Over the past decade, many professional organizations have called for universal screening for depression and anxiety in pregnant and postpartum women. The aim of screening is to identify women with depression and start treatment early. While this is certainly an important aspect of mental health care for pregnant and postpartum women, optimal screening of this population should include identifying women at increased risk for perinatal mental health conditions prior to symptom onset .
To date, epidemiological studies have revealed that the strongest predictor of risk for perinatal depression is a history of mood or anxiety disorder before pregnancy. Other risk factors include history of childhood adversity, recent life stressors, intimate partner violence, and overall physical health. Although there are data to support the validity of these risk factors at the population level, it is difficult to use these factors when it comes to calculating an individual’s risk for perinatal psychiatric illness. In addition, there are also factors that reduce risk (for example, social supports) and it is often difficult to account for these mitigating factors in our risk estimates.
Given the limited utility of these clinical and demographic risk factors for perinatal psychiatric illness, many researchers have focused on identifying biomarkers that could help quantify an individual’s risk for perinatal mood and anxiety disorders. Biomarkers are measurable indicators of a biological process or condition and can provide a more comprehensive assessment of an individual’s risk for developing perinatal mood and anxiety disorders. Examples of biomarkers include genetic markers, brain imaging, and biochemical tests.
A new study by Sheng and colleagues examined the levels of various metabolites in the cerebrospinal fluid of women at the time of delivery as potential biomarkers for postpartum depression. In this study, 75 women undergoing cesarean delivery were enrolled for CSF collection during labor. Women with identified risk factors for PPD, including a history of mood disorder and/or antidepressant use, as well as other PPD risk factors, were excluded. After this procedure, only 28 subjects remained: 10 with low EPDS scores at 6 weeks (less than 5), 10 with higher EPDS scores (13 or greater), and 8 in the middle range.
Gas chromatography-mass spectrometry (GC-MS) analysis of CSF was used to perform metabolomic assessments of CSF. Although the sample was very small, the researchers observed that the levels of several metabolites in CSF-Capric acid, dodecanoic acid, arachidic acid and behenic acid – were negatively associated with PPD symptoms. On the other hand, L-tryptophan levels were positively associated with postpartum depressive symptoms.
The Clinical Utility of CSF Biomarkers
This is the first study to investigate the use of maternal CSF metabolomics to predict postpartum depression risk. CSF levels of capric acid, dodecanoic acid, arachidic acid, behenic acid, and L-tryptophan were associated with PPD symptoms. Even more strikingly, all five CSF metabolites could be used as prognostic biomarkers for PPD due to their excellent discriminatory performance.
While several studies have assessed levels of neurotransmitter metabolites in blood, the use of CSF may have some benefits in that it assesses neurotransmitter levels without blood-brain barrier interference. The women in this study underwent caesarean section and thus received spinal anesthesia. This facilitated the procurement of CSF samples. Obtaining a CSF sample from women undergoing vaginal delivery can present some obstacles.
Furthermore, the current study may shed some light on the etiology of PPD. L-tryptophan is metabolized into neuroactive compounds, including serotonin. Arachidic acid, behenic acid, capric acid, and dodecanoic acid are byproducts of fatty acid metabolism. Although not traditional neurotransmitters, fatty acids are involved in regulating brain function, including cognitive performance and mood. Consequently, it may be constructive to examine more closely the relationship between CSF fatty acid concentrations and L-tryptophan with the onset of PPD. Such research could potentially reveal new therapeutic targets for the treatment or prevention of PPD.
This was a very small study conducted in a carefully selected population of women who underwent cesarean delivery. Although these findings need to be replicated in larger studies in more populations, this innovative study shows that changes in brain metabolism – as seen with changes in CSF levels of fatty acid metabolites and L-tryptophan, may precede of the onset of PPD and may be useful in risk prediction.
Ruta Nonacs, MD PhD
bibliographical references
Sheng Z, Liu Q, Lin R, Zhao Y, Liu W, Xu Z, Liu Z. Potential CSF biomarkers of postpartum depression after cesarean delivery. J Affect Disord. 2023 Dec 1;342:177-181.
