Using Metabolic Biomarkers to Predict Risk for Postpartum Depression

Over the last decade, many professional organizations have called for universal screening for depression and anxiety in pregnant and postpartum women. The goal of screening is to identify women with depression and to initiate treatment early. While this is certainly an important aspect of caring for the mental health of pregnant and postpartum women, optimal screening of this population should include the identification of women at increased risk for perinatal mental health conditions before the onset of symptoms.

Thus far, epidemiologic studies have revealed that the most robust predictor of risk for perinatal depression is a history of mood or anxiety disorder prior to pregnancy. Other risk factors include history of childhood adversity, recent life stressors, intimate partner violence, and overall physical health. Although there is data to support the validity of these population-level risk factors, it is difficult to utilize these factors when it comes to calculating an individual’s risk for perinatal psychiatric illness. In addition, there are also factors that decrease risk (for example, social supports), and it is often difficult to account for these mitigating factors in our estimations of risk.

Given the limited utility of these clinical and demographic risk factors of perinatal psychiatric illness, many researchers have focused on the identification of biomarkers that could help to quantify an individual’s risk for perinatal mood and anxiety disorders. Biomarkers are measurable indicators of a biological process or state 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 from Sheng and colleagues examined levels of various metabolites in the cerebrospinal fluid of women at the time of delivery as possible biomarkers for postpartum depression. In this study, 75 women undergoing delivery by cesarean section were enrolled for CSF collection at delivery. Women with identified risk factors for PPD, including history of mood disorder and/or use of antidepressant, as well as other PPD risk factors, were excluded; after this process, 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 carry out metabolomic assessments of the CSF. Although the sample was very small, the researchers observed that levels of several metabolites in CSF–capric acid, dodecanoic acid, arachidic acid and behenic acid–were negatively correlated with PPD symptoms. On the other hand, levels of L-tryptophan were positively correlated 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 risk of postpartum depression. The CSF levels of capric acid, dodecanoic acid, arachidic acid, behenic acid, and L-tryptophan correlated with PPD symptoms. Even more impressive is that all five CSF metabolites could be used as predictive biomarkers for PPD by virtue of their excellent discriminatory performance.

While several studies have assessed levels of neurotransmitter metabolites in blood, the use of CSF may have certain benefits in that it assesses neurotransmitter levels without interference of the blood-brain barrier. The women participating in this study were undergoing cesarean section and thus received spinal anesthesia; this facilitated the procurement of CSF samples. Obtaining a CSF sample from women undergoing vaginal delivery may present certain barriers. 

In addition, 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. While not traditional neurotransmitters, fatty acids are involved in the modulation of brain function, including cognitive performance and mood. Consequently, it may be fruitful to more closely examine the link between CSF concentrations of fatty acids and L-tryptophan to the onset of PPD. Such investigations could potentially uncover new therapeutic targets for the treatment of PPD, or its prevention. 

This was a very small study carried out in a carefully selected population of women undergoing cesarean section at delivery. Although these findings must be replicated in larger studies in more populations, this innovative study indicates that changes in brain metabolism–as seen with alterations in CSF levels of fatty acid metabolites and L-tryptophan, may precede the onset of PPD and may be useful in predicting risk. 

Ruta Nonacs, MD PhD

References

Sheng Z, Liu Q, Lin R, Zhao Y, Liu W, Xu Z, Liu Z. Potential CSF biomarkers of postpartum depression following delivery via caesarian section. J Affect Disord. 2023 Dec 1;342:177-181.