Depression – The Emotional Response to Your Microbiome

Holy Hormones Journal:

I have been patiently waiting to post this incredibly powerful article by Bonnie Kaplan, PhD on the emerging field of nutritional mental health. According to Freud, the ego is part of  Healthy-womanpersonality that mediates the demands of the id, the superego and reality. However, Freud has had his day in the limelight – and has for hundreds of year convinced millions that we are driven by this part of the personality.

Now we know it is time to throw the ego out with the bathwater – because the concept has done us more harm then good – at least in my humble opinion. The “I”, and “me” is now known to be driven from the biochemical makeup of your self. Your microbiome. The healthier you are – the healthier your personality.

I hear from so many women who experience hormone related depression, and anxiety. I have heard so many women cry out – “What is wrong with me?” And then I hear their story which in most cases increases with age – and perimenopause and childbirth. All which deplete vital nutrients from the body.

It is becoming increasingly common to hear from women suffering from depression and/or mental illness who are very young. That is very scary. But as each generation passes we are becoming more and more nutrient depleted. And exposed to so many more toxins.

I have interviewed Bonnie Kaplan, PhD before on my radio show (she will be on the air with me on May 13, 2015) and one of the most brilliant statements I have heard: “Nutrition is the primary treatment, medication the supplement.” Think about it.

A whole new world is emerging that in essence takes away our dependence on labels, diagnosis, medications and therapies. The first line is of healing is rebuilding your nutritional status.

Think of it this way – if your experiencing depression and anxiety – it is the emotional response to an imbalance in your body. Correct the imbalance – and heal the emotional response. Your health is now in your control. That is an amazing turn of events for the millions of people who have been diagnosed, labeled, and medicated and who continue to suffer.

Medication masks. Nutrition heals.

Your choice.

It is amazing to contemplate the implications of the fact that at least 90% of the cells in and on our bodies are not human:
They are the microbial cells (especially bacteria) that constitute our microbiome. ~ Bonnie Kaplan, PhD

The Emerging Field of Nutritional Mental Health

Inflammation, the Microbiome, Oxidative Stress, and Mitochondrial Function


Foundation for Excellence in Mental Health Care
by Bonnie J Kaplan PhD et al | Clinical Psychological Science
February 2, 2015


We live in a transformational moment for understanding the etiology of mental disorders. The previous leap in understanding occurred 60 years ago, which led us to incorporate Bonnie Kaplan headshot - OKpsychopharmacology into our curricula to address the chemical basis of neurotransmitter function, especially as explained through the then-popular catecholamine hypothesis. The current revolution is broader, consisting of the rapidly accumulating knowledge of how inflammation, microbiome imbalance (gut dysbiosis), oxidative stress, and impaired mitochondrial output affect brain function. Suitable interventions for fighting inflammation, restoring normal gut function, reducing oxidative stress, and improving mitochondrial metabolism incorporate lifestyle variables, including nutrients and probiotics. This article invites readers to stay abreast of this emerging model of the biological basis of mental illness, given that it has particular relevance for those readers interested in alleviating the suffering of individuals with mental disorders. This overview describes the basis for a new field in mental health: nutritional psychiatry/psychology.

In the mid-1960s, psychiatry researchers developed what became known as the catecholamine or biogenic amine hypothesis of mood disorders, which led to the concept that abnormal mood states were caused by imbalances in neurotransmitters such as serotonin. Although the public still embraces the construct of “chemical imbalance” as a full explanation of etiology, the theory seems impossibly superficial and vague by 21st-century standards. As Gardner and Boles (2005) pointed out in their seminal article “Beyond the Serotonin Hypothesis,” there is still a role for neurotransmitters such as serotonin in the new models, but only when embedded in a current understanding of brain metabolism. Metabolic mechanisms currently being studied extensively relate to inflammation, the microbiome, oxidative stress, and impaired mitochondrial function. It is particularly imperative that mental-health professionals understand the treatment implications of these new discoveries and models, given that the most appropriate therapeutic approaches often involve lifestyle modifications that are within their scope of practice (Walsh, 2011). The overview presented here summarizes the literature that constitutes the basis for a new field in mental health: nutritional psychiatry/psychology.

Inflammation and Mental Health

It has been almost 25 years since Maes et al. (1990) first reported enhanced immune activity in major depression. In the ensuing decades, the “immunity hypothesis” of depression has been strongly supported: Depression is associated with activation of inflammatory responses (Berk et al., 2013; Dowlati et al., 2010). Studies on mental health in relation to low-grade, systemic inflammatory activity often employ serum levels of biomarkers, such as the amino acid homocysteine (associated with elevated risk of cardiovascular disease), C-reactive protein (which rises in response to inflammation or infection), or any of a series of cytokines (cell-signaling molecules involved in intracellular communication) that promote systemic inflammation, especially tumor necrosis factor alpha (TNF-alpha) and Interleukin 6 (IL-6). One example of this type of research is the Cooper Center Study of almost 12,000 adults: Elevated homocysteine levels were associated with 26% increased odds of scoring in the depression range on the Center for Epidemiologic Studies Depression Scale, even after researchers controlled for many variables likely to influence both inflammation and depression (e.g., age, sex, body mass index, exercise; Gu et al., 2012; Reber, 2012). A meta-analytic review of the role of cytokines in depression reported that in spite of some inconsistent findings, the association of TNF-alpha and IL-6 with diagnosed depression was strongly supported (Dowlati et al., 2010).

Abundant evidence from both experimental and clinical studies has shown that inflammation can induce symptoms of depression (Dantzer, 2012), which has led to a lively debate about whether inflammation causes depression, depression causes inflammation, or both. Even longitudinal data suggest that the causal relationships are complex, with depression sometimes preceding elevations in biomarkers of inflammation, and the biomarker elevation sometimes preceding symptoms of depression.

Inflammatory processes have also been demonstrated in bipolar disorder (Hamdani, Tamouza, & Leboyer, 2012) and psychosis (Borovcanin et al., 2012), although, again, the picture is complicated. In a few cases, some inflammatory biomarkers have shown the elevated levels expected in association with symptom severity, but other inflammatory markers have been low, thereby resulting in the hypothesis that lower markers of inflammation may indicate the body’s attempt to limit proinflammatory processes. Given the overall strength of the data associating inflammation with mental-health symptoms, it is relevant that a meta-analysis of clinical trials of nonsteroidal anti-inflammatory drugs (NSAIDs) used as adjuncts in treatment for schizophrenia showed a mean effect size of 0.43, indicating that the NSAIDs (celecoxib in four studies, and aspirin in the fifth) had a moderately beneficial impact on symptoms (Sommer, de Witte, Begemann, & Kahn, 2012). In terms of etiology, the logical question is this: What causes systemic, chronic inflammation? One very promising area of research focuses on the role of the gastrointestinal (GI) system.

The Microbiome and Mental Health

It is amazing to contemplate the implications of the fact that at least 90% of the cells in and on our bodies are not human: They are the microbial cells (especially bacteria) that constitute our microbiome. Most reside in the GI system, where they protect the intestinal barrier defense system, digest our food, extract the nutrients that we need, and in some cases synthesize those nutrients for us (Carpenter, 2012). This ecological community of 1013 to 1014 microorganisms in the GI tract is an integral part of the system of bidirectional communication between the gut and the brain, termed the “gut-brain axis.” An imbalance in gut bacteria (dysbiosis) can have various negative repercussions for the host, including the potential for overgrowth of already-present opportunistic microorganisms, such as Clostridium difficile, a decrease in production of short-chain fatty acids, and an increased susceptibility to intestinal pathogens (Bailey et al., 2011). Evidence has suggested that the depletion or absence of beneficial bacteria that promote the development of the immune system can lead to the induction of inflammatory responses (Berk et al., 2013) and that this altered immune response could underlie many known chronic inflammatory disorders, including inflammatory bowel disease, rheumatoid arthritis (Round & Mazmanian, 2009), and possibly—as mentioned earlier—some mental disorders, particularly depression, which has been strongly associated with increased inflammatory activation (Berk et al., 2013).

There are many possible causes of gut dysbiosis, including the use of broad-spectrum antibiotics, a poor diet, and the modern environment’s being too clean (the hygiene, or “Old Friends,” hypothesis; Hawrelak & Myers, 2004; Rook, Raison, & Lowry, 2012). Psychological stress also appears to have a significant effect on the composition of the microbiota: This has been shown in animal models prenatally (Bailey, Lubach, & Coe, 2004), in early life (Bailey & Coe, 1999; Berk et al., 2013), and in adulthood (Bailey et al., 2011). These effects can last for a long time: Changes to the gut microbiota of rats that had undergone maternal separation 3 hr per day for 10 days after birth were maintained through to adulthood (O’Mahony et al., 2009). In observing these long-term effects, together with changes in behavior, systemic immune responses, and hypothalamic-pituitary-adrenal (HPA) axis function, O’Mahony et al. (2009) concluded that early life stress induces persistent changes to the gut-brain axis and that these changes could contribute to symptoms of irritable bowel syndrome and psychiatric disorders in adulthood. This effect of psychological stress on the microbiota has also been demonstrated in humans (Knowles, Nelson, & Palombo, 2008).

Several studies have suggested that administering probiotic bacteria can affect emotional behavior in animal models (Bravo et al., 2011; Desbonnet et al., 2010;Desbonnet, Garrett, Clarke, Bienenstock, & Dinan, 2008; Messaoudi et al., 2010). For example, Bravo et al. (2011) treated healthy mice with a probiotic formulation containing Lactobacillus rhamnosus or a placebo and then subjected all animals to a battery of anxiety- and depression-related behavioral tests. Results showed that chronic treatment with Lactobacillus rhamnosus reduced anxiety- and depression-related behavior. This study also showed that probiotic administration induced region-dependent alterations in GABA in the brains of the mice. GABA is the main inhibitory neurotransmitter in the mammalian central nervous system, and alterations in its receptor expression are implicated in the development of anxiety and depression (Cryan & Kaupmann, 2005). In addition, the neurochemical and behavioral effects were not seen in mice whose vagus nerve was surgically severed, identifying the vagus nerve as a plausible major communication pathway between the gut microbiota and the brain.

Read full article…


Author: Leslie Carol Botha

Author, publisher, radio talk show host and internationally recognized expert on women's hormone cycles. Social/political activist on Gardasil the HPV vaccine for adolescent girls. Co-author of "Understanding Your Mood, Mind and Hormone Cycle." Honorary advisory board member for the Foundation for the Study of Cycles and member of the Society for Menstrual Cycle Research.


  1. Can you tell me what the radio station is in Asheville NC?

  2. Do not understand your question?

  3. Great Post…!! Adrenal fatigue is the symptoms of depression and now a days I am feeling it. This problem gives very stress and specially for the women. Please suggest me for Adrenal Fatigue Supplements.

  4. Hello, James – Glad you found the post so interesting.
    Dr. Kaplan and I had a great interview last night as well.

    I highly suggest that EMPowerplus Q96 on my blog. The most highly researched nutritional supplement on the market.
    Extremely bio-available. Perfect ratio of vitamins, aminos and minerals.

    Let me know if you need more information.

    Hormone regards,


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