Main Text
1 Introduction
Stroke is a type of disease in which the blood vessels in the brain are blocked or suddenly ruptured, resulting in brain tissue damage caused by the obstruction of blood flow to the brain. Post-stroke depression combined with insomnia is a relatively common mood disorder in stroke patients after brain tissue damage [1,2]. Post-stroke depression combined with insomnia may be easily misdiagnosed or underdiagnosed due to the early onset of symptoms such as anxiety, depression, and sleep disorders, and may increase the risk of second stroke in patients with later severity [2].
Drugs and acupuncture are often used for clinical treatment of post-stroke depression combined with insomnia. However, there are still problems such as poor efficacy due to large individual differences between patients [3]. Acupuncture alone or in combination with other therapies has been reported to improve depression symptoms in stroke patients [4]. Hyperbaric oxygen is one of the main therapeutic methods in the rehabilitation period of stroke, previous studies have clarified the potential mechanism of hyperbaric oxygen therapy on stroke, which can promote brain oxygenation and improve the metabolism, protect the blood-brain barrier, anti-inflammation and brain edema, regulate intracranial pressure, reduce oxidative stress and cell apoptosis [5,6]. In addition, hyperbaric oxygen therapy can help stroke patients to regulate anxiety and depression, which used in the treatment of post-stroke depression combined with insomnia with better results [7,8]. For Wuyintiaoshen therapy, there is a tonal musical composition formed by fusing five scales with different emotional attributes, namely Gong, Yu, Jue, Zhi, and Shang, which can play a role in improving blood circulation, relieving depression, and improving sleep quality [9,10]. It has been reported that the Wuyintiaoshen therapy can effectively reduce the degree of depression in patients with post-stroke depression [11]. At present, there are few researches on hyperbaric oxygen-assisted Wuyintiaoshen therapy in patients with post-stroke depression combined with insomnia in China.
Based on these data, the present study was conducted to investigate the efficacy of hyperbaric oxygen-assisted Wuyintiaoshen therapy on post-stroke depression combined with insomnia and its effect on neurotransmitter levels by comparing the changes in the scores for Hamilton Depression Scale (HAMD) and Pittsburgh Sleep Quality Index (PSQI), as well as neurotransmitter levels before and after the treatments, with the purpose of investigating the application value of hyperbaric oxygen-assisted Wuyintiaoshen therapy in the treatment of patients with post-stroke depression combined with insomnia, and providing reference and guidance for the treatment of this disease in the clinic.
2 Materials and methods
2.1 General data
A total of 136 patients with post-stroke depression combined with insomnia admitted to our hospital from July 2020 to February 2023 were included and grouped according to treatment methods. 44 patients treated with hyperbaric oxygen were assigned to the hyperbaric oxygen group, 47 patients receiving Wuyintiaoshen therapy were allocated to the Wuyintiaoshen group, and 45 patients treated with hyperbaric oxygen combined with Wuyintiaoshen therapy were divided to the combined group. There was no statistically significant difference in the comparison of gender, age, duration of disease, and type of stroke among the three groups (p > 0.05), as shown in Table 1.
Table 1 Comparison of general data between the three groups.
| Group | Hyperbaric oxygen group (n = 44) | Wuyintiaoshen group (n = 47) | Combined group (n=45) | X2/F | p | |
|---|---|---|---|---|---|---|
| Gender (case) | Male | 28 | 22 | 26 | 2.708 | 0.258 |
| Female | 16 | 25 | 19 | |||
| Age (years old) | 46.38 ± 3.10 | 45.87 ± 3.25 | 46.12 ± 2.96 | 0.306 | 0.737 | |
| Duration of disease (h) | 47.21 ± 5.36 | 48.14 ± 5.78 | 46.88 ± 5.29 | 0.654 | 0.521 | |
| Type of stroke (cases) | Cerebral infarction | 24 | 21 | 23 | 0.918 | 0.632 |
| Cerebral hemorrhage | 20 | 26 | 22 | |||
2.2 Inclusion and exclusion criteria
2.2.1 Inclusion criteria
(1) Patients met the criteria for the diagnosis of stroke, depression, and insomnia in Chinese Guidelines for the Diagnosis and Treatment of Cerebral Hemorrhage (2019) [12], Chinese Classification of Mental Disorders-Third Edition [13], and Sleep-related Breathing Disorders in the International Classification of Sleep Disorders-3 [14]. (2) Patients aged 20-65 years. (3) Patients with stable vital signs. (4) Patients without symptoms such as teeth grinding, somniloquy, and snoring when they were living alone, living apart, or sleeping with their partners.
2.2.2 Exclusion criteria
(1) Patients receiving psychotropic drugs or related treatment within the last 3 months. (2) Patients with insensitivity or non-acceptance of music therapy. (3) Patients with sleep disorders prior to the onset of the disease. (4) Patients with cardiac, hepatic, and renal insufficiencies. (5) Patients with malignant tumors. (6) Patients with psychiatric disorders and poor treatment adherence. (7) Patients with incomplete clinical data. (8) Pregnant and lactating women.
2.3 Methods
Patients in all three groups were given antidepressant medication, and 0.99 g of Wuling capsule (Zhejiang Jolly Pharmaceutical Co., Ltd., National Medical Products Administration (NMPA) Approval No.: Z19990048, 0.33 g/capsule) was taken orally after meals 3 times a day.
On the basis of antidepressant medication, a large medical air-pressurized oxygen chamber (Yantai Moon Hyperbaric Oxygen Chamber Co., Ltd., model: YG3600J-X) was applied in hyperbaric oxygen group. Patients were asked to take the supine position, with the pressure set to 2.0 ATA. The pressure was stabilized for 60 min after 20 min of pressurization, followed by inhalation of pure oxygen for 1 h after disconnecting masks and change to breathe the air in the chamber. After 20 min, patients could get out of the chamber. Above hyperbaric oxygen therapy was performed once a day, with 10 times as a course of treatment and 3-5 days of intervals between each course.
On the basis of antidepressant medication, patients in Wuyintiaoshen group underwent treatment from Traditional Five Elements Music of China (Orthodox Form)-Jue Tune (People's Electronic Audiovisual Publishing House). Patients emptied their bladder before the treatment, lay flat in the treatment room with a quiet environment and soft light, and relaxed for 2-3 min. Then the music of Jue tone was played with the decibel of 40-60 dB, and needling was carried out on Baihui, Shenting, and Yindang acupoints for 1 min at the interval of 15 min, a total of 30 min every day and 5 times per week.
Additionally, patients in combined group received hyperbaric oxygen-assisted Wuyintiaoshen therapy. The treatment in the three groups was performed for 5 weeks.
2.4 Observation indicators
2.4.1 HAMD score
HAMD score in the three groups of patients before and after treatment was evaluated and compared. There were 17 items in HAMD scale [15] (7-17 points: mild depression, 17-24 points: moderate depression, above 24 points: severe depression). The higher score of HAMD suggested the more severe depression.
2.4.2 PSQI
PSQI score was assessed and compared among the three groups of patients before and after treatment. PSQI score [16] included seven dimensions, including sleep duration, sleep latency, subjective sleep quality, etc., with a total of 21 points. The higher PSQI score hinted the poorer sleep quality.
2.4.3 Clinical efficacy
Clinical efficacy in the three groups of patients after treatment was quantified and compared. Assessment criteria were listed below. Significantly effective: disappearance of patients' clinical symptoms; no depression, and sleep disorder. Effective: alleviation of patients' clinical symptoms and improvement of depression and sleep disorder. Invalid: no obvious change or even deterioration of patients' clinical symptoms. Total effective rate = the number of (significantly effective + effective) cases/total number of cases × 100%.
2.4.4 5-hydroxytryptamine (5-HT) and norepinephrine (NE) levels
Levels of 5-HT and NE before and after treatment in the three groups of patients were tested and compared. 5 mL of fasting peripheral venous blood was drawn from all patients in the early morning, left to stand at room temperature for 30-60 min and centrifuged at 3,000 r/min for 10 min. Afterwards, serum was separated and stored at -20 ℃ for measurement. Levels of 5-HT (ml057425) and NE (ml024646) were detected by enzyme-linked immunosorbent assay (ELISA), with the kits from Shanghai Enzyme-linked Biotechnology Co., Ltd (Shanghai, China).
2.5 Statistical methods
Statistical analysis was performed using SPSS 20.0. Count data were expressed as cases (%), comparisons between the three groups were carried out using X2 test, and measurement data were described as mean ± standard deviation. One-way ANOVA was used for comparisons between groups, LSD test was employed for two-by-two comparisons between groups, and paired samples t-test was applied for the comparison in the same group at different time points. Differences were considered to be statistically significant at p < 0.05.
3 Results
3.1 Comparison of HAMD score before and after treatment in three groups
Before treatment, there was no statistically significant difference in the comparison of HAMD score among the three groups (p > 0.05). After treatment, HAMD score in the three groups was decreased (p < 0.05). HAMD score in combined group was lower than that in hyperbaric oxygen group and Wuyintiaoshen group (p < 0.05), and the score in Wuyintiaoshen group was lower than that in hyperbaric oxygen group (p < 0.05). The results were displayed in Table 2.
Table 2 Comparison of HAMD score before and after treatment in three groups (mean ± standard deviation, point).
| Group | Case | HAMD score | |
|---|---|---|---|
| Before treatment | After treatment | ||
| Hyperbaric oxygen group | 44 | 17.65 ± 3.47 | 11.38 ± 2.05 * |
| Wuyintiaoshen group | 47 | 17.43 ± 3.62 | 9.93 ± 1.78 *a |
| Combined group | 45 | 17.96 ± 2.86 | 6.54 ± 1.32 *ab |
| F | 0.292 | 91.020 | |
| p | 0.747 | 0.000 | |
Note: * p < 0.05 vs. before treatment; a p < 0.05 vs. hyperbaric oxygen group; b p < 0.05 vs. Wuyintiaoshen group.
3.2 Comparison of PSQI score before and after treatment in three groups
Before treatment, the difference of PSQI score in the three groups was of no statistical significance (p > 0.05). After treatment, PSQI score in the three groups was decreased (p < 0.05). PSQI score in the combined group was lower than that in hyperbaric oxygen group and Wuyintiaoshen group (p < 0.05), and the score in Wuyintiaoshen group was also lower than that in hyperbaric oxygen group (p < 0.05). The results were seen in Table 3.
Table 3 Comparison of PSQI score before and after treatment in three groups (mean ± standard deviation, point).
| Group | Case | PSQI score | |
|---|---|---|---|
| Before treatment | After treatment | ||
| Hyperbaric oxygen group | 44 | 11.98 ± 4.26 | 10.13 ± 2.41 * |
| Wuyintiaoshen group | 47 | 12.15 ± 4.30 | 8.56 ± 2.17 *a |
| Combined group | 45 | 11.76 ± 3.45 | 6.34 ± 2.11 *ab |
| F | 0.108 | 32.460 | |
| p | 0.897 | 0.000 | |
Note: * p < 0.05 vs. before treatment; a p < 0.05 vs. hyperbaric oxygen group; b p < 0.05 vs. Wuyintiaoshen group.
3.3 Comparison of clinical efficacy in three groups
The total effective rate in combined group was higher than that in hyperbaric oxygen group and Wuyintiaoshen group (p < 0.05). The results were shown in Table 4.
Table 4 Comparison of clinical efficacy in three groups [case (%)].
| Groups | Case | Significantly effective | Effective | Invalid | Total effective rate |
|---|---|---|---|---|---|
| Hyperbaric oxygen group | 44 | 9 (20.45) | 14 (31.82) | 21 (47.73) | 23 (52.27) |
| Wuyintiaoshen group | 47 | 18 (38.30) | 16 (34.04) | 13 (27.66) | 34 (72.34) |
| Combined group | 45 | 24 (53.33) | 17 (37.78) | 4 (8.89) | 41 (91.11) |
| X2 | 16.670 | ||||
| p | 0.000 |
Note: * p < 0.05 vs. before treatment.
3.4 Comparison of serum 5-HT and NE levels before and after treatment in three groups
Before treatment, there was no statistically significant difference in the comparison of serum 5-HT and NE levels among the three groups (p > 0.05). After treatment, the serum levels of 5-HT and NE in three groups were increased (p < 0.05). Specifically, 5-HT and NE levels in the combined group were higher than those in hyperbaric oxygen group and Wuyintiaoshen group (p < 0.05). Likewise, these levels in Wuyintiaoshen group were higher than those in hyperbaric oxygen group (p < 0.05). The results were shown in Table 5.
Table 5 Comparison of serum 5-HT and NE levels before and after treatment in three groups (means ± standard deviation, μg/L).
| Groups | Case | 5-HT | NE | ||
|---|---|---|---|---|---|
| Before treatment | After treatment | Before treatment | After treatment | ||
| Hyperbaric oxygen group | 44 | 74.58±11.42 | 96.52 ± 12.65 * | 4.21 ± 0.36 | 4.96 ± 0.34 * |
| Wuyintiaoshen group | 47 | 72.84 ± 10.39 | 99.34 ± 11.40 *a | 4.18 ± 0.30 | 5.28 ± 0.54 *a |
| Combined group | 45 | 73.65 ± 9.46 | 153.27 ± 13.72 *ab | 4.23 ± 0.28 | 6.17 ± 0.43 *ab |
| F | 0.315 | 290.100 | 0.295 | 88.240 | |
| p | 0.730 | 0.000 | 0.745 | 0.000 | |
Note: * p < 0.05 vs. before treatment; a p < 0.05 vs. hyperbaric oxygen group; bp < 0.05 vs. Wuyintiaoshen group.
4 Discussion
With the purpose of finding a more effective way to treat patients with post-stroke depression combined with insomnia, this study explored the application value of hyperbaric oxygen-assisted Wuyintiaoshen therapy for them. Results in our study revealed that hyperbaric oxygen-assisted Wuyintiaoshen therapy had a better efficacy for patients with post-stroke depression combined with insomnia.
HAMD scale is clinically used to assess the degree of depression, with higher score indicating more severe depression. This study uncovered that the degree of depression improved in all patients after treatment, and the efficacy of patients treated with hyperbaric oxygen-assisted Wuyintiaoshen therapy was better, with greater improvement in the degree of depression. Neurological deficits in post-stroke patients lead to impaired physical functioning and trigger emotional and behavioral changes [17]. Hyperbaric oxygen therapy can improve tissue oxygen supply and brain tissue metabolism, and prevent the damage of oxygen free radicals to the neural structure, thus promoting the repair of brain damage, increasing the levels of 5-HT and NE in the body, and achieving the purpose of treating post-stroke depression [18]. By the way of adjusting the music and sound waves based on the patient's own condition, Wuyintiaoshen method, which includes psychological, physiological, and physical therapies, can regulate the abnormal vibration frequency caused by the patient's organs, and strengthen the effect of acupuncture while treating the specific vibration frequency to soothe the patient's emotion, and then effectively reduce the depression [19]. Therefore, hyperbaric oxygen-assisted Wuyintiaoshen therapy may be able to better improve the degree of depression in patients with post-stroke depression combined with insomnia.
PSQI scale is clinically used to estimate patients' sleep, with a higher score indicating poorer sleep quality. In our current study, the sleep quality of all patients was improved after treatment, and better improvement of the sleep quality was witnessed in patients treated with hyperbaric oxygen-assisted Wuyintiaoshen therapy. Post-stroke patients with impaired cerebral aerobic metabolism will trigger changes in brain cell function and morphology, blocking neural pathways and inhibiting nervous system excitability, thereby leading to sleep disorders such as difficulty in falling asleep and inability to sleep deeply. Some medications used in the treatment of stroke and its comorbidities will also trigger sleep disorders [20,21]. Hyperbaric oxygen therapy can help patients accelerate the establishment of collateral circulation and cerebral vascular repair process, elevate the tissue oxygen content, maintain the normal level of intra- and extracellular ions, enhance cerebral microcirculation, activate the aerobic metabolic activity of cerebral nerve cells, restore the function of cerebral cortex, potentiate the ability of self-regulation, and improve the quality of sleep [22,23]. Wuyintiaoshen therapy stimulates the parietal and frontal lobes of the brain by needling Shenting, Yindang, and Baihui acupoints to build up the damaged neural reflex arcs, and simultaneously regulates 5-HT neurons in the medulla oblongata and pons to promote the secretion and synthesis of 5-HT and help them convert into melatonin to regulate patients' sleep [19]. Hence, hyperbaric oxygen-assisted Wuyintiaoshen therapy may be able to better improve the sleep quality of patients with post-stroke depression combined with insomnia.
5-HT, as an inhibitory neurotransmitter, is mainly secreted and regulated by the hypothalamus, which can regulate physiological activities such as mood, sleep, behavior, etc. NE mainly acts in the hypothalamus, thalamus, and basal forebrain, which can stimulate and regulate cortical activity and arousal, and is involved in the maintenance of electroencephalographic arousal. A decrease in its level indicates depression and poor quality of sleep [24,25].Our study demonstrated that the sleep quality of patients treated with hyperbaric oxygen-assisted Wuyintiaoshen therapy was better, further illustrating the better efficacy of hyperbaric oxygen-assisted Wuyintiaoshen therapy. Hyperbaric oxygen-assisted Wuyintiaoshen can strengthen the nerve repair function, reduce the severity of neuroinflammatory response to stroke, regulate the abnormal release of neurotransmitters, inhibit 5-HT uptake, promote the synthesis and secretion of NE in large quantities, and effectively prevent the occurrence of depression and sleep disorders [26,27]. Thus, hyperbaric oxygen-assisted Wuyintiaoshen may have better efficacy on the patients with post-stroke depression complicated with insomnia, which can increase the 5-HT and NE levels.
In conclusion, hyperbaric oxygen-assisted Wuyintiaoshen therapy may have a better efficacy on patients with post-stroke depression complicated with insomnia, which can improve the degree of depression and sleep quality of patients, and promote the secretion of neurotransmitters.
Back Matter
Acknowledgments
Not applicable.
Conflict-of-Interest
The authors declare no conflicts of interest.
Authors' contributions
Conceptualization: Xiaoyang Chen; Data curation: Chenfei Huang; Formal analysis:Xiaoyang Chen; Methodology: Chenfei Huang; Writing – original draft:Xiaoyang Chen; Writing – review and editing:Chenfei Huang; All authors have read and agreed to the published version of manuscript.
Ethics approval and consent to participate
This study was approved by Medical Ethics Committee, and patients were informed and agreed.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Availability of Data and Materials
The analyzed data sets generated during the study are available from the corresponding author on reasonable request.
Supplementary Material
Not applicable.
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