Tuesday July 2 2013
Around 1 in 7 women develop postnatal depression
The results of a study examining the genetics of postnatal depression have hit the headlines, with The Guardian reporting that, "British doctors have identified the first advance blood test for postnatal depression".
The study in question looked at small genetic variations called single nucleotide polymorphisms (SNPs), which previous research suggested can increase the risk of postnatal depression. Women were tested for these SNPs, and a screening test for postnatal depression was given both before and after birth.
Researchers found that two SNPs were associated with elevated depression screening test scores, and therefore may be associated with an increased risk of developing the condition.
An accurate screening programme for postnatal depression risk would potentially be very beneficial – prompt diagnosis and treatment can reduce the severity and duration of symptoms.
But, as the researchers concede themselves, this small study has not established that a blood test can accurately diagnose the condition.
The research did not look at the associations between these variations and whether there was a confirmed diagnosis of postnatal depression among new mothers. It also did not assess the effectiveness or the cost effectiveness of using this test as a screening tool.
Further, larger studies are planned, and should provide more detailed information on the feasibility of a screening programme for postnatal depression.
Where did the story come from?
The study was carried out by researchers from the University of Warwick and the University Hospitals Coventry and Warwickshire NHS Trust, and was supported by the Robert Gaddie Memorial Fund and the Birmingham-Warwick Science City Research Alliance.
It was published in the peer-reviewed Journal of Psychiatric Research.
Media coverage of the research focused on the potential for an inexpensive diagnostic test to detect postnatal depression, rather than covering the study itself.
While the potential for inexpensive screening of postnatal depression is genuinely exciting, the limitations of the study – such as its size and the fact that it did not assess associations with diagnosed postnatal depression – should have been made more explicit by the papers. The researchers themselves went to great pains to outline the limitations of their study.
Many papers also quoted that blood tests would cost £10, but it is uncertain where this cost has emerged from.
What kind of research was this?
This was a prospective cohort study that sought to identify genetic variations associated with an increased risk of postnatal depression (PND) among new mothers.
Although individual circumstances and stressful life events can trigger depressive episodes, PND (as with other depressive illnesses) is thought to have a genetic component – a family history of depression is a known risk factor for the disease. The researchers suggest that certain genetic variations may predispose women to PND, while stress-driven hormonal responses may be a trigger.
During pregnancy, the placenta produces corticotrophin-releasing hormone (CRH), which affects what is known as the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis is essentially a biological network consisting of a number of different hormones and glands involved in how a person responds to stressful events. Increased production of CRH during pregnancy causes gradual hormonal changes in the hormones associated with the HPA axis.
After birth there is an abrupt drop in CRH, which can cause an imbalance in the HPA axis that can lead to mood changes, irritability and episodes of tearfulness after birth – the so-called baby blues.
In most women, the HPA axis rebalances in a few days. It is thought that a failure of this rebalancing may be why some women experience postnatal depression.
The researchers investigated two key signalling molecules in the HPA axis: glucocorticoid receptor (GR) and corticotrophin-releasing hormone receptor type 1 (CRH-R1). This was because genetic variations in the genes for these molecules have previously been shown to be correlated with depression.
What did the research involve?
The researchers recruited 200 white pregnant women during antenatal clinic visits. They drew blood from each woman in order to identify specific genetic variations in the GR and CRH-R1 genes. The variations, known as single nucleotide polymorphisms (SNPs), were selected based on their association with depression in previous studies.
The women completed a questionnaire validated to assess PND twice during hospital visits at 20-28 weeks gestation and again between two and eight weeks post-delivery. The Edinburgh Postnatal Depression Scale (EPDS) is a questionnaire consisting of questions such as, "in the past seven days I have been able to laugh and see the funny side of things", with answers ranging from "as much as I always could" to "not at all".
Women with an EPDS score of 10 or greater were considered to be at high risk of developing PND, while women with scores below 10 were classified as low PND risk. Several PND risk factors were assessed during the visit, including:
- family history of PND
- personal history of depression
- presence of depressive symptoms at the time of study recruitment
Women were excluded from the study if they had anaemia, thyroid disease or pre-existing mental illness, or if they were taking antidepressants or other medications that could influence the likelihood of developing PND.
The researchers then analysed the data to identify correlations between specific genetic variations and PND. They then calculated the odds of being at high risk for PND (EPDS score of 10 and above) for each selected genetic variant.
What were the basic results?
Of the 200 women recruited into the study, 140 (70%) completed the study. The majority of the women were considered low risk for PND based on a prenatal EPDS score of less than 10 (111 women, 80%).
Based on EPDS assessments two to eight weeks post-delivery, 34 women (24%) were considered to be high risk for PND. Of these women, 44% had a prenatal EPDS score of 10 or above.
When assessing the association between genetic variants and EPDS scores, the researchers found that:
- There was no significant difference in EPDS scores among women with the two SNPs for the glucocorticoid receptor (GR) gene.
- There was no significant difference in EPDS scores among women with one of the three SNPs for the corticotrophin-releasing hormone receptor type 1 (CRH-R1) gene.
- One of the three SNPs for the corticotrophin-releasing hormone receptor type 1 (CRH-R1) gene was associated with increased EPDS scores during both the pre- and post-natal periods. This may suggest that the variant is not specific to postnatal depression, but depression in general.
- A weak but statistically significant association was detected between one of the three genetic variants for the corticotrophin-releasing hormone receptor type 1 (CRH-R1) gene and postnatal EPDS scores. This suggests that this variant may be specific to postnatal depression only.
When assessing the association between genetic variants and the likelihood of being at high risk for developing PND, the researchers found that:
- There was no significant association between three of the variants assessed and being at high risk for PND.
- There was a significant increase in the likelihood of being at risk for developing PND among women with two of the assessed genetic variants, with odds ratios (OR) ranging from 2.2 (95% confidence interval [CI] 1.2 to 6.9) to 4.9 (95% CI 2.0 to 12.0).
- Among women with specific variations on both the GR and the CRH-R1 genes, there was an even higher increase in the likelihood of being considered at risk for postnatal depression (OR 5.48, 95% CI 2.13 to 14.10), which researchers feel suggests that each variant contributes to PND risk independently.
How did the researchers interpret the results?
According to the researchers, these results provide the first preliminary evidence that specific variations of two genes "involved in stress responses might contribute to the genetics of high risk for depression during pregnancy and post-partum".
This study found that two specific genetic variations known to be associated with "stress responses" may also be associated with elevated scores on a validated, but not routinely used, screening questionnaire for postnatal depression.
This study suggests that certain genetic variations may increase the risk for postnatal depression, but it cannot tell us how these variations interact with environmental and social factors to trigger the condition. As with most mental health conditions, postnatal depression is thought to be a complex disorder associated with many factors.
Researchers report that this is the first study of its kind to look at these genetic variations (or SNPs) and their association with women considered at high risk for developing postnatal depression. There are, however, several limitations of this study that should be considered.
This study assessed postnatal depression risk using a validated pre-screening tool. It did not assess the correlation between genetic variants and an actual diagnosis of PND. Further research is required to determine whether these variants are also linked to PND diagnoses.
The analysis also only included women who completed both questionnaires, and the completion rate was fairly low at 70%. It is unclear whether this biased the results, as women with PND may have been less likely to return for the postnatal hospital visits that provide the data for analysis.
The researchers report that there were not enough participants in the study to "provide adequate power for all SNPs associations". They estimate that further research will need to involve approximately four times as many patients.
It should be noted that the results of this study should not be generalised to other ethnicities, as only white women were included in the research and the prevalence of PND varies among different ethnic groups.
In spite of these limitations, the results of this study are encouraging. It would be surprising if this piece of research was not followed up by a larger study.
Read more about the signs and symptoms, diagnosis and treatment of postnatal depression.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.