Depression during pregnancy and postpartum: An Integrative and Precision Medicine-based Approach

An Overview of Depression during the Perinatal Period

Depressive episodes during the pregnancy and post-partum period are common, affecting 10 to 20% of women. Postpartum depression (PPD) in particular, impacts 15% of women. In addition, depression during the perinatal period is often under-recognized by healthcare professionals and many women struggle without support or treatment. So what are some holistic and personalized approaches to prevent and treat depression experienced by women during pregnancy and post-partum? Let's dive in.

Precision Medicine and Integrative Medicine for Mental Health

Personalized, or precision medicine, involves utilizing genetic information, biomarkers, and technology to determine personalized treatment decisions for people. Integrative medicine is a holistic approach to health, taking into consideration both conventional psychiatric treatments (like medication and therapy), as well as other treatments such as mind-body practices, supplements, nutrition, lifestyle, and spirituality. So when we combine personalized and integrative medicine, we really can individualize treatment that is not only effective but also aligned with a patient's values.

Hormones, Inflammation, and Depression during Pregnancy

Levels of the hormones, estradiol and progesterone increase throughout pregnancy and are higher than pre-pregnancy levels. Estradiol and progesterone rapidly decrease after delivery and that rapid estrogen withdrawal has been linked to anxiety and depression during the post-partum period. However, hormones are much more complicated than that; estrogen has also been shown to increase inflammatory markers and pro-inflammatory activity is also associated with depression. There is still a lot that is unknown.

The Microbiome as a Biomarker for Perinatal Mental Health

The diversity of the microbiome has an impact on immune response and levels of inflammation. Dysbiosis, or a shift towards more disease-causing microbes and less diversity in the gut, is associated with mental health conditions such as anxiety and depression. With dysbiosis, there is an increased risk of losing an intact intestinal barrier. When the intestinal barrier is no longer intact, bacteria can get into the blood circulation which activates the immune response and produces pro-inflammatory cytokines. This is often called "leaky gut". Dysbiosis can also reduce levels of estrogen in the bloodstream, which could further contribute to mood symptoms.

The Impact of the HPA Axis and Autonomic Nervous System on Perinatal Mental Health

The Hypothalamic-Pituitary-Adrenal (HPA) axis and Autonomic Nervous System (ANS) can significantly impact mental health and in particular, anxiety and depression have been associated with dysfunction in the HPA axis and ANS.

Cortisol, an important hormone that gets released in response to stress, is a biomarker that is frequently assessed in integrative and precision psychiatry. It seems that women with elevated cortisol during pregnancy are more likely to have an increased risk of post-partum depression.

Heart rate variability (HRV) is a measure of how the sympathetic and parasympathetic nervous system affects your heart beat and measures the beat-to-beat changes in the heart rate. When you have high HRV, it means that your body is responsive to input from both the sympathetic and parasympathetic nervous system and that your nervous system is balanced. A low HRV means that either the sympathetic or parasympathetic nervous system is dominating and that your body is in a less resilient state. Higher HRV measures have been associated with a lower likelihood of future depression symptoms, as well as lower pro-inflammatory activity. A study in 2008 (Shea et al.) found that women experiencing depression during pregnancy had lower HRV.

Current Treatments for Depression during Pregnancy and Post-Partum

Conventional treatments for depression during pregnancy typically involve talk therapy and/or antidepressant medications and particularly, SSRIs. SSRIs, or Selective Serotonin Reuptake Inhibitors, are considered to be safe to take during pregnancy and are effective options for many pregnant women experiencing depression. However, there is a need for new treatments. Some women and healthcare providers do not feel safe using SSRIs during pregnancy and post-partum. Additionally, not all symptoms are improved with SSRIs and some women experience side effects that are intolerable.

Depression treatment needs to move beyond a "one size fits all" model and move towards a precision-based approach. There are specific biomarkers that can be assessed via lab work and wearable technology that can help guide treatment. Depression seems to have different subtypes, such as an inflammatory subtype. Those with higher levels of inflammation tend to have a poorer response to antidepressants, at least in individuals who are not pregnant. There is a lack of research studying the effectiveness of antidepressants in pregnant women with higher levels of inflammation.

Precision-based and Integrative Treatments for Depression during Pregnancy and Post-Partum

Microbiome-Focused Treatments

A double blind placebo controlled randomized trial found that women who supplemented with the probiotic, Lactobacilus rhamnolsus HN001, had significantly decreased postpartum anxiety and depression. It was noted to be safe and well tolerated in the study (Slykerman, 2017). Prebiotics may be helpful as well but there have not been any randomized controlled trials done yet.

Vagus Nerve Regulation Treatments and Practices

The vagus nerve connects the gut and brain, serving as the brake we can use when we need to decrease our physiological response to stress. There are many practices and treatments that can help regulate the vagus nerve and therefore, regulate our body's response to stress. This has downstream positive effects on the immune system, inflammatory response, and gut microbiome.

• Vagus Nerve Stimulation: Using a surgically implanted device to stimulate the vagus nerve, this is a non-pharmacological but invasive treatment that may be effective for some people with treatment resistant depression. There has only been one case study of a woman successfully treated with vagus nerve stimulation during pregnancy. This may be an option for pregnant women with severe treatment resistant depression but is considered experimental since there is not enough research.

• Vagal breathing: The fastest way to regulate the vagus nerve and autonomic nervous system. It is safe and effective during pregnancy.

  • 4-7-8 breathing technique: Breathe in for 4 seconds, hold the breath for 7 seconds, and exhale for 8 seconds. Repeat 4-8 times, at least once a day.

  • Diaphragmatic breathing technique: Slow down the breath from 10-14 breaths per minute to 5 - 7 breaths per minute. Emphasize the exhale.

• Meditation and Mindfulness: This involves training oneself to be aware of their thoughts, breathing, heart rate, and other signs of tension. This helps us recognize stress when it begins and develops the ability to become an objective observer of stressful thoughts instead of a victim of them.

Heart Rate Variability Training

Heart rate variability training can also help regulate the vagus nerve and potentially help lessen depressive symptoms and increase overall resiliency. Wearable technology such as the Oura ring, WHOOP, or ear sensors through Heart Math are helpful tools for heart rate variability training. (As a side note, I am not affiliated with any of these products)

Nutrition and Omega 3 Fatty Acids

Targeted nutritional recommendations are personalized for each individual depending on many factors, including biomarkers. Nutrition recommendations for women experiencing depression or wanting to prevent depression during pregnancy or postpartum may include focusing on blood sugar stabilization, healthy fats and high quality protein, or timed nutrition rather than making huge dietary pattern changes during pregnancy. Omega 3 fatty acids decrease cortisol levels and have also been shown to be an effective and safe option during pregnancy for women experiencing mild to moderate depression.

Supplements and Herbs

Many (most) supplements and herbs, such as adaptogens are not well-studied in women who are pregnant or lactating. The above treatments have been found to be safe and effective during pregnancy and with breastfeeding. It is recommended that you discuss any supplements or herbs that you are considering taking with your health care provider.

The information and any products mentioned in this article are not intended to diagnose, treat, cure, or prevent any disease. The information provided is for educational purposes only and not intended to replace the relationships with your physician(s). Before initiating any conventional or integrative treatments, please first consult with a licensed medical provider. Please review references provided at the end of article for scientific support of any claims made.

Looking for an integrative psychiatrist with a personalized medicine approach? Work with me: https://www.driftlessintegrativepsychiatry.com/workwithme

Sources:

Fransson, E. (2021). Psychoneuroimmunology in the context of perinatal depression - Tools for improved clinical practice. Brain, Behavior, & Immunity (17). https://www.sciencedirect.com/science/article/pii/S2666354621001356#bib54

MGH Center for Women's Mental Health. What about vagus nerve stimulation? https://womensmentalhealth.org/posts/what-about-vagus-nerve-stimulation/

Slykerman, R.F., et al. (2017). Effect of lactobacillus rhamnosus HN001 in pregnancy on postpartum symptoms of depression and anxiety: A randomised double-blind placebo-controlled trial. The Lancet, 24(159-165). https://pubmed.ncbi.nlm.nih.gov/28943228/

Zhang, MM., Zou, Y., Li, SM. et al. The efficacy and safety of omega-3 fatty acids on depressive symptoms in perinatal women: a meta-analysis of randomized placebo-controlled trials. Transl Psychiatry, 10, 193 (2020). https://doi.org/10.1038/s41398-020-00886-3