Zhuojun Chen

Abstract: In modern society, due to the pressures of work and academics, there is an increasing trend in the incidence of depression. As people pay more and more attention to mental health and the mind-body connection, the current state of Western medical treatment for depression is not ideal. There is an urgent need for natural therapies with safe and comfortable treatments. Since serotonin imbalance is an important factor in depression, this article takes serotonin as the starting point and analyzes the correspondence between the brain-gut axis and the traditional Chinese medicine concept of liver stagnation and spleen deficiency. It proposes a new approach to the treatment of depression, guided by the theory of the brain-gut axis, integrating both Western and Chinese medicine. It also introduces a number of cases and clinical experiences in treating patients with depression, as well as the results of existing research on traditional Chinese medicine methods for the treatment of depression.

The principal symptoms of depression are that patients are trapped in sadness and anxiety, and not being able to derive interest, happiness, or pleasure from daily activities. The mechanism of depression is not fully understood, but it is currently believed that the hormones that bring feelings of pleasure and happiness to the human body include endorphins and serotonin. Although there is still debate within the academic field whether serotonin deficiency is the main factor in the onset of depression, the current antidepressant medications developed based on the theory of serotonins control over human emotions include: Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs), Tricyclic Antidepressants (TCAs), Monoamine Oxidase Inhibitors (MAOIs), Tetracyclic Antidepressants (TeCAs), and Noradrenaline and Specific Serotonergic Antidepressants (NaSSAs).^［1］

Production and distribution of serotonin

Serotonin, also known as serum tonicity factor or 5-hydroxytryptamine/serotonamine, is a type of monoamine neurotransmitter. It cannot be directly produced in the human body. Instead, humans must ingest tryptophan (which is one of the 22 standard amino acids and an essential amino acid that cannot be synthesized by the body and must be obtained from food). In the digestive tract, tryptophan is converted into 5-hydroxytryptophan by tryptophan hydroxylase, and then into serotonin by 5-hydroxytryptophan decarboxylase in the central nervous neurons and the enterochromaffin cells of the digestive tract of animals, including humans. About 90% of serotonin is primarily distributed in the mucosal enterochromaffin cells and myenteric plexus, and participates in the regulation of intestinal peristalsis in the intestine. Only 2% of the total serotonin is present in the brain, where it is involved in regulating sleep and emotions, contributing to states of ‘excitation’ or ‘inhibition.’ An additional 8-9% is absorbed through the intestinal mucosa into the bloodstream and stored in platelets. When the body is injured, platelets aggregate and release serotonin, causing blood vessels to constrict and aiding in blood coagulation and hemostasis. Serotonin also acts as a growth factor for some cells and plays a role in wound healing. There are various serotonin receptors. It is worth noting that serotonin cannot cross the blood-brain barrier, so the levels of serotonin in the gut and blood do not affect the serotonin levels in the central nervous system, maintaining a stable and independent system.

The relationship between serotonin and the brain-gut axis

The brain-gut axis is a bidirectional communication network between the brain and the gastrointestinal tract. The concept of the brain-gut axis originated from a 2004 study that found a significant connection between the gut microbiota of mice and the hypothalamic-pituitary-adrenal axis. Subsequent research has increasingly discovered the regulatory effect of gut microbiota on the brain, as seen in conditions like autism and Parkinsons disease, where imbalances in gut microbiota are present. Adjusting the gut microbiota can lead to significant improvements in symptoms. Since serotonin is present in both the brain and the gut, it is considered a very important theoretical basis for the brain-gut axis. Recent studies indicate that changes in the gut microbiota might help regulate 5-hydroxytryptamine (serotonin) signaling. Imbalances in serotonin levels and changes in the gut microbiome are thought to contribute to the onset and severity of depression. Research shows that changes in the composition of the gut microbiota (referred to as dysbiosis) can affect brain function and behavior. Specific bacteria within the gut microbiome can produce or regulate neurotransmitters, including serotonin. Therefore, dysbiosis of the gut microbiota may lead to depressive symptoms. Additionally, the gut microbiome influences the integrity of the intestinal barrier, thus affecting the production of immune molecules and the release of inflammatory mediators related to depression.

The Relationship between Serotonin and Stress

In nature, when mammals face stress, the amygdala in the brain gets activated, and cortisol (a glucocorticoid hormone) secretion increases. This process leads to the breakdown of amino acids into glucose to meet the body’s ‘fight or flight’ needs. In other words, amino acids like tyrosine and tryptophan are also broken down into glucose for these needs, leading to a deficiency in the precursors of serotonin and norepinephrine. This deficiency can cause a range of symptoms in individuals under stress, such as low mood, loss of interest, and even suicidal tendencies. To counter the dual impact of stress on serotonin and norepinephrine, pharmaceutical companies developed SNRI class antidepressants in 1993, which increase the levels of serotonin and norepinephrine in the body to combat negative emotions. However, in the natural world, the increase in cortisol and the breakdown of amino acids into glucose is a normal physiological response to stress, usually resolving after the ‘fight or flight’situation ends. This is not a pathological reaction, so as long as stress exists, the body will respond to it, and this stress response cannot be stopped as it is a normal physiological state. However, the stress in modern human society is different from the ‘fight or flight’mechanism of primitive societies, often being slow and long-term, and not resolvable through ‘fight or flight,’ leading to prolonged stress responses and resulting in depression and anxiety. Since this is not actually a pathological state, it cannot be cured through medication or the passage of time. Antidepressants can only help maintain a temporary state of happiness, and symptoms may reappear after stopping the medication.^［2］

Side Effects of Antidepressant Medication

Since the occurrence of depression may be a normal physiological reaction, it is just because we are in a modern civilized society that it cannot eliminate stress factors. Therefore, it may not be cured by drug treatment at all, so long-term antidepressant drugs are needed for relief. Various side effects may occur due to low mood, such as increased appetite, insomnia, dry mouth, fatigue, decreased sexual function, etc. At present, more and more psychiatrists and patients are noticing this and trying to find treatment methods other than drugs. For example, depression can be treated by adjusting stress or changing lifestyle and diet. Among them, traditional Chinese medicine therapy is very popular because of its low incidence of side effects and remarkable effects.

Common Traditional Chinese Medicine Diagnoses for Depression

The most common syndrome type of depression diagnosed in traditional Chinese medicine (TCM) is liver stagnation syndrome, and the main causes of liver stagnation syndrome are divided into two types: liver stagnation and spleen deficiency and kidney deficiency and liver stagnation. This article mainly analyzes the syndrome types of liver stagnation and spleen deficiency. Literally understood, liver stagnation and spleen deficiency means that the low function of the digestive system will affect a persons emotional deficiency and lead to depression. The syndrome of liver stagnation and spleen deficiency can be better explained from the five-element theory of viscera. In the five-element theory, the liver is wood and the spleen is soil. When trees are planted in narrow or poor soil, it is not conducive to the growth of trees. Therefore, in the treatment of liver stagnation and spleen deficiency, traditional Chinese medicine can transplant trees to wider land and the liver wood is overly suppressed, it is equivalent to transplanting a big tree into a small piece of land. This will cause the tree to over absorb nutrients from the soil and lead to serious soil loss. This is a syndrome of liver stagnation insulting the spleen. The main symptoms are that the patient’s depression affects the digestive system, leading to indigestion, loss of appetite, diarrhea, constipation, weight loss, etc.

The relationship between “Liver stagnation and Spleen deficiency” in traditional Chinese medicine and the “brain-gut axis,” as well as some speculations about their role in serotonin regulation

The brain-gut axis is an axis with two-way influence, that is, intestinal microbiota intestinal function, and the brain interact with each other. The theory of liver stagnation and spleen deficiency in traditional Chinese medicine is very consistent with the brain-gut axis theory of western medicine. It reveals that the digestive system not only absorbs nutrients, but also regulates the human nervous system. Conversely, whether the brain is functioning normally or not also affects the digestive system. whether it can operate normally.^［3］At present, there is no research on the relationship between “liver stagnation and spleen deficiency” and serotonin. However, since serotonin deficiency is mainly related to excessive stress, traditional Chinese medicine is very helpful in relieving stress and replenishing physical strength, and can solve the root cause. Problems of excessive cortisol and excessive serotonin consumption: Studies by Xu Hong^［4］and Wang Shuping et al.^［5］ found that acupuncture has an adjustment effect on adrenocortical hormones.

The function of serotonin is mainly responsible for regulating the body’s sleep, mood, appetite and digestive functions. Therefore, when it comes to traditional Chinese medicine’s approach to regulating serotonin for treating depression, there are four potential directions: improving digestion (strengthening the Spleen), relieving stress (smoothing Liver Qi), enhancing mood (tonifying Heart Qi and Yang), and improving sleep (calming the Shen and settling the mind). For patients with digestive issues, focusing on strengthening the Spleen may be an effective approach. Observing symptom improvement and changes in serotonin levels after some time of treatment could be a promising research direction.

Clinical experiences and insights from our clinic in treating patients with depression

Patient A, an 18 year old female, has been treated in our clinic for anxiety-depression since she was 16 years old. She started with acupuncture treatment once a week, and then changed to acupuncture treatment once every two weeks for half a year, with occasional Chinese medicine treatment (5 times in total) ). The tongue is pale and fat with thorns and teeth marks, the tip to stretch the trees, which are a method of soothing the liver; or fertilize the soil, which is a method of strengthening of the tongue is red, and there are veins under the tongue. The pulse is thin and weak. The main symptoms are premenstrual stress, vomiting, reticence, and difficulty falling asleep. Treatment method: Mainly regulate menstruation, soothe liver qi before menstruation, regulate Chong and Ren after menstruation, and also regulate and replenish the spleen and stomach. So far, the patient’s mood and sleep have been greatly improved, with basically no episodes of vomiting, only occasional nausea, and the tongue color has changed from light to slightly red.

Patient B, a 38-year-old male, has a high pressure job, frequent fatigue, anxiety, and body pain, and loose stools. Observation of the tongue and pulse revealed that the patient had a pale, fat tongue with thin and slippery coating, and a slippery pulse. The patient is advised not to eat raw or cold food, and to add yams, millet porridge, and chestnuts to his diet every day, and receive acupuncture treatment once a week or every two weeks. After three months of treatment, the patient’s anxiety and stress were greatly improved, and the pain he experienced was also reduced.

Patient C, female, 35 years old, is usually busy at work and cannot receive acupuncture treatment. Before menstruation, she often experiences uncontrollable depression and sadness, as well as fatigue and muscle aches throughout the body. After 3 years of traditional Chinese medicine, emphasizing nourishing the spleen and kidneys, as well as soothing the liver and relieving depression, the feeling of depression and fatigue have improved significantly.

References

［1］Wikipedia: Serotonin, 09 October 2023, Wikimedia Foundation, Inc. Available at:

https://en.wikipedia.org/wiki/ HYPERLINK “https://en.wikipedia.org/wiki/serotonin”HYPERLINK “https://en.wikipedia.org/wiki/ HYPERLINK ”“https://en .wikipedia.org/wiki/serotonin”serotoninHYPERLINK“https://en.wikipedia.org/wiki/serotonin” HYPERLINK “https://en.wikipedia.org/wiki/serotonin”serotonin

［2］ YouTube Channel: Joseph Psychological Counseling Room, dismantling: Why is serotonin insufficient? (Chinese subtitles) Why does the brain have secretory disorders? Is depression and anxiety an “abnormal” result of the “normal” functioning of the brain? Available at: https://www.youtube.com/watch?v=4uiVsk1mQWw

［3］ Xuebin Sun, Jiaxu Chen, Meifang Song, Chenxi Peng, Yueyun Liu, Research progress on the correlation between liver stagnation and spleen deficiency syndrome and brain-gut peptide, World Science and Technology: Modernization of Traditional Chinese Medicine 2018, 11(5): 1969-1973

［4］ Hong Xu, Zhongren Sun, Liping Li, et al., Acupuncture treatment of depression and its impact on patients hypothalamic-pituitary-adrenal axis ［J］, Chinese Acupuncture 2004, 24(2): 78-80

［5］ Shuling Wang, Lin Li, Xuelian Jiang, etc., Effects of Najia method acupuncture on serum cortisol content in AA rats ［J］, Chinese Medical Journal, 2009.27(1): 170-172

Author information:

Zhuoyun Chen, Second Clinical School of Guangzhou University of Traditional Chinese Medicine