Research progress on the effect and mechanism of Tai Ji Quan in the treatment of post-stroke depression

ZHANG Jianzhong (张建忠), LIU Yang (刘杨), LI Zhaoyuan (李昭缘), BIAN Yuefeng (卞跃峰), ZHOU Qian (周茜),SHAN Chunlei (单春雷),3, QI Rui (齐瑞)

1 Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine,Shanghai 200437, China

2 Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, China

3 School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

Abstract

Keywords: Tai Ji Quan; Physical and Breathing Exercises; Stroke Rehabilitation; Stroke; Complications; Depression; Review

Post-stroke depression (PSD) is a common complication after a stroke, and patients with PSD often show more dysfunctions[1]. The recurrence rate and mortality of stroke within one year after onset in these patients are also higher than those in non-PSD

[2]patients. Depression after a stroke usually persists,and there is a high risk of recurrence even after treatment remission[3]. A relevant epidemiological study has shown that the prevalence of PSD in stroke patients is 25% to 79%, and about 33% of stroke patients have a depressive mood[4]. More and more studies have shown that depression is an independent risk factor for stroke[5].

Tai Ji Quan is one of the most widely spread traditional exercise therapies in China and is widely used in healthcare. Relevant studies have found that Tai Ji Quan training can improve the motor and balance functions of stroke patients and has a positive effect on regulating emotions and preventing negative emotions[6]. In order to provide a reference for formulating an individualized and accurate Tai Ji Quan training program and enhancing the clinical efficacy of PSD, the clinical study and mechanism research of Tai Ji Quan improving PSD were summarized as follows.

1 Pathogenesis and Treatment of PSD

The physiological pathogenesis of PSD is complex,and there is no unified conclusion on the mechanism of its onset and development occurrence. There are a variety of related factors leading to depression before and after stroke, including social psychology,neuroendocrine factors, neural factors, inflammatory factors, and brain function remodeling[7-8]. The degree of motor dysfunction and cognitive level in stroke patients may also be related to the pathogenesis of PSD[9]. In terms of physiological mechanism,metabolomics study has found that amino acid metabolism, lipid metabolism, and oxidative stress are related to the onset of PSD[10]. PSD is often accompanied by endocrine disorders, autonomic disorders, and inflammatory factor aggregation. These changes can induce a depressive mood, aggravate cardiovascular and cerebrovascular damage, increase the risk of re-stroke[11], and reduce patients’ subjective intention of exercise[12]. In recent years, studies based on brain function imaging and neuroelectrophysiology have revealed PSD-related neural pathways and brain networks from the perspective of functional brain activity. Depressive mood occurs when the patient’s dorsolateral prefrontal cortex has dysfunction, and when the dorsolateral prefrontal cortex dysfunction is improved, the symptoms of PSD will also be relieved[13].In addition, PSD also occurs when the stroke site is not in the frontal lobe, suggesting that the occurrence of PSD involves multiple brain networks, which may be related to the damage of the default mode network of the brain[13-14]. A subgroup analysis of brain function network study for different disease locations found that the stroke location, brain compensation mechanism,and wholeness and locality of the brain also jointly affected the brain network changes in PSD[15].

At present, the clinical management of PSD is mainly based on the combination of prevention and treatment,among which the early application of antidepressants is a common clinical intervention. Commonly used antidepressants include monoamine oxidase inhibitors,tricyclic antidepressants, tetracyclic antidepressants,and selective serotonin reuptake inhibitors[16-17].Psychological intervention is another important measure for the comprehensive rehabilitation of PSD patients. Early and timely psychological intervention can effectively reduce the depression of patients, enhance the effect of rehabilitation treatment, reduce the degree of disability, and improve the quality of life.Among them, good life nursing and caring companionship of the patient’s family is an important content of psychological intervention[18].Neuromodulation techniques such as transcranial direct current stimulation and repetitive transcranial magnetic stimulation also play a key role in the treatment of PSD.After treatment, the patient’s brain-derived neurotrophic factor expression, glucose metabolism,oxygen metabolism, and neural remodeling function can be further improved[13,19].

PSD belongs to the concurrent meridian pattern of depression syndrome and stroke in traditional Chinese medicine (TCM). Clinically, PSD mostly belongs to Yin deficiency syndrome or liver Qi stagnation syndrome.The disease is located in the brain and is closely related to the liver, kidney, heart, and spleen. In TCM, oral administration of Chinese medicine and acupuncture therapy are widely used. In addition, there are also intervention methods such as Tuina (Chinese therapeutic massage) treatment, five-element music therapy, and Gongfa exercise, which provide more options for the treatment of PSD[20].

2 Clinical Efficacy of Tai Ji Quan for PSD

In stroke rehabilitation, Tai Ji Quan training is mainly used to improve patients’ motor and balance dysfunction and enhance cardiopulmonary function,while there are relatively few studies focusing on Tai Ji Quan training in regulating depression in stroke patients.

WANG W,et al[21]compared the effects of Tai Ji Quan and conventional rehabilitation on the general health scale scores of patients with cerebrovascular diseases. It was found that after the intervention, both groups had improvement in a depressive mood, and the Tai Ji Quan group was significantly superior to the conventional rehabilitation group. WANG L,et al[22]used YANG’s 24-form simplified Tai Ji Quan to treat patients with cerebral infarction and found that the Hamilton depression scale (HAMD) score in the Tai Ji Quan group improved more significantly, and the comprehensive quality of life assessment questionnaire score was also higher. LI Y L,et al[23-24]enrolled patients with difficulty walking after stroke as study subjects, and treated them with a designed 10-form sitting Tai Ji Quan. The results showed that Tai Ji Quan had better efficacy in improving the PSD state than daily physical exercise.TAYLOR-PILIAE R E,et al[25]reported a study on the safety and reliability of Tai Ji Quan training in the community. It was found that the center for epidemiologic studies depression scale (CES-D) score was lower in the stroke patients who had 12 weeks of Tai Ji Quan training than those who had no Tai Ji Quan training. Since the scale scores of some subjects reached the lower limit, the improving effect of Tai Ji Quan on depressive emotion turned up a floor effect. In the follow-up study, the Tai Ji Quan training,comprehensive aerobic exercise, and routine health guidance were compared after expanding the sample size. And it was found that the 36-item short-form health survey (SF-36) scores in the three groups were all improved after the intervention. However, there was no significant between-group difference in the SF-36 or CES-D score. Compared with the other two exercises,Tai Ji Quan had significant advantages in preventing falls and improving balance[6]. ZHENG W C,et al[26]applied the HAMD in the 12-month follow-up of stroke patients with continuous Tai Ji Quan training and found that whether it was short-term (3 months) or relatively long-term (12 months) intervention, there was no significant difference in HAMD score between stroke patients with additional Tai Ji Quan training and those with conventional rehabilitation. ZHAO B,et al[27]divided stroke patients into two groups for 8 weeks of treatment. The HAMD score in the group of conventional rehabilitation plus simplified Tai Ji Quan training was lower than that in the conventional rehabilitation group, suggesting that Tai Ji Quan can effectively improve depressive emotion in post-stroke patients. LI X H,et al[28]had similar results by applying the improved 24-form Tai Ji Quan training. Compared with a single oral antidepressant, Tai Ji Quan treatment had more advantages in HAMD score and effective rate.ZHANG L,et al[29]compared the effect of acupuncture plus Tai Ji Quan with oral antidepressants on the depressive state of stroke patients. The HAMD score was followed up after 1-month and 12-month treatments. It was found that acupuncture plus Tai Ji Quan had a significant curative effect and was superior to oral medication alone.

The efficacy of Tai Ji Quan in the treatment of PSD varies in different reports, which may be caused by different training programs, subject selection, course of treatment, and evaluation methods. There is still a need for large-sample, randomized, double-blind controlled studies for further verification. Combined with the study on the pathogenesis of PSD, it can be found that the improvement of dysfunction in stroke patients, the location of stroke injury, and the disease duration all can affect the changes in depression in the patients.Based on the repair principle of dysfunction in stroke,exploring the possible mechanism of Tai Ji Quan improving PSD is of great significance for formulating an effective Tai Ji Quan rehabilitation training prescription.

3 Possible Mechanisms of Tai Ji Quan in the Treatment of PSD

At present, the application of Tai Ji Quan in stroke rehabilitation mainly focuses on improving cognitive and motor functions. During Tai Ji Quan training,practitioners need to adjust their mentality, breathing,awareness, and thinking to achieve the purpose of improving their emotions[30]. Tai Ji Quan exercise has achieved good efficacy in the treatment of non-stroke-related depression, providing a safer option for patients who are not suitable for drug intervention[31]. Its mechanism may involve multiple pathways, such as human biofeedback, conscious psychological activity, nervous system functional activity,and the guidance of emotions through intention movement[31-32].

3.1 Social psychological factors

Social psychology believes that the occurrence of mood disorders is closely related to social stressors, and there is an interaction between cognition and emotion,which dynamically determines the stress level of the body[33]. A study has pointed out that the psychosocial characteristics of the elderly, such as self-efficacy, social support, and coping behavior, play an important role in the occurrence of depressive mood[34]. Physical exercise is an important method to buffer the stress effect between cognition and emotion. It can regulate the perceived pressure through a certain intensity of exercise, forming a dynamic beneficial cycle[35-36]. Tai Ji Quan is considered a “mind-body” therapy with meditation and mindfulness characteristics that can relieve psychological stress, regulate autonomic nervous function, and have a positive impact on emotion improvement[37-38]. The long-term participation of stroke patients in leisure activities and outdoor activities can promote their interpersonal relations and interpersonal communication, help to obtain social support, and improve life satisfaction[39].

3.2 Brain-derived neurotrophic factor (BDNF)

BDNF is a neurotrophic factor widely distributed in the brain. Recent studies have found that BDNF not only plays an important role in the repair of brain tissue injury, but also can be used as an entry target for the treatment of depression, helping the development of antidepressants[40]. BDNF is difficult to persist in plasma.Exercise training is an effective way to increase BDNF levels and can promote the release of BDNF in the brain[41]. SUNGKARAT S,et al[42]performed a study on the effect of Tai Ji Quan training at home in the elderly with mild cognitive disorder and found that after 6 months of Tai Ji Quan training at home, the memory function and emotion conversion-executive function of the subjects were significantly improved. The level of plasma BDNF in the Tai Ji Quan training group increased after intervention, indicating that it might be one of the reasons for the improvement of cognitive function.

3.3 Neuroendocrine

Neuroendocrine plays an important role in emotion regulation. Tai Ji Quan training may improve negative emotions by regulating specific hormone levels and neuroendocrine function. JIN P[43]studied the change in salivary cortisol levels in Tai Ji Quan trainers earlier and found that Tai Ji Quan training could reduce the concentration of cortisol in saliva. WALTHER A,et al[44]observed and found that compared with Tai Ji Quan training 3 times a week, subjects with training 4 times a week or more had a lower ratio of cortisol to testosterone, fewer depressive symptoms, and higher life satisfaction. It suggests that different intensities of Tai Ji Quan training produce different results in the regulation of neuroendocrine.

3.4 Inflammatory factors

Tai Ji Quan training shows a certain anti-inflammatory effect. The intensity of Tai Ji Quan training and the disease condition of the participants can affect the level of inflammatory factors before and after training[45]. In the study of Tai Ji Quan training plus citalopram for older patients with depression, it was found that the Tai Ji Quan training group achieved a better curative effect and a reduced C-reactive protein level[46]. Inflammatory factors and cellular immune responses also play an important role in the process of emotional regulation.Tai Ji Quan may participate in the body’s inflammatory response in multiple ways such as regulating the secretion of anti-inflammatory substances and reducing gene expression of pro-inflammatory mediators[47-49].IRWIN M R,et al[50]found that the effects of Tai Ji Quan on the elderly with high level of interleukin (IL)-6 might be better than those with relatively low level.MENDOZA-NUNEZ V M,et al[51]found that Tai Ji Quan could lower the IL-8 level. It has also been reported that Tai Ji Quan is not closely related to the inflammatory response. Due to the complex mechanism of inflammatory factors and cellular immunity, Tai Ji Quan’s effect on inflammation and oxidative stress in the body is still under investigation[52].

3.5 Regulation of neural circuits

Tai Ji Quan reduces functional connectivity in the prefrontal cortex and right medial frontal lobe[53].However, it should be pointed out that the decrease and interruption of functional connectivity in some brain regions may be one of the mechanisms of depression[54]. Tai Ji Quan training can also improve the functional activity of the insula, middle frontal sulcus and superior temporal gyrus, thereby enhancing emotional control[55]. The cortex of the precentral gyrus of the right hemisphere and the superior temporal gyrus of the left hemisphere is thicker in the Tai Ji Quan participants who have trained for a long time, and some brain regions show functional differentiation and integration compared with those who have not participated in Tai Ji Quan training for a long time,suggesting that Tai Ji Quan training has a remodeling effect on brain networks related to motor and emotional control[56-57]. Some researchers have the resting-state functional connectivity (rsFC) with the bilateral dorsolateral prefrontal cortex in the elderly as the seed and found that compared with the health education group, participants after Tai Ji Quan training were more significantly improved in the mind control ability, and the rsFC between the bilateral dorsolateral prefrontal cortex and left superior frontal gyrus and anterior cingulate cortex decreased. This effect is consistent with the results of meditation-related studies,suggesting that Tai Ji Quan training can enhance cognitive control and is associated with the cortical function in the superior frontal gyrus[58].

3.6 Mechanism of “combined physique-spirit treatment” between exercise and emotion

Tai Ji Quan is a rehabilitation therapy that integrates Qi-monism in TCM and takes the Yin-Yang theory as the core guiding ideology. Practicing Tai Ji Quan can regulate three Jiao (energizer) and muscle interspace, maintain the temperament, and strengthen the body[59]. Tai Ji Quan also involves the transformation of Yin and Yang and the five elements and the forms of ancient Daoyin(physical and breathing exercises) and exhalationinhalation, thus achieving the aim of both internal and external cultivation. Different from general rehabilitation training, a lot of Tai Ji movements, such as“a white crane spreads its wings”, “grasp sparrow’s tail”,and “reverse reeling forearm”, require the eyes to follow the hand and the body to follow the heart. Tai Ji Quan exercise pays attention to the integration of motion and stillness and the balance of Yin and Yang and takes into account the exerciser’s physical,psychological, and spiritual state[60]. Tai Ji Quan training can balance emotion and movement and strengthen the connection between them, thereby achieving a“combined physique-spirit treatment”. Its mechanism may be similar to that of exercise therapy. The antidepressant effect of exercise training has been confirmed by many studies via observing neurotrophic factor levels[61], perceived coping ability, and self-evaluation[62]. Exercise also has a wide range of regulation mechanisms for emotion: exercise can provoke physical receptors, produce unconscious emotions in the brain, and then connect with subjective emotions[63]. Through mirror neurons and their neural networks, post-stroke patients can also observe similar emotions and feelings after receiving or perceiving simulated exercises[64-66].

Motor dysfunction and mood disorder in stroke patients are closely related. It is also a rehabilitation problem that needs to be solved urgently. Related studies have shown that post-stroke mood disorders and emotion control are associated with the imbalance between the cerebral hemispheres, which affects the recovery of motor function[67]. For most stroke patients,motor dysfunction is the most obvious symptom, and how to improve limb dysfunction is the prior problem they want to solve. However, the long re-learning time of rehabilitation training, the poor training effect, and the complications caused by wrong rehabilitation methods often lead to various mood disorders such as depression, irritability, and anxiety in the patients[68].Either single or mixed negative emotions may reduce the rehabilitation effect in stroke patients or even aggravate the condition throughout the disease process[69]. In contrast, improving the long-term quality of life after a stroke can be achieved by improving emotion[70]. By adjusting the form and method of rehabilitation training to meet the requirements of different patients for rehabilitation training in different stages, it can objectively improve the emotion, guide patients to build up rehabilitation confidence, and improve rehabilitation efficacy[71].

4 Conclusion

Together with the previous studies, it is found that the brain regions activated by Tai Ji Quan in regulating cognition, emotion, and motor ability are partially overlapped, which explains the positive effects of Tai Ji Quan as a comprehensive rehabilitation exercise in regulating multiple brain functions in post-stroke patients. With the accumulation of research on the pathogenesis of PSD and the regulation of neural networks by Tai Ji Quan, it has been found that Tai Ji Quan has a common effect between “regulating the mind” and exercise, that is, controlling the motor function simultaneously while controlling the emotion.At present, the effect of depression-related neural pathways on the establishment of functional connectivity is still not clear. There are few studies on whether there is a sequential or coexisting relationship between motor control and emotion regulation.Compared with the common exercise methods, the effects of Tai Ji Quan in most clinical reports are quite different, which may be related to the differences in training intensity and training design. Revealing the regulation mechanism of Tai Ji Quan’s “regulating the mind” on motor function, formulating a pertinent Tai Ji Quan training method, enhancing the individualization of rehabilitation prescriptions, and further exploring the efficacy of Tai Ji Quan in improving depression and other functional disorders in stroke patients should receive more attention in the future.

Conflict of Interest

The authors declare that there is no potential conflict of interest in this article.

Acknowledgments

This work was supported by the Subproject of Three-year Action Plan of Shanghai: Non-drug Treatment Project [上海市三年行动计划子项目——非药物治疗项目, No. ZY(2018-2020)CCCX-2004-05]; Comprehensive Planning Project of Shanghai Sports Science and Technology (上海市体育科技“综合计划”项目, No.18Z016); Promotion Project for Advanced Suitable Technology of Shanghai Municipal Health Commission(上海市卫生健康委先进适宜技术推广项目, No.2019SY052); Key Clinical Specialty (Traditional Chinese Medicine) in the 13th Five-year of Shanghai:Rehabilitation Department of Traditional Chinese Medicine [上海市十三五临床重点专科(中医)——中医康复科, No. hslczdzk04601].

Received: 23 August 2021/Accepted: 29 November 2021