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The incidence of depression is increasing year by year, and the corresponding suicide rate is also increasing, which also brings a heavy burden to patients, families and society, and has become one of the most concerned and urgent problems in the medical community.
However, so far, the pathogenesis, physiology and pathological mechanism of depression are not clear, and there is a lack of unified biological indicators, and depression can only be diagnosed by the experience of clinicians and verified and quantified by some scales.
Therefore, experts at home and abroad have persistently explored the pathogenesis, hoping to discover markers for diagnosing depression in order to improve the diagnostic rate of depression. With the development of genomics, proteomics, serum inflammatory factors and other aspects of research.
At present, the more recognized biomarkers of depression mainly include brain-derived neurotrophic factor (BDNF), tumor necrosis factor (TNF-a), interleukin 2, 6, 18, etc. (IL-2, 6, 1, etc.), aminobutyric acid (GABA), etc.
Women's innate physiological characteristics, personality characteristics, and roles in the family and society determine this phenomenon. From the perspective of traditional Chinese medicine, it is mostly related to the physiological function of the liver and the physiological function of the kidney. Compared with modern medicine, it is found that both are essentially analyzed from the perspectives of women's own physiology, personality characteristics, psychological and social environment, and their understanding is relatively unified.
Starting from traditional Chinese medicine is conducive to the early prevention of depression in women, and women, as a special group of women, have attracted the attention of many experts. Prevention of maternal depression through acupuncture, tuina combined with psychotherapy.
There was no difference in age between healthy control and depression, nor in hepatic qi depression and renal yang deficiency depression. Because the inclusion criteria for this study were set between 18 and 50 years, the average age of patients in the depression group in this study was 30 years.
This age group was distributed within the age group with a high prevalence of depression reported by the WHO in 2017. It may be related to the increased burden of family, work, society and other aspects.
MoCA and HAMA scale scores differed between control and depression groups
The Montreal Cognitive Assessment Scale (MoCA) is mainly used to evaluate human cognitive function, and this scale is more reliable than the Simple Intelligent State Check (MMSE). There was no difference in years of schooling between the control group and the depressed volunteers.
However, the mean score of the depression group was smaller than that of the control group (27.32±2.64VS28.77±1.92). Since the patients admitted to this institute are all first-onset and have a short course of disease, their cognitive impairment may be slightly impaired, but some patients with depression already have mild cognitive impairment.
A systematic review of depression combined with mild cognitive impairment. and meta-analysis found that approximately 32% of 20,892 depressed patients had mild cognitive impairment.
Hamilton Anxiety Scale (HAMA) is a commonly used scale in psychiatry, and CCMD-3 Chinese Diagnostic Standards for Mental Disorders lists it as an important diagnostic tool for anxiety disorders, and is mainly used clinically for the diagnosis and degree of anxiety disorders.
This study found that the depression group had a higher HAMA score than the healthy control group (19.71±6.61VS0.82±0.95), and almost all patients in the depression group had anxiety disorders.
Studies have found that depressed patients are prone to physical disorders, which brings great damage to the social function of patients, and in-depth research has found that the more severe the depression, the higher the score.
The results of this study showed that most patients in the depression group were accompanied by social function deficits, but since the patients with depression selected in this study were all moderately depressed, the correlation between depression degree and social function deficit scale scores could not be discussed.
Further analysis of the scores of the Social Deficit Scale in the renal yang deficiency depression group and the liver qi depression depression group showed that the renal yang deficiency depression group had a higher score than the liver qi depression depression, and the difference between the two was comparable.
The main content of the SDSS scale is various daily functions, such as work, parental functions, etc., as well as hobbies, motivation, such as external interests, participation in activities, etc. Kidney essence is the innate foundation of the human body, which is related to human reproduction, growth and development, and kidney essence breeds the yuan yin and yuan yang of the human body.
The "Neijing" cloud: "Heavenly luck should be the light of the sun", when discussing the importance of yang in the human body, compared yang qi to the sun in the sky, and yang deficiency will lead to people's mental malaise. Therefore, patients are prone to burnout, loss of various interests and love, and even unable to perform their basic duties.
Association of brain-derived neurotrophic factor (BDNF) with depression and its TCM symptoms
Association of brain-derived neurotrophic factor with depression
Brain-derived neurotrophic factor (BDNF) is an important member of the neurotrophic protein family, mainly found in the hippocampus, amygdala and frontal cortex areas, which can penetrate the blood-brain barrier, and its function is related to neuronal survival, synaptic signaling and synaptic consolidation.
The framework for the neurotrophic hypothesis for depression was first proposed by HeningerG, which states that the reduction or absence of brain-derived neurotrophic factors in the brain or blood leads to corresponding brain dysfunction and leading to depression.
The results of this experiment showed that the serum BDNF of patients with the first episode of depression was lower than that of healthy controls, which was not only in line with neurotrophic Tan, but also the same as Tadi6A, DeveciA, and the results of the study tl6_18]. Karege et al. not only found that patients with first-episode depression had lower serum BDNF levels than normal controls.
It was also found that BDNF concentration was inversely correlated with the degree and course of depression, and serum BDNF levels increased after antidepressant treatment compared with before treatment. Wen Youlu et al. found that there were differences in serum BDNF in patients with mild, moderate and severe depression, and the lowest serum BDNF in patients with major depression, which also proved that serum BDNF was negatively correlated with the degree of depression.
Because the serum BDNF changes in patients with mild depression are not obvious, and patients with major depression mostly have other chronic diseases or other secondary psychiatric diseases, this project only selected patients with moderate depression as the research target, because the HAMD scores of the included patients were relatively close, so the correlation between the degree of depression and the level of serum BDNF was not observed.
Correlation between different TCM symptom types of depression and brain-derived nutritional factors
By comparing the serum BDNF levels of patients with depressed liver qi and renal yang deficiency and renal yang deficiency type, it was found that renal yang deficiency depression was lower than that of liver qi deficiency (14.70±3.54VS18.25±1.51). Serum levels of BDNF are lower in the renal yang deficiency type, suggesting that it may be more closely related to renal yang deficiency.
The "Medical Sect Must Read" discusses in detail the size, position, shape, and meridian connection of the kidney, and points out that the kidney is closely related to the spinal cord and the medullary sea, such as "the upper spinal cord, to the brain, connected to the medullary sea". The relationship between the kidney and the pith is also recorded in the "Essence of the Inner Classic", such as "the kidney produces essence, which is transformed into the pith and hidden in the brain".
The main bone of the kidney produces pulp and plays a leading role in human life activities. The study found that one of the modern biological foundations of the "brain medulla" referred to in traditional Chinese medicine is the brain metatrophic factor.
In addition, it is also recorded in the "Lingshu Benshen " that the kidney is related to spiritual and emotional activities, such as "the god of the two essences fighting each other", and it dominates people's spirit, thinking and emotions. It indirectly shows that Chinese medicine kidneys are closely related to emotional diseases, including depression.
As the functional manifestation of kidney essence in the human body, kidney yang deficiency can lead to deficiency of the medullary sea and cerebral myeloid deficiency, which in turn leads to a decrease in BDNF content; Therefore, the decrease in serum BDNF of renal yang deficiency depression is related to the main essence storage of the kidney, nourishing the medullary sea and spermatizing blood.
Association of inflammatory factors with depression and its TCM symptoms
Association of inflammatory factors with depression
Maes et al. first found that depression may be accompanied by systemic immune activation or inflammation, and accompanied by phagocytic (monocytes, neutrophil) cells, T cell activation, B cell proliferation, and in the "acute" stage of depression, the production of interleukins by peripheral blood mononuclear cells increased, which laid the foundation for the "cellular hypothesis of depression".
After in-depth research by many researchers, the "cytokine hypothesis" of depression was finally perfected. This hypothesis holds that depression is a class of neuropsychological immune imbalance diseases that activate immune function through various pathological factors, resulting in abnormal secretion of multiple cytokines.
Cytokines are roughly divided into two categories, one is inflammatory cytokines, such as: IL-1, IL-6, IFN-y and TNF-a; One class is anti-inflammatory cytokines, such as IL-4, IL-10, transforming growth factor 3 (Transforming growth factor-16·1) and so on.
Further studies of two types of cytokines found that cytokines such as IL-1, IL-6, IFN-Y and TNF-a were associated with the onset of depression, and some factors could be used as biomarkers of depression, and their levels were higher in patients with depression than in healthy people.
This is consistent with the results of this experiment (IL-6 and TNF-a were higher in the depression group than in the healthy control group). The other is anti-inflammatory factors, such as IL-10, IL-13, TGF-P, which have been shown to antagonize the expression of inflammatory cytokines and have the function of protecting their own cells in immune response or inflammation.
The study found that such cells were expressed at reduced levels in depressed patients, and serum IL-10 levels increased in depressed patients after taking antidepressants.
Correlation between different TCM symptom types of depression and TNF-a and IL-6
By comparing the serum TNF-a and IL-6 levels of patients with depressed liver qi and renal yang deficiency and nephrogenic deficiency, it was found that the serum TNF-a and IL-6 levels were higher than those in patients with hepatic qi depression depression.
Therefore, serum TNF-a and IL-6 can be used as an objective basis for differentiation and classification in traditional Chinese medicine, and they are more inclined to liver qi depression depression.
The main drainage of the liver regulates the qi machine of the human body. The functions of the human body's internal organs, qi, blood, essence, and yin all rely on the lifting and exiting of qi machines, such as the "Essays on Reading Medicine", "All the gasification of the twelve meridians of the internal organs must be encouraged by the gasification of the liver and gallbladder, so that it can be adjusted without disease". In addition, the main drainage of the liver regulates people's emotional responses, and emotional activities also hurt the liver first.
For example, it is recorded in the "Suwen Yin and Yang Ying Elephant Theory" that the causes of diseases are caused by abnormal movement of qi, seven emotions hurt the liver, liver loss and leakage cause qi slowness, knots, chaos, etc., and eventually lead to emotional abnormalities. There are two situations of liver main drainage dysfunction, one is poor liver drainage, that is, liver qi stagnation;
One is that the liver is too excessive, that is, the liver is hyperactive. Patients with depression are often caused by poor liver drainage, that is, liver qi stagnation, and symptoms such as depression, and then depression and fire, resulting in liver fire inflammation symptoms.
From the perspective of traditional Chinese medicine, when the human body responds to psychological stress, the first pathological feature is the abnormal operation of qi machines, followed by a series of other pathological reactions, such as abnormal qi, blood, jin and fluid, imbalance of internal organs, yin and yang imbalance, etc.
Therefore, the primary method for regulating psychological stress is to regulate the ventilator, and this function is closely related to the liver drainage function. Based on this, modern medical scholars have proposed that the main drainage of the liver dominates human psychological stress (such as mental illness). Psychological stress, in turn, activates the immune system, leading to the production of inflammatory cytokines.
Through the administration of mental stress to the volunteers, including a 5-minute Stroop task and a 5-minute mirror tracking task, the patient's IL-6 was found to be elevated after 45 minutes.
Through the experiments of electroacupuncture in rats with chronic stress depression models, it was also found that the serum TNF-a and IL-6 expression levels of stress depression rats were elevated before treatment. All of the above indicate that the increase in serum TNF-a and IL-6 levels in patients with hepatic qi depression depression is related to hepatic main excretory disorders.
Correlation of serum BDNF, TNF-a, IL-6 with the scale used in this topic
The 24-item Hamilton Depression Scale (HAMD-24) was used to evaluate patients with depression, the Hamiltonian Anxiety Scale (HAMA) was used to assess patients for anxiety, the Young Mania Rating Scale (YMRS) was used to exclude people with mania, and the Montreal Cognitive Rating Scale (MoCA) was used to assess patients for cognitive impairment.
The Social Deficit Scale (SDSS) assesses people with depression with functional deficits. Multiple linear regression analysis showed that the correlation between serum BDNF, TNF-a, IL-6 and HAMD-24 and HAMA was obvious.
Correlation between serum BDNF, TNF-a, IL-6 and HAMD-24
The Hamilton Depression Scale (HAMD-24) was developed by Hamilton in 1960. Due to its credibility and good effect, it is currently the main and commonly used scale for psychiatric evaluation of depression.
Clinicians not only use it to help diagnose depression, but also to distinguish the mild, moderate and severe degree of depression through the final score. The scale is often scaled by communicating with and observing the subject by two experienced evaluators, who are then graded independently.
The study found that the effect of serum interleukin-6 (IL-6) content on the score of the HAMD-24 scale was not statistically significant. The content of brain-derived neurotrophic factor (BDNF) and tumor necrosis factor (TNF-a) had significant effects on the score of HAMD-24 scale.
Among them, BDNF content was negatively correlated with HAMD-24 scale score, and each increase in BDNF lmg/ml reduced HAMD24 score by 1.01 points. The TNF-a content was positively correlated with the score of HAMD-24 scale, and the H_24 score increased by 0.88 points for each increase in lPg/ml of TNF-a.
BDNF belongs to the neurotrophic protein family, which is mainly found in the hippocampus and can penetrate the blood-brain barrier. BDNF plays a role in neuronal survival and neurotransmitter transmission. A summary of studies with BDNF found that serum BDNF levels were inversely correlated with the degree of depression.
Through the analysis of serum BDNF content and HAMD-24 scale score in depressed patients, it was found that BDNF content was negatively correlated with HAMD-24 score. The above results are consistent with the results of this study.
In 1975, after injecting bacterial lipopolysaccharides into BCG-vaccinated mice, it was found that a substance that can cause hemorrhagic necrosis in a variety of tumors was produced in the serum, and then it was named tumor necrosis factor, and then Shalaby et al. named TNF produced by macrophages TNF-a.
Studies have found that TNF-a in the serum of patients with depression may be associated with immune dysregulation of depression; DowlatiYW2] et al. conducted meta-analysis of specific inflammatory cytokines in depressed patients and found that TNF-a was higher than normal in depressed patients, and after anti-inflammatory therapy, it could improve symptoms in depressed patients.
The results of this study also showed that TNF-a content was positively correlated with the -24 scale score.
Interleukin 6 (IL-6) belongs to a type of interleukin, produced by macrophages, lymphocytes, a variety of tumor cells, etc., and belongs to the pre-inflammatory cytokines. Associated with rabbit plague-mediated and inflammatory responses.
The Hamilton Anxiety Scale (HAMA) was developed by Hamilton in 1959 and consists of 14 items. Due to its credibility and validity, it is currently commonly used by psychiatrists to diagnose anxiety disorders.
This scale not only acts as a diagnostic tool for anxiety disorders, but also distinguishes the severity of anxiety disorders through the final score of the scale. According to the HAMA score, the results can be divided into 5 types, (1) normal: 0 to 5 points; (2) mild: 6 to 12 points; (3) moderate: 13 to 19 points; (4) Severe: 20 to 29 points; (5) Extremely severe: 30 points or more.
The depressed patients included in this group all had a HAMA score of more than 10 points, and all had anxiety.
The study found that serum interleukin-6 (IL-6) content also had no significant effect on the HAMA scale score. The contents of brain-derived neurotrophic factor (BDNF) and tumor necrosis factor (TNF-a) had significant effects on the score of the HAMA scale, and the content of BDNF was negatively correlated with the score of the HAMA scale
For each increase in lrag/ml BDNF, the HAMA score decreased by 0.73 points. TNF-a content was positively correlated with the HAMA scale score, and the HAMA score increased by 0.63 points for each increase in lPg/ml of TNF-a.
Brain-derived neurotrophic factor (BDNF) plays an important role in the development of the human nervous system, which is related to the survival and differentiation of neurons, and maintains many functions of neurons. Decreased levels of BDNF in the hippocampus or in serum can trigger anxiety disorders.
Comparing the serum BDNF content of anxious patients with the serum BDMF content of healthy people, it was found that the serum BDNF content of patients with anxiety disorders was lower than that of healthy people, and the difference was statistically significant.
Although this study did not specifically study the serum BDNF of patients with anxiety disorder, the study found that the HAMA scale score was inversely correlated with the serum BDNF content, and anxiety disorders could be diagnosed by the HAMA scale score, so the results of this experiment can be inferred that the serum BDNF level of anxiety patients is reduced, which is consistent with the existing research results.
Tumor necrosis factor (TNF-a) is a monocytes cytokine that is mainly produced by monocytes and macrophages. TNF-a is an important inflammatory factor in the human body, and can promote inflammatory factors such as interleukin 1 and interleukin 6 to participate in autoimmunity, thereby guiding the inflammatory response.
By summarizing the existing studies on anxiety disorders and inflammatory factors, it was found that the increase in serum TNF-a levels was closely related to the occurrence of anxiety disorders.
Serum TNF-a in patients with coronary heart disease and anxiety disorder found that serum TNF-a levels were elevated in patients with anxiety disorder, and further analysis found that serum TNF-a levels were directly proportional to Hamilton Anxiety Scale scores.
This study found that the serum TNF-a content was directly proportional to the HAMA scale score, which indirectly proved the correlation between TNF-a and anxiety disorders, which is consistent with the above results.
Interleukin-6 (IL-6), a type of interleukin, is also a cytokine. IL-6 stimulates and participates in the proliferation, differentiation and function of cells involved in immune responses.
The elderly patients with coronary heart disease were divided into combined anxiety and non-anxiety disorders by anxiety self-rating scale, and serum IL-6 was detected in the two groups, and it was found that the serum IL-6 level was positively correlated with the degree of anxiety. Serum IL-6 testing in patients with first-onset generalized anxiety disorder found that serum IL-6 levels were higher in patients with anxiety disorders compared with healthy people.
This study found no association between serum IL-6 levels and HAMA scores, possibly due to small sample sizes and the predominantly depression of patients included in this study.