Open access peer-reviewed chapter
Summary of acupuncture and moxibustion for depression.
Abstract
Depression is one of the most common mood disorders, which seriously affects public health. The efficacy of acupuncture and moxibustion on depression is clear without obvious adverse reactions, which has high clinical value. This chapter reviews the clinical research of acupuncture and moxibustion in the treatment of depression in recent years, summarizes and discusses the pathophysiological mechanism of acupuncture and moxibustion in the treatment of depression and the integrated treatment of acupuncture and moxibustion, in order to provide theoretical guidance and scientific basis for clinical acupuncture and moxibustion in the treatment of depression.
Keywords
- chinese traditional medicine
- acupuncture and moxibustion
- depression
- mechanism
- theoretical guidance
- scientific basis
1. Introduction
Depression is a kind of mental disease that seriously affects public health. There were about 322 million patients with depression worldwide, accounting for 6.2% of the total disease burden [1]. There is still a bottleneck in the treatment of depression in modern medicine, and only 27% of patients have achieved clinical recovery [2]. At the same time, the treatment of commonly used antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAS), has delayed efficacy and a variety of adverse reactions, which seriously affect the medication compliance. Acupuncture and moxibustion has definite curative effect on depression without obvious adverse reactions, and has high clinical application value.
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2. Pathophysiological mechanism of depression
The pathogenesis and etiology of depression are complex, and have not yet been fully clarified. The biological factors that may be involved include neurobiochemical mechanism, neuroendocrine mechanism, neuroelectrophysiological mechanism and neuroimaging changes [3, 4, 5, 6]. In addition to the above biological mechanisms, psychological and social environmental factors also play an important role in the occurrence and development of depression. However, traditional Chinese medicine classifies depression as “depression disease”, which is caused by sudden, strong and lasting negative emotional stimulation or thoughtful and sentimental personality. In the early stage, qi stagnation is the main factor, and qi stagnation is caused by stagnation of liver qi, and qi stagnation is caused by blood stasis and phlegm coagulation, which can further turn into fire, but the disease is based on stagnation of liver qi; It can be seen that the Qi and blood in the heart, spleen, liver and kidney are deficient in Yin and Yang. In addition, in the early stage, it is mostly stagnation of liver qi, stagnation of liver qi and deficiency of spleen or damp heat of liver and gall. Over time, it will lead to deficiency of both heart and spleen, kidney deficiency, stagnation of liver Qi or deficiency of heart and gall Qi [7].
2.1 Neurotransmitters and receptors
At present, most studies believe that the pathogenesis of depression is mainly related to the changes of monoamine neurotransmitters such as 5-hydroxytryptamine (5-HT), dopamine (DA) and noradrenaline (NE) in the hippocampus of the brain. The disorder of these neurotransmitters is the basis of the pathophysiology of depression [8]. Some experiments have proved that cranial suture needle can enhance the stimulation to the amygdala of temporal lobe, so as to regulate the metabolism and release of 5-HT and NE, and increase their content and function [9]. Xiao [10] observed the effect of Jieyu Anshen acupuncture on neurotransmitters in post-stroke depression model rats. After treatment, the contents of 5-HT, NE, Gamma-amino butyric acid (GABA) and other neurotransmitters in hippocampus of rats in the acupuncture group increased significantly, indicating that acupuncture treatment of depression may play an antidepressant role by regulating the contents of the above neurotransmitters. In addition, the incidence of depression is also related to the functional changes of neurotransmitter receptors. The content of 5-HT and the function of 5-HT1A receptor in frontal cortex of rats with chronic unpredictable mild stress depression were measured after acupuncture treatment. The results showed that correcting the dysfunction of 5-HT1A receptor may be one of the ways for acupuncture to exert its antidepressant effect [11].
2.2 The neural plasticity
The changes of neuroplasticity are specifically manifested in the changes of neurons and glial cells, as well as the obstacles of signal transduction in neurons, which are closely related to the occurrence and development of depression [12, 13]. Therefore, regulating the regeneration of neurons and glial cells and mediating related signal pathways to restore neural plasticity is also one of the main mechanisms of acupuncture and moxibustion in the treatment of depression. Sun [14] used Tongdu Tiaosheng acupuncture to treat post-stroke depression model rats. The results showed that acupuncture could improve the behavior of depression rats by repairing the damage of hippocampal neurons. When Baihui (GV20) and Anmian (EX-HN17) were stimulated with 4/60 Hz for 3 weeks, the proliferation of hippocampal progenitor cells was up-regulated [15]. Other experiments showed that 2/100 Hz electrical stimulation every other day in Baihui (GV20) and Yanglingquan (GB34) for 15 days could increase the proliferation of neural progenitor cells [16, 17]. Glial fibrillary acidic protein (GFAP) is a protein marker of astrocyte activation. The experiment showed that the expression of GFAP in hippocampus and prefrontal cortex of depression rat model increased. When acupuncture was given to Baihui (GV 20) and Yintang (GV 29) and bilateral Sanyinjiao (SP 6) for 20 minutes, once a day for 28 days, it was found that the expression of GFAP was inhibited and the morphology of astrocytes in depressed rats was significantly improved [18]. So acupuncture may play an antidepressant effect by regulating the expression of GFAP and repairing astrocyte damage.
The mechanism of acupuncture in treating depression may be related to the inflammatory response and amino acid metabolism mediated by different signal pathways [19]. c-Jun N-terminal kinase (JNK) is a member of mitogen activated protein kinase mitogen-activated protein kinases MAPKs pathway, and its activation plays an important role in the etiology and pathogenesis of depression [20, 21, 22]. Acupuncture or electroacupuncture can reverse the stress-induced upregulation of mitogen-activated protein kinase kinase 4 (MKK4), mitogen-activated protein kinase kinase 7(MKK7) and p-JNK in hippocampus, and may reduce the rate of hippocampal apoptosis. Inhibition of JNK activity can protect nerve cells [23].
In addition, the typical symptoms of depression patients include inability to feel happy and lack of motivation. These negative symptoms can be attributed to the destruction of reward circuit [24]. Wang [25] after acupuncture combined with fluoxetine for 8 weeks, the increase of resting-state functional connectivity between the lower ventral striatum and the medial prefrontal cortex, the ventral cranial nucleus and the amygdala / parahippocampal area was significantly positively correlated with the decrease of depression scale score (Montgomery–Åsberg Depression Rating Scale and Self-Rating Depression Scale scores), indicating that acupuncture may achieve the therapeutic effect by regulating the reward / motivation circuit of the cortical striatum in patients with severe depression.
2.3 Neuroendocrine regulation
The relationship between nervous system and endocrine system is mainly manifested in the regulation of hypothalamus pituitary adrenal axis (HPA), hypothalamus pituitary thyroid axis and hypothalamus pituitary gonad axis. The activation and disorder of HPA axis are closely related to depression [26]. The changes of corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and serum cortisol (CORT) in hypothalamus and plasma of patients with depression can reflect the regulatory function of HPA axis on nervous system. Studies have conducted Electroacupuncture Treatment on Guanyuan (CV4) and Zusanli (ST36) of rats with chronic mild stress depression, and found that electroacupuncture can down regulate the expression of CRH mRNA in rat hypothalamus and reduce the levels of ACTH and CORT in plasma [27]. In the mild depression model of rats induced by water immersion stress for 1 week, acupuncture at Baihui (GV 20) and Yintang (EX-HN3) was used to measure the immobility time and serum corticosterone level of rats. It was found that the immobility time and serum corticosterone level decreased after acupuncture stimulation [28]. These results suggest that acupuncture can regulate HPA function to improve depression.
2.4 Neuro immune regulation
The abnormal activation of immune system in patients with depression may be related to the abnormal secretion of inflammatory cytokines, and the level of inflammatory cytokines is significantly different before and after antidepressant treatment [29]. Li [30] found that acupuncture treatment can reduce the number of NLRP3 inflammatory corpuscles and TUNEL positive cells in the prefrontal cortex of depression like rats, indicating that acupuncture may participate in inhibiting the activation and apoptosis of NLRP3 inflammatory corpuscles in the prefrontal cortex to produce antidepressant effect. Wang [31] found that acupuncture and moxibustion reversed the up regulation of gene sets related to toll like receptor signaling pathway and nod like receptor signaling pathway related to inflammatory response and immune response. Therefore, increasing the content of anti-inflammatory cytokines or inhibiting the level of pro-inflammatory cytokines may be one of the mechanisms of acupuncture and moxibustion in the treatment of depression by regulating the immune system.
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3. Integrated acupuncture and moxibustion therapy
On the basis of holistic concept and syndrome differentiation and treatment, subthreshold depression and mild to moderate depression may be more suitable for intervention with traditional Chinese medicine or integrated traditional and Western medicine; Some special types and groups of depression can also give priority to the intervention of traditional Chinese medicine or the combination of traditional Chinese and Western medicine, such as children and adolescents’ depression, perimenopausal depression, postpartum depression, stroke, tumor, diabetes and other associated depression. The dose of Western medicine can be appropriately reduced to reduce or avoid the adverse reactions caused by western medicine.
Acupuncture and moxibustion treatment of depression is mainly based on disease differentiation, supplemented by syndrome differentiation and symptomatic selection. The course of treatment is generally 4 ~ 6 weeks. The main effect in acute stage is to improve symptoms and reduce adverse reactions of Western medicine; Consolidation period and maintenance period are to prevent recurrence and relapse. Mild depression can be treated with acupuncture alone, moderate depression can be treated with intensive cranial electroacupuncture stimulation, and severe depression can be treated with western medicine and acupuncture. According to the recommendations of relevant Chinese guidelines, the general population with depression is recommended to adopt the method of regulating mind and soothing the liver, with electroacupuncture at Yintang and Baihui as the main points; For patients who could not afford electroacupuncture, it is recommended to use filiform needling, and the acupoint selection and course of treatment are the same as that of electroacupuncture; For patients with more somatization symptoms, it is suggested to select corresponding acupoints for symptomatic treatment according to the main clinical manifestations; For patients with sleep disorders, it is suggested to adopt the method of regulating the mind and soothing the liver, with electroacupuncture at Baihui, Yintang or Sishencong as the main points. Mild to moderate depression patients who could not tolerate acupuncture treatment can be treated by pressing beans on ear points, and moderate to severe depression can be treated by regulating mind and soothing the liver. The treatment of post-stroke depression and menopausal depression should consider the treatment of primary disease while treating depression. In addition, according to the patient’s condition, acupoint massage, acupoint stimulation and regulation, traditional Chinese medicine psychotherapy, five element music therapy and other treatments can be used at the same time [32, 33].
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4. Summary and prospect
The therapeutic effect of acupuncture and moxibustion on depression is clearly the result of multi-target and multi-dimensional interaction (Table 1), but the depth of research on this mechanism still needs to be strengthened. Future research should explore the difference of acupuncture and moxibustion intervention mechanism on different Traditional Chinese medicine (TCM) syndrome types of depression. And explore the differences of different acupuncture therapies or different acupoint selection mechanisms. In conclusion, although the research on the mechanism of acupuncture and moxibustion in the treatment of depression has made some progress, it is still necessary to continuously broaden the thinking and strengthen the research, so as to give full play to the advantages of acupuncture and moxibustion in the treatment of depression and contribute to better clinical efficacy of depression.
| Investigators | Sample size | Intervention | Acupoints | Frequency | Outcomes | Mechanisms |
|---|---|---|---|---|---|---|
| Wei Xiao et al. | 40 | normal group, model group, medication group and acupuncture group, with 10 rats in each. | “Baihui”(GV 20), “Fengfu” (GV 16), bilateral “Shenmen” (HT 7) and “Taichong” (LR 3) | 20 min, once a day for 21 days | Acupuncture can improve the locomotor function changes in stroke rats with depression after stroke | Suppressing the up-regulated cortical ACh, GABA, Glu contents, the expression levels of 5-HT1AR and NEα2R proteins in the hippocampus, raphe nucleus and LC, and the down-regulated 5-HT and NE contents in the cerebral cortex and 5-HTT protein expression levels in the hippocampus, raphe nucleus and LC. |
| Lixing Chen et al. | 40 | normal control, chronic unpredictable mild stress, electroacupuncture, and paroxetine groups. | GV 20, “Yintang”(GV 29) | 30 minutes daily | Electroacupuncture treatment can alleviate depression-like symptoms in chronic unpredictable mild stress rats. | The underlying mechanism may include promoting the expression of 5-HT1A receptor mRNA and protein, thereby improving synaptic plasticity in the hippocampus. |
| Pei-Yang Sun et al. | 48 | a sham-operation group, a model group, a Tongdu Tiaoshen acupuncture group and a non-meridian-non-acupoint group | GV 20, “Shuigou” (GV 26), “Shenting” (CV 24) and “Dazhui” (GV 14) | 40 min in each treatment and the needles were manipulated at the acupoints once in 20 min | The Tongdu Tiaoshen acupuncture improves the behavior of the model rats with post-stroke depression, repairs hippocampal neuronal damage, | It’s probably related to the contents of hippocampal monoamine neurotransmitters (NE, 5-HT and DA). |
| Liu Yang et al. | GV20, Yang-Ling-Quan(GB34) | on day 15 and were treated for 2 weeks | After 8 treatments, electroacupunture generated a clear antidepressant effect on the stressed rats. | Promoted the neural stem cell proliferation | ||
| Sha Dong et al. | 32 | control, model, acupuncture, and medication | GV20,GV29, “Sanyinjiao” (SP 6) | 20 min, once daily for 28 days | GFAP protein expression were considerably suppressed in medication and acupuncture groups | Acupuncture may play an antidepressant effect by regulating the expression of GFAP and repairing astrocyte damage. |
| Zengjian Wang et al. | 46 | fluoxetine group and acupuncture plus fluoxetine | 8 weeks | The increase of resting-state functional connectivity between the lower ventral striatum and the medial prefrontal cortex, the ventral cranial nucleus and the amygdala / parahippocampal area was significantly positively correlated with the decrease of depression scale score. | Acupuncture may achieve the therapeutic effect by regulating the reward / motivation circuit of the cortical striatum in patients with severe depression | |
| Jing-jing Le et al. | Guanyuan (CV4) and Zusanli (ST36) | 14 days | Electroacupuncture treatment reversed The behavioral deficiency induced by chronic unpredictable mild stress in rats. | Electroacupuncture treatment could act on depression by modulating HPA axis and enhancing hippocampal 5-HT/5-HT1AR in chronic unpredictable mild stress Rats. |
Table 1.
ACH: acetylcholine;GABA: gamma aminobutyric acid; Glu: glutamate; 5-HT1AR: 5-HT 1 A receptor; NE: norepinephrine; NEα2R: alpha receptor 2; LC: locus coeruleus; and DA: dopamine.
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Acknowledgments
This work was supported by Fund Project of Taihe Hospital, Hubei University of Medicine, [No. 2017JJXM103].
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Conflict of interest
The authors declared that there was no potential conflict of interest in this article.
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