Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatr. Mar 22, 2015; 5(1): 103-111
Published online Mar 22, 2015. doi: 10.5498/wjp.v5.i1.103
Postpartum depression: A systematic review of the genetics involved
Tiago Castro e Couto, Mayra Yara Martins Brancaglion, António Alvim-Soares, Lafaiete Moreira, Frederico Duarte Garcia, Rodrigo Nicolato, Regina Amélia Lopes P Aguiar, Henrique Vitor Leite, Humberto Corrêa
Tiago Castro e Couto, Mayra Yara Martins Brancaglion, António Alvim-Soares, Lafaiete Moreira, Frederico Duarte Garcia, Rodrigo Nicolato, Humberto Corrêa, Postgraduate Program in Molecular Medicine, School of Medicine, Universidade Federal de Minas Gerais , Belo Horizonte 30130100, MG, Brazil
Regina Amélia Lopes P Aguiar, Henrique Vitor Leite, Department of Obstetrics and Gynecology, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, MG, Brazil
Frederico Duarte Garcia, Humberto Corrêa, Department of Mental Health, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, MG, Brazil
Author contributions: All authors equally contributed to this paper.
Supported by Humberto Corrêa has received research funding from Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
Conflict-of-interest: The others authors have no conflicts-of-interest or received any grant.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Tiago Castro e Couto, MD, Postgraduate Program in Molecular Medicine, School of Medicine, Universidade Federal de Minas Gerais, Alfredo Balena Av, 190/240 Santa Efigênia, Belo Horizonte 30130100, MG, Brazil. tiagocastrocouto@gmail.com
Telephone: +55-31-34099785 Fax: +55-34-32242884
Received: July 17, 2011
Peer-review started: July 19, 20114
First decision: October 14, 2014
Revised: November 21, 2014
Accepted: December 16, 2014
Article in press: December 17, 2014
Published online: March 22, 2015

Abstract

Postpartum depression is one of the most prevalent psychopathologies. Its prevalence is estimated to be between 10% and 15%. Despite its multifactorial etiology, it is known that genetics play an important role in the genesis of this disorder. This paper reviews epidemiological evidence supporting the role of genetics in postpartum depression (PPD). The main objectives of this review are to determine which genes and polymorphisms are associated with PPD and discuss how this association may occur. In addition, this paper explores whether these genes are somehow related to or even the same as those linked to Major Depression (MD). To identify gaps in the current knowledge that require investigation, a systematic review was conducted in the electronic databases PubMed, LILACS and SciELO using the index terms “postpartum depression” and “genetics”. Literature searches for articles in peer-reviewed journals were made until April 2014. PPD was indexed 56 times with genetics. The inclusion criteria were articles in Portuguese, Spanish or English that were available by institutional means or sent by authors upon request; this search resulted in 20 papers. Genes and polymorphisms traditionally related to MD, which are those involved in the serotonin, catecholamine, brain-derived neurotrophic factor and tryptophan metabolism, have been the most studied, and some have been related to PPD. The results are conflicting and some depend on epigenetics, which makes the data incipient. Further studies are required to determine the genes that are involved in PPD and establish the nature of the relationship between these genes and PPD.

Key Words: Genetics, Single nucleotide polymorphisms, Molecular, Postpartum depression, Genes

Core tip: 5HTT and 5HTTLPR were the most studied gene and polymorphism, respectively. 5HTTLPR is associated with postpartum depression (PPD) in the majority of papers, but epigenetics must be considered. TPH1 and TPH2 polymorphisms are related to peripartum depression. COMT and MAOA polymorphisms were also risk factors for PPD. Once again, only when epigenetic was analyzed, an association with BDNF polymorphism was possible. MTHFR, CYP2D6 and PER2 polymorphisms were not related to this mood disorder. Polymorphisms of oxytocin, steroids and estrogen genes were positively correlated with PPD.


Citation: Couto TCE, Brancaglion MYM, Alvim-Soares A, Moreira L, Garcia FD, Nicolato R, Aguiar RALP, Leite HV, Corrêa H. Postpartum depression: A systematic review of the genetics involved. World J Psychiatr 2015; 5(1): 103-111
INTRODUCTION

Historically, pregnancy and puerperium have been considered periods that protect women from mental disorders. It is now known that the opposite is true: those periods confer a higher risk of appearance and recurrence of mental disorders and should therefore be a public health concern. Postpartum depression (PPD) is one of these disorders. Epidemiological papers demonstrated that the prevalence of postpartum depression is between 10% and 15%[1-3].

The adverse impacts of PPD are not limited to mothers; PPD also affects other family members and influences family dynamics. Recent studies have shown that PPD can also lead to significant language, cognitive and emotional processing problems in children[4-6]. Psychopathologies in children may not be restricted to the first years of life; it is possible to find manifestations, such as conduct disorder, that persist even until adolescence[7]. The partners of women with PPD also tend to have depression more frequently than expected[8,9].

Psychological and social changes mark the transition to motherhood. Those changes, together with clinical history and obstetrical aspects, may be related to PPD. Self-esteem, childcare stress, life stress, social support, marital relationship, infant temperament, marital status, socioeconomic status, unplanned/unwanted pregnancy[10], previous psychiatric disorder[1,10], method of childbirth, and previous abortion[11] are the main findings associated with PPD.

In addition, biological changes are related to PPD. According to some investigations, these changes may be partly genetically determined. A study conducted in England evaluated 44 pairs of sisters who had unipolar depression and found that those pairs in which one sister fulfilled the PPD criteria according to DSM-IV, 42% of the other sisters developed PPD after giving birth. For those who had no family history of depression, the rates dropped to 15% (P = 0.01). In this study, the evidence of a genetic influence is even greater when the PPD period was restricted for 6 to 8 wk postpartum[12]. Another study, conducted in Australia, involved the interview of 838 pairs of adult twins about their postpartum experiences. The authors reported that genetic factors explained 25% of the variance in the occurrence of PPD[13]. Over the last decade, many studies have been devoted to verifying the impact of this type of genetic variation in PPD, and it is thus important to know the concept of Single Nucleotide Polymorphisms (SNPs). SNP is a genetic variation that affects only one base pair in the DNA sequence. These variations in DNA sequence can affect the individual response to diseases, bacteria, viruses, chemicals, pharmaceuticals. To be considered an SNP, the variation should occur in at least 1% of a given population.

The present report aims to assess molecular studies associated with PPD and highlight the most studied genes and polymorphisms.

RESEARCH

The present paper is a systematic, integrative review that includes several studies with different methodologies to answer questions about the relationship between genetic factors and the development of postpartum depression. For guidance, the following questions were raised: Are there genes or polymorphisms that are more related than others to postpartum depression? What is their relevance? Are Major Depression (MD) and Postpartum Depression the same or different disorders? Is PPD only a temporal variant of MD?

This study consisted of a search of all articles describing a clear relationship between genetics and postpartum depression that were indexed in PubMed, LILACS and SciELO published before April 2014.

To accurately answer the questions that guided this review, the abstracts were read and classified during a selection process. If, after reading the abstract, there was reasonable doubt about the inclusion or exclusion of the paper, the whole article was read. The same procedure was adopted when abstracts were not available. Thereafter, a reverse search was carried out.

The following inclusion and exclusion criteria were used.

Included: papers in Portuguese, Spanish or English in the researched databases, with index terms “postpartum depression” and “genetics”, which assessed the genes and polymorphisms related to PPD. For this purpose, the following algorithms were used: (“Depression, Postpartum”[Mesh]) AND (“Genetics”[Mesh] OR “genetics”[Subheading]).

Excluded: review articles and animal models; articles that were not available by CAPES (Brazilian governmental agency that sponsors studies) and not provided by authors upon request; those that researched another postpartum psychopathology, finding or result; and those that did not address genetics involved in PPD.

RESULTS

The LILACS and SciELO searches did not result in any article fulfilling the criteria. The PubMed search resulted in 56 papers. After reading the abstracts, 36 were excluded: 6 reviews[14-19], 2 papers that were not available by CAPES and not sent by the authors upon request[20,21], 5 animal models[22-26], 12 investigating another postpartum psychopathology (psychoses and bipolar)[27-38], 3 evaluating the children[6,39,40], 1 on breastfeeding[41] and 7 that did not address the genetic factors involved in PPD[12,13,42-46]. A reverse search resulted in no additional items. Finally, a sample was formed[47-66].

The 20 selected studies were conducted in 10 different countries. Sweden[48,50,53] and the United States of America[49,57,64] had three publications each (15%). Germany[56,61], China (Taiwan)[55,60], Spain[51,58], Canada[63,66], the United Kingdom[54,65] and Brazil[47,62] had two papers each (10%). Israel[59] and Netherlands[52] had one paper (5%) each (Table 1).

Table 1 Genes and polymorphisms associated with postpartum depression.
ArticleRef.CountryInstrumentGenesPolymorphisms
CYP2D6 genotypes and depressive symptoms during late pregnancy and postpartumJosefsson et al[53]SwedenEPDSCYP2D6CYP2D6*1 (wild type), CYP2D6*3, CYP2D6*4
Association of tryptophan hydroxylase gene polymorphism with depression, anxiety and comorbid depression and anxiety in a population-based sample of postpartum Taiwanese womenSun et al[60]ChinaSADSTPH1T3840A, A12517C, A20004C, G347T, T27224C
Mood changes after delivery: role of the serotonin transporter geneSanjuan et al[58]SpainEPDS/DIGS5HTT5HTTLPR, STin2 VNTR
The development of peripartum depressive symptoms is associated with gene polymorphisms of MAOA, 5-HTT and COMTDoornbos et al[52]NetherlandEPDSMAOA, 5HTT, COMTMAOA , 5HTTLPR, COMT Val158Met
Population-specific functional variant of the TPH2 gene 2755C>A polymorphism contributes risk association to major depression and anxiety in Chinese peripartum womenLin et al[55]ChinaSADSTPH2T-703G, T-473A, A90G, C2755A, C10662T, G93329A
Genome-wide linkage and follow-up association study of postpartum mood symptomsMahon et al[64]United StatesDIGS417 microsatellite markers in linkage studies / 16.916 SNPs in the 1 and 9 chromosomes for GWAS.
Blood mononuclear cell gene expression signature of postpartum depressionSegman et al[59]IsraelEPDSPBMC gene expression3142 active transcripts set
A serotonin transporter gene polymorphism predicts peripartum depressive symptoms in an at-risk psychiatric cohortBinder et al[49]United StatesSCID/HRSD-175HTT5HTTLPR
Association study of 44 candidate genes with depressive and anxiety symptoms in post-partum womenCostas et al[51]SpainEPDS/DIGS44 genes involved in pathways hipothetically related to the etiology of postpartum mood disorders: HPA axis, effects of stress in the prefrontal cortex, and regulation of sex hormones388 SNPs
An association study between the Val66Met polymorphism of the BDNF gene and postpartum depressionFigueira et al[47]BrazilEPDSBDNFBDNF Val66Met
Postpartum depression symptoms: a case-control study on monoaminergic functional polymorphisms and environmental stressorsComasco et al[50]SwedenEPDSCOMT, MAOA, 5HTTCOMT Val158Met, MAOA uVTNR, 5HTTLPR.
Role of mother’s genes and environment in postpartum depressionMitchell et al[57]United StatesCIDI-SF5HTT5HTTLPR , STin2 VNTR
Postpartum depressive symptoms and the BDNF Val66Met functional polymorphism: effect of season of deliveryComasco et al[50]SwedenEPDSBDNF, 5HTT, PER2BDNF Val66Met, PER2 SNP 10870 (G and A), 5HTTPLR (L and S)
Folic acid supplementation during pregnancy may protect against depression 21 months after pregnancy, an effect modified by MTHFR C677T genotypeLewis et al[54]EnglandEPDSMTHFRC677T
The 5-HTTLPR polymorphism modulates the influence on environmental stressors on peripartum depression symptomsMehta et al[56]GermanyEPDS5HTT5HTTLPR
Genetic variants in the tryptophan hydroxylase 2 gene (TPH2) and depression during and after pregnancyFasching et al[61]GermanyEPDSTPH2rs11178993, rs6582071, rs11178997, rs7955501, rs17110536, rs4760814, rs7300641, rs4760820, rs10879354, rs1487275, rs10879358, rs11615016, rs17110747, rs1872824
Postpartum depression symptoms associated with Val158Met COMT polymorphismAlvim-Soares et al[62]BrazilEPDSCOMTCOMT Val158Met
Interaction between oxytocin genotypes and early experience predicts quality of mothering and postpartum moodMileva-Seitz et al[63]CanadaCES-DOXT, OXTROXT: rs2740210, rs4813627/ OXTR: rs237885
Association of glucocorticoid and type 1 corticotropin-releasing hormone receptors gene variants and risk for depression during pregnancy and post-partumEngineer et al[65]United KingdomEPDSGR, CRHR1GR: BclI, ER22/23EK/CRHR1: s1876828, rs242939, rs242941
Association study of the estrogen receptor gene ESR1 with postpartum depression - a pilot studyPinsonneault et al[66]CanadaMINI, SCID, EPDS and/or MADRSESR1, COMT, TPH2, DRD2, HTR2A, DAT, MAOA, 5HTTESR1: TA repeat, rs2077647, rs1801132, rs3798577, rs988328, rs1884051, rs3020327, rs9340958, rs3020434/HTR2A: rs6314, rs6311/DAT: rs27072, rs6347, In8VNTR/5HTTLPR/MAOA: rs1137070, pVNTR/TPH2: rs7305115 / DRD2: rs2283265 / COMT: rs4680

Of the selected sample, the 5HTT gene was the most studied[48-50,52,56-58,66]. Genes associated with tryptophan metabolism[55,60,61,66] and Catechol-O-methyl transferase (COMT)[48,52,62,66] were the next most researched. Monoamine Oxidase (MAO) gene was studied in three of the articles included in this review[48,52,66], and the Brain-Derived Neurotrophic Factor (BDNF) gene was studied in two articles[47,50]. Two articles analyzed genes that are not commonly evaluated in depression studies: the Methylenetetrahydrofolate Reductase (MTHFR) gene[54] and the CYP2D6 gene[53]. One article was about circadian gene Per 2[50], and one was about the oxytocin gene (OXT) and oxytocin receptor gene (OXTR)[63]. Costas et al[51] assessed 44 genes involved in pathways that are hypothetically related to the etiology of postpartum mood disorders, that is, those included in the HPA axis, in the effects of stress in the prefrontal cortex, and in the regulation of sex hormones. Looking for an association between PPD and the HPA axis, Engineer et al[65] tested the glucocorticoid (GR) and type 1 corticotropin-releasing hormone (CRHR1) receptor genes. Based on the results of Costas’ paper, Pinssoneault et al[66] researched the ESR1 gene both as a principal outcome and under the additive power of other genes: COMT, TPH2, MAOA, 5HTT, dopamine receptor D2 (DRD2), serotonin receptor 2A (HTR2A) and dopamine transporter (DAT). An Israeli study evaluated peripheral blood mononuclear cell (PBMC) gene expression[59]. Finally, an American study analyzed 417 microsatellite markers in linkage studies and chromosomes 1 and 9 by Genome-Wide Association Studies (GWAS)[64].

The most studied polymorphism was the 5-HTTLPR, which was addressed in eight articles[48-50,52,56-58,66]; some of these articles also analyzed other polymorphisms in the 5HTT, such as STin2 VNTR[57,58] and rs140700[51]. The remaining studied polymorphisms were those of TPH 1 and 2[55,60,61,66], COMT[48,52,62,66], MAO[48,52,66], BDNF[47,50], CYP2D6[53], MTHFR[54], Per 2[50], OXT/OXTR genes[63] and GR/CRHR1 genes[65]. Pinssoneault et al[66] adopted a different strategy: in addition to looking for polymorphisms of the estrogen receptor alpha gene (ESR1), they looked for associations with the polymorphisms already cited in this report (MAOA, COMT, TPH2, 5HTTLPR SNPs) besides those of the genes HTR2A, DAT and DRD2[66]. Segman et al[59] used a different approach, analyzing not polymorphisms but 3142 active transcripts, whereas Mahon et al[64] studied 16.916 SNPs through GWAS (Table 1).

DISCUSSION

The data regarding 5HTT gene polymorphisms were variable. Doornbos et al[52] performed the only study that found an independent relationship between PPD and the 5HTTLPR polymorphism whereby subjects with the 5HTTLPR long allele variable developed PPD. Binder et al[49] and Sanjuan et al[58] found a significant association between 5HTTLPR and PPD only at 8 wk postpartum, but the results became nonsignificant in a posteriori analysis, suggesting that the findings were dependent on the evaluation time point. The remaining 5HTTLPR studies also depended on covariates to achieve statistically significant associations with PPD: unfavorable environments[57]; previous psychiatric history, maternity stressors and COMT-Val158Met allele[48]; autumn or winter delivery[50]; stressful life events[56]; and a gene-gene interaction with ESR1 TA repeat[66].

The TPH gene study showed a significant difference in genotype frequency for the T27224C polymorphism between standard groups and those with comorbid depression and anxiety, with risk analysis showing that the C allele conferred a strong protective effect for depression and anxiety. This finding suggests that the TPH1 gene has an important role in the pathogenesis of postpartum mental disorders[60]. Similarly, one of the TPH2 gene studies attested that the C2755A polymorphism could be considered a risk factor for depression. The C2755A polymorphism occurred only in women with peripartum major depression and anxiety disorders (P = 0.043) and exhibited a dominant gene action (P = 0.038) with an estimated disease risk of 1.73. Hence, despite its small sample size, this study suggests that TPH2 represent a population-specific risk factor for peripartum major depression[55]. A recent study supports that conclusion; it found that a haplotype block in the promoter region of TPH2 showed significant associations with depression values during pregnancy and 6-8 mo after pregnancy[61]. This last paper also showed that the SNP rs10879354 had a significant association with depression throughout the postpartum period. A gene-gene interaction with ESR1 gene was not found[66].

Four papers focused on the COMT genes[48,52,62,66], with three of them also focusing on the MAOA gene[48,52,66]. COMT-Val158Met allele polymorphism was one of the main risk factors for PPD[48,52,62], despite not being an independent risk factor[48,52,66]. Previous psychiatric contact, maternity stressors and the time of the evaluation (6 wk or 6 mo postpartum) influenced the relationship[48]. Similarly, the interaction with MAOA - L polymorphism was associated with more pronounced depressive symptoms than when the COMT-Val158 Met allele was considered alone[52]. MAOA rs1137070 and COMT rs4680 polymorphisms were found to have an additive effect plus ESR1 in producing PPD[66].

Figueira et al[47] and Comasco et al[50] did not find any linear correlation between PPD and the BDNF ValMet polymorphism. The correlation showed a trend toward significance among Met allele carriers[47,50]. There was a cumulative and significant effect of the presence of Met allele and autumn/winter delivery[50].

The C677T polymorphism was also studied in a study that focused on the association between MTHFR and PPD. Its results indicated that low folate levels do not appear to be a significant risk factor for peripartum depression but may be a factor for non-gestational-related depression, especially in women with the MTHFR C677T TT genotype[54]. The study on CYP2D6 showed that in a sample that included 45 women reporting symptoms of depression only during pregnancy, 56 women reporting symptoms of depression only after pregnancy and 44 women reporting symptoms of depression both during and after pregnancy, there were no differences in CYP2D6 genotyping and depressive symptoms[53].

Circadian genes did not appear to have a “family“ effect. Despite the correlation between postpartum depressive onset in bipolar disorder and Per3 4/4 homozygotes[37], the circadian gene Per 2 was not related to PPD[50].

As in Major Depression[67], the OXTR gene appears to be related to perinatal depression. Its SNP rs237885 was associated with pre-natal, but not post-natal, depression scores[63]. There was also a correlation between OXT SNPs rs2740210 and rs4813627 and depression score 6 mo after delivery. However, this finding seems to be mediated by mother’s early life quality of care because the association was not retained in the regression model. That is, these appear to be separate effects rather than causally linked outcomes[63].

Costas et al[51] studied 44 genes that are hypothetically linked to depression and, after correcting for multiple tests, did not find a significant relation between any of the SNPs tested and PPD. Nevertheless, a post hoc analysis showed that a combination of three SNPs of the protein kinase C beta gene (PRKCB): rs198183, rs381901 and rs2051684, achieved statistical significance (global P = 0.0001596)[51], turning it into a potential target.

The GR polymorphism BclI, but not the ER22/23EK, showed a positive association with high EPDS score and, therefore, PPD. This correlation was also positive for the minor allele rs242939 SNP of the CRHR1 gene, with the particularity that a relation with prenatal EPDS score could also be found in this case[65]. This result supports Brummelte and Galea’s statement that there are changes in all aspects of the HPA system (ACTH, CRH and cortisol) during pregnancy and the postpartum period. Women who are susceptible to HPA axis dysregulation may be particularly vulnerable for developing stress-related disorders at this time[68].

Two variants in the ESR1 gene, the TA repeat and rs2077647, were statistically associated with EPDS scores and PPD[66], suggesting that estrogen-linked molecular mechanisms could also be involved in PPD genesis. Conversely, gene-gene interactions detected with encoding serotonergic signaling proteins (5HTT and HTR2A) reinforce serotonin’s contribution to PPD.

Segman et al[59], analyzing PBMC gene expression and its 3142 active transcripts, found a signature of 73 active transcripts showing 1.5-fold or higher significant association with PPD. Of those, a subsample of 57 transcripts remained significant in the secondary analysis. Despite the small sample size of the study, both the 73 and 57 differential transcript sets (but not the 3142) correctly distinguished PPD patients from controls. This capability could be used as a prognostic tool, allowing for the initial screening of mothers who are at higher risk for PPD development.

Finally, Mahon et al[64] used linkage and GWAS techniques and found that the chromosomes 1q21.3-q32.1 and 9p24.3p22.3 were associated with postpartum depressive mood. The authors suggest that Hemicentin 1 (HMCN1) and Methyltransferase like 13 (METTL13) genes on chromosome 1 contain polymorphisms that confer vulnerability for PPD, highlighting the notion that specific studies of those genes should be attempted[64]. These results must be watched with caution because bipolar patients with postpartum depressive onset were mingled in the sample. However, a study published last month also confirmed that an HMCN1 polymorphism (rs2891230) is associated with PPD diagnosis in a population without bipolar diagnosis[69].

Despite the substantial number of genes and polymorphisms reviewed here, there are still others that need testing. For instance, Maguire et al[24] noticed a relationship between GABAA receptor plasticity during pregnancy and PPD and proposed an animal model using GABAAR δ subunit deficient mice. Therefore, GABAergic genes may also be potential targets[24]. Another important genetic mechanism involved in Major Depression and not tested in PPD studies is the course of inflammation genes. Because functional allelic variants of the genes for IL-1β and TNF-α increase the risk for depression and are associated with reduced responsiveness to antidepressant therapy[70-72], their influence under PPD would be interesting to measure.

Overall, all of the articles selected had large sample sizes, thus rendering reliable results. Some of the differences found for the same polymorphism may be attributed to different methods used for PPD diagnosis, as observed in Table 1. Another important point to note is that it seems, as in other psychiatric disorders, that genetic influence appears not to be sufficient by itself to cause the disorder. The development of psychiatric disorders is often dependent on epigenetics, and an environmental trigger is often required for these diseases to develop[48,50,57].

Riecher-Rössler et al[73] stated that there is no doubt that sex and gender, with their biological and psychosocial correlates, strongly affect mental health, given the marked difference regarding the prevalence, symptoms, risk factors and outcomes of psychiatric disorders between the sexes. Nevertheless, using PPD as an example, the author shows that such influence is necessary to ensure better clinical care and not to justify the existence of a distinct diagnostic entity. It was possible to demonstrate that the factors used to define “true” or “valid” psychiatric disorders: descriptive validity (the same symptoms), construct validity (the same risk factors) and predictive validity (the same course) are not satisfied in PPD[73]. MD and PPD apparently share the same genetic background because PPD seems to be linked to MAO, COMT, 5HTT and other pathways usually related to MD. In our opinion, this strengthens the possibility that they are the same disorder with a temporal variant[74,75]. However, there are not sufficient published data to determine whether there is a specific etiological factor that is capable of differentiating those two disorders. Further studies are needed to nullify this hypothesis, and for that, other candidate genes must also be researched.

CONCLUSION

This review summarizes the representative findings in the literature regarding the genetics involved in Postpartum Depression.

The main conclusion of this review is that similar genes tend to be studied in Postpartum Depression and that these genes have a similar pattern to those already associated with Major Depression in the literature.

The relationship between molecular genetics and PPD is an extremely current issue. The oldest article selected was from 2004, and the newest was from 2013. However, there is still little research in this area compared with other psychiatric disorders, and it deserves further study due to its importance in terms of public health.

Footnotes

P- Reviewer: Khajehei M, Lonardo F S- Editor: Qi Y L- Editor: A E- Editor: Lu YJ

References
1.  O’hara MW, Swain AM. Rates and risk of postpartum depression-a meta-analysis. Int Rev Psychiatry. 1996;8:37-54.  [PubMed]  [DOI]
2.  Miller LJ. Postpartum depression. JAMA. 2002;287:762-765.  [PubMed]  [DOI]
3.  Gavin NI, Gaynes BN, Lohr KN, Meltzer-Brody S, Gartlehner G, Swinson T. Perinatal depression: a systematic review of prevalence and incidence. Obstet Gynecol. 2005;106:1071-1083.  [PubMed]  [DOI]
4.  Murray L, Cooper P. Effects of postnatal depression on infant development. Arch Dis Child. 1997;77:99-101.  [PubMed]  [DOI]
5.  Tronick E, Reck C. Infants of depressed mothers. Harv Rev Psychiatry. 2009;17:147-156.  [PubMed]  [DOI]
6.  Bagner DM, Pettit JW, Lewinsohn PM, Seeley JR. Effect of maternal depression on child behavior: a sensitive period? J Am Acad Child Adolesc Psychiatry. 2010;49:699-707.  [PubMed]  [DOI]
7.  Beck CT. Maternal depression and child behaviour problems: a meta-analysis. J Adv Nurs. 1999;29:623-629.  [PubMed]  [DOI]
8.  Pinheiro RT, Magalhães PV, Horta BL, Pinheiro KA, da Silva RA, Pinto RH. Is paternal postpartum depression associated with maternal postpartum depression? Population-based study in Brazil. Acta Psychiatr Scand. 2006;113:230-232.  [PubMed]  [DOI]
9.  Paulson JF, Bazemore SD. Prenatal and postpartum depression in fathers and its association with maternal depression: a meta-analysis. JAMA. 2010;303:1961-1969.  [PubMed]  [DOI]
10.  Beck CT. Predictors of postpartum depression: an update. Nurs Res. 2001;50:275-285.  [PubMed]  [DOI]
11.  Cantilino A, Zambaldi CF, Albuquerque T, Paes JA, Montenegro ACP, Sougey EB. Postpartum depression in Recife-Brazil: prevalence and association with bio-socio-demographic factors. J Bras Psiquiatr. 2010;59:1-9.  [PubMed]  [DOI]
12.  Forty L, Jones L, Macgregor S, Caesar S, Cooper C, Hough A, Dean L, Dave S, Farmer A, McGuffin P. Familiality of postpartum depression in unipolar disorder: results of a family study. Am J Psychiatry. 2006;163:1549-1553.  [PubMed]  [DOI]
13.  Treloar SA, Martin NG, Bucholz KK, Madden PA, Heath AC. Genetic influences on post-natal depressive symptoms: findings from an Australian twin sample. Psychol Med. 1999;29:645-654.  [PubMed]  [DOI]
14.  Fink G, Sumner BE, Rosie R, Grace O, Quinn JP. Estrogen control of central neurotransmission: effect on mood, mental state, and memory. Cell Mol Neurobiol. 1996;16:325-344.  [PubMed]  [DOI]
15.  Beck CT. Acculturation: implications for perinatal research. MCN Am J Matern Child Nurs. 2006;31:114-120.  [PubMed]  [DOI]
16.  Phillips PJ, Jeffries B. Gestational diabetes--worth finding and actively treating. Aust Fam Physician. 2006;35:701-703.  [PubMed]  [DOI]
17.  Corwin EJ, Kohen R, Jarrett M, Stafford B. The heritability of postpartum depression. Biol Res Nurs. 2010;12:73-83.  [PubMed]  [DOI]
18.  Meltzer-Brody S. New insights into perinatal depression: pathogenesis and treatment during pregnancy and postpartum. Dialogues Clin Neurosci. 2011;13:89-100.  [PubMed]  [DOI]
19.  Shapiro GD, Fraser WD, Séguin JR. Emerging risk factors for postpartum depression: serotonin transporter genotype and omega-3 fatty acid status. Can J Psychiatry. 2012;57:704-712.  [PubMed]  [DOI]
20.  Xie L, Innis SM. Association of fatty acid desaturase gene polymorphisms with blood lipid essential fatty acids and perinatal depression among Canadian women: a pilot study. J Nutrigenet Nutrigenomics. 2009;2:243-250.  [PubMed]  [DOI]
21.  Pinheiro RT, Coelho FM, Silva RA, Pinheiro KA, Oses JP, Quevedo Lde Á, Souza LD, Jansen K, Zimmermann Peruzatto JM, Manfro GG. Association of a serotonin transporter gene polymorphism (5-HTTLPR) and stressful life events with postpartum depressive symptoms: a population-based study. J Psychosom Obstet Gynaecol. 2013;34:29-33.  [PubMed]  [DOI]
22.  Levant B, Ozias MK, Davis PF, Winter M, Russell KL, Carlson SE, Reed GA, McCarson KE. Decreased brain docosahexaenoic acid content produces neurobiological effects associated with depression: Interactions with reproductive status in female rats. Psychoneuroendocrinology. 2008;33:1279-1292.  [PubMed]  [DOI]
23.  Suda S, Segi-Nishida E, Newton SS, Duman RS. A postpartum model in rat: behavioral and gene expression changes induced by ovarian steroid deprivation. Biol Psychiatry. 2008;64:311-319.  [PubMed]  [DOI]
24.  Maguire J, Mody I. GABA(A)R plasticity during pregnancy: relevance to postpartum depression. Neuron. 2008;59:207-213.  [PubMed]  [DOI]
25.  Maniam J, Morris MJ. Long-term postpartum anxiety and depression-like behavior in mother rats subjected to maternal separation are ameliorated by palatable high fat diet. Behav Brain Res. 2010;208:72-79.  [PubMed]  [DOI]
26.  Quilter CR, Sargent CA, Bauer J, Bagga MR, Reiter CP, Hutchinson EL, Southwood OI, Evans G, Mileham A, Griffin DK. An association and haplotype analysis of porcine maternal infanticide: a model for human puerperal psychosis? Am J Med Genet B Neuropsychiatr Genet. 2012;159B:908-927.  [PubMed]  [DOI]
27.  Sharma V, Persad E. Effect of pregnancy on three patients with bipolar disorder. Ann Clin Psychiatry. 1995;7:39-42.  [PubMed]  [DOI]
28.  Kunugi H, Nanko S, Kazamatsuri H. A case of bipolar disorder with balanced chromosomal translocation. Biol Psychiatry. 1995;38:116-118.  [PubMed]  [DOI]
29.  McCandless F, Jones I, Harper K, Craddock N. Intrafamilial association of pericentric inversion of chromosome 9, inv (9)(p11-q21), and rapid cycling bipolar disorder. Psychiatr Genet. 1998;8:259-262.  [PubMed]  [DOI]
30.  Jones I, Middle F, McCandless F, Coyle N, Robertson E, Brockington I, Lendon C, Craddock N. Molecular genetic studies of bipolar disorder and puerperal psychosis at two polymorphisms in the estrogen receptor alpha gene (ESR 1). Am J Med Genet. 2000;96:850-853.  [PubMed]  [DOI]
31.  Jones I, Craddock N. Familiality of the puerperal trigger in bipolar disorder: results of a family study. Am J Psychiatry. 2001;158:913-917.  [PubMed]  [DOI]
32.  Robertson E, Jones I, Haque S, Holder R, Craddock N. Risk of puerperal and non-puerperal recurrence of illness following bipolar affective puerperal (post-partum) psychosis. Br J Psychiatry. 2005;186:258-259.  [PubMed]  [DOI]
33.  Jones I, Craddock N. Searching for the puerperal trigger: molecular genetic studies of bipolar affective puerperal psychosis. Psychopharmacol Bull. 2007;40:115-128.  [PubMed]  [DOI]
34.  Babu GN, Subbakrishna DK, Chandra PS. Prevalence and correlates of suicidality among Indian women with post-partum psychosis in an inpatient setting. Aust N Z J Psychiatry. 2008;42:976-980.  [PubMed]  [DOI]
35.  Payne JL, MacKinnon DF, Mondimore FM, McInnis MG, Schweizer B, Zamoiski RB, McMahon FJ, Nurnberger JI, Rice JP, Scheftner W. Familial aggregation of postpartum mood symptoms in bipolar disorder pedigrees. Bipolar Disord. 2008;10:38-44.  [PubMed]  [DOI]
36.  Spinelli MG. Postpartum psychosis: detection of risk and management. Am J Psychiatry. 2009;166:405-408.  [PubMed]  [DOI]
37.  Dallaspezia S, Lorenzi C, Pirovano A, Colombo C, Smeraldi E, Benedetti F. Circadian clock gene Per3 variants influence the postpartum onset of bipolar disorder. Eur Psychiatry. 2011;26:138-140.  [PubMed]  [DOI]
38.  Weigelt K, Bergink V, Burgerhout KM, Pescatori M, Wijkhuijs A, Drexhage HA. Down-regulation of inflammation-protective microRNAs 146a and 212 in monocytes of patients with postpartum psychosis. Brain Behav Immun. 2013;29:147-155.  [PubMed]  [DOI]
39.  Evans J, Xu K, Heron J, Enoch MA, Araya R, Lewis G, Timpson N, Davies S, Nutt D, Goldman D. Emotional symptoms in children: The effect of maternal depression, life events, and COMT genotype. Am J Med Genet B Neuropsychiatr Genet. 2009;150B:209-218.  [PubMed]  [DOI]
40.  Apter-Levy Y, Feldman M, Vakart A, Ebstein RP, Feldman R. Impact of maternal depression across the first 6 years of life on the child’s mental health, social engagement, and empathy: The moderating role of oxytocin. Am J Psychiatry. 2013;170:1161-1168.  [PubMed]  [DOI]
41.  Berle JØ, Steen VM, Aamo TO, Breilid H, Zahlsen K, Spigset O. Breastfeeding during maternal antidepressant treatment with serotonin reuptake inhibitors: infant exposure, clinical symptoms, and cytochrome p450 genotypes. J Clin Psychiatry. 2004;65:1228-1234.  [PubMed]  [DOI]
42.  Tammentie T, Tarkka MT, Astedt-Kurki P, Paavilainen E. Sociodemographic factors of families related to postnatal depressive symptoms of mothers. Int J Nurs Pract. 2002;8:240-246.  [PubMed]  [DOI]
43.  Murphy-Eberenz K, Zandi PP, March D, Crowe RR, Scheftner WA, Alexander M, McInnis MG, Coryell W, Adams P, DePaulo JR. Is perinatal depression familial? J Affect Disord. 2006;90:49-55.  [PubMed]  [DOI]
44.  Rambelli C, Montagnani MS, Oppo A, Banti S, Borri C, Cortopassi C, Ramacciotti D, Camilleri V, Mula M, Cassano GB. Panic disorder as a risk factor for post-partum depression: Results from the Perinatal Depression-Research & amp; Screening Unit (PND-ReScU) study. J Affect Disord. 2010;122:139-143.  [PubMed]  [DOI]
45.  Savarimuthu RJ, Ezhilarasu P, Charles H, Antonisamy B, Kurian S, Jacob KS. Post-partum depression in the community: a qualitative study from rural South India. Int J Soc Psychiatry. 2010;56:94-102.  [PubMed]  [DOI]
46.  Walker P. Postpartum depression: is it mood disorder or medical condition? J Genet Couns. 2012;21:239-240.  [PubMed]  [DOI]
47.  Figueira P, Malloy-Diniz L, Campos SB, Miranda DM, Romano-Silva MA, De Marco L, Neves FS, Correa H. An association study between the Val66Met polymorphism of the BDNF gene and postpartum depression. Arch Womens Ment Health. 2010;13:285-289.  [PubMed]  [DOI]
48.  Comasco E, Sylvén SM, Papadopoulos FC, Sundström-Poromaa I, Oreland L, Skalkidou A. Postpartum depression symptoms: a case-control study on monoaminergic functional polymorphisms and environmental stressors. Psychiatr Genet. 2011;21:19-28.  [PubMed]  [DOI]
49.  Binder EB, Newport DJ, Zach EB, Smith AK, Deveau TC, Altshuler LL, Cohen LS, Stowe ZN, Cubells JF. A serotonin transporter gene polymorphism predicts peripartum depressive symptoms in an at-risk psychiatric cohort. J Psychiatr Res. 2010;44:640-646.  [PubMed]  [DOI]
50.  Comasco E, Sylvén SM, Papadopoulos FC, Oreland L, Sundström-Poromaa I, Skalkidou A. Postpartum depressive symptoms and the BDNF Val66Met functional polymorphism: effect of season of delivery. Arch Womens Ment Health. 2011;14:453-463.  [PubMed]  [DOI]
51.  Costas J, Gratacòs M, Escaramís G, Martín-Santos R, de Diego Y, Baca-García E, Canellas F, Estivill X, Guillamat R, Guitart M. Association study of 44 candidate genes with depressive and anxiety symptoms in post-partum women. J Psychiatr Res. 2010;44:717-724.  [PubMed]  [DOI]
52.  Doornbos B, Dijck-Brouwer DA, Kema IP, Tanke MA, van Goor SA, Muskiet FA, Korf J. The development of peripartum depressive symptoms is associated with gene polymorphisms of MAOA, 5-HTT and COMT. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33:1250-1254.  [PubMed]  [DOI]
53.  Josefsson A, Sydsjö G, Berg G, Dahl ML, Wadelius M, Nordin C. CYP2D6 genotypes and depressive symptoms during late pregnancy and postpartum. Nord J Psychiatry. 2004;58:61-64.  [PubMed]  [DOI]
54.  Lewis SJ, Araya R, Leary S, Smith GD, Ness A. Folic acid supplementation during pregnancy may protect against depression 21 months after pregnancy, an effect modified by MTHFR C677T genotype. Eur J Clin Nutr. 2012;66:97-103.  [PubMed]  [DOI]
55.  Lin YM, Ko HC, Chang FM, Yeh TL, Sun HS. Population-specific functional variant of the TPH2 gene 2755C& gt; A polymorphism contributes risk association to major depression and anxiety in Chinese peripartum women. Arch Womens Ment Health. 2009;12:401-408.  [PubMed]  [DOI]
56.  Mehta D, Quast C, Fasching PA, Seifert A, Voigt F, Beckmann MW, Faschingbauer F, Burger P, Ekici AB, Kornhuber J. The 5-HTTLPR polymorphism modulates the influence on environmental stressors on peripartum depression symptoms. J Affect Disord. 2012;136:1192-1197.  [PubMed]  [DOI]
57.  Mitchell C, Notterman D, Brooks-Gunn J, Hobcraft J, Garfinkel I, Jaeger K, Kotenko I, McLanahan S. Role of mother’s genes and environment in postpartum depression. Proc Natl Acad Sci USA. 2011;108:8189-8193.  [PubMed]  [DOI]
58.  Sanjuan J, Martin-Santos R, Garcia-Esteve L, Carot JM, Guillamat R, Gutierrez-Zotes A, Gornemann I, Canellas F, Baca-Garcia E, Jover M. Mood changes after delivery: role of the serotonin transporter gene. Br J Psychiatry. 2008;193:383-388.  [PubMed]  [DOI]
59.  Segman RH, Goltser-Dubner T, Weiner I, Canetti L, Galili-Weisstub E, Milwidsky A, Pablov V, Friedman N, Hochner-Celnikier D. Blood mononuclear cell gene expression signature of postpartum depression. Mol Psychiatry. 2010;15:93-100, 2.  [PubMed]  [DOI]
60.  Sun HS, Tsai HW, Ko HC, Chang FM, Yeh TL. Association of tryptophan hydroxylase gene polymorphism with depression, anxiety and comorbid depression and anxiety in a population-based sample of postpartum Taiwanese women. Genes Brain Behav. 2004;3:328-336.  [PubMed]  [DOI]
61.  Fasching PA, Faschingbauer F, Goecke TW, Engel A, Häberle L, Seifert A, Voigt F, Amann M, Rebhan D, Burger P. Genetic variants in the tryptophan hydroxylase 2 gene (TPH2) and depression during and after pregnancy. J Psychiatr Res. 2012;46:1109-1117.  [PubMed]  [DOI]
62.  Alvim-Soares A, Miranda D, Campos SB, Figueira P, Romano-Silva MA, Correa H. Postpartum depression symptoms associated with Val158Met COMT polymorphism. Arch Womens Ment Health. 2013;16:339-340.  [PubMed]  [DOI]
63.  Mileva-Seitz V, Steiner M, Atkinson L, Meaney MJ, Levitan R, Kennedy JL, Sokolowski MB, Fleming AS. Interaction between oxytocin genotypes and early experience predicts quality of mothering and postpartum mood. PLoS One. 2013;8:e61443.  [PubMed]  [DOI]
64.  Mahon PB, Payne JL, MacKinnon DF, Mondimore FM, Goes FS, Schweizer B, Jancic D, Coryell WH, Holmans PA, Shi J. Genome-wide linkage and follow-up association study of postpartum mood symptoms. Am J Psychiatry. 2009;166:1229-1237.  [PubMed]  [DOI]
65.  Engineer N, Darwin L, Nishigandh D, Ngianga-Bakwin K, Smith SC, Grammatopoulos DK. Association of glucocorticoid and type 1 corticotropin-releasing hormone receptors gene variants and risk for depression during pregnancy and post-partum. J Psychiatr Res. 2013;47:1166-1173.  [PubMed]  [DOI]
66.  Pinsonneault JK, Sullivan D, Sadee W, Soares CN, Hampson E, Steiner M. Association study of the estrogen receptor gene ESR1 with postpartum depression--a pilot study. Arch Womens Ment Health. 2013;16:499-509.  [PubMed]  [DOI]
67.  Saphire-Bernstein S, Way BM, Kim HS, Sherman DK, Taylor SE. Oxytocin receptor gene (OXTR) is related to psychological resources. Proc Natl Acad Sci USA. 2011;108:15118-15122.  [PubMed]  [DOI]
68.  Brummelte S, Galea LA. Depression during pregnancy and postpartum: contribution of stress and ovarian hormones. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34:766-776.  [PubMed]  [DOI]
69.  Alvim-Soares AM, Miranda DM, Campos SB, Figueira P, Correa H, Romano-Silva MA. HMNC1 gene polymorphism associated with postpartum depression. Rev Bras Psiquiatr. 2014;36:96-97.  [PubMed]  [DOI]
70.  Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006;27:24-31.  [PubMed]  [DOI]
71.  Yu YW, Chen TJ, Hong CJ, Chen HM, Tsai SJ. Association study of the interleukin-1 beta (C-511T) genetic polymorphism with major depressive disorder, associated symptomatology, and antidepressant response. Neuropsychopharmacology. 2003;28:1182-1185.  [PubMed]  [DOI]
72.  Jun TY, Pae CU, Hoon-Han JH, Bahk WM, Kim KS, Serretti A. Possible association between -G308A tumour necrosis factor-alpha gene polymorphism and major depressive disorder in the Korean population. Psychiatr Genet. 2003;13:179-181.  [PubMed]  [DOI]
73.  Riecher-Rössler A. Prospects for the classification of mental disorders in women. Eur Psychiatry. 2010;25:189-196.  [PubMed]  [DOI]
74.  Brockington I. Postpartum psychiatric disorders. Lancet. 2004;363:303-310.  [PubMed]  [DOI]
75.  Riecher-Rössler A, Rohde A. Diagnostic Classification of Perinatal Mood Disorders. In: Riecher-Rössler A, Steiner M (eds): Perinatal Stress, Mood and Anxiety Disorders: From Bench to Bedside. Bibl Psychiatr Basel Karger. 2005;173:6-27.  [PubMed]  [DOI]