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Using Metabolic Biomarkers to Predict Risk for Postpartum Depression

Using Metabolic Biomarkers to Predict Risk for Postpartum Depression

During the last decade, many skilled organizations have called for universal screening for depression and anxiety in pregnant and postpartum women. The goal of screening is to discover women with depression and to initiate treatment early. While that is definitely a very important aspect of caring for the mental health of pregnant and postpartum women, optimal screening of this population should include the identification of ladies at increased risk for perinatal mental health conditions before the onset of symptoms.

To this point, epidemiologic studies have revealed that probably the most robust predictor of risk for perinatal depression is a history of mood or anxiety disorder prior to pregnancy. Other risk aspects include history of childhood adversity, recent life stressors, intimate partner violence, and overall physical health. Although there may be data to support the validity of those population-level risk aspects, it’s difficult to utilize these aspects in terms of calculating a person’s risk for perinatal psychiatric illness. As well as, there are also aspects that decrease risk (for instance, social supports), and it is usually difficult to account for these mitigating aspects in our estimations of risk.

Given the limited utility of those clinical and demographic risk aspects of perinatal psychiatric illness, many researchers have focused on the identification of biomarkers that might help to quantify a person’s risk for perinatal mood and anxiety disorders. Biomarkers are measurable indicators of a biological process or state and may provide a more comprehensive assessment of a person’s risk for developing perinatal mood and anxiety disorders. Examples of biomarkers include genetic markers, brain imaging, and biochemical tests.

A brand new study from Sheng and colleagues examined levels of assorted metabolites within the cerebrospinal fluid of ladies on the time of delivery as possible biomarkers for postpartum depression. On this study, 75 women undergoing delivery by cesarean section were enrolled for CSF collection at delivery. Women with identified risk aspects for PPD, including history of mood disorder and/or use of antidepressant, in addition to other PPD risk aspects, were excluded; after this process, only 28 subjects remained: 10 with low EPDS scores at 6 weeks (lower than 5), 10 with higher EPDS scores (13 or greater), and eight in the center range.

Gas chromatography-mass spectrometry (GC-MS) evaluation of CSF was used to perform 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. Then again, levels of L-tryptophan were positively correlated with postpartum depressive symptoms. 

The Clinical Utility of CSF Biomarkers

That is the primary study to analyze the usage 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. Much more impressive is that each one five CSF metabolites may very well 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 usage of CSF can have certain advantages in that it assesses neurotransmitter levels without interference of the blood-brain barrier. The ladies participating on 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. 

As well as, the present 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 within the modulation of brain function, including cognitive performance and mood. Consequently, it could 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 latest therapeutic targets for the treatment of PPD, or its prevention. 

This was a really small study carried out in a fastidiously chosen population of ladies undergoing cesarean section at delivery. Although these findings have to be replicated in larger studies in additional populations, this progressive 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 will be useful in predicting risk. 

Ruta Nonacs, MD PhD


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.


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