50.000%) |
PPD | Presence of A Allele in OXT_rs4813627 Genotype | Total | Presence of G Allele in OXT_rs4813627 Genotype | Total | |||||
---|---|---|---|---|---|---|---|---|---|
NA = No Results | No | Yes | NA = No Results | No | Yes | ||||
With PPD | Count | 1 | 6 | 9 | 16 | 1 | 2 | 13 | 16 |
% within PPD | 6.3% | 37.5% | 56.3% | 100.0% | 6.3% | 12.5% | 81.3% | 100.0% | |
Without PPD | Count | 0 | 17 | 67 | 84 | 0 | 22 | 62 | 84 |
% within PPD | 0.0% | 20.2% | 79.8% | 100.0% | 0.0% | 26.2% | 73.8% | 100.0% | |
Total | Count | 1 | 23 | 76 | 100 | 1 | 24 | 75 | 100 |
% within PPD | 1.0% | 23.0% | 76.0% | 100.0% | 1.0% | 24.0% | 75.0% | 100.0% |
Group | N | Mean EPDS SCORE | SD | SE | Coefficient of Variation | |
---|---|---|---|---|---|---|
Presence of A allele in OXT_rs4813627 genotype | No | 23 | 10.217 | 5.161 | 1.076 | 0.505 |
Yes | 76 | 9.605 | 3.667 | 0.421 | 0.382 | |
Presence of G allele in OXT_rs4813627 genotype | No | 24 | 9.208 | 4.139 | 0.845 | 0.449 |
Yes | 75 | 9.92 | 4.023 | 0.465 | 0.406 |
Variable | OXTR_rs237885 Genotype | p Test | ||
---|---|---|---|---|
GG (37) | GT (45) | TT (15) | ||
Presence of PPD | ||||
No | 32 (38.100%) | 37 (44.000%) | 13 (15.500%) | 0.795 (C) |
Yes | 5 (31.300%) | 8 (50.000%) | 2 (12.500%) | |
EPDS score | 9.081 ± 4.468 11 (5–11) | 10.111 ± 4.013 11 (8–12) | 10.467 ± 3.021 11 (10.5–12) | 0.406 (K-W) |
Marital status | ||||
Cohabiting | 5 (45.455%) | 4 (36.364%) | 2 (18.182%) | 0.820 (C) |
Divorced | 1 (33.333%) | 1 (33.333%) | 1 (33.333%) | |
Married | 28 (37.333%) | 35 (46.667%) | 12 (16.000%) | |
Single | 3 (37.500%) | 5 (62.500%) | 0 (0.000%) | |
Residence | ||||
Rural | 26 (44.828%) | 26 (44.828%) | 6 (10.345%) | 0.122 (C) |
Urban | 11 (28.205%) | 19 (48.718%) | 9 (23.077%) | |
Education | ||||
High school | 11 (39.286%) | 11 (39.286%) | 6 (21.429%) | 0.765 (C) |
Higher education | 19 (38.776%) | 22 (44.898%) | 8 (16.327%) | |
Middle school | 5 (41.667%) | 7 (58.333%) | 0 (0.000%) | |
Primary education | 1 (50.000%) | 1 (50.000%) | 0 (0.000%) | |
Vocational school | 1 (16.667%) | 4 (66.667%) | 1 (16.667%) | |
Socio-economic conditions | ||||
Good standard of living | 24 (42.105%) | 26 (45.614%) | 7 (12.281%) | 0.665 (C) |
Poor living conditions | 0 (0.000%) | 1 (100.000%) | 0 (0.000%) | |
Satisfactory conditions | 8 (38.095%) | 10 (47.619%) | 3 (14.286%) | |
Very good standard of living | 5 (27.778%) | 8 (44.444%) | 5 (27.778%) | |
Health status | ||||
Good | 37 (40.659%) | 41 (45.055%) | 13 (14.286%) | 0.115 (C) |
Satisfactory | 0 (0.000%) | 4 (66.667%) | 2 (33.333%) | |
Type of birth | ||||
Caesarean section | 23 (37.705%) | 27 (44.262%) | 11 (18.033%) | 0.647 (C) |
Vaginal delivery | 14 (38.889%) | 18 (50.000%) | 4 (11.111%) | |
Preterm birth | ||||
No | 31 (38.272%) | 36 (44.444%) | 14 (17.284%) | 0.483 (C) |
Yes | 6 (37.500%) | 9 (56.250%) | 1 (6.250%) | |
History of depressive disorder | ||||
No | 36 (38.710%) | 43 (46.237%) | 14 (15.054%) | 0.800 (C) |
Yes | 1 (25.000%) | 2 (50.000%) | 1 (25.000%) | |
History of postpartum depressive disorder | ||||
No | 36 (39.130%) | 43 (46.739%) | 13 (14.130%) | 0.279 (C) |
Yes | 1 (20.000%) | 2 (40.000%) | 2 (40.000%) | |
Insomnia | ||||
No | 29 (39.726%) | 34 (46.575%) | 10 (13.699%) | 0.674 (C) |
Yes | 8 (33.333%) | 11 (45.833%) | 5 (20.833%) | |
Anxiety | ||||
No | 30 (40.541%) | 36 (48.649%) | 8 (10.811%) | 0.075 (C) |
Yes | 7 (30.435%) | 9 (39.130%) | 7 (30.435%) | |
Family history of psychiatric disorders | ||||
No | 36 (37.895%) | 44 (46.316%) | 15 (15.789%) | 0.820 (C) |
Yes | 1 (50.000%) | 1 (50.000%) | 0 (0.000%) | |
History of psychotherapy | ||||
No | 36 (37.895%) | 44 (46.316%) | 15 (15.789%) | 0.820 (C) |
Yes | 1 (50.000%) | 1 (50.000%) | 0 (0.000%) |
PPD | Presence of G Allele in OXTR_rs237885 Genotype | Total | Presence of T Allele in OXTR_rs237885 Genotype | Total | |||||
---|---|---|---|---|---|---|---|---|---|
NA = No results | No | Yes | NA = No Results | No | Yes | ||||
With PPD | Count | 1 | 2 | 13 | 16 | 1 | 5 | 10 | 16 |
% within PPD | 6.3% | 12.5% | 81.3% | 100.0% | 6.3% | 31.3% | 62.5% | 100.0% | |
Without PPD | Count | 2 | 13 | 69 | 84 | 2 | 32 | 50 | 84 |
% within PPD | 2.4% | 15.5% | 82.1% | 100.0% | 2.4% | 38.1% | 59.5% | 100.0% | |
Total | Count | 3 | 15 | 82 | 100 | 3 | 37 | 60 | 100 |
% within PPD | 3.0% | 15.0% | 82.0% | 100.0% | 3.0% | 37.0% | 60.0% | 100.0% |
Group | N | Mean EPDS SCORE | SD | SE | Coefficient of Variation | |
---|---|---|---|---|---|---|
Presence of G allele in OXTR_rs237885 genotype | No | 15 | 10.467 | 3.021 | 0.78 | 0.289 |
Yes | 82 | 9.646 | 4.229 | 0.467 | 0.438 | |
Presence of T allele in OXTR_rs237885 genotype | No | 37 | 9.081 | 4.468 | 0.735 | 0.492 |
Yes | 60 | 10.2 | 3.768 | 0.486 | 0.369 |
Age | |
---|---|
Range | 18–46 |
Mean ± Standard Deviation | 29.17 ± 6.08 |
Residence | |
Rural | 60% (60) |
Urban | 40% (40) |
Education | |
High School | 31% (31) |
Higher education | 49% (49) |
Middle school | 12% (12) |
Primary education | 2% (2) |
Vocational school | 6% (6) |
Socio-economic conditions | |
Poor living conditions | 1% (1) |
Satisfactory conditions | 21% (21) |
Good standard of living | 57% (57) |
Very good standard of living | 21% (21) |
Workplace hazard | |
High | 5% (5) |
Medium | 15% (15) |
Low | 80% (80) |
Health status | |
Good | 94% (94) |
Satisfactory | 6% (6) |
Gravidity | |
1 | 43% (43) |
2 | 26% (26) |
3 | 15% (15) |
4 | 7% (7) |
5 | 6% (6) |
6 | 1% (1) |
7 | 1% (1) |
9 | 1% (1) |
Parity | |
1 | 55% (55) |
2 | 26% (26) |
3 | 12% (12) |
4 | 2% (2) |
5 | 2% (2) |
6 | 3% (3) |
Miscarriages | |
0 | 81% (81) |
1 | 14% (14) |
2 | 3% (3) |
3 | 2% (2) |
Abortions performed upon request | |
0 | 87% (87) |
1 | 11% (11) |
2 | 2% (2) |
Method of achieving pregnancy | |
In vitro fertilization | 1% (1) |
Naturally | 98% (98) |
With previous treatment | 1% (1) |
Type of birth | |
Caesarean section | 63% (63) |
Vaginal delivery | 37% (37) |
Preterm birth | |
No | 83% (83) |
Yes | 17% (17) |
Psychiatric disorders | |
No | 100% (100) |
Current depressive disorder | |
No | 100% (100) |
History of depressive disorder | |
No | 96% (96) |
Yes | 4% (4) |
History of postpartum depressive disorder | |
No | 95% (95) |
Yes | 5% (5) |
Insomnia | |
No | 75% (75) |
Yes | 25% (25) |
Anxiety | |
No | 76% (76) |
Yes | 24% (24) |
Family history of psychiatric disorders | |
No | 98% (98) |
Yes | 2% (2) |
History of psychotherapy | |
No | 98% (98) |
Yes | 2% (2) |
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Ciolac, L.; Andreescu, N.I.; Farcaș, S.S.; Bernad, E.S.; Tudor, A.; Nițu, D.-R.; Popa, D.-I.; Maghiari, A.-L.; Craina, M.L. Genetic Variants in Oxytocinergic System Genes and Their Association with Postpartum Depression Susceptibility. Int. J. Mol. Sci. 2025, 26, 2129. https://doi.org/10.3390/ijms26052129
Ciolac L, Andreescu NI, Farcaș SS, Bernad ES, Tudor A, Nițu D-R, Popa D-I, Maghiari A-L, Craina ML. Genetic Variants in Oxytocinergic System Genes and Their Association with Postpartum Depression Susceptibility. International Journal of Molecular Sciences. 2025; 26(5):2129. https://doi.org/10.3390/ijms26052129
Chicago/Turabian StyleCiolac, Livia, Nicoleta Ioana Andreescu, Simona Sorina Farcaș, Elena Silvia Bernad, Anca Tudor, Dumitru-Răzvan Nițu, Daian-Ionel Popa, Anca-Laura Maghiari, and Marius Lucian Craina. 2025. "Genetic Variants in Oxytocinergic System Genes and Their Association with Postpartum Depression Susceptibility" International Journal of Molecular Sciences 26, no. 5: 2129. https://doi.org/10.3390/ijms26052129
APA StyleCiolac, L., Andreescu, N. I., Farcaș, S. S., Bernad, E. S., Tudor, A., Nițu, D.-R., Popa, D.-I., Maghiari, A.-L., & Craina, M. L. (2025). Genetic Variants in Oxytocinergic System Genes and Their Association with Postpartum Depression Susceptibility. International Journal of Molecular Sciences, 26(5), 2129. https://doi.org/10.3390/ijms26052129