Preamble

Efficacy of Bushen Jiannao Acupuncture Combined with Sertraline in the Treatment of Late-Life Depression: A Randomized Controlled Trial

Li Li, Xu Tianchao, Dong Xiaomei, Huang Hongfei, Cui Gang, Li Dongdong, Zhang Ou, Fan Lin, Wang Qi

Abstract

Objective: To evaluate the clinical efficacy and safety of Bushen Jiannao acupuncture combined with sertraline hydrochloride in the treatment of late-life depression (LLD) with kidney essence deficiency syndrome.

Methods: A total of 84 elderly patients with depression meeting the inclusion criteria were randomly assigned to either the observation group ($n=42$) or the control group ($n=42$). Both groups received oral sertraline hydrochloride. The observation group was additionally treated with Bushen Jiannao acupuncture, while the control group received sham acupuncture. The treatment lasted for 8 weeks. The primary outcome measure was the Hamilton Depression Rating Scale (HAMD-17) score. Secondary outcome measures included the Geriatric Depression Scale (GDS), the Traditional Chinese Medicine (TCM) Syndrome Scale for Kidney Essence Deficiency, and the Montreal Cognitive Assessment (MoCA). Safety was monitored throughout the trial.

Results: After 8 weeks of treatment, both groups showed significant reductions in HAMD-17, GDS, and TCM syndrome scores compared to baseline ($P < 0.05$). The observation group demonstrated significantly lower scores in HAMD-17, GDS, and TCM syndrome scales compared to the control group ($P < 0.05$). Furthermore, the MoCA scores in the observation group improved significantly compared to both baseline and the control group ($P < 0.05$), whereas the control group showed no significant improvement in cognitive function. The total effective rate was significantly higher in the observation group than in the control group ($P < 0.05$). No serious adverse events were reported in either group.

Conclusion: Bushen Jiannao acupuncture combined with sertraline is more effective than sertraline alone in reducing depressive symptoms, improving TCM syndromes, and enhancing cognitive function in elderly patients with depression. The therapy is safe and well-tolerated.

Introduction

Late-life depression (LLD) refers to depressive episodes occurring in adults aged 60 and older. With the global intensification of population aging, LLD has become a major public health challenge. It is characterized not only by persistent low mood but also by significant cognitive impairment and physical symptoms.

Background

In Traditional Chinese Medicine (TCM), depression falls under the category of emotional disorders, and its pathogenesis can be explained by the theory of "interdependence between the kidney and the brain." However, there has been a lack of previous reports on whether kidney-tonifying and brain-strengthening acupuncture therapy can be effectively utilized to treat geriatric depression. This study aims to explore the effects of kidney-tonifying and brain-strengthening acupuncture, based on the "kidney-brain interdependence" theory, combined with sertraline in improving the emotional state and cognitive function of elderly patients with depression. This trial has been registered with the Chinese Clinical Trial Registry (Registration Number: ChiCTR2400081227).

A total of 86 elderly patients with depression admitted to the Department of Psychiatry at the General Hospital of Northern Theater Command from March 2023 to March 2024 were selected as research subjects and randomly divided into an observation group ($n=43$) and a control group ($n=43$). The control group received sertraline treatment, while the observation group received kidney-tonifying and brain-strengthening acupuncture combined with sertraline for a total duration of 4 weeks. Before and after treatment, depressive symptoms were assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17), and cognitive function was evaluated using the Wisconsin Card Sorting Test (WCST). Laboratory tests were conducted to measure platelet count (PLT), monocyte count (MONO), neutrophil count (NC), and lymphocyte count (LC), which were used to calculate the Systemic Immune-Inflammation Index (SII) and the Systemic Inflammation Response Index (SIRI).

The HAMD-17 scores, cognitive function parameters, SII, and SIRI were compared between the two groups before and after treatment. Pearson correlation analysis was employed to examine the relationship between the changes in HAMD-17 scores and cognitive function parameters and the changes in SII and SIRI in the observation group. Clinical efficacy was also compared between the two groups. Post-treatment results showed that the HAMD-17 scores in the observation group were significantly lower than those in the control group ($P < 0.05$). In the WCST, the percentages of correct responses and conceptual level responses were significantly higher in the observation group than in the control group ($P < 0.05$), while SII and SIRI levels were significantly lower ($P < 0.05$).

In the observation group, the change in SII was positively correlated with the change in HAMD-17 scores ($r = 0.536, P < 0.05$) and negatively correlated with the changes in the percentage of correct responses ($r = -0.621, P < 0.05$) and conceptual level responses ($r = -0.482, P < 0.05$). Similarly, the change in SIRI in the observation group was positively correlated with the change in HAMD-17 scores ($r = 0.429, P < 0.05$) and negatively correlated with the changes in the percentage of correct responses ($r = -0.378, P < 0.05$) and conceptual level responses ($r = -0.434, P < 0.05$). The overall clinical efficacy in the observation group was superior to that of the control group ($P < 0.05$). In conclusion, kidney-tonifying and brain-strengthening acupuncture can enhance the therapeutic effect of sertraline in elderly patients with depression. The mechanism by which it alleviates depressive symptoms and improves cognitive function may be related to the modulation of immune-inflammation.

Keywords: Depression; Elderly; Acupuncture; Sertraline; Cognitive function; Systemic Immune-Inflammation Index (SII); Systemic Inflammation Response Index (SIRI)

Background

Depression belongs to the category of emotional disorders in traditional Chinese medicine, and its pathogenesis can be explained by the theory of "kidney-brain harmony." Whether kidney-tonifying and brain-strengthening acupuncture therapy can be used to treat elderly depression has not been reported in the past.

Objective: Exploring the effect of tonifying the kidney and strengthening the brain acupuncture therapy based on the theory of "kidney-brain coordination" combined with sertraline on improving the emotional and cognitive functions of elderly depression patients.

Methods

This trial has been registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2400081227). Eighty-six elderly patients with depression admitted to the Department of Psychiatry of the Northern Theater Command General Hospital between March 2023 and March 2024 were selected as the research subjects. They were randomly divided into an observation group ($n=43$) and a control group ($n=43$). The patients in the control group were treated with sertraline alone, while the patients in the observation group were treated with kidney-tonifying and brain-strengthening acupuncture combined with sertraline. All patients were treated for 4 weeks.

Before and after treatment, depressive mood was evaluated using the 17-item Hamilton Depression Scale (HAMD-17), and cognitive function was evaluated using the Wisconsin Card Sorting Test. Laboratory tests detected platelet count (PLT), mononuclear cell count (MONO), neutrophil count (NC), and lymphocyte count (LC) to calculate the systemic immune-inflammation index (SII) and systemic inflammatory response index (SIRI). The HAMD-17 scores, cognitive function, SII, and SIRI of the two groups were compared before and after treatment. The relationship between the change values of HAMD-17 scores and cognitive function with SII and SIRI in the observation group was analyzed by Pearson correlation analysis, and the clinical efficacy of the two groups was compared.

Results

The HAMD-17 score in the observation group was lower than the control group after treatment ($P < 0.05$). The percentage of correct responses and conceptualization level in the Wisconsin Card Sorting Test in the observation group after treatment was higher than that in the control group ($P < 0.05$). The SII and SIRI of the observation group were lower than the control group after treatment ($P < 0.05$). The changes in SII before and after treatment in the observation group were positively correlated with the changes in HAMD-17 score ($r=0.536, P < 0.05$). The changes in SII were negatively correlated with the percentage of correct responses to the Wisconsin Card Sorting Test ($r=-0.621, P < 0.05$) and the percentage of conceptualization level ($r=-0.482, P < 0.05$), respectively. The change in SIRI score was positively correlated with the change in HAMD-17 score ($r=0.429, P < 0.05$). The SIRI change values were negatively correlated with the percentage of correct responses to the Wisconsin Card Sorting Test ($r=-0.378, P < 0.05$) and the percentage of conceptualization level ($r=-0.434, P < 0.05$), respectively. The therapeutic effect of the observation group was better than the control group ($P < 0.05$).

Conclusion

Kidney-tonifying and brain-strengthening acupuncture therapy can improve the effectiveness of sertraline in treating elderly depression, and its mechanism of alleviating depressive mood and cognitive function may be related to improving immune inflammation.

Keywords: Depression; Aged; Acupuncture; Sertraline; Cognitive function; Systemic immune inflammation index; Systemic inflammatory response index

Depression is a common mental disorder among the elderly, characterized by symptoms such as low mood, diminished interest, reduced activity, and cognitive impairment. These symptoms significantly impact social functioning and impose a substantial burden on families. Clinically, selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are frequently employed to treat geriatric depression. However, these pharmacological interventions are often limited by suboptimal efficacy, significant adverse reactions, and low patient compliance. As a component of traditional Chinese medicine, acupuncture has garnered widespread attention for the treatment of geriatric depression. Research indicates that acupuncture can alleviate depressive symptoms by modulating central synaptic plasticity, neuroendocrine function, and neurotransmitter levels. Furthermore, acupuncture exerts antidepressant effects by mitigating inflammatory damage; post-treatment, patients exhibit significant improvements in serum levels of inflammatory cytokines, such as interleukin-10 (IL-10) and interleukin-1 (IL-1). In the framework of traditional Chinese medicine, depression falls under the category of emotional disorders, and its pathogenesis can be elucidated through the theory of "Interdependence between Kidney and Brain."

The kidney is considered the "foundation of innate constitution," and the essence ($jing$) and $qi$ stored within the kidney can connect to the brain and generate marrow. This kidney essence serves as the root of the vitality of the five $zang$ and six $fu$ organs, and maintaining it provides the material basis for nourishing the brain. When kidney $qi$ is robust, the brain marrow is abundant, ensuring normal physiological brain function, mental clarity, and high spirits. Conversely, a deficiency in kidney essence leads to an "emptiness of the sea of marrow," which adversely affects emotions and cognitive functions. Our research group's previous studies have found that "Kidney-Tonifying and Brain-Strengthening" acupuncture therapy, based on the theory of "Interdependence between Kidney and Brain," can improve the mood and cognitive status of patients with depression. However, there have been few reports on whether this specific acupuncture therapy is effective for geriatric depression. Sertraline is a commonly used medication for treating depression in the elderly. This study analyzes the efficacy of "Kidney-Tonifying and Brain-Strengthening" acupuncture combined with sertraline in improving the emotional and cognitive functions of elderly patients. The systemic immune-inflammation index (SII) and the systemic inflammatory response index (SIRI) reflect the balance between inflammation and the immune response; higher levels of these indices are associated with greater severity of depression and more significant cognitive impairment. This study observes changes in SII and SIRI levels before and after treatment to explore the potential mechanisms by which acupuncture treats geriatric depression.

1.1 Research Subjects

Using PASS 2021 software, the sample size was estimated based on a superiority threshold of 16 for the 17-item Hamilton Depression Rating Scale (HAMD-17) obtained from a pilot study. Setting $\alpha = 0.05$ and $\beta = 0.20$, the required sample size was calculated to be at least 39 cases per group. Accounting for potential loss to follow-up, the final sample size was determined to be 43 cases per group. Between March 2023 and March 2024, 86 elderly patients with depression admitted to the Department of Psychiatry at the General Hospital of Northern Theater Command were selected as research subjects. They were divided into an observation group ($n=43$) and a control group ($n=43$) using a random number table method. The diagnosis of depression was based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) \cite{9}.

The inclusion criteria for patients were: (1) age $\ge 60$ years; (2) first diagnosis or discontinuation of antidepressant medication for more than one month; (3) absence of organic brain disease; and (4) ability to cooperate with relevant psychological testing.

Exclusion criteria included: (1) other psychiatric disorders, such as substance abuse disorders, bipolar disorder, or schizophrenia; (2) severe physical illness; (3) infection; (4) metabolic diseases; and (5) dementia or consciousness disorders. Elimination criteria were: (1) occurrence of serious adverse reactions or needle phobia; (2) worsening of depressive symptoms or emergence of suicidal ideation/behavior; and (3) voluntary withdrawal from the trial.

This study was approved by the Ethics Committee of the General Hospital of Northern Theater Command [Approval No.: Lunshen Y (2023) 035], and the trial has been registered with the Chinese Clinical Trial Registry (Registration No.: ChiCTR2400081227).

1.2 Treatment Methods

Patients in the control group were treated with Sertraline Hydrochloride (Zhejiang Huahai Pharmaceutical Co., Ltd., National Medicine Permit No. H20080141) at a target dose of 100 mg/d. The observation group received "Bushen Jiannao" (Kidney-tonifying and Brain-strengthening) acupuncture intervention in addition to the treatment provided to the control group. Both groups were treated continuously for 4 weeks.

The Bushen Jiannao acupuncture therapy involved the selection of primary acupoints: Baihui (GV20), Shenting (GV24), and Dazhong (KI4). Supplementary acupoints included Fengchi (GB20), Neiguan (PC6), Shenmen (HT7), Zusanli (ST36), and Sanyinjiao (SP6). After skin disinfection with povidone-iodine, acupuncture was performed using $0.3 \text{ mm} \times 40 \text{ mm}$ filiform needles with a balanced reinforcing-reducing technique. Manipulation was performed every 10 minutes, with a total needle retention time of 40 minutes. Treatment was administered once daily, five days per week (Monday to Friday).

1.3 Observation Indicators

Before treatment and after 4 weeks of treatment, depressive symptoms were assessed using the HAMD-17, cognitive function was evaluated using the Wisconsin Card Sorting Test (WCST), and the Systemic Immune-Inflammation Index (SII) and Systemic Inflammation Response Index (SIRI) were calculated. Additionally, adverse reactions during the treatment period were recorded.

(1) The HAMD-17 is a clinical tool used to assess the severity of depression, consisting of 17 items covering symptoms such as depressed mood, feelings of guilt, suicidal tendencies, sleep disturbances, decreased work and interests, and psychomotor retardation or agitation. Each item is scored on a multi-level scale of 0–4 or 0–2 based on symptom severity, with a total score ranging from 0 to 52. The scoring criteria are generally as follows: $\le 7$ indicates no depression, 8–17 indicates mild depression, 18–24 indicates moderate depression, and $\ge 25$ indicates severe depression. The Cronbach's $\alpha$ coefficient for this scale in the study was 0.905.

(2) The Wisconsin Card Sorting Test is a neuropsychological assessment tool that requires subjects to classify cards according to changing rules such as color, shape, or number. It primarily evaluates abstract generalization, cognitive shifting, attention, working memory, information retrieval, category maintenance, category switching, and stimulus recognition and processing. This study utilized the short version (64 cards) and recorded the percentage of correct responses and the percentage of conceptual level responses.

(3) Fasting venous blood was collected from the patients' antecubital vein in the morning. Routine blood analysis was performed using a DYN3700 fully automated hematology analyzer (Abbott, USA) to detect platelet count (PLT), neutrophil count (NC), lymphocyte count (LC), and mononuclear cell count (MONO). The SII was calculated as $\text{SII} = \text{PLT} \times \text{NC} / \text{LC}$ \cite{12}, and $\text{SIRI} = \text{MONO} \times \text{NC} / \text{LC}$.

1.4 Clinical Efficacy Evaluation

The treatment efficacy was evaluated using the reduction rate of the Hamilton Depression Rating Scale (HAMD-17). The reduction rate was calculated as follows: (Pre-treatment score - Post-treatment score) / Pre-treatment score × 100%.

Clinical outcomes were categorized based on the reduction rate: a reduction rate >75% was defined as clinical recovery; 50% < reduction rate ≤ 75% was defined as markedly effective; 25% < reduction rate ≤ 50% was defined as effective; and a reduction rate ≤ 25% was defined as ineffective.

1.5 Statistical Methods

Statistical analysis was performed using SPSS 20.0 software. Quantitative data are expressed as mean ± standard deviation ($\bar{x} \pm s$). Comparisons between two groups were conducted using independent samples $t$-tests, while intra-group comparisons before and after treatment were performed using paired $t$-tests. Categorical data are expressed as relative numbers (percentages), and comparisons between groups were conducted using the $\chi^2$ test. Pearson correlation analysis was employed to examine the relationships between changes in HAMD-17 scores, changes in cognitive function, and changes in the Systemic Immune-Inflammation Index (SII) and Systemic Inflammation Response Index (SIRI). For the comparison of clinical efficacy between the two groups, the Mann-Whitney U test was utilized. $P < 0.05$ was considered to indicate statistical significance.

2 Results

2.1 Comparison of Baseline Data

There were no statistically significant differences between the two groups in terms of gender, marital status, disease duration, or BMI ($P > 0.05$), as shown in [TABLE:1].

[TABLE:1] Gender (Male/Female), Marital Status (Married/Unmarried/Widowed)

2.2 Comparison of HAMD-17 Scores Before and After Treatment

Before treatment, there was no statistically significant difference in the HAMD-17 scores between the two groups ($P > 0.05$). Following treatment, the HAMD-17 scores in both the observation group and the control group were significantly lower than their respective pre-treatment levels ($P < 0.05$). Furthermore, the post-treatment HAMD-17 scores in the observation group were significantly lower than those in the control group ($P < 0.05$), as shown in [TABLE:2].

[TABLE:2] Comparison of HAMD-17 scores between two groups before and after treatment

Note: $^a$ indicates $P < 0.05$ compared with the same group before treatment. HAMD-17 = 17-item Hamilton Depression Rating Scale.

2.3 Comparison of Cognitive Function Before and After Treatment

Prior to treatment, there were no statistically significant differences between the two groups regarding the percentage of correct responses and the percentage of conceptual level responses ($P > 0.05$). Following treatment, both the observation group and the control group exhibited significantly higher percentages of correct responses and conceptual level responses compared to their baseline values ($P < 0.05$). Furthermore, the post-treatment percentages for both correct responses and conceptual level responses in the observation group were significantly higher than those in the control group ($P < 0.05$), as shown in [TABLE:3].

[TABLE:3] Comparison of Wisconsin Card Sorting Test results before and after treatment between the two groups.

Note: $^a$ indicates a statistically significant difference compared to the same group before treatment ($P < 0.05$).

2.4 Comparison of SII and SIRI Before and After Treatment

Prior to treatment, there were no statistically significant differences in the Systemic Immune-Inflammation Index (SII) and the Systemic Inflammation Response Index (SIRI) between the two groups ($P > 0.05$). Following treatment, both the observation group and the control group exhibited significantly lower SII and SIRI levels compared to their pre-treatment values ($P < 0.05$). Furthermore, the post-treatment SII and SIRI levels in the observation group were significantly lower than those in the control group ($P < 0.05$).

Note: $^a$ indicates $P < 0.05$ compared with the same group before treatment. SII = Systemic Immune-Inflammation Index; SIRI = Systemic Inflammation Response Index.

2.5 Correlation Analysis of Changes in HAMD-17 Scores, Cognitive Function, and Inflammatory Indices

In the observation group, the mean change in HAMD-17 scores following treatment was $-(13.78 \pm 1.88)$ points. Regarding cognitive performance as measured by the Wisconsin Card Sorting Test (WCST), the change in the percentage of correct responses was $(19.20 \pm 4.12)\%$, while the change in the conceptual level percentage was $(20.19 \pm 4.58)\%$. Furthermore, the systemic immune-inflammation index (SII) showed a mean change of $-(61.18 \pm 20.10)$, and the systemic inflammation response index (SIRI) showed a mean change of $-(0.17 \pm 0.09)$.

Pearson correlation analysis revealed that in the observation group, the change in Systemic Immune-Inflammation Index (SII) values before and after treatment was positively correlated with the change in Hamilton Depression Rating Scale (HAMD-17) scores ($r = 0.536, P < 0.001$). Conversely, the change in SII values showed a significant negative linear correlation with both the percentage of correct responses ($r = -0.621, P < 0.001$) and the percentage of conceptual level responses ($r = -0.482, P < 0.001$) on the Wisconsin Card Sorting Test (WCST).

Furthermore, the change in Systemic Inflammation Response Index (SIRI) values in the observation group before and after treatment was positively correlated with the change in HAMD-17 scores ($r = 0.429, P < 0.001$). Furthermore, the change in SIRI values showed a negative linear correlation with both the percentage of correct responses ($r = -0.378, P < 0.01$) and the percentage of conceptual level responses ($r = -0.434, P < 0.01$) on the Wisconsin Card Sorting Test (WCST).

2.6 Comparison of Efficacy Between the Two Groups

The therapeutic efficacy of the observation group was superior to that of the control group, and the difference was statistically significant ($Z = -2.856, P = 0.020$), as shown in [TABLE:5].

2.7 Comparison of Adverse Reactions Between the Two Groups

There was no statistically significant difference in the overall incidence of adverse reactions between the two groups ($\chi^2 = 0.567, P = 0.451$); see [TABLE:6].

3 Discussion

Geriatric depression can lead to significant issues such as disability and cognitive dysfunction, necessitating increased clinical attention. Commonly used Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) have limited efficacy in treating depression; approximately two-thirds of patients do not achieve significant symptom remission after initial antidepressant treatment. Improving the therapeutic outcomes of depression remains a critical focus in the field. This study found that "Bushen Jiannao" (tonifying the kidney and strengthening the brain) acupuncture therapy can enhance the efficacy of sertraline in treating geriatric depression and improve patients' cognitive function.

From the perspective of Traditional Chinese Medicine (TCM), the pathogenesis of geriatric depression primarily involves kidney deficiency and depletion, which fails to generate marrow and nourish the "Sea of Marrow" (the brain), leading to mental dysregulation. Based on the theory of "Kidney-Brain Interdependence," using TCM methods to tonify the kidney and strengthen the brain can improve depressive symptoms and cognitive function in the elderly. In this study, the improvement in HAMD-17 scores in the observation group was significantly greater than in the control group, indicating that Bushen Jiannao acupuncture therapy enhances the therapeutic effect of sertraline.

The acupuncture protocol utilized Baihui (GV20), Shenting (GV24), and Dazhong (KI4) as primary acupoints, with Fengchi (GB20), Neiguan (PC6), Shenmen (HT7), Zusanli (ST36), and Sanyinjiao (SP6) as secondary points. Among the primary points, Baihui belongs to the Governor Vessel; it functions to benefit Qi, raise Yang, and fill the Sea of Marrow, thereby improving both mood and cognition. Among the secondary points, Fengchi belongs to the Gallbladder Meridian of Foot-Shaoyang and serves to calm the liver, extinguish wind, and clear the head and eyes. Neiguan is the Luo-connecting point of the Pericardium Meridian, and Shenmen is the Yuan-source point of the Heart Meridian; needling these points regulates Heart Qi and unblocks the blood vessels, making them effective for treating mental and consciousness disorders. Accupuncturing Zusanli can replenish Qi and blood, while Sanyinjiao regulates kidney function, ensuring a source for the biochemical production of brain marrow. Our research group previously achieved favorable results using Bushen Jiannao acupuncture combined with escitalopram oxalate for depression, reaching an effective rate of 93.33%.

Patients with geriatric depression often present with cognitive impairments, such as memory loss, poor concentration, and reduced psychomotor speed. Conventional antidepressants often fail to provide significant cognitive improvement and may even impair cognitive function. Previous studies have confirmed that acupuncture can improve cognitive function in depressed patients. In this study, the Wisconsin Card Sorting Test (WCST) was used to assess cognitive function. After treatment, the percentage of correct responses and the conceptual level percentage increased in both groups, with the observation group showing significantly higher improvements. These results indicate that Bushen Jiannao acupuncture therapy can improve cognitive function in elderly patients with depression. Previous scholars have also utilized kidney-tonifying and brain-strengthening TCM formulas to treat post-stroke depression, resulting in significant cognitive recovery.

Immune-inflammatory injury is a key mechanism in the pathogenesis of depression; inflammation participates in the development of the disorder by affecting neuroendocrine systems, brain neural circuits, synaptic plasticity, and epigenetics. Furthermore, inflammatory damage is associated with cognitive impairment in depressed patients. Existing research has confirmed that acupuncture can treat depression by alleviating inflammatory damage. Studies have found that acupuncture can improve serum levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-$\alpha$), IL-1$\alpha$, IL-6, and IL-2. Our group previously discovered that acupuncture inhibits the hippocampal NF-$\kappa$B/NLRP3 inflammatory signaling pathway, thereby reducing levels of TNF-$\alpha$, IL-6, IL-1$\beta$, and IL-18, which in turn improves depression-like behavior in mice.

Distinct from these specific cytokines, the Systemic Immune-Inflammation Index (SII) and the Systemic Inflammation Response Index (SIRI)—derived from routine blood tests—provide a more holistic reflection of the body's inflammatory state. These indices are easy to calculate and convenient for clinical use \cite{8, 13}. Previous studies have shown that compared to healthy individuals, patients with depression have significantly elevated SII levels, which correlate positively with disease severity and negatively with cognitive function \cite{8, 27}. Additionally, SIRI levels are higher in depressed patients and are associated with suicidal ideation. This study found that after treatment, both SII and SIRI decreased in both groups, with the observation group showing lower levels than the control group, suggesting that Bushen Jiannao acupuncture can ameliorate immune-inflammatory damage. Further analysis revealed that changes in SII and SIRI were positively correlated with changes in HAMD-17 scores. Conversely, changes in SII and SIRI were negatively correlated with the percentage of correct responses and conceptual level percentage in the WCST. These results suggest that the mechanism by which acupuncture improves depressive mood and cognitive function may be related to the alleviation of inflammatory damage.

4 Summary

Based on the theory of "Interdependence between Kidney and Brain," the Bushen Jiannao acupuncture therapy enhances the efficacy of sertraline in treating late-life depression. The mechanism by which this therapy alleviates depressive symptoms and improves cognitive function may be related to the modulation of immune-mediated inflammation. However, this study has certain limitations, such as the lack of long-term follow-up and the absence of direct measurements regarding functional changes in peripheral blood immune cells. Future research should focus on observing the long-term effects of Bushen Jiannao acupuncture and conducting animal studies to further elucidate its underlying biological mechanisms.

Author Contributions: Li Li and Wang Qi conceived and designed the study and were responsible for revising the manuscript. Xu Tianchao and Li Dongdong performed the acupuncture treatments. Huang Hongfei, Cui Gang, Zhang Ou, and Fan Lin were responsible for scale collection and data organization. Dong Xiaomei performed the statistical analysis. Xu Tianchao provided experimental guidance. Wang Qi supervised the project and held overall responsibility.

The authors declare no conflicts of interest.

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Manuscript History: (Received: 2025-01-13; Revised: 2025-05-08)
Editor: Wang Fengwei

Abstract

Objective: To investigate the correlation between the Systemic Immune-Inflammation Index (SII) and suicidal ideation in children and adolescents diagnosed with depression, and to evaluate the clinical utility of SII as a biological marker for assessing suicide risk in this population.

Methods: A retrospective analysis was conducted on clinical data from children and adolescent patients with depression admitted to our hospital. Patients were divided into a suicidal ideation group and a non-suicidal ideation group based on standardized clinical assessments. Peripheral blood cell counts were used to calculate the SII using the formula: $\text{SII} = P \times N / L$, where $P$, $N$, and $L$ represent platelet, neutrophil, and lymphocyte counts, respectively. Statistical analyses were performed to compare SII levels between the two groups and to identify independent risk factors for suicidal ideation.

Results: Preliminary findings indicate that patients in the suicidal ideation group exhibited significantly higher SII levels compared to those in the non-suicidal ideation group ($P < 0.05$). Multivariate logistic regression analysis demonstrated that elevated SII is an independent risk factor for suicidal ideation in children and adolescents with depression. Furthermore, receiver operating characteristic (ROC) curve analysis suggested that SII has moderate diagnostic value in predicting the presence of suicidal ideation.

Conclusion: The Systemic Immune-Inflammation Index (SII) is significantly correlated with suicidal ideation in children and adolescents with depression. As a cost-effective and readily available inflammatory marker, SII may serve as a valuable supplementary tool for the early identification and risk stratification of suicidal behavior in pediatric psychiatric practice.

Introduction

Depression in children and adolescents has become a major global public health concern, characterized by high prevalence, high recurrence rates, and a significant risk of self-harm and suicide. Suicidal ideation is often the precursor to suicidal behavior, making its early detection critical for intervention. Recent research has increasingly focused on the "immuno-inflammatory hypothesis" of depression, suggesting that systemic low-grade inflammation plays a role in its pathogenesis.