IMR Press / FBL / Volume 25 / Issue 8 / DOI: 10.2741/4863
Open Access Review
Psychiatric disorders and changes in immune response in labor and postpartum
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1 Department of Psychiatry, Centre of Postgraduate Medical Education, Warsaw, Poland
2 2nd Department of Obstetrics and Gynecology, Centre of Postgraduate Medical Education, Warsaw, Poland
Front. Biosci. (Landmark Ed) 2020, 25(8), 1433–1461;
Published: 1 March 2020

Women may present with psychiatric disorders during pregnancy, normal labor, following delivery by caesarean section, or in the postpartum period. The accumulating evidence suggests that these disorders may be due to changes in immune responses. During pregnancy complications such as the prolongation of cervical ripening or descent, placental abruption, premature labor, and preeclampsia increase the risk of postpartum psychiatric disorders. Women may exhibit depression and postpartum psychosis following either normal birth or caesarean section. Since psychiatric disorders like schizophrenia, major depression, and bipolar disorder are associated with both alterations in the immune response and changes in immune cell subpopulations, in this study we have chosen to examine whether the psychiatric disorders in women during labor or postpartum also lead to aberrant immune responses.

: Immune system
Peripartum depression
Perinatal mental health
Postpartum psychosis

There is a growing interest in the subject of postpartum psychiatric disorders due not only to their wide social repercussions but also to their potentially detrimental effect on the child’s development and the functioning of the family. Up to 85% of women suffer from mood disturbances during the postpartum period; however, these disturbances are usually self-limiting and do not require medication (1). The singularity of this period is acknowledged by the fact that the ICD-10 classification sets apart psychiatric disorders that manifest postpartum. However, in both the ICD-10 and DSM-V classifications, the time period for diagnosis has been narrowed down to several weeks after labor (4 in the DSM-V and 6 in the ICD-10), even though it is known that both postpartum psychosis and postpartum depression may take as long as 6 months to manifest. Despite the increased interest, the etiology of these disorders remains elusive. The prevailing notion that hormonal changes play a major role in the pathophysiology of postpartum psychiatric disorders has not been entirely disproven. Furthermore, evidence suggests that the growing number of elective caesarean sections is related to the increased prevalence of postpartum depression (2-3).

On account of this evidence, a search for additional factors that might be involved in the development of postpartum psychiatric disorders has been initiated. Studies have looked into the potential role of the immune system in the etiology and pathophysiology of such psychiatric disorders as schizophrenia, mood disorders, anxiety, dementia, pervasive developmental disorder, and suicidal ideation. There are also preliminary reports confirming the usefulness of adding non-steroidal anti-inflammatory drugs (NSAIDs) to the therapy for schizophrenia (4), depression (5), bipolar disorder (6), and obsessive-compulsive disorder (7).

Pregnancy and birth are characterized by the exceptional phenomenon of maternal immunological tolerance towards fetal antigens. The precise regulation of the interaction between maternal and fetal immune systems is essential for a pregnancy to develop undisturbed (8). Over time the regulatory process becomes more complex as the growing fetus begins to influence the maternal immune response. Consequently, women are especially vulnerable to complications caused by a dysfunction of this delicate balance when they are close to labor. Shah et al. have concluded that during the spontaneous beginning of labor the maternal immune system is transforming into a more reactive phenotype (9). Furthermore, it has been observed that as the fetus develops, fetal macrophages also begin to play a role in the regulation of the maternal immune response (10). This complex process may be disturbed on many levels, especially by the instrumentalization of the labor or as a secondary effect of an abnormal immune response associated with pregnancy complications such as preterm birth, preeclampsia, or premature rupture of membranes (PROM) (11-16).

On the one hand, it has been confirmed that women with psychiatric diseases like schizophrenia and depression have an increased risk of pregnancy-related complications caused by the dysregulation of this delicate immunological balance (schizophrenia: 17-18; depression: 19). On the other hand, patients who develop complications of pregnancy and delivery with a confirmed underlying immunological component (for example, placental abruption, preeclampsia, premature rupture of membranes (PROM), preterm birth, and elective caesarean section) have an increased risk of postpartum depression, postpartum psychosis, anxiety, and post-traumatic stress disorder (PTSD) (20-23).

There is a growing interest in the role of immune system disturbances in psychiatric disorders. It has been postulated that some, if not all, psychiatric disorders may be triggered by an underlying immune dysregulation. Accordingly, we formulated the hypothesis that maternal postpartum psychiatric disorders are caused in part by disturbances in the maternal immune response during pregnancy that manifest clinically in complications of pregnancy and labor. This study aims to review the current literature on the relationship between the maternal immune response during labor and postpartum psychiatric disorders and to present prospects for future research.


Immunopsychiatry is developing as a field even as the evidence of immune system dysregulation in such psychiatric disorders as schizophrenia, bipolar disorder, and major depressive disorder accumulates. Studies examining multiple factors, from a genetic predisposition found in the immune response related genes to changes in the levels of immune cells and cytokines as well as in the percentages of immune cell subtypes, may shed more light on the neurobiological basis of these psychiatric disorders.

For example, polymorphisms in the MHC locus on chromosome 6, among which was the gene variant C4 (a coding protein of the complement system) (24), were found in patients suffering from schizophrenia (25). It has also been reported that the complement proteins Cq, C3, and C4 play an important role in brain development during the period of synaptic pruning. These proteins mark abnormal synapses, and this process later leads to synaptic elimination by phagocytic microglia cells (26). A decrease in the number of synapses was observed in patients suffering from schizophrenia (24). Furthermore, there is a report suggesting a link between T-cell deficits in 22q11.2DS deficiency, and particularly in Th17, and the presence of positive psychotic symptoms. This genetic defect has even been proposed as a model for the development of psychosis (27).

Changes in immune system activity have been observed in patients with schizophrenia. Moreover, changes in the peripheral blood and cerebro-spinal fluid (CSF) have been found in patients as early as the time of the first episode of psychosis. Autopsies of the brain and brain imaging with positron emission tomography (PET) with peripheral benzodiazepine receptor ligand have confirmed the role of neuroinflammation and the activation of microglia in patients with schizophrenia (4, 28-30). Schizophrenia also constitutes a risk factor for a number of autoimmune diseases including diabetes mellitus type 1, multiple sclerosis, systemic lupus erythematosus, celiac disease, Sjörgen’s syndrome, thyrotoxicosis, and acquired autoimmune hemolytic anemia (4, 28, 31-34). A recent analysis has led to the confirmation of shared genetic risk factors, consistent with epidemiological data, between schizophrenia and inflammatory bowel disease, Crohn’s disease, ulcerative colitis, primary biliary cirrhosis, psoriasis, and systemic lupus erythematosus (35).

As the MHC complex’s role in the proper functioning of T cells CD3+ is so essential, it would seem logical to search for alterations in this cell population (36-40). A meta-analysis of 16 studies on immune system dysregulation in schizophrenia published in 2013 reported a significant increase in the percentages of CD4+ and CD56+ cells, total lymphocyte levels, total CD3+ cells, and CD4+ cells, as well as an increase in the CD4/CD8 ratio. Furthermore, the percentage of CD3+ cells in patients at the first onset of psychosis was significantly decreased. Antipsychotic treatment led to a decrease in the CD4/CD8 ratio along with an increase in the total number of CD56+ cells (38). Two extensive meta-analyses of the extent of cytokine alterations in patients with schizophrenia were also published (41-42).

The role of T regulatory cells (Tregs) in schizophrenia seems particularly important. In several studies, an increase in the percentage of Treg cells as well as in sIl-2R was reported in patients with schizophrenia. Furthermore, this increase correlated with the percentage of CD3+CD25+ cells and lymphocytes with Il-4. An increased Treg cell level upon admission of the patient correlated with a better Global Assessment of Functioning score upon discharge (GAF). It is thus believed that Treg cells have the ability to suppress excessive activity of the immune system in the central nervous system (CNS) (36, 39).

In cases of depression, single nucleotide polymorphisms (SNP) PSMB4 and TBX21 (related to the functioning of T lymphocytes) and STAT3 (responsible for signal transduction) have been described (43-44). Furthermore, certain SNP (CD3E, PRKCH, PSMD9, and STAT3 related to the function of T lymphocytes) were linked with a better response to treatment. Other polymorphisms in genes linked with Il-6 and genes participating in prostaglandin synthesis were found in certain circumstances to be connected with depression (45-47).

Furthermore, an increase in TNF, Il-1, and Il-6 CRP in the blood serum was reported in cases of major depressive disorder, especially those that were treatment-resistant (48-52). The administration of cytokines, including INF-alfa and their induction with either lipopolysaccharide or the typhoid fever vaccination, led to symptoms similar to those of depression. On the one hand, the administration of drugs that inhibit cytokines may lead to better control of the symptoms and a decrease in the inflammatory response. On the other hand, however, it has been confirmed that antidepressants can decrease the in vitro production of pro-inflammatory cytokines. Furthermore, it has been conjectured that these cytokines may influence the metabolism of such neurotransmitters as serotonin, noradrenalin, and dopamine. These cytokines can also influence the daily excretion curve of cortisol and increase its evening level (52).

Patients with major depressive disorders were reported to have decreased total levels of lymphocytes, including T lymphocytes and Tregs. The Treg level correlated with the intensity of the patient’s symptoms (53-56). CD4+ cells have an increased tendency towards spontaneous apoptosis and a higher expression of FAS receptor (CD95). Furthermore, a correlation has been reported between depression in patients with HIV, liver cirrhosis, multiple sclerosis, and an increase in CD8+ cells. Higher levels of CD3+CD8+ at the beginning of treatment are related to a poorer response to treatment (56).

Patients suffering from major depressive disorder were reported to have lower levels of T regulatory lymphocytes and an increased INF-gamma/TGF-beta ratio compared to the control group. Additionally, in such cases there was a negative correlation of serum TGF-beta with depressive symptoms (52). It has been observed that even though Treg levels increase in response to treatment, they are not a predictive factor of treatment effectiveness. In those patients who responded well to treatment, an increase in monocyte percentage and a decrease in total lymphocyte levels were observed (56). Patients who were resistant to treatment prior to its initiation had an increased level of cytotoxic CD8+ cells and decreased levels of NK cells compared to those patients who responded well to treatment. Consequently, it is believed that antidepressants may directly influence Treg cell activity. It has been reported that Tregs have both adrenergic (57) and serotoninergic receptors on their surface (58). There are also indications that Tregs may constitute a potential target for stimulation in patients with major depressive disorder (59).

In cases of bipolar disorder, mutations of toll-like receptor (TLR) genes have been described. It is worth mentioning that a genetic overlap has been observed between schizophrenia, bipolar disorder, and major depressive disorder, suggesting that these disorders share at least some pathophysiological mechanisms (35). Moreover, there is an epidemiological correlation between bipolar disorder and many inflammatory diseases, such as atony, cardiovascular diseases, osteoporosis, and diabetes mellitus. Like patients with schizophrenia, those with bipolar disorder are twice as likely as the rest of the population to develop metabolic syndrome. It is speculated that this risk is not a side effect of the drugs, but a part of the disorder symptomatology (60-61). Comorbidity of bipolar disorder with autoimmune diseases, including pemphigus (62), Crohn’s disease (34), and thyroid autoimmunity (63) has been reported. Furthermore, in cases of bipolar disorder, an increase in pro-inflammatory cytokines (Il-4, TNF-alfa, aIL-2R, Il-1b, Il-6, STNFR1, and CRP) in the blood serum as well as an increase in Treg-activated T lymphocytes and pro-inflammatory monocyte cytokine levels were observed (64-68).

The dysregulation of the immune system in patients with other psychiatric disorders, such as post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD), has been reported. Half of patients with PTSD also suffer from other psychiatric disorders, particularly anxiety or affective disorders. Studies conducted on twins, confirmed that there is a genetic component to the development of these disorders. Furthermore, patients with PTSD were found to have a significant drop (48%) in the percentage of Treg cells (69).

In patients suffering from OCD, comorbidity with some autoimmunological diseases, including systemic lupus erythematosus and thyroid diseases, has been reported. This disorder may develop in children following infection with group A Streptococci (Pediatric Acute-onset Neuropsychiatric Syndrome -PANS). In patients with OCD, the presence of anti-basal ganglia antibodies (ABGA), a decrease in both NK cell and lymphocyte CD4+ activity, an increase in the number of CD8+ cells, a decrease in levels of Il-1 β, and an increase in TNF-alfa and Il-6 were all reported (70). However, these observed changes normalized in the wake of successful therapy with selective serotonin-reuptake inhibitors (SSRIs). In patients with Tourette syndrome, a decrease in Tregs was observed compared to the control group and symptom intensity was positively correlated with the levels of these cells (71). However, as studies on this subject have been rare, it is too early to make any definitive conclusions.

Most current studies have been conducted on small groups of patients and have neglected to analyze all of the immune system components, focusing instead mainly on cytokines. Only a few studies on T lymphocyte subpopulations, particularly Tregs, have been conducted. Tregs are important because of their regulatory function and have proved useful in other fields of medicine, especially oncology, as a target for immunotherapy (72). Moreover, few studies specifically analyze the correlation between immune cell subsets and cytokines in the blood and the CSF of patients with psychiatric disorders.

The present study does not aspire to be a comprehensive review of the subject of immunopsychiatry, especially since a number of fine works have now been published in that field (for example, 28, 38, 45, 52, 59, 61, 73, 74). The study aims instead to present immunopsychiatry as a dynamically expanding field worthy of further investigation.


The most commonly reported psychiatric disorders to occur during the postpartum period are postpartum depression, depressive or manic episode as a manifestation of bipolar disorder, and postpartum psychosis. There is also an increasing amount of evidence of other disorders that present in the postpartum period, for instance, obsessive-compulsive disorder (OCD), social anxiety, and postpartum childbirth-related post-traumatic stress disorder (CB-PTSD). However, these disorders in the postpartum period have not yet been studied in depth and are frequently misdiagnosed (75).

The risk factors for psychiatric disorders during the postpartum period are unclear. One of the first studies on this topic was conducted by Kendell et al. The authors reported that the risk of hospitalization due to psychiatric disorders was considerably higher in primiparous women (76), and this observation was confirmed by subsequent studies. Additionally, risk factors such as in vitro fertilization and twin pregnancy were reported (77-79). Finally, there seems to be a familial predisposition towards postpartum psychiatric disorders, though the genes responsible for the increased risk have yet to be identified (19, 23).

One of the most predictive factors of postpartum psychiatric disorders is previous psychiatric morbidity. Many of those patients suffering from schizophrenia, bipolar disorder, and major depression experience a relapse or an exacerbation of symptoms after giving birth. It is believed that postpartum psychosis and depression are to some extent manifestations of a bipolar disorder. It has been reported that 74% of patients with bipolar disorder and a family history of postpartum psychosis develop postpartum psychosis; however, for those patients with bipolar disorder but no family history of postpartum psychosis, the risk was considerably lower (80). Women with psychotic disorders were found to be at a higher risk for complications including induced labor, hemorrhage, and premature rupture of membranes. They were also at a greater risk for fetal complications like stillbirth, fetal abnormalities, poor fetal growth, and fetal distress (81-82). Moreover, it has been reported that women with schizophrenia and an immunological background that includes preeclampsia, uterine atony, Rh disease, bleeding, hypertension, or diabetes are at a greater risk of developing complications during pregnancy and birth. Such patients often have an increased prevalence of thromboembolic disease (17). Furthermore, in women with schizophrenia, complications such as asphyxia, low birth weight, and higher new born mortality have been reported (18).

On the other hand, some studies have suggested a correlation between the complications of pregnancy and birth and the risk of postpartum psychiatric disorders. One such complication that has received special attention due to its immunological background is preeclampsia. A comparison between preeclampsia and postpartum psychosis reveals many clinical similarities: both conditions have primiparity as a risk factor, and their development after the first pregnancy increases the risk in subsequent pregnancies (23). The first study reporting an increased prevalence of postpartum depression in patients who suffered from preeclampsia was published by Kurki et al. in 2000 (83). Subsequent studies confirmed an increased prevalence of postpartum depression following a hypertensive disorder of pregnancy (HDP) (84-89) and first-onset postpartum episodes, including both postpartum depression and postpartum psychosis (23, 90).

A systematic review of this topic begun in 2013 found an association between preeclampsia, HELLP syndrome (consisting of hemolysis, elevated liver enzymes, and a low platelet count), and postpartum depression. However, in patients with anxiety and PTSD, the results of the review were either conflicting or insignificant (21). A more recent review of literature concluded that hypertensive disorder of pregnancy (HDP) is correlated with an increased prevalence of depression (7-44% of patients with HDP) and PTSD (5-43%).The correlation was proportional to the severity of the HDP. Although higher anxiety scores were reported in those patients with preeclampsia, the associations were not significant (22). Furthermore, comorbidity between postpartum depression and CB-PTS was observed (91).

Preterm birth and placental abruption have also been strongly linked to the increased risk of postpartum depression, postpartum psychosis, anxiety, and PTSD (20, 22, 81, 87). Not only is preterm birth a risk factor for postpartum depression, but patients with depression are also at increased risk of preterm birth (19). Moreover, an increased prevalence of postpartum depression was observed following uterine atony, induced labor, prolongation of cervical ripening, protracted descent, intrauterine growth restriction, low birthweight, amniotic fluid anomaly, and suspicion of fetal distress (85-88). The evidence linking postpartum depression with placenta previa (86-87) was conflicting. It was also observed that a statistically significantly higher number of postpartum psychosis patients had experienced a protracted descent (82).

It might be conjectured that maternal depressive symptoms represent a psychological inadaptation to the impact of pregnancy complications on the child’s health. Interestingly, Blom et al. failed to find any association between the newborn’s Apgar score and the mother’s postpartum depression, suggesting that maternal psychiatric disorders are not necessarily triggered by the child’s medical complications. They further reported that the risk of postpartum depression increased with the number of complications (85). Dekel et al. also observed that many women experienced postpartum depression and CB-PTSD regardless of the status of their child’s health. However, there are still only a limited number of studies on this subject (21-22).

In 1987, Kendell et al. had already observed an increased prevalence of psychiatric disorders in those patients who underwent caesarean section compared to those who experienced vaginal delivery (76). Since then the subject has received considerable attention (for example, see 81, 85, 87-88), but the results of the studies were often inconsistent; in some cases, undergoing a caesarean section was even found to have a protective effect (92). In 2017, a meta-analysis including 532,630 women was published that reported an increased prevalence of postpartum depression following caesarean section; however, there were considerable differences between the studies included in the meta-analysis. Xu et al. reported an increased risk of postpartum depression in patients with unplanned and emergency caesarean section, but not in patients with elective caesarean section (93). However, a study by Dekel et al. found that women who underwent either a caesarean section (whether planned or unplanned) or instrumental vaginal delivery had a greater prevalence of somatization, obsessive-compulsive disorder, depression, anxiety, and hostility postpartum compared to those women who had experienced a vaginal or natural delivery. Unplanned caesarean section was also correlated with a greater risk of PTSD (1).

This subject is worth investigating in the context of immunopsychiatry as, to our knowledge, none of the studies so far conducted in this field have considered the progression of the birth process and cervix dilation. Most elective caesarean sections are performed prior to the beginning of spontaneous birth; this is not a rule, however, as emergency indications that warrant performing a caesarean section may arise either before or after the spontaneous beginning of birth, which is defined as the beginning of cervix ripening and contractions.

The inclusion of cervix ripening in such an analysis is crucial to understanding the immunology of pregnancy. Cervix ripening is associated with the alteration of the maternal immune system tolerance towards fetal antigens. Winkler et al. have reported that maternal immune system activation is essential for the initiation of cervix ripening. Maternal immune response increases until dilation reaches 2 cm. The main factor responsible for this process is the concentration of Il-8 in the cervix, which derives mostly from maternal immune cells. This is followed by several mechanisms suppressing the maternal immune response until full dilation of the cervix is achieved. Prior to that matrix, metalloproteinases were secreted from immune cells, mediating further ripening of the cervix (94-96).

Although the correlation between psychiatric disorders and complications of pregnancy and birth has not been thoroughly studied, the research in this area is promising and suggests a causal relation between immune dysregulation and postpartum psychiatric disorders as well as birth and pregnancy complications. Considering cervix dilation when analyzing the prevalence of psychiatric disorders in women according to the type of delivery they experienced may shed more light on this subject and explain the discrepancies found in the previous studies. Table 1 summarizes the association between psychiatric disorders and pregnancy complications.

Table 1 The association of pregnancy and labor complications with psychiatric disorders
Postpartum depression Postpartum psychosis Anxiety Post-traumatic stress disorder PTSD References
• Caesarean section,• HDP,• HELLP syndrome,• Preterm birth,• Placental abruption,• Uterine atony,• Induction labor,• Prolongation of cervical ripening,• Protraction of descent,• Intrauterine growth restriction,• Low birthweight,• Amniotic fluid anomaly,• Suspicion of fetal distress • HDP,• Preterm birth• Placental abruption Preterm birth Placenta abruption •HDP,• Preterm birth• Placenta abruption 20-23, 81, 83-90
HDP - hypertensive disorder of pregnancy; HELLP - hemolysis, elevated liver enzymes, and low platelet count

Psychiatric disorders that arise during pregnancy and the postpartum period are especially interesting due to the phenomenon of fetal evasion of maternal immune system detection and to the interaction between the immune system and the hormonal changes associated with pregnancy. However, the mechanisms leading to an increased risk of psychiatric disorders following labor are still elusive.

Even though the link between psychiatric disorders and hormonal changes appears clear, the exact mechanisms involved remain far from evident (23). This is partly because of the increase in the prevalence of psychiatric disorders at certain periods of life, such as postpartum or menopause, that are associated with major hormonal changes. Sex steroid hormones have a multidimensional effect on dopamine, serotonin, and noradrenalin (97). In particular, estrogen was found to have antipsychotic properties as well as a neuroprotective effect in patients suffering from such diseases as multiple sclerosis, Parkinson’s disease, and Alzheimer’s. Additionally, estrogen suppresses neuroinflammation (4, 98-99). On the other hand, however, no correlation between hormone concentration and postpartum depression symptoms has been found (100). Studies on mice reported no changes in serotonin levels in the hippocampus correlating with any particular phase of the estrous cycle in the females. This lack of change is explained by a tighter autoreceptor control (101).

It seems that sudden changes in hormone levels, in particular, a drop in estrogen after the expulsion of the placenta, may be related to the risk of postpartum psychiatric disorders, especially in susceptible women, yet the precise neurobiological mechanisms involved are elusive (100, 102). Moreover, there is evidence linking major depression to glucocorticoid resistance (45). Reports on cortisol levels and the risk of postpartum depression are inconsistent; however, an association with glucocorticoid resistance has been reported in cases of postpartum psychosis (100, 103). It is also important to note that cytokines have a direct influence on the expression of glucocorticoid receptors (52).

The current predominant theory posits that sudden changes in hormone levels connected with pregnancy, labor, and postpartum may lead to the development of psychiatric disorders in predisposed woman, though the evidence for this is still insufficient (23, 100, 102). A familial prevalence of postpartum psychiatric disorders has been reported, though the exact genes responsible for the increased risk have not been identified (104, 105). It is also possible that postpartum psychiatric disorders constitute a more heterogeneous group than the classifications would seem to indicate, and consequently, only a portion of patients actually have hormone-dependent psychiatric disorders (102, 106). Finally, the missing link in our understanding could have to do with the interaction of the immune system with the endocrine and nervous systems.


There is an increasing quantity of literature on the possible associations between postpartum psychiatric disorders and autoimmune diseases. The postpartum period is characterized by a „rebound phenomenon” where an increase in both autoimmune diseases (such as multiple sclerosis) and psychiatric disorders has been observed. Moreover, comorbidity has been confirmed between postpartum psychosis and autoimmune thyroid disorders (107), the latter of which have already been established as a risk factor for postpartum depression and other psychiatric disorders (108, 109).

Women are especially vulnerable to developing depressive symptoms during the postpartum period. It has been estimated that in 40% of cases, the first episode of depression manifests within 6 weeks postpartum, and in 33% of cases, during pregnancy. Additionally, up to 20% of deaths in women postpartum are due to suicide (110, 111). Several risk factors for suicide have been reported, such as poor social support, positive history of depression or anxiety, positive family history of psychiatric disorders, abortion, and substance abuse, among others, including the obstetric complications discussed above. Although the link is still controversial, primiparity also seems to be a risk factor for postpartum (87).

Krause et al. have observed that decreased antenatal and postnatal levels of Tregs correlate with the symptoms of postpartum depression. In patients with postpartum depression the authors have also reported an increase in prenatal and a decrease in postnatal CXCR1 expression on monocytes along with a statistically nonsignificant increase in postnatal CCR2-positive monocytes (112). Bränn et al. analyzed 92 inflammation-associated markers and found that STAM-BP (or otherwise AMSH), AXIN-1, ADA, ST1A1, and IL-10 were all statistically significantly lower in women with postpartum depressive symptoms compared to controls (113). Previous studies also reported lower INF-γ along with a lower ratio of INF-γ to Il-10. Additionally, a positive correlation of TNF-α (in CSF and plasma) and cytokines Il-1β, Il-8, and Il-18 (both maternal and in the cord blood) with depressive symptoms was observed. The results concerning Il-6 were contradictory. Lastly, an association between total lymphocyte count and postpartum depression was reported (114).

Postpartum psychosis is a rare disorder, estimated to occur in only 1-2/1000 births. Although there is a strong correlation with bipolar disorder, the main risk factor for postpartum psychosis is primiparity (80, 115). Moreover, a greater prevalence of autoimmune thyroid disorders has been confirmed in patients suffering from postpartum psychosis (107). In one study, it was observed that 4% of such patients had autoimmune encephalitis; 2% were NMDA positive, and in 2% the condition was caused by antibodies against an unknown target (116). A study by de Witte et al. has found no correlation between postpartum psychosis and the seroprevalence of antibodies against herpes simplex 1, herpes simplex 2, the Epstein-Barr virus, cytomegalovirus, or Toxoplasmosis gondii (82).

In cases of physiological postpartum, a decrease in peripheral NK cells and B lymphocytes, along with an increase in T lymphocytes, especially Th and Treg, was reported, suggesting a balance between the effector and regulatory arms of the immune response. In patients with postpartum psychosis (PP), such a physiological drop in NK and B cells with a corresponding rise in T cells was not observed. Moreover, these patients were found to have a greater number of monocytes compared to both healthy postpartum controls (HP) and healthy controls who were not postpartum (HC). Additionally, a greater expression of immune-related genes was reported within the monocytes of women with PP (103).

These observations were largely confirmed in a subsequent study by Kumar et al. Although that study also found that the number of monocytes was increased, the level was not considered statistically significant. Additionally, the number of non-classical monocytes (CD14-CD16+) was decreased in the patients with PP compared to those who were HP. Furthermore, Kumar et al. reported a decrease in the number of naïve CD4+ and CD8+ T cells in patients suffering from PP compared to those who were HP along with an increase in the number of activated CD8+ T cells. While the numbers of total Tregs (CD4+ CD25+ CD127dim) were similar, the number of memory Tregs was increased in patients with PP compared to those who were HP. As for dendritic cells, the number of mDCs (CD11c+ HLADR+) was decreased in patients with PP compared to those who were HP; however, no difference was reported in the number of pDCs. Furthermore, the number of CD56dimCD16+ NK cells was decreased in patients suffering from PP compared to those who were HP, while CD56brtCD16+/- NK cells were increased in patients with PP compared to those who were HP (117). As for cytokines, it was observed that the levels of Il-8 and Il-6 were increased compared to those of the healthy non-postpartum control, but not to those of the healthy postpartum control. Sathyanarayanan et al. also failed to confirm an association between Il-1β and MCP1 noted in the 2013 study by Bergink et al. (103, 118).

Overall, an increased maternal cytotoxic response to fetal antigens was observed in patients with postpartum psychosis; this finding is similar to what was observed in patients with preeclampsia and placental abruption (13, 14, 148). The abrupt increase in maternal immune activation that mediates physiological labor, in the case of inadequate response, may be a factor contributing to the manifestation of psychiatric symptoms after giving birth (10). This finding would confirm the hypothesis that immune system dysregulation is a cause of postpartum psychosis (117).

The manifestation of obsessive compulsive disorder (OCD) is strongly linked with a woman's first menstrual period, first pregnancy, or to the postpartum time period. A link with pregnancy and birth complications has also been reported. Additionally, most OCD patients have other coexisting psychiatric disorders such as depression (119). Postpartum OCD has been set apart due to characteristic symptoms, including obsessive thoughts and compulsions that are focused on the child and a different kind of disorder progression. Recently, it has been reported that 11% of women had symptoms of OCD 2 weeks after giving birth and in almost half of these women the symptoms persisted for 6 months. The majority of patients with OCD also had other psychiatric diagnoses, such as anxiety disorders (27.5%) and depression (70.6%). Furthermore, 25-75% of patients with a history of OCD suffered a relapse after giving birth. As obsessive-compulsive symptoms may be an early manifestation of bipolar disorder or schizophrenia, any coexisting diseases and family history should be thoroughly studied (75). To the best of our knowledge, no studies on immune cell levels, subpopulation percentages, or cytokine levels in postpartum OCD have been conducted.

Additionally, the postpartum period is characterized by an increased prevalence of anxiety and panic attacks. It has been observed that 11% of women develop symptoms in the 12 weeks after giving birth (120). The first study on CRP, Il-6, and TNF-α in patients with anxiety postpartum found no changes in the levels of these cytokines; however, the authors did not include immune cell levels in their analysis (121).

During pregnancy and the postpartum period, patients with schizophrenia and bipolar disorder are especially vulnerable to relapses and exacerbation of symptoms. Bipolar disorder in particular is associated with the postpartum period. In many cases, symptoms that develop during the postpartum period are considered to constitute the first onset of bipolar disorder. Furthermore, in the first 6 months after giving birth, women are at a greater risk of conversion from major depression to bipolar disorder than at any other time in their lives (122-123). Diagnosis of postpartum depression triples the risk of a subsequent diagnosis of bipolar disorder. This subject is especially important because there is a risk that treatment with antidepressants will induce a maniac episode in a patient. The link between other disorders in the postpartum period, such as OCD or anxiety, has not been closely studied; however, it is possible that these conditions are, in part, also an early manifestation of bipolar disorder (122). (The familial risk factor for these diseases has been discussed elsewhere.) (80). The subject of schizophrenia in pregnancy has not been studied in-depth, and the results of the research performed are conflicting (115). There are presently no studies that focus specifically on maternal immune system dysregulation in patients with bipolar disorder and schizophrenia in the context of pregnancy and the postpartum period.

Many of the reported complications of pregnancy and delivery are due to immune system dysfunction. The increased prevalence of psychiatric disorders in the postpartum period is related to immune system changes following pregnancy and birth. The maternal immune tolerance towards fetal antigens is regulated on many different levels by both the mother and the growing fetus. Thus, even a relatively small disruption of the regulating mechanisms may manifest as an increase in postpartum psychiatric disorders. Table 2 summarizes the association between changes in the immune system and psychiatric disorders during pregnancy and the postpartum period.

Table 2 The relationship between alterations in immune system with pregnancy related psychiatric disorders
Psychiatric Manifesation Immunological Manifestations References
Antenatal depression Positive association of symptoms with IL-6 and IL-1β concentration 114
Postpartum Depression Association with autoimmune diseases Mother’s serum• Decreased antenatal and postnatal levels of Tregs• Increased prenatal and decreased postnatal CXCR1 expression on monocytes• Lowered STAM-BP (AMSH), AXIN-1, ADA, ST1A1, and IL-10• Lowered INF-γ• Lowered INF-γ / Il-10 ratio• Increased TNF-α (both in CSF and plasma)• Increased Il-1β, Il-8 and Il-18 (both maternal and cord blood)• Positive association with Il-6 and TNF-α 108, 109, 112-114
Postpartum Psychosis • Increased maternal cytotoxic response to the fetal antigens• Association with autoimmune diseases• Association with autoimmune encephalitis• Lack of physiological decrease of NK and B cells and increase of T cells in peripheral blood• Increased number of monocytes• Greater expression of immune-related genes in the monocytes• Decreased number of non-classical monocytes (CD14-CD16+)• Decrease in naïve CD4+ and CD8+ T cells• Increase in activated CD8+ T cells• Increased number of memory Tregs• Decreased number of mDCs (CD11c+ HLADR+)• Decreased number of CD56dimCD16+ NK cells• Increased number of CD56brtCD16+/- NK cells 13, 14, 103, 107, 116-118, 148
Tregs - regulatory T cells; CXCR1 - C-X-C motif chemokine receptor 1; STAM-BP - STAM-binding protein (AMSH); ST1A1 - Sulfotransferase 1A1; Il - interleuin; INF - interferon; TNF - tumor necrosis factor; CD - cluster of differentiation;

From the perspective of immune system functioning, pregnancy represents a unique period during which the fetus manages to escape maternal immune system surveillance without hindering the physiological maternal immune response against pathogens. Various molecular mechanisms are involved in the development of maternal immune tolerance. Complete cytotoxic activation of maternal immune cells is essential for the successful implantation and development of pregnancy (124-127). It has been reported that the total lack of NK cells prevents the possibility of pregnancy. This correlation was proven through a genetically modified mouse model in which NK cells were depleted (125, 128).

First, trophoblast cells mask their presence; this occurs because of the lack of HLA-A and HLA-B antigens on their cell membranes. Next, increased expression of the non-classic antigens HLA-C, HLA-G, and HLA-E is observed. These antigens suppress NK cells and cytotoxic T lymphocytes through killer Ig-like receptors (KIR). An increased expression of proteins from the B7 and FAS families is then observed on the cell membranes. In the physiological situation, those proteins are found in the immune cells and their interaction with a corresponding ligand is responsible for the suppression of activated lymphocytes (127, 129, 130). The microenvironment of the implanted ovum and, later on, of the placenta is rebuilt, and the Th2 phenotype of immune response is predominant (131). The maintenance of pregnancy is related to indoleamine dioxygenase (IDO) pathway activation, mainly in macrophages infiltrating the decidua (132). The subsequent steps of maternal immune tolerance are linked with the increased activity of Treg cells infiltrating the maternal-fetal interface (133-135). The accumulation of the T regulatory cells on the maternal-fetal interface is essential to determining the level of T lymphocytes and NK cell suppression. The size of this cell’s population within the reproductive organs and peripheral blood vessels determines the cytotoxic reaction (134, 136-137).

T regulatory lymphocytes have CD25 receptors via which they are activated in an environment rich in Il-2, a cytokine essential to the development of the cytotoxic response. Furthermore, these lymphocytes have an ability to suppress this response thanks to molecular mechanisms mediated by TGF-β and CTLA-4, as well as other pathways. Their activation is gradual and indirectly dependent on the level of the initiated immune system response. With the proper level of activation, these cells are able to completely suppress the immune system response. Moreover, all the evidence suggests that the immune system has an ability to match the immune response to the particular pathogen. The antigens used for monitoring the Treg activity are FoxP3 transcription factor, CD127 antigen, and chemokines CCL4 and CCL5 (72, 138-142).

The phenomenon of immune system tolerance during pregnancy, understood as a balance between the activation and suppression of the maternal and fetal immune responses, is intriguing because it both protects the fetus and directs the proper development of the pregnancy. It regulates the implantation process, proper trophoblast invasion (135), and the remodeling of the spiral artery (143). It also regulates fetal immune system development (8, 127, 129) and the initiation of term delivery (9).

Disturbance of the regulation of immune tolerance has been found to contribute to preterm premature rupture of membranes (144) as well as to preterm labor (145). It has also been found to be responsible for spontaneous abortion (146), unexplained infertility (135), the development of preeclampsia, and placental abruption (146). Nguyen et al. have demonstrated that Treg cell suppressing activity differs depending on the localization of the placenta during pregnancy following a caesarean section. For example, those patients whose placentas were located far from the uterine scar (on the posterior wall of the uterus) had a different Treg cell phenotype in the cord blood compared to those patients with localization close to the scar (the anterior wall of the uterus). If the placenta was localized in contact with the scar from a previous caesarean section, the Tregs were of a more activated phenotype (147). Thus, while the level of maternal immune tolerance is related to maternal-fetal interaction, it is also affected by medical intervention and behavioral events. In particular, surgical intervention within the uterus may have a negative influence on immune tolerance in a subsequent pregnancy (148).

Advancing gestation and the beginning of spontaneous labor are associated with an increasing number of monocytes and neutrophils in the peripheral blood of the mother (9). Macrophages seem not only to be involved in the onset of labor but to be responsible for other aspects of parturition, such as cervix ripening and the postpartum repair of the uterine cervix (143). Macrophages infiltrating the lower segment of the uterus in the peripartum period alter the polarized phenotype from M2 to M1. The M1 phenotype is an inflammatory phenotype related to the secretion of tumor necrosis factor (TNF) and interleukin-12 (IL-12) by macrophages. It contrasts with the more suppressive M2 phenotype (connected with tissue repair and inflammation inhibition) (149). Kopřivová et al. have found a slight decrease in peripheral Treg cells on the day of delivery along with a prevalence of the Helios (+) phenotype in the Treg subpopulation, suggesting that the predominate portion of Treg cells present during pregnancy may be of thymic origin (150). During the spontaneous beginning of labor, a reduction in active Treg cells (CD4+CD25+CD127+FOXp3+HLA-DR-CD45A+) was observed. Furthermore, TLR-induced monocyte interaction with T cells is suppressed during cervix ripening (9). Shah et al. demonstrated that Th1/Th17 suppression related to Treg cell activity was diminished at the onset of labor. These changes were observed at the beginning of cervix ripening when dilation was less than 4 cm. Similarly, Galazka et al. demonstrated that the percentage of Treg cells CD4+CD25+FOXP3+ within the population of CD4+ lymphocytes was decreased in the maternal decidua deriving from term labor when the dilation of the ripening uterine cervix was less than 2 cm (151).

This data, along with the studies of Winkler on the ripening of the cervix mentioned above, suggest that the advancement of labor may influence or, conversely, depend on the immune tolerance level. An interpretation of a potential relationship between pregnancy complication and the mode of delivery and predisposition to psychiatric disorder appearance in the peripartum period should be supported by an analysis of the degree of cervix ripening at the time of placental detachment. Shah et al. have concluded that the maternal immune system is transformed during the spontaneous beginning of labor into a more reactive phenotype (9). The immune reaction during labor is not limited to the decidua and cervix. Singh et al. have assessed the mRNA levels of interleukins and chemokines (IL-1β, TNFα, IL-6, IL-4, IL-10, CCL2, CXCL8, CXCL1, and CXCL2) in the myometrium derived from both women who delivered prematurely and those who delivered at term. They found that myometrial inflammation is secondary to an established labor and unrelated to its onset (152).

Even today preterm delivery is associated with newborn mortality and morbidity. One of the main causes of the spontaneous beginning of preterm labor is intra-amniotic inflammation (153). Not all cases of intra-amniotic inflammation are related to microorganism detection using both cultivation and molecular microbiology techniques. When the intra-amniotic fluid is sterile, intra-amniotic inflammation is diagnosed (11, 144). In cases of preterm delivery increasing concentrations of cytokines IL-6, IL-1β (154), and IL-18 (155) were observed in the amniotic fluid and correlated with increasing symptoms of infection. Additionally, the concentration of IL-6 was higher for those women with preterm delivery compared to those who experienced term delivery (11). Elevated levels of CD14+ monocytes and neutrophils were detected in maternal blood during preterm delivery. The monocytes were typified by bearing enhanced expression of toll-like receptors (TLR4) (156). TLR4 are essential for the induction of innate immune responses and its activation influences the expression of a set of genes for the cytokines Il-1, Il-6, and Il-8 (157). Kumazaki et al. have found increased expression of TLR4 on the villous Hofbauer cells of preterm placentas (157). Aberrant inflammatory reactions may be related to the appearance of such complications as preterm labor, intrauterine growth restriction, and spontaneous abortion (158). Singh et al. have examined the distribution of inflammation and its relationship with pro-labor gene expression during preterm labor associated with chorioamnionitis and idiopathic inflammation and found that in idiopathic preterm labor inflammation was limited to the choriodecidua (159).

The pathogenesis of preeclampsia is complex. Generally, two different placental pathways may be distinguished: trophoblast and endothelial cell dysfunction (160). These two pathways are connected by immune cells. On the one hand, these cells are responsible for enabling trophoblast cell invasion, but on the other hand, they support endothelial cell differentiation. Immune cell activation in women with preeclampsia may be assessed in a number of ways. Moreover, the abnormal immune response to the allogeneic fetus in preeclampsia is similar to the immunological background of graft versus host disease (12). In women experiencing normal pregnancy, Tregs are present both at the maternal-fetal interface and in the peripheral blood (161). However, in patients with preeclampsia, Tregs are decreased in both the peripheral blood and at the maternal-fetal interface (146). The percentage of the subpopulation of activated CD4+ CD25high FoxP3high Tregs among CD4+ CD25high cells was greater in patients with normal pregnancies compared to those with preeclampsia (162). Increasing apoptotic and stress signaling protein levels in the placenta and umbilical cord, such as p38 phosphorylation, ratio of Bax/Bcl-2, and caspase-9 placental expression, were significantly higher in patients with preeclampsia compared to those with normal pregnancies (160). Increasing apoptosis on the maternal-fetal interface influences the macrophage cell population that is responsible for the removal of apoptotic cells (12). During pregnancy, macrophages predominantly differentiate into the M2 phenotype (143) that produces abundant IL-10. Those cells also participate in the remodeling of uterine vasculature. The uterine vessels lose smooth muscle and endothelial content, and the uterine spiral artery is replaced by extravillous trophoblast cells. Macrophages participate in these processes through the secretion of vascular endothelial growth factor VEGF and fms-like tyrosine kinase-1 (Flt-1) as well as other mechanisms (163). The biological function of VEGF depends on the interaction with Ftl-1 (143). Extravillous trophoblast cells infiltrate both the decidua and the myometrium of the uterus and are surrounded by maternal dNK cells. Abnormal placental implantation observed in patients with preeclampsia is related to increased NK cell activity (12; 164-165). Human dNK (CD56Bright CD16−) cells are a subpopulation of peripheral NK cells. They express KIRs, present reduced cytotoxicity, and are granular (containing perforin and Granzyme B) (166). These cells are responsible for the secretion of the vascular endothelial growth factor VEGF and placental growth factor PLGF (167). They also secrete metalloproteinase MMP7 and MMP9. Abnormal activity of these cells is related to the development of preeclampsia.

Control over the phenomenon of maternal immune tolerance is essential for both maternal and fetal health, including but not limited to the development of the placenta (168).


Over the last few years, T regulatory lymphocytes have become a frequent topic of research. The development of immunotherapy has stimulated breakthrough studies on this subject and led to a better understanding of the mechanisms underlying the functioning of these cells. Treg cells have the ability to suppress most types of immune cells, including CD4+ and CD8+ cells, B lymphocytes, NK and NKT cells, APC cells, monocytes, macrophages, and dendritic cells (139). Furthermore, it is believed that Treg cells can use multiple suppressive pathways, depending on the strength of the antigen stimulation, the anatomic localization, and the type of immune response (138).

It has been suggested that insufficient nonpathological antigen stimulation may lead to the inappropriate development of the Treg cell population, causing an impairment of immunosuppressive abilities (52). This conjecture is similar to the finding that the localization of the placenta after caesarean section leads to a different immunosuppressive phenotype in subsequent pregnancies (147). Because of their special role in immune system regulation, T regulatory cells may also be essential for studying the possible influence of immune system dysregulation during pregnancy on the risk for psychiatric disorders (75).

On the one hand, the increasing prevalence of the instrumentalization of birth and of elective caesarean sections seems to be responsible for the increased prevalence of postpartum psychiatric disorders. On the other hand, learning the details of the immunological mechanisms involved in the beginning of labor, the advancement of labor, placental detachment, and the puerperal period, and, more specifically, discovering the precise role of Treg cells in these processes may lead to a decreased risk of postpartum psychiatric disorders. Such a decrease would not be brought about through the prevention of immune dysfunction and complications but through new treatments that would manipulate the level of maternal immune response and tolerance, thereby nullifying the negative consequences of the inevitable instrumentalization of delivery.


We would also like to thank Prof. Christine Maisto for proofreading the manuscript.


Diagnostic and Statistical Manual of Mental Disorders


international statistical classification of diseases and related health problems


premature rupture of membranes


post-traumatic stress disorder


cerebro-spinal fluid


positron emission tomography


Major histocompatibility complex


regulatory T cells


single nucleotide polymorphisms


Proteasome subunit beta type-4


T-box transcription factor TBX21


signal transducer and activator of transcription 3


CD3e Antigen, Epsilon Polypeptide


C-X-C motif chemokine receptor 1


Protein kinase C eta type


26S proteasome non-ATPase regulatory subunit 9






FasR, apoptosis antigen 1 (APO-1 or APT)


human immunodeficiency virus


Transforming growth factor


toll-like receptor


C-reactive protein


obsessive-compulsive disorder


selective serotonin-reuptake inhibitors


anti-basal ganglia antibodies


postpartum childbirth-related posttraumatic stress disorder


hypertensive disorder of pregnancy


hemolysis, elevated liver enzymes, and low platelet count


STAM-binding protein (AMSH)


Sulfotransferase 1A1


N-methyl D-aspartate


postpartum psychosis


Human Leukocyte Antigen


indoleamine dioxygenase


cytotoxic T cell antigen 4


cluster of differentiation


Killer-cell immunoglobulin-like receptor


vascular-endothelial growth factor




Antigen-presenting cells

DekelSEin-DorTBermanZBarsoumianISAgarwalSPitmanRKDelivery mode is associated with maternal mental health following childbirth. Arch Womens Ment Health20196817824DOI: 10.1007/s00737-019-00968-2
CruzCZ de laThompsonELO'RourkeKNembhardWN Cesarean section and the risk of emergency peripartum hysterectomy in high-income countries: a systematic review. Arch Gynecol Obstet201529212011215DOI: 10.1007/s00404-015-3790-2
PearsonGAMacKenzieIZA cross-sectional study exploring the incidence of and indications for second-stage cesarean delivery over three decades. Int J Gynaecol Obstet2017138340345DOI: 10.1002/ijgo.12236
SommerIEWestrhenenR vanBegemannMJWitteLD deLeuchtSKahnRSEfficacy of anti-inflammatoryagents to improvesymptoms in patients with schizophrenia: an update. Schizophr Bull201440181191DOI: 10.1093/schbul/sbt139
IyengarRLGandhiSAnejaAThorpeKRazzoukLGreenbergJMosovichSFarkouhMENSAIDs are associated with lower depression scores in patients with osteoarthritis. Am J Med20131261017e11-8DOI: 10.1016/j.amjmed.2013.02.037
RosenblatJDKakarRBerkMKessingLVVinbergMBauneBTMansurRBBrietzkeEGoldsteinBIMcIntyreRSAnti-inflammatory agents in the treatment of bipolar depression: a systematic review and meta-analysis. Bipolar Disord20161889101DOI: 10.1111/bdi.12373
ShalbafanMMohammadinejadPShariatSVAlaviKZeinoddiniASalehiMAskariNAkhondzadehSCelecoxib as an Adjuvant to Fluvoxamine in Moderate to Severe Obsessive-compulsive Disorder: A Double-blind, Placebo-controlled, Randomized Trial. Pharmacopsychiatry20154-5136140DOI: 10.1055/s-0035-1549929
RacicotKKwonJYAldoPSilasiMMorGUnderstanding the complexity of the immune system during pregnancy. Am J Reprod Immunol2014722107116DOI: 10.1111/aji.12289
ShahNMEdeyLFImamiNJohnsonMRHuman Labour is Associated with Altered Regulatory T Cell Function and Maternal Immune Activation. Clin Exp Immunol2019DOI: 10.1111/cei.13384
SteinbornASohnCSayehliCBaudendistelAHüwelmeierDSolbachCSchmittEKaufmannMSpontaneous labour at term is associated with fetal monocyte activation. Clin Exp Immunol1999117147152DOI: 10.1046/j.1365-2249.1999.00938.x
Gomez-LopezNRomeroRMaymonEKusanovicJPPanaitescuBMillerDPacoraPTarcaALMotomuraKErezOJungEHassanSSHsuCDClinical chorioamnionitis at term IX in vivo evidence of intra-amniotic inflammasome activation. J Perinat Med201947276287DOI: 10.1515/jpm-2018-0271
RambaldiMPWeinerEMecacciFBarJPetragliaFImmunomodulation and preeclampsia. Best Pract Res Clin Obstet Gynaecol2019608796DOI: 10.1016/j.bpobgyn.2019.06.005
HuangQTChenJHZhongMXuYYCaiCXWeiSSHangLLLiuQYuYHThe risk of placental abruption and placenta previa in pregnant women with chronic hepatitis B viral infection: a systematic review and meta-analysis. Placenta201435539545DOI: 10.1016/j.placenta.2014.05.007
Darmochwal-KolarzDKludka-SternikMTabarkiewiczJBB KolarzJRolinskiBLeszczynska-GorzelakJOleszczukThe predominance of Th17 lymphocytes and decreased number and function of Treg cells in preeclampsia. J Reprod Immunol2012937578DOI: 10.1016/j.jri.2012.01.006
WicherekLThe role of the endometrium in the regulation of immune cell activity. Front Biosci20081310181035DOI: 10.2741/2740
WicherekLGalazkaKThe possible correlation between the patient's immune tolerance level during cesaerean section and the incidence of subsequent emergency peripartum hysterectomy. Clin Dev Immunol2007DOI: 10.1155/2007/63596
VigodSNKurdyakPADennisCLGruneirANewmanASeemanMVRochonPAAndersonGMGrigoriadisSRayJGMaternal and newborn outcomes among women with schizophrenia: a retrospective population-based cohort study. BJOG2014121566574DOI: 10.1111/1471-0528.12567
CannonMJonesPBMurrayRMObstetric complications and schizophrenia: historical and meta-analytic review. Am J Psychiatry200215910801092DOI: 10.1176/appi.ajp.159.7.1080
GuintivanoJManuckTMeltzer-BrodySPredictors of Postpartum Depression: A Comprehensive Review of the Last Decade of Evidence. Clin Obstet Gynecol201861591603DOI: 10.1097/GRF.0000000000000368
PazNC deSanchezSEHuamanLEChangGDPacoraPNGarciaPJAnanthCVQiuCWilliamsMARisk of placental abruption in relation to maternal depressive, anxiety and stress symptoms. J Affect Disord2011130280284DOI: 10.1016/j.jad.2010.07.024
DelahaijeDHDirksenCDPeetersLLSmitsLJAnxiety and depression following preeclampsia or hemolysis, elevated liver enzymes, and low platelets syndrome. A systematic review. Acta Obstetricia et Gynecologica Scandinavica201392746761DOI: 10.1111/aogs.12175
RobertsLDavisGKHomerCSEDepression, Anxiety and Post-traumatic Stress Disorder Following a Hypertensive Disorder of Pregnancy: A Narrative Literature Review. Front Cardiovasc Med2019DOI: 10.3389/fcvm.2019.00147
BerginkVLaursenTMJohannsenBMKushnerSAMeltzer-BrodySMunk-OlsenTPre-eclampsia and first-onset postpartum psychiatric episodes: a Danish population-based cohort study. Psychol Med20154534813489DOI: 10.1017/S0033291715001385
SekarABialasARRiveraH deDavisAHammondTRKamitakiNTooleyKPresumeyJBaumMDorenV VanGenoveseGRoseSAHandsakerRESchizophrenia risk from complex variation of complement component 4. Nature2016530177183DOI: 10.1038/nature16549
ShiJLevinsonDFDuanJSandersARZhengYPe'erIDudbridgeFHolmansPAWhittemoreASMowryBJOlincyAAminFCloningerCRSilvermanJMBuccolaNGByerleyWFBlackDWCroweRROksenbergJRMirelDBKendlerKSFreedmanRGejmanPVCommon variants on chromosome 6p22.1 are associated with schizophrenia. Nature2009460753757DOI: 10.1038/nature08192
PresumeyJBialasARCarrollMCComplement System in Neural Synapse Elimination in Development and Disease. Adv Immunol20171355379DOI: 10.1016/
VergaelenESchiweckCSteelandK VanCounotteJVelingWSwillenADrexhageHClaesSA pilot study on immuno-psychiatry in the 22q11.2 deletion syndrome: A role for Th17 cells in psychosis? Brain Behav Immun2018708895DOI: 10.1016/j.bbi.2018.03.022
MillerBJGoldsmithDTowards immunophenotype of Schizophrenia: Progress, Potential Mechanisms, and Future Directions. Neuropsychopharmiacology Review201742299317DOI: 10.1038/npp.2016.211
BerckelBN vanBossongMGBoellaardRKloetRSchuitemakerACaspersELuurtsemaGWindhorstADCahnWLammertsmaAAKahnRSMicroglia activation in recent-onset schizophrenia: a quantitative ®-(11C)PK11195 positron emission tomography study. Biol Psychiatry200864820822DOI: 10.1016/j.biopsych.2008.04.025
DoorduinJVriesEF deWillemsenATGrootJC deDierckxRAKleinHCNeuroinflammation in schizophrenia-related psychosis: a PET study. J Nucl Med20095018011807DOI: 10.2967/jnumed.109.066647
PorcelliBVerdinoVBossiniLTerzuoliLFagioliniACeliac and nonceliac gluten sensitivity: a review on the association with schizophrenia and mood disorders. Auto Immun Highlights201455561DOI: 10.1007/s13317-014-0064-0
BenrosMENielsenPRNordentoftMEatonWWDaltonSOMortensenPBAutoimmune diseases and severe infections as risk factors for schizophrenia: a 30-year population-based register study. Am J Psychiatry201116813031310DOI: 10.1176/appi.ajp.2011.11030516
BenrosMEMortensenPBEatonWWAutoimmune diseases and infections as risk factors for schizophrenia. Ann N Y Acad Sci201212625666DOI: 10.1111/j.1749-6632.2012.06638.x
EatonWWByrneMEwaldHMorsOChenCYAgerboEMortensenPBAssociation of schizophrenia and autoimmune diseases: linkage of Danish national registers. Am J Psychiatry2006163521528DOI: 10.1176/appi.ajp.163.3.521
PougetJGConsortiumSchizophrenia Working Group of the Psychiatric GenomicsHanBWuYMignotEOllilaHMBarkerJSpainSDandNTrembathRMartinJMayesMDBossini-CastilloLLópez-IsacEJinYSantoricoSASpritzRAHakonarsonHPolychronakosCRaychaudhuriSJJ Knight Cross-disorder analysis of schizophrenia and 19 immune-mediated diseases identifies shared genetic risk. Hum Mol Genet2019DOI: 10.1093/hmg/ddz145
KellyDLLiXKildayCFeldmanSClarkSLiuFBuchananRWTonelliLHIncreased circulating regulatory T cells in medicated people with schizophrenia. Psychiatry Res2018269517523DOI: 10.1016/j.psychres.2018.09.006
Fernandez-EgeaEVértesPEFlintSMTurnerLMustafaSHattonASmithKGLyonsPABullmoreETPeripheral Immune Cell Populations Associated with Cognitive Deficits and Negative Symptoms of Treatment-Resistant Schizophrenia. PLoS One201611DOI: 10.1371/journal.pone.0155631
MillerBJGassamaBSebastianDBuckleyPMellorAMeta-analysis of lymphocytes in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatry201373993999DOI: 10.1016/j.biopsych.2012.09.007
DrexhageRCHoogenboezemTACohenDVersnelMANolenWABeverenNJ vanDrexhageHAAn activated set point of T-cell and monocyte inflammatory networks in recent-onset schizophrenia patient involves both pro- and anti-inflammatoryforces. Int J Neuropsychopharmacol201114746755DOI: 10.1017/S1461145710001653
CraddockRLockstoneHRiderDWaylandMHarrisLJMcKennaPJBahnSAltered T-Cell Function in Schizophrenia: A Cellular Model to Investigate Molecular Disease Mechanisms. PLoS One20072DOI: 10.1371/journal.pone.0000692
UpthegroveRKhandakerGMCytokines, Oxidative Stress and Cellular Markers of Inflammation in Schizophrenia. Curr Top Behav Neurosci2019DOI: 10.1007/7854_2018_88
MillerBJBuckleyPSeaboltWMellorAKirkpatrickBMeta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatry201170663671DOI: 10.1016/j.biopsych.2011.04.013
WongMLDongCMaestre-MesaJLicinioJPolymorphisms in inflammation-related genes are associated with susceptibility to major depression and antidepressant response. Mol Psychiatry200813800812DOI: 10.1038/mp.2008.59
MouihateAMehdawiHToll-like receptor 4-mediated immune stress in pregnant rats activates STAT3 in the fetal brain: role of interleukin-6. Pediatr Res201679781787DOI: 10.1038/pr.2015.86
ParianteCMWhy are depressed patients inflamed? A reflection on 20 years of research on depression, glucocorticoid resistance and inflammation. Eur Neuropsychopharmacol201727554559DOI: 10.1016/j.euroneuro.2017.04.001
SuKPHuangSYPengCYLaiHCHuangCLChenYCAitchisonKJParianteCMPhospholipase A2 and cyclooxygenase 2 genes influence the risk of interferon-alpha-induced depression by regulating polyunsaturated fatty acids levels. Biol Psychiatry201067550557DOI: 10.1016/j.biopsych.2009.11.005
BullSJHuezo-DiazPBinderEBCubellsJFRanjithGMaddockCMiyazakiCAlexanderNHotopfMCleareAJNorrisSCassidyEAitchisonKJMillerAHParianteCMFunctional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-alpha and ribavirin treatment. Mol Psychiatry20091410951104DOI: 10.1038/mp.2008.48
DowlatiYHerrmannNSwardfagerWLiuHShamLReimEKLanctotKLA meta-analysis of cytokines in major depression. Biol Psychiatry201067446457DOI: 10.1016/j.biopsych.2009.09.033
BenedettiFLuccaABrambillaFColomboCSmeraldiEInterleukine-6 serum levels correlate with response to antidepressant sleep deprivation and sleep phase advance. Prog Neuropsychopharmacol Biol Psychiatry20022611671170DOI: 10.1016/S0278-5846(02)00255-5
LanquillonSKriegJCBening-Abu-ShachUVedderHCytokine production and treatment response in major depressive disorder. Neuropsychopharmacol200022370379DOI: 10.1016/S0893-133X(99)00134-7
SluzewskaASobieskaMRybakowskiJKChanges in acute phase proteins during lithium potentiation of antidepressants in refractory depression. Neuropsychobiology199735123127DOI: 10.1159/000119332
AH MillerDepression Immunity: A Role for T cells? Brain Behav Immun20102418DOI: 10.1016/j.bbi.2009.09.009
ZorrillaEPLuborskyLMcKayJRRosenthalRHouldinATaxAMcCorkleRSeligmanDASchmidtKThe relationship of depression and stressors to immunological assays: a meta-analytic review. Brain Behav Immun200115199226DOI: 10.1006/brbi.2000.0597
ChenYJiangTChenPOuyangJXuGZengZSunYEmerging tendency towards autoimmune process in major depressive patients: a novel insight from Th17 cells. Psychiatry Res2011188224230DOI: 10.1016/j.psychres.2010.10.029
Szuster-CiesielskaASlotwinskaMStachuraAMarmurowska-MichalowskaHDubas-SlempHBojarska-JunakAKandefer-SzerszeńMAccelerated apoptosis of blood leukocytes and oxidative stress in blood of patients with major depression. Prog Neuropsychopharmacol Biol Psychiatry200832686694DOI: 10.1016/j.pnpbp.2007.11.012
GrosseLCarvalhoLABirkenhagerTKHoogendijkWKushnerSADrexhageHABerginkVCirculating cytotoxic T cells and natural killer cells as potential predictors for antidepressant response in melancholic depression. Restoration of T regulatory cell populations after antidepressant therapy. Psychopharmacology (Berl)201623316791688DOI: 10.1007/s00213-015-3943-9
FreierEWeberCSNowottneUHornCBartelsKMeyerSHildebrandtYLuetkensTCaoYPabstCMuzzuliniJSchneeBBrunner-WeinzierlMCMarangoloMBokemeyerCDeterHCAtanackovicDDecrease of CD4(+)FOXP3(+) T regulatory cells in the peripheral blood of human subjects undergoing a mental stressor. Psychoneuroendocrinology;201035663673DOI: 10.1016/j.psyneuen.2009.10.005
YLiBXiaoWQiuLYangBHuXTianHYangAltered expression of CD4(+)CD25(+) regulatory T cells and its 5-HT(1a) receptor in patients with major depression disorder. J Affect Disord20101246875DOI: 10.1016/j.jad.2009.10.018
EllulPMariotti-FerrandizELeboyerMKlatzmannDRegulatory T Cells As Supporters of Psychoimmune Resilience: Toward Immunotherapy of Major Depressive Disorder. Front Neurol20189DOI: 10.3389/fneur.2018.00167
LeboyerMBerkMYolkenRTamouzaRKupferDImmuno-psychiatryL Grocan agenda for clinical practice and innovative research. BMC Med201614173DOI: 10.1186/s12916-016-0712-5
LeboyerMOliveiraJTamouzaRGrocLIs it time for immunopsychiatry in psychotic disorders? Psychopharmacology (Berl)201623316511660DOI: 10.1007/s00213-016-4266-1
KridinKZelber-SagiSComaneshterDCohenADBipolar Disorder Associated with Another Autoimmune Disease-Pemphigus: A Population-based Study. Can J Psychiatry201863474480DOI: 10.1177/0706743717740344
BarbutiMCarvalhoAFKöhlerCAMurruAVerdoliniNGuisoGSamalinLMaesMStubbsBPerugiGVietaEPacchiarottiIThyroid autoimmunity in bipolar disorder: A systematic review. J Affect Disord201722197106DOI: 10.1016/j.jad.2017.06.019
DrexhageRCHoogenboezemTHVersnelMABerghoutANolenWADrexhageHAThe activation of monocyte and T cell networks in patients with bipolar disorder. Brain Behav Immun20112512061213DOI: 10.1016/j.bbi.2011.03.013
WieckAGrassi-OliveiraRPradoCH doViolaTWPetersenLEPortoBTeixeiraALBauerME Toll-like receptor expression and function in type I bipolar disorder. Brain Behav Immun201654110121DOI: 10.1016/j.bbi.2016.01.011
BarbosaIGBauerMEMachado-VieiraRTeixeiraALCytokines in bipolar disorder: paving the way for neuroprogression. Neural Plast2014DOI: 10.1155/2014/360481
ModabberniaATaslimiSBrietzkeEAshrafiMCytokine alterations in bipolar disorder: a meta-analysis of 30 studies. Biol Psychiatry2013741525DOI: 10.1016/j.biopsych.2013.01.007
MunkholmKBraunerJVKessingLVVinbergMCytokines in bipolar disorder vs. healthy control subjects: a systematic review and meta-analysis. J Psychiatr Res20134711191133DOI: 10.1016/j.jpsychires.2013.05.018
SommershofAAichingerHEnglerHAdenauerHCataniCBonebergEMElbertTGroettrupMKolassaITSubstantial reduction of naive and regulatory T cells following traumatic stress. Brain Behav Immun20092311171124DOI: 10.1016/j.bbi.2009.07.003
KonukNTekınOOzturkUAtikLAtasoyNBektasSErdoganAPlasma Levels of Tumor Necrosis Factor-Alpha and Interleukin-6 in Obsessive Compulsive Disorder. Mediators Inflamm2007DOI: 10.1155/2007/65704
KawikovaILeckmanJFKronigHKatsovichLBessenDEGhebremichaelMBothwellALDecreased numbers of regulatory T cells suggest impaired immune tolerance in children with Tourette syndrome: a preliminary study. Biol Psychiatry200761273278DOI: 10.1016/j.biopsych.2006.06.012
TanakaASakaguchiSRegulatory T cells in cancer immunotherapy. Cell Res201727109118DOI: 10.1038/cr.2016.151
PapeKTamouzaRLeboyerMZippFImmunoneuropsychiatry - novel perspectives on brain disorders. Nat Rev Neurol201915317328DOI: 10.1038/s41582-019-0174-4
KhandakerGMDantzerRImmunopsychiatryPB Jonesimportant facts. Psychol Med20174722292237DOI: 10.1017/S0033291717000745
SharmaVSommerdykCObsessive-compulsive disorder in the postpartum period: diagnosis, differential diagnosis and management. Womens Health (Lond)201511543552DOI: 10.2217/WHE.15.20
KendellREChalmersJCPlatzCEpidemiology of puerperal psychoses. Br J Psychiatry1987150662673DOI: 10.1192/bjp.150.5.662
Munk-OlsenTAgerboEDoes Childbirth Cause Psychiatric Disorders? A Population-Based Study Paralleling a Natural Experiment. Epidemiology2015267984DOI: 10.1097/EDE.0000000000000193
Vesga-LópezOBlancoCKeyesKOlfsonMGrantBFHasinDSPsychiatric disorders in pregnant and postpartum women in the United States. Arch Gen Psychiatry200865805815DOI: 10.1001/archpsyc.65.7.805
Munk-OlsenTLaursenTMPedersenCBMorsOMortensenPBNew parents and mental disorders: a population-based register study. JAMA200629625822589DOI: 10.1001/jama.296.21.2582
JonesICraddockNFamiliality of the puerperal trigger in bipolar disorder: results of a family study. Am J Psychiatry2001158913917DOI: 10.1176/appi.ajp.158.6.913
ZhongQYGelayeBFricchioneGLAvillachPKarlsonEWWilliamsMAAdverse obstetric and neonatal outcomes complicated by psychosis among pregnant women in the United States. BMC Pregnancy Childbirth201818120DOI: 10.1186/s12884-018-1750-0
WitteLD deSnijdersGLitjensMKampermanAMKushnerSAKahnRSBerginkVAre infectious agents involved in the pathogenesis of postpartum psychosis? J Affect Disord2018229141144DOI: 10.1016/j.jad.2017.12.069
KurkiTHiilesmaaVRaitasaloRMattilaHYlikorkalaODepression and anxiety in early pregnancy and risk for preeclampsia. Obstet Gynecol200095487490DOI: 10.1097/00006250-200004000-00003
QiuCSanchezSELamNGarciaPWilliamsMAAssociations of depression and depressive symptoms with preeclampsia: results from Peruvian case-control study. BMC Womens Health20077DOI: 10.1186/1472-6874-7-15
BlomEAJansenPWVerhulstFCHofmanARaatHJaddoeVWCoolmanMSteegersEATiemeierHPerinatal complications increase the risk of postpartum depression. The Generation R Study. BJOG201011713901398DOI: 10.1111/j.1471-0528.2010.02660.x
ZhaoYKaneIMaoLShiSWangJLinQLuoJThe Prevalence of Antenatal Depression and its Related Factors in Chinese Pregnant Women who Present with Obstetrical Complications. Arch Psychiatr Nurs201630316321DOI: 10.1016/j.apnu.2015.11.012
YounHLeeSHanSWKimLYLeeTSOhMJJeongHGChoGJObstetric risk factors for depression during the postpartum period in South Korea: a nationwide study. J Psychosom Res20171021520DOI: 10.1016/j.jpsychores.2017.09.003
HompothEAPetőZBaloghV FűrésznéTörekiA Associations Between Depression Symptoms, Psychological Intervention and Perinatal Complications. J Clin Psychol Med Settings2019DOI: 10.1007/s10880-019-09632-4
ChenLWangXDingQShanNQiHDevelopment of Postpartum Depression in Pregnant Women with Preeclampsia: A Retrospective Study. Biomed Res Int2019DOI: 10.1155/2019/9601476
Meltzer-BrodySMaegbaekMLMedlandSEMillerWCSullivanPMunk-OlsenTObstetrical, pregnancy and socio-economic predictors for new-onset severe postpartum psychiatric disorders in primiparous women. Psychol Med20174714271441DOI: 10.1017/S0033291716003020
DekelSEin-DorTDishyGAMayopoulosPABeyond postpartum depression: posttraumatic stress-depressive response following childbirth. Arch Womens Ment Health2019DOI: 10.1007/s00737-019-01006-x
ChaayaMCampbellOMRKakF ElShaarDHarbHKaddourAPostpartum depression: prevalence and determinants in Lebanon. Arch Womens Ment Health200256572DOI: 10.1007/s00737-002-0140-8
XuHDingYMaYXinXZhangDCesarean section and risk of postpartum depression: A meta-analysis. Psychosom Res201797118126DOI: 10.1016/j.jpsychores.2017.04.016
Törnblom SA Klimaviciute A Byström B Chromek M Brauner A Ekman-Ordeberg G Non-infected preterm parturition is related to increased concentrations of IL-6, IL-8 and MCP-1 in human cervix. Reprod Biol Endocrinol 2005 2
SakamotoYMoranPSearleRFBulmerJNRobsonSCInterleukin-8 is involved in cervical dilatation but not in prelabour cervical ripening. Clin Exp Immunol2004138151157DOI: 10.1111/j.1365-2249.2004.02584.x
WinklerMRathWChanges in the cervical extracellular matrix during pregnancy and parturition. J Perinat Med1999274560DOI: 10.1515/JPM.1999.006
SchillerCEJohnsonSLAbateACSchmidtPJRubinowDRReproductive Steroid Regulation of Mood and Behavior. Compr Physiol2016611351160DOI: 10.1002/cphy.c150014
TskitishviliEPequeuxCMunautCViellevoyeRNisolleMNoëlAFoidartJMEstrogen receptors and estetrol-dependent neuroprotective actions: a pilot study. J Endocrinol20172328595DOI: 10.1530/JOE-16-0434
TskitishviliENisolleMMunautCPequeuxCGerardCNoelAFoidartJMEstetrol attenuates neonatal hypoxic-ischemic brain injury. Exp Neurol2014261298307DOI: 10.1016/j.expneurol.2014.07.015
BlochMDalyRCRubinowDREndocrine factors in the etiology of postpartum depression. Comprehensive Psychiatry200344234246DOI: 10.1016/S0010-440X(03)00034-8
SaylorRAHerseyMWestABuchananAMBergerSNNijhoutHFReedMCBestJHashemiPIn vivo Hippocampal Serotonin Dynamics in Male and Female Mice: Determining Effects of Acute Escitalopram Using Fast Scan Cyclic Voltammetry. Front Neurosci 201913362DOI: 10.3389/fnins.2019.00726
SchillerCEMeltzer-BrodySRubinowDRThe role of reproductive hormones in postpartum depression. CNS Spectr2015204859DOI: 10.1017/S1092852914000480
BerginkVBurgerhoutKMWeigeltKPopVJWitH deDrexhageRCKushnerSADrexhageHAImmune system dysregulation in first-onset postpartum psychosis. Biol Psychiatry20137310001007DOI: 10.1016/j.biopsych.2012.11.006
JonesIHamshereMNangleJMBennettPGreenEHeronJSeguradoRLambertDHolmansPCorvinAOwenMJonesLGillMCraddockNBipolar affective puerperal psychosis: genome-wide significant evidence for linkage to chromosome 16. American Journal of Psychiatry200716410991104DOI: 10.1176/ajp.2007.164.7.1099
ByrneEMCarrillo-RoaTPenninxBWSallisHMViktorinAChapmanBHendersAKGroupPsychiatric Genomic Consortium Major Depressive Disorder WorkingPergadiaMLHeathACMaddenPASullivanPFBoschlooLGrootheestG vanMcMahonGLawlorDALandénMLichtensteinPMagnussonPKEvansDMMontgomeryGWBoomsmaDIMartinNGMeltzer-BrodySWrayNR Applying polygenic risk scores to postpartum depression. Archives of Women's Mental Health201417519528DOI: 10.1007/s00737-014-0428-5
BlochMSchmidtPJDanaceauMMurphyJNiemanLRubinowDREffects of gonadal steroids in women with a history of postpartum depression. Am J Psychiatry2000157924930DOI: 10.1176/appi.ajp.157.6.924
BerginkVKushnerSAPopVKuijpensHBergMP Lambregtse-van denDrexhageRCWiersingaWNolenWADrexhageHA Prevalence of autoimmune thyroid dysfunction in postpartum psychosis. Br J Psychiatry2011198264268DOI: 10.1192/bjp.bp.110.082990
BerginkVPopVJMNielsenPRAgerboEMunk-OlsenTLiuXComorbidity of autoimmune thyroid disorders and psychiatric disorders during the postpartum period: a Danish nationwide register-based cohort study. Psychol Med20184812911298DOI: 10.1017/S0033291717002732
HarrisBOthmanSDaviesJAWeppnerGJRichardsCJNewcombeRGLazarusJHParkesABHallRPhillipsDIAssociation between postpartum thyroid dysfunction and thyroid antibodies and depression. BMJ1992305152156DOI: 10.1136/bmj.305.6846.152
BeckerMWeinbergerTChandyASchmuklerS Depression During Pregnancy and Postpartum. Curr Psychiatry Rep201618DOI: 10.1007/s11920-016-0664-7
WisnerKLSitDKMcSheaMCRizzoDMZoretichRAHughesCLEngHFLutherJFWisniewskiSRCostantinoMLConferALMoses-KolkoELFamyCSHanusaBHOnset timing, thoughts of self-harm, and diagnoses in postpartum women with screen-positive depression findings. AMA Psychiatry201370490498DOI: 10.1001/jamapsychiatry.2013.87
KrauseDJobstAKirchbergFKieperSHärtlKKästnerRMyintAMMüllerNSchwarzMJPrenatal immunologic predictors of postpartum depressive symptoms: a prospective study for potential diagnostic markers. Eur Arch Psychiatry Clin Neurosci2014264615624DOI: 10.1007/s00406-014-0494-8
BrännEPapadopoulosFFranssonEWhiteREdvinssonÅHellgrenCKamali-MoghaddamMBoströmASchiöthHBSundström-PoromaaISkalkidouAInflammatory markers in late pregnancy in association with postpartum-A nested case-control study. Psychoneuroendocrinology201779146159DOI: 10.1016/j.psyneuen.2017.02.029
OsborneLMMonkCPerinatal depression - the fourth inflammatory morbidity of pregnancy?: Theory and literature review. Psychoneuroendocrinology20133819291952DOI: 10.1016/j.psyneuen.2013.03.019
JonesIChandraPSDazzanPHowardLMBipolar disorder, affective psychosis, and schizophrenia in pregnancy and the post-partum period. Lancet201438417891799DOI: 10.1016/S0140-6736(14)61278-2
BerginkVArmangueTTitulaerMJMarkxSDalmauJKushnerSAAutoimmune Encephalitis in Postpartum Psychosis. Am J Psychiatry2015172901908DOI: 10.1176/appi.ajp.2015.14101332
KumarMMVenkataswamyMMSathyanarayananGThippeswamyHChandraPSManiRSImmune system aberrations in postpartum psychosis: An immunophenotyping study from a tertiary care neuropsychiatric hospital in India. J Neuroimmunol2017310813DOI: 10.1016/j.jneuroim.2017.06.002
SathyanarayananGThippeswamyHManiRVenkataswamyMKumarMPhilipMChandraPSCytokine alterations in first-onset postpartum psychosis-clues for underlying immune dysregulation. Asian J Psychiatr2019427478DOI: 10.1016/j.ajp.2019.03.012
UguzFAyhanM GiyansEpidemiology and clinical features of obsessive-compulsive disorder during pregnancy and postpartum period: a review. J Mood Disord20111178186DOI: 10.5455/jmood.20111219111846
Sholomskas DE Wichamaratne PJ Dogolo L O'Brien DW Leaf PJ Woods SW Postpartum onset of panic disorder: a coincidental event? J Clin Psychiatry 1993 54 476 480
FurtadoMLieshoutRJ VanAmeringenM VanGreenSMFreyBNBiological and psychosocial predictors of anxiety worsening in the postpartum period: A longitudinal study. J Affect Disord2019250218225DOI: 10.1016/j.jad.2019.02.064
SharmaVRelationship of bipolar disorder with psychiatric comorbidity in the postpartum period-a scoping review. Arch Women's Ment Health201821141147DOI: 10.1007/s00737-017-0782-1
SharmaVXieBCampbellMKPenavaDHampsonEMazmanianDPopeCJA prospective study of diagnostic conversion of major depressive disorder to bipolar disorder in pregnancy and postpartum. Bipolar Disord2014161621DOI: 10.1111/bdi.12140
RobertsonSACareASMoldenhauerLMRegulatory T cells in embryo implantation and the immune response to pregnancy. J Clin Invest201812842244235DOI: 10.1172/JCI122182
BloisSMFreitagNTirado-GonzálezIChengSBHeimesaatMMBereswillSRoseMConradMLBarrientosGSharmaSNK cell-derived IL-10 is critical for DC-NK cell dialogue at the maternal-fetal interface. Sci Rep20177DOI: 10.1038/s41598-017-02333-8
SharmaSNatural killer cells and regulatory T cells in early pregnancy loss. Int J Dev Biol20145821929DOI: 10.1387/ijdb.140109ss
DekelNGnainskyYGranotIRacicotKMorGThe role of inflammation for a successful implantation. Am J Reprod Immunol201472141147DOI: 10.1111/aji.12266
MuyayaloKPLiXHMorGLiaoAHModulatory effect of intravenous immunoglobulin on Th17/Treg cell balance in women with unexplained recurrent spontaneous abortion. Am J Reprod Immunol201880DOI: 10.1111/aji.13018
PrabhuDasMBonneyECaronKDeySErlebacherAFazleabasAFisherSGolosTMatzukMMcCuneJMMorGSchulzLSoaresMSpencerTStromingerJWaySSYoshinagaKImmune mechanisms at the maternal-fetal interface: perspectives and challenges. Nat Immunol201516328334DOI: 10.1038/ni.3131
LinscheidCPetroffMGMinor histocompatibility antigens and the maternal immune response to the fetus during pregnancy. Am J Reprod Immunol201369304314DOI: 10.1111/aji.12075
MiyazakiSTsudaHSakaiMHoriSSasakiYFutataniTMiyawakiTSaitoSPredominance of Th2-promoting dendritic cells in early human pregnancy decidua. J Leukoc Biol200374514522DOI: 10.1189/jlb.1102566
MunnDHZhouMAttwoodJTBondarevIConwaySJMarshallBBrownCMellorALPrevention of allogeneic fetal rejection by tryptophan catabolism. Science199828111911193DOI: 10.1126/science.281.5380.1191
SakaguchiSSakaguchiNShimizuJYamazakiSSakihamaTItohMKuniyasuYNomuraTTodaMTakahashiTImmunologic tolerance maintained by CD25+ CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol Rev20011821832DOI: 10.1034/j.1600-065X.2001.1820102.x
SasakiYSakaiMMiyazakiSHigumaSShiozakiASaitoSDecidual and peripheral blood CD4+CD25+ regulatory T cells in early pregnancy subjects and spontaneous abortion cases. Mol Hum Reprod200410347353DOI: 10.1093/molehr/gah044
JasperMJTremellenKPRobertsonSAPrimary unexplained infertility is associated with reduced expression of the T-regulatory cell transcription factor Foxp3 in endometrial tissue. Mol Hum Reprod200612301308DOI: 10.1093/molehr/gal032
SaitoSSasakiYSakaiMCD4(+)CD25high regulatory T cells in human pregnancy. J Reprod Immunol200565111120DOI: 10.1016/j.jri.2005.01.004
AluvihareVRKallikourdisMBetzAGRegulatory T cells mediate maternal tolerance to the fetus. Nat Immunol20045266271DOI: 10.1038/ni1037
WingJBTanakaASakaguchiSHuman FOXP3+ Regulatory T Cell Heterogeneity and Function in Autoimmunity and Cancer. Immunity201950302316DOI: 10.1016/j.immuni.2019.01.020
FrydrychowiczMBoruczkowskiMKolecka-BednarczykADworackiGThe Dual Role of Treg in Cancer. Scand J Immunol201786436443DOI: 10.1111/sji.12615
WicherekLBastaPPitynskiKMarianowskiPKijowskiJWiatrJMajkaMThe characterization of the subpopulation of suppressive B7H4(+) macrophages and the subpopulation of CD25(+) CD4(+) and FOXP3(+) regulatory T-cells in decidua during the secretory cycle phase, Arias Stella reaction, and spontaneous abortion - a preliminary report. Am J Reprod Immunol200961303312DOI: 10.1111/j.1600-0897.2009.00696.x
HoriSSakaguchiSFoxp3: a critical regulator of the development and function of regulatory T cells. Microbes Infect20046745751DOI: 10.1016/j.micinf.2004.02.020
Sindram-TrujilloAPScherjonSAMiertPP Van Hulst-vanKanhaiHHRoelenDLClaasFHComparison of decidual leukocytes following spontaneous vaginal delivery and elective cesarean section in uncomplicated human term pregnancy. J Reprod Immunol200462125137DOI: 10.1016/j.jri.2003.11.007
NagamatsuTSchustDJThe contribution of macrophages to normal and pathological pregnancies. Am J Reprod Immunol201063460471DOI: 10.1111/j.1600-0897.2010.00813.x
Gomez-LopezNRomeroRPanaitescuBLengYXuYTarcaALFaroJPacoraPHassanSSHsuCDInflammasome activation during spontaneous preterm labor with intra-amniotic infection or sterile intra-amniotic inflammation. Am J Reprod Immunol201880DOI: 10.1111/aji.13049
KimJKoYKwonKKooSRheeYKangBLeeMAnalysis of monocyte subsets and toll-like receptor 4 expression in peripheral blood monocytes of women in preterm labor. J Reprod Immunol201294190195DOI: 10.1016/j.jri.2012.02.002
SasakiYDarmochwal-KolarzDSuzukiDSakaiMItoMShimaTShiozakiARolinskiJSaitoSProportion of peripheral blood and decidual CD4(+) CD25(bright) regulatory T cells in pre-eclampsia. Clin Exp Immunol2007149139145DOI: 10.1111/j.1365-2249.2007.03397.x
NguyenTAKahnDALoewendorfAIPlacental implantation over prior cesarean scar causes activation of fetal regulatory T cells. Immun Inflamm Dis2018DOI: 10.1002/iid3.214
WicherekLGalazkaKLazarARCAS1 decidual immunoreactivity during placental abruption: immune cell presence and activity. Am J Reprod Immunol2007584655DOI: 10.1111/j.1600-0897.2007.00490.x
FujiiTNagamatsuTSchustDJIchikawaMKumasawaKYabeSIriyamaTHirotaYOsugaYAokiJYatomiYFujiiTPlacental expression of lysophosphatidic acid receptors in normal pregnancy and preeclampsia. Am J Reprod Immunol201982DOI: 10.1111/aji.13176
KopřivováHHájkováMKouckýMMalíčkováKHoláňVKrulováMKinetics of Helios(+) and Helios(-) T regulatory cell subsets in the circulation of healthy pregnant women. Scand J Immunol201989DOI: 10.1111/sji.12754
GalazkaKWicherekLPitynskiKKijowskiJZajacKBednarekWDutsch-WicherekMRytlewskiKKalinkaJBastaAMajkaMChanges in the subpopulation of CD25+ CD4+ and FOXP3+ regulatory T cells in decidua with respect to the progression of labor at term and the lack of analogical changes in the subpopulation of suppressive B7-H4 macrophages--a preliminary report. Am J Reprod Immunol200961136146DOI: 10.1111/j.1600-0897.2008.00674.x
SinghNHerbertBSoorannaGROrsiNMEdeyLDasguptaTSoorannaSRYellonSMJohnsonMRIs myometrial inflammation a cause or a consequence of term human labour? J Endocrinol20172356983DOI: 10.1530/JOE-17-0318
AreiaALMouraPMota-PintoA PROSPERO Nº CRD42018089859. The role of innate immunity in spontaneous preterm labor: A systematic review. J Reprod Immunol2019136DOI: 10.1016/j.jri.2019.102616
RomeroRMazorMBrandtFSepulvedaWAvilaCCottonDBDinarelloCAInterleukin-1 alpha and interleukin-1 beta in preterm and term human parturition. Am J Reprod Immunol199227117123DOI: 10.1111/j.1600-0897.1992.tb00737.x
PacoraPRomeroRMaymonEGervasiMTGomezREdwinSSYoonBHParticipation of the novel cytokine interleukin 18 in the host response to intra-amniotic infection. Am J Obstet Gynecol200018311381143DOI: 10.1067/mob.2000.108881
PawelczykENowickiBJIzbanMGPratapSSashtiNASandersonMNowickiSSpontaneous preterm labor is associated with an increase in the proinflammatory signal transducer TLR4 receptor on maternal blood monocytes. BMC Pregnancy Childbirth201010DOI: 10.1186/1471-2393-10-66
KumazakiKNakayamaMYanagiharaISueharaNWadaYImmunohistochemical distribution of Toll-like receptor 4 in term and preterm human placentas from normal and complicated pregnancy including chorioamnionitis. Human Pathology2004354754DOI: 10.1016/j.humpath.2003.08.027
KalagiriRRCarderTChoudhurySVoraNBallardARGovandeVDreverNBeeramMRUddinMNInflammation in Complicated Pregnancy and Its Outcome. Am J Perinatol20163313371356DOI: 10.1055/s-0036-1582397
SinghNHerbertBSoorannaGDasASoorannaSRYellonSMJohnsonMRDistinct preterm labour phenotypes have unique inflammatory signatures and contraction associated protein profiles. Biol Reprod2019DOI: 10.1093/biolre/ioz144
AfrozeSHKalagiriRRReyesMZimmermanJDBeeramMRDreverNZawiejaDCKuehlTJUddinMNApoptotic and stress signaling markers are augmented in preeclamptic placenta and umbilical cord. BBA Clin201662530DOI: 10.1016/j.bbacli.2016.05.003
CerdeiraASKopcowHDKarumanchiSARegulatory T cells in preeclampsia: some answers, more questions? Am J Pathol201218119001902DOI: 10.1016/j.ajpath.2012.09.020
ToldiGSaitoSShimaTHalmosAVereshZVásárhelyiBJrJ RigóMolvarecAThe frequency of peripheral blood CD4+ CD25high FoxP3+ and CD4+ CD25- FoxP3+ regulatory T cells in normal pregnancy and pre-eclampsia. Am J Reprod Immunol201268175180DOI: 10.1111/j.1600-0897.2012.01145.x
ClarkDESmithSKLicenceDEvansALCharnock-JonesDSComparison of expression patterns for placenta growth factor, vascular endothelial growth factor (VEGF), VEGF-B and VEGF-C in the human placenta throughout gestation. J Endocrinol1998159459467DOI: 10.1677/joe.0.1590459
KopcowHDKarumanchiSAAngiogenic factors and natural killer (NK) cells in the pathogenesis of preeclampsia. J Reprod Immunol2007762329DOI: 10.1016/j.jri.2007.03.018
HoyaMNagamatsuTFujiiTSchustDJOdaHAkibaNIriyamaTKawanaKOsugaYFujiiTImpact of Th1/Th2 cytokine polarity induced by invariant NKT cells on the incidence of pregnancy loss in mice. Am J Reprod Immunol201879DOI: 10.1111/aji.12813
FukuiAKwak-KimJNtrivalasEGilman-SachsASKLeeKBeamanIntracellular cytokine expression of peripheral blood natural killer cell subsets in women with recurrent spontaneous abortions and implantation failures. Fertil Steril200889157165DOI: 10.1016/j.fertnstert.2007.02.012
CerdeiraASRajakumarARoyleCMLoAHusainZThadhaniRISukhatmeVPKarumanchiSAKopcowHDConversion of peripheral blood NK cells to a decidual NK-like phenotype by a cocktail of defined factors. J Immunol201319039393948DOI: 10.4049/jimmunol.1202582
WalkerCKKrakowiakPBakerAHansenRLOzonoffSHertz-PicciottoIPreeclampsia, placental insufficiency, and autism spectrum disorder or developmental delay. JAMA Pediatr2015169154162DOI: 10.1001/jamapediatrics.2014.2645
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