Sarcopenia and dynapenia are associated with depression rather than anxiety in Chinese hemodialysis patients

doi:10.21203/rs.3.rs-4694613/v1

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Research Article

Sarcopenia and dynapenia are associated with depression rather than anxiety in Chinese hemodialysis patients

https://doi.org/10.21203/rs.3.rs-4694613/v1

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Background

Affective disorders contribute to poorer outcomes in hemodialysis patients. We aimed to investigate the association of depression and anxiety with sarcopenia and dynapenia among patients receiving maintenance hemodialysis.

Methods

A total of 1074 patients (676 men, mean aged 61.3 ± 12.6 years) undergoing hemodialysis from 7 facilities in Shanghai of China from 2020 to 2023. Depression was evaluated by the Patient Health Questionnaire-9 (PHQ-9) and anxiety was assessed by the 7-item Generalized Anxiety Disorder Questionnaire (GAD-7). The cut-off values of muscle mass and muscle function to define sarcopenia, dynapenia, and presarcopenia were according to the consensus by the Asia Working Group of Sarcopenia in 2019.

Results

Among 1074 participants, 160 (14.9%) had depression, 85(7.9%) had anxiety. Patients were divided into four groups: sarcopenia (n = 211), dynapenia(n = 267), presarcopenia(n = 100), and the robust (n = 496) group. The proportion of depression in the group sarcopenia, dynapenia, presarcopenia and robust were 19.4%, 22.8%, 14.0%, and 8.9% (sarcopenia vs robust P < 0.001; dynapenia vs robust P < 0.001; overall p value < 0.001). The proportion of anxiety in the four group were 10.4%, 10.5%, 6.0%, and 5.8%, respectively (overall p value > 0.05). Multivariate analysis revealed that sarcopenia, dynapenia, Malnutrition Inflammation Score (MIS), Charlson Comorbidity Index (CCI) and Fractional clearance index for urea (Kt/V) were significant factors linked to the presence of depression.

Conclusion

Our findings suggest that sarcopenia and dynapenia are associated with depression rather than anxiety in hemodialysis patients. Interventions or programs aiming to alleviate sarcopenia or dynapenia can be effective strategies to prevent depression in the hemodialysis population.

Depression

anxiety

sarcopenia

dynapenia

hemodialysis

Depression and anxiety are the most common psychological symptoms observed in patients receiving hemodialysis therapy, with higher prevalence in this population than the general population[1, 2]. These psychiatric comorbid conditions have elevated risk of adverse impact on hemodialysis patients, such as poorer dialysis treatment outcomes, lower quality of life, higher hospitalization rates and higher mortality[3, 4]. However, both depressive and anxiety symptoms in hemodialysis patients are frequently underdiagnosed and untreated[5]. Therefore, early identification of modifiable risk factors and corresponding management of affective disorders in patients undergoing maintenance hemodialysis is essential.

According to previous study, several factors are related to mental health, such as genetics, serious illness, drugs, social factors and lifestyle[6]. Furthermore, recent studies have focused on evaluating the relationship between mental health and muscle function. Some studies have indicated that muscle secretion, for example irisin, is thought to be involved in the development of depression and anxiety[7]. Sarcopenia is another common condition among hemodialysis individuals, characterized by low muscle mass and poor muscle function[8]. Since the European Working Group on Sarcopenia in Older Adults (EWGSOP) defined presarcopenia and sarcopenia in 2010, muscle mass and muscle strength have been discussed together. Interestingly, the presence of low muscle strength is used in conjunction with normal muscle mass to diagnose dynapenia, which is an important risk for mortality among dialysis patients[9].Hence, it makes sense to correctly distinguish between loss of muscle mass and strength. In fact, this bias between the relationship of muscle mass with muscle strength and adverse clinical effects is a matter of interest and debate in the international scientific community.

Since sarcopenia and psychiatric disorders have similar consequences and risk factors, sarcopenia is correlated with depression was reported by a recent systematic review involving community and outpatient settings[10]. In addition to depression, sarcopenia is also linked to anxiety in the general population[11]. In particular, several study involving hemodialysis patients showed a strong association between sarcopenia and depression as well as anxiety [12–14]. However, incomplete diagnostic criteria for sarcopenia and small sample size are limitations of the above studies. Regarding dynapenia, although some studies have indicated that it is related to mental health in older adults[15, 16] and obese patients[17]. To date, there have been no studies on putative associations of dynapenia and depression and anxiety among hemodialysis patients. Clarifying the association of sarcopenia and dynapenia with affective disorders is clinically important as it may serve as a basis for the establishment of interventions to improve muscle mass and muscle function and effectively prevent psychiatric impairment.

Therefore, we performed a cross-sectional multi-center study in seven hospital setting to investigate the association between sarcopenia, dynapenia, presarcopenia with depression and anxiety among patients undergoing hemodialysis.

Study design and participants

A cross-sectional multi-center study enrolling hemodialysis patients from seven hospital was performed in Shanghai from 2020 to 2023. Participants were eligible to participate if they were over 18 years of age, receiving maintenance hemodialysis for at least 3months, and able to provide informed consent. Patients were excluded as following criteria: (1) missing data on diagnostic criteria for sarcopenia or dynapenia, (2) did not complete date on the depression and anxiety assessments, (3) patients with hearing impairment, or visual impairment difficulties; (4) clinical instability (presented with an infection, heart failure, or malignancy), and (5) unable to communicate with the researchers or refusal to participate in this study. The final analytic sample consisted of 1074 patients (men 676, women 398) after excluding 62 subjects. 36 patients refused to participant in depression or anxiety assessment due to personal reasons; 4 were unable to complete the handgrip strength test due to hand disability;22 unable to measure the body composition. The study was approved by the Ethics Committee of Shanghai University of Medicine and Health Sciences and these methods were implement in accordance with the principles of the Declaration of Helsinki. All of the participants provided the informed consent prior to enrollment in the study.

Covariates

All participants were invited to a face-to-face interview to finish a standardized questionnaire. Covariates consisted of sociodemographic characteristics, chronic disease condition, health behaviors. Demographic characteristics included age, sex, post-dialysis weight, education level and dialysis vintage. Comorbidity was assessed using the Charlson Comorbidity Index(CCI), which describes multiple comorbidities and forms a summation score based on the presence of 19 comorbidities[18]. Physical activity was evaluated by the International Physical Activity Questionnaire (IPAQ)[19]. In addition, all the blood sample were drawn before dialysis. Fractional clearance index for urea (Kt/V) was used to assess the dialysis quality, which was monitored in every dialysis treatment using the OCM® (On-line Clearance Monitor; Fresenius Medical Care, Bad Homburg, Germany). Nutritional status was assessed according to the Malnutrition Inflammation Score (MIS)[20], which is a comprehensive scoring system with significant relationships with prospective hospitalization and mortality in hemodialysis patients.

Definition of sarcopenia, dynapenia, and presarcopenia

Muscle mass was measured by a direct segmental multi-frequency bioelectrical impedance analysis (BIA; InBody S10; Biospace, Seoul, Korea)[21]. Low muscle mass was defined as skeletal muscle index (SMI) < 7.0 kg/m² in male and < 5.7 kg/m² in female, respectively. Muscle strength was evaluated using the dynamometer (GRIP-D; Takei Ltd, Niigata, Japan) on the non-fistula hand prior to the dialysis. We used the dominant hand to test muscle strength for those patients with an indwelling dialysis catheter. Low muscle strength was defined as handgrip strength less than 28kg and 18kg in men and women, respectively. Poor physical performance was assessed using the usual gait speed, which was less than 1.0 m/s in both men and women. All participants underwent these tests on dialysis days prior to dialysis treatment by a physical therapist at each facility using the same measurement method.

2019 new version of the Asian Working Group for Sarcopenia (AWGS) criteria was used to diagnose sarcopenia[8]. The criteria included both low muscle mass and low muscle strength and/or poor physical performance. Dynapenia was diagnosed as patients with decreased muscle strength and normal muscle mass[22]. Presarcopenia

was defined as low SMI with normal handgrip strength and normal gait speed[23].

Assessment of depression

The Patient Health Questionnaire-9 (PHQ-9) was administered to assess depression over the last two weeks[24]. The total score ranges from 0 to 27, with an overall score of ≥ 10 representing clinically significant depression[25]. Details of measurement methods can be found in our previous study[20].

Assessment of anxiety

Anxiety was measured by the 7-item Generalized Anxiety Disorder Questionnaire (GAD-7)[26].Patients reported the frequency with which they had experienced each of the seven symptoms during the last two weeks on a 4-point scale (0 = not at all; 1 = several days; 2 = more than half of the days; and 3 = nearly every day). A score of 8 or higher was defined as anxiety[27, 28], and the scale was proved to be reliable and valid in dialysis patients.

Statistical analysis

For continuous parameters, the Student's t test or Mann-Whitney U test was used to estimate the difference between groups, as appropriate. Continuous parameter data were expressed as mean ± standard deviation (SD). In terms of categorical parameters, Fisher’s exact tests or Pearson χ2 test was applied to estimate between-group difference, as appropriate. Factors with p < 0.05 linked to the presence of depression in the univariate analysis were entered into the multivariate logistic regression analysis to identify independent factors. All statistical analyses were performed using SPSS v 29.0 (SPSS Inc., Chicago, IL), and P values of less than 0.05 were considered statistically significant.

Characteristics of the patients for depression and anxiety

Among 1074 participants (676 men, 398 women; mean age 61.3 ± 12.6 years) who were available to be analyzed, 160 (14.9%) had depression and 85 (7.9%) had anxiety. Socio-economic and health-related characteristics of hemodialysis patients stratified by depressed or anxious status were presented in Table 1. Depressed patients tend to older, lower education level, poor nutritional status, lower activity level, larger number of medications, higher CCI, lower albumin and Kt/V. IPAQ and albumin significantly differed between groups when stratified by anxious status.

Table 1

Baseline Characteristics of Study Participants According to the Presence of Depression and Anxiety.
Variables	Non-depression	Depression	P value	Non-anxiety	Anxiety	P value
	(n = 914)	(n = 160)		(n = 989)	(n = 85)
Age (y)	60.8 ± 12.5	64.5 ± 12.2	0.001	61.3 ± 12.7	62.2 ± 10.6	0.478
Male (%)	571(62.5)	105(65.6)	0.446	628(63.5)	48(56.5)	0.198
Dry weight (kg)	63.06 ± 12.72	61.85 ± 13.24	0.271	63.04 ± 12.89	61.09 ± 11.60	0.179
BMI (kg/m2)	23.35 ± 3.83	23.23 ± 3.96	0.721	23.35 ± 3.87	23.11 ± 3.67	0.574
SMI (kg/m2)	7.06 ± 1.24	6.89 ± 1.25	0.098	7.04 ± 1.24	6.93 ± 1.29	0.430
Muscle strength (kg)	25.49 ± 8.77	22.34 ± 8.20	< 0.001	25.17 ± 8.77	23.28 ± 8.47	0.056
Gait speed (m/s)	1.02 ± 0.29	0.82 ± 0.32	< 0.001	1.00 ± 0.30	0.93 ± 0.32	0.039
Vintage (months)	43.1(19.5,93.4)	34.1(12.7,73.3)	0.080	43.0(18.3,91.4)	36.1(12.0,72.0)	0.337
Widowed (%)	70(7.7)	11(6.9)	0.322	73(7.4)	8(9.4)	0.186
Living alone (%)	50(5.5)	7(4.4)	0.559	56(5.7)	1(1.2)	0.076
Education (%)			0.022			0.111
Less than high school	204(22.3)	49(30.6)		227(23.0)	26(30.6)
High school or higher school	710(77.7)	111(69.4)		762(77.0)	59(69.4)
Dringking (%)	11(1.2)	1(0.6)	0.158	11(1.1)	1(1.2)	0.296
Smoking (%)	208(22.8)	29(18.1)	0.159	223(22.6)	14(16.5)	0.373
PHQ-9	3.07 ± 2.77	14.10 ± 3.96	< 0.001	4.01 ± 4.16	12.94 ± 5.68	< 0.001
GAD-7	1.14 ± 2.23	6.34 ± 5.79	< 0.001	1.06 ± 1.84	11.86 ± 3.58	< 0.001
MIS	4.17 ± 2.93	5.59 ± 3.53	< 0.001	4.34 ± 3.05	4.87 ± 3.28	0.127
IPAQ (Met-min/wk)	1386(523,3066)	693(0,1533)	< 0.001	1386(462,3008)	693(119,2079)	0.016
Number of medications (n)	4.43 ± 2.41	4.96 ± 2.76	0.014	4.49 ± 2.43	4.80 ± 2.96	0.269
CCI	3.92 ± 1.70	4.76 ± 1.95	< 0.001	4.03 ± 1.75	4.24 ± 1.93	0.310
Laboratory parameters
Hemoglobin (g/dL)	110.44 ± 16.11	109.22 ± 17.85	0.387	110.09 ± 16.40	112.31 ± 16.02	0.208
Albumin (g/L)	39.37 ± 3.84	38.50 ± 4.20	0.009	39.31 ± 3.89	38.51 ± 4.02	0.007
PTH(pg/dL)	346.45 ± 313.11	343.45 ± 316.48	0.913	343.90 ± 308.98	370.76 ± 363.06	0.451
Calcium (mg/dL)	2.26 ± 0.25	2.25 ± 0.25	0.527	2.26 ± 0.25	2.29 ± 0.25	0.478
Phosphorus (mg/dL)	1.98 ± 0.66	1.99 ± 0.62	0.745	1.97 ± 0.65	2.02 ± 0.66	0.593
Kt/v	1.37 ± 0.34	1.31 ± 0.31	0.040	1.36 ± 0.34	1.34 ± 0.32	0.670
BMI, body mass index; SMI, muscle mass index; PHQ-9, patient health questionnaire-9; GAD-7, Generalized Anxiety Disorder Scale; MIS, malnutrition inflammation score; IPAQ, international physical activity questionnaire; Met-min/wk, metabolic equivalent task minutes per week; CCI, Charlson Comorbidity Index; PTH, parathyroid hormone; Kt/V, fractional clearance index for urea.

Characteristics of the patients for sarcopenia, dynapenia and presarcopenia

Participants were classified into mutually exclusive groups based on sarcopenia status and dynapenia: sarcopenia (n = 211), dynapenia (n = 267), presarcopenia (n = 100) and robust (n = 496) groups. Age, BMI, SMI, muscle strength, gait speed, vintage, widowed, education, smoking, depression, anxiety, MIS, IPAQ, CCI, hemoglobin, albumin, PTH and Kt/V significantly differed between groups (P < 0.05, Table 2). Figure 1 shows the proportion of depression and anxiety in four groups respectively. Overall significance for the proportion of depression was found among the 4 groups (overall p value < 0.001). P values between any two groups are demonstrated in Fig. 1A. However, overall significance for the proportion of anxiety was not found among the 4 groups (overall p value = 0.053). When sarcopenia and dynapenia were compared with the normal group, there was statistical significance either in depression or anxiety.

Table 2

Baseline subject characteristics according to categories of sarcopenia and dynapenia.
Variables	Sarcopenia	Dynapenia	Presarcoepnia	Robust	P value
	(n = 211)	(n = 267)	(n = 100)	(n = 496)
Age (y)	69.5 ± 10.5	64.3 ± 11.1a	59.0 ± 11.6a,b	56.8 ± 12.1a,b	< 0.001
Male (%)	129(61.1)	158(59.2)	58(58.0)	331(66.7)	0.111
Dry weight (kg)	53.14 ± 7.98	65.56 ± 11.05a	53.59 ± 7.77b	67.46 ± 12.96a,b,c	< 0.001
BMI (kg/m2)	21.06 ± 2.91	24.60 ± 3.83a	20.24 ± 2.36b	24.25 ± 3.70a,c	< 0.001
SMI (kg/m2)	5.80 ± 0.76	7.31 ± 1.02a	6.02 ± 0.72b	7.61 ± 1.09a,b,c	< 0.001
Muscle strength (kg)	18.0 ± 5.94	18.97 ± 5.05	27.18 ± 6.00a,b	30.82 ± 7.41a,b,c	< 0.001
Gait speed (m/s)	0.79 ± 0.32	0.89 ± 0.28a	1.15 ± 0.19a,b	1.11 ± 0.25a,b	< 0.001
Vintage (months)	45.8(20.0,113.1)	37.4(13.8,91.4)	57.3(28.0,106.3)	39.7(19.0,78.1)a,c	0.007
Widowed (%)	25(11.8)	27(10.1)	4(4.0)	25(5.0)	0.003
Living alone (%)	10(4.7)	21(7.9)	4(4.0)	22(4.4)	0.190
Education (%)					< 0.001
Less than high school	71(33.6)	67(25.1)	22(22.0)	93(18.8)
High school or higher school	140(66.4)	200(74.9)	78(78.0)	403(81.3)
Dringking (%)	2(1.0)	4(1.5)	2(2.0)	4(0.8)	0.472
Smoking (%)	28(13.3)	50(18.7)	28(28.0)	131(26.4)	0.001
Depression (%)	41(19.4)	61(22.8)	14(14.0)	44(8.9)	< 0.001
Anxiety (%)	22(10.4)	28(10.5)	6(6.0)	29(5.8)	0.053
MIS	5.75 ± 3.42	4.87 ± 3.28a	4.11 ± 2.27a,b	3.60 ± 2.67a,b	< 0.001
IPAQ (Met-min/wk)	693(0,1619)	693(179,2639)	1990(693,3439)a	1485(693,3707)a,b	< 0.001
Number of medications (n)	4.57 ± 2.56	4.72 ± 2.50	4.27 ± 2.49	4.42 ± 2.42	0.309
CCI	4.59 ± 1.85	4.37 ± 1.88	3.57 ± 1.39a,b	3.74 ± 1.63a,b	< 0.001
Laboratory parameters
Hemoglobin (g/dL)	110.37 ± 15.84	109.55 ± 15.87	116.07 ± 17.16a,b	109.43 ± 16.52c	0.002
Albumin (g/L)	38.24 ± 3.62	38.63 ± 3.94	40.61 ± 4.04a,b	39.73 ± 3.84a,b,c	< 0.001
PTH(pg/dL)	291.52 ± 275.44	356.39 ± 346.05a	326.57 ± 298.49	367.43 ± 311.09a	0.027
Calcium (mg/dL)	2.24 ± 0.27	2.26 ± 0.23	2.28 ± 0.25	2.26 ± 0.25	0.590
Phosphorus (mg/dL)	1.90 ± 0.65	1.96 ± 0.66	1.93 ± 0.63	2.03 ± 0.64a	0.063
Kt/v	1.48 ± 0.31	1.34 ± 0.39a	1.44 ± 0.26b	1.31 ± 0.32a,c	< 0.001
BMI, body mass index; SMI, muscle mass index; MIS, malnutrition inflammation score; IPAQ, international physical activity questionnaire; Met-min/wk, metabolic equivalent task minutes per week; CCI, Charlson Comorbidity Index; PTH, parathyroid hormone; Kt/V, fractional clearance index for urea.

Multivariate analyses of factors associated with the presence of depression

According to the diagnostic criteria of MIS, albumin is included in the calculation of MIS, so albumin was not entered into the analysis. Age, education, MIS, IPAQ, number of medications, CCI, and Kt/v were significant factors linked to the presence of depression in the univariate analysis (Table 1). Sarcopenia (p = 0.030), dynapenia (P = 0.001), MIS (P = 0.001), CCI (P < 0.001) and Kt/v (P = 0.027) were significant factors linked to the presence of depression in the multivariate analysis (Table 3). Odds ratios (OR) and 95% confidence intervals (CI) in each factor are shown in Table 3 and Fig. 2.

Table 3

Multivariate analyses of factors linked to the presence of depression.
	Multivariate Analysis
	Odds ratio	95%CI	P value
Sarcopenia	1.76	1.06–2.93	0.030
Dynapenia	2.20	1.41–3.44	0.001
Presarcopenia	1.84	0.95–3.57	0.070
Robust	1.00	Reference
MIS	1.10	1.04–1.16	0.001
CCI	1.19	1.08–1.31	< 0.001
Kt/v	0.50	0.27–0.93	0.027
MIS, malnutrition inflammation score; CCI, Charlson Comorbidity Index; Kt/V, fractional clearance index for urea; CI, confidence interval.

To the best of our knowledge, this is the first study to investigate the association of sarcopenia, dynapenia and presarcopenia with depression and anxiety in a multi-center hemodialysis population. We found that both sarcopenia and dynapenia were associated with depression but not anxiety among patients undergoing hemodialysis. These findings highlight the importance of integrating of muscle mass and muscle function into clinical practice throughout the dialysis treatment to prevent depression disorders.

This study shows that the prevalence of depression and anxiety are 14.9% and 7.9%. Dano et al. and Mapes et al. reported that the prevalence of depression in hemodialysis patients was 19% and 20%, respectively. Similarly, Mohamed et al. showed the prevalence of anxiety was 7%. However, it is important to note that the prevalence of depression and anxiety was notably lower than the estimated prevalence of 22.8%-39.3% for depression and 12%-52% for anxiety reported in comprehensive systematic reviews[29, 30]. It is worth pointing out that one reason why the prevalence of depression in this study is lower than other studies is that the cut-off of PHQ-9 score in this study is greater than or equal to 10. This means that only grades above moderate depression are included. It was proved to be reliable and valid to detect depression determined by this cut-off in dialysis patients (sensitivity = 92%, specificity = 92%)[31]. While many studies use the same scale as ours, they used a PHQ-9 score ≥ 5 as a reference[32]. There is some mild depression mixed in, so this also partly explains why their prevalence is higher than our results. Using the same scale, Nguyen et al. reported that the prevalence of depression in hemodialysis patients was 42.5% (5 as the cutoff). When using 10 as the cut-off, the prevalence of depression was 12.6%, which is consistent with the results of this study. Another possible reason is that people in Shanghai of China have a better economic status, and the universal health insurance system allows all dialysis patients to get better treatment, which also reduces their psychological pressure to a certain extent. It is estimated that 7–8% of patients seen in a primary care setting have a diagnosis of anxiety disorder[33]. To some extent, it indicates that the patients in this study had a relatively low anxiety level; on the other hand, it indicates that more professional personnel or tools are needed to accurately diagnose anxiety.

Our findings regarding the association between sarcopenia and depression align well with those of previous studies conducted among the general population[10] and patients undergoing the hemodialysis[12–14]. However, compared with the three previous studies on dialysis, our study differs in several aspects. First, the diagnosis of sarcopenia in Kim et al. 's study was incomplete, using only muscle mass and muscle strength to diagnose sarcopenia[13]. In addition, the sample size of Kim et al.’s study[13] included 95 hemodialysis patients, while that of Khoury et al.’s study[14] only contained 42 patients on hemodialysis, both of which had certain limitations. Our study used the 2019 new version of the AWGS criteria to diagnose sarcopenia and included 7 hemodialysis centers with a sample size of more than 1000 individuals. Second, although Kurita et al. found that depression was associated with sarcopenia in dialysis patients, the study mixed peritoneal dialysis as well as non-dialysis chronic kidney disease patients. Similarly, the diagnosis of sarcopenia in this study was not rigorous, using only a questionnaire, and some of the potential confounders of sarcopenia were not collected in the study, such as nutritional measures[12]. Our study addresses these limitations well, but further longitudinal studies are needed to confirm our results. Studies on the association between anxiety and sarcopenia are very rare, with only one report to date, and the conclusion is inconsistent with the finding of our study[14]. Part of the reason for the difference is that the sample size of that study was only 42 hemodialysis patients, and other difference may be in the setting of the pandemic, inflation, and the Beirut blast. Further studies are needed to confirm the relationship.

Some previous studies have demonstrated that dynapenia is associated with mental health in older adults[15, 16] and obese patients[17]. Presently, no study has explored the link between dynapenia and depression and anxiety in patients on hemodialysis. This study was the first to demonstrate that dynapenia is associated with depression in hemodialysis patients. Although there are no studies of dynapenia and depression in dialysis populations, there is still a link between a certain element such as muscle strength and depression, and the finding is consistent with ours. Zhang et al.[6] suggested that lower muscle strength is associated with a higher prevalence of depression in Chinese patients undergoing hemodialysis. Our study also found no evidence that dynapenia was associated with anxiety. This finding is consistent with the only study conducted to date which found no associations between dynapenia and anxiety in older adults[16]. Further research is needed to determine whether the selected GAD-7 recognizes anxiety states in hemodialysis populations that are associated with dynapenia, which would also aid in development of interventions.

The mechanism underlying the associations between sarcopenia and dynapenia with depression are not clearly understood but appear to be complicated and multifactorial. Studies have shown that skeletal muscle, as an endocrine organ, can secrete myokines. Muscle contraction leads to changes in the skeletal muscle environment, which can affect the physiological state of myokines[34]. It is worth noting that myokines can improve brain function. Several studies have shown that a variety of myokines, such as brain-derived neurotrophic factor[35], irisin[36], etc., can act on the nervous system through gene regulation and various endocrine signaling pathways. Moreover, depression has been consistently related to a low-grade inflammatory state[37]. The decrease of inflammation and oxidative free radicals may reduce the risk of depression by improving muscle function[38, 39]. Psychosocial mechanisms may also at least partly explain the associations between sarcopenia, dynapenia and depression in the current study. Depressed hemodialysis patients typically experienced a decrease in physical activity, thereby declining the likelihood of social contact with others and increasing the likelihood of developing depression through a vicious cycle.

We believe that the present findings suggest that strategies to increase muscle mass and function may provide suitable adjunctive treatments for depression among hemodialysis population. Thus, this highlights a need for nephrology physicians and co-medical staff to pay attention to these patients. Emerging evidence indicates that resistance training and nutritional supplements may improve depression among older adults[40, 41]. Early screening and management of musculoskeletal disorders, and encouraging patients to engage in effective exercise and nutritional programs may help reduce the likelihood of developing depression.

Our study also confirmed the association of nutritional status, comorbidity and dialysis efficiency with depression. More details of the relationship between malnutrition and depression can be found in our previous study[20]. In fact, patients on hemodialysis usually have poorer disease status and numerous complications. Our study showed that patients undergoing hemodialysis with more comorbidities were at elevated risk of depression. In addition, effective hemodialysis efficiency is associated with a lower risk of depression.

This study has several strengths. To our knowledge, this is the first study to examine the association between sarcopenia, dynapenia, and depression and anxiety in a multi-center hemodialysis population. Understanding this association is essential for the prevention and treatment of mental disorders in patients on hemodialysis. Second, we used new version criteria to diagnose sarcopenia and dynapenia, as opposed to other studies that used only one element. However, several limitations should be considered.

This study is based on a cross-sectional design. Thus, it is not possible to elucidate clear causal associations among sarcopenia, dynapenia and depression in the patients receiving hemodialysis. More prospective cohort studies are needed for further investigation.

In conclusion, our study showed that sarcopenia as well as dynapenia were associated with a higher risk of depression rather than anxiety in patients undergoing hemodialysis, therefore suggesting that improving muscle mass and muscle function may have potentially beneficial effects on depression. Furthermore, the association between sarcopenia, dynapenia and depression in patients on hemodialysis should be investigated in a large cohort study to clarify this finding.

Asian Working Group for Sarcopenia, AWGS; BMI, Body mass index; CI, Confidence interval; Charlson comorbidity index, CCI; Fractional clearance index for urea, Kt/V; 7-item Generalized Anxiety Disorder Questionnaire, GAD-7; International Physical Activity Questionnaire, IPAQ; Malnutrition inflammation score, MIS; PHQ-9, Patient Health Questionnaire-9; SMI, Skeletal muscle index.

Acknowledgements

We are grateful to all the medical staff at the multi-center dialysis for their generous technical assistance and guidance. We also thank all the study participants for their kind participation and cooperation.

Author contributions

X.C. and P.H. conceived the concept and design of the study; X.C., Z.L., K.D., S.Z. and Y.X. contributed to data collection, entry, and data cleaning. X.C. and P. H. contributed to the data analysis and interpretation of study results. L.C., J.G. and Q.G. contributed to acquisition of funding, study design and provided administrative support. All authors wrote the manuscript and approved the final version.

Funding

This work was supported by the funding of Capacity Building project of Local Colleges of Shanghai Science and Technology Commission (23010502800); Shanghai Sailing Program (22YF1417900).

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Ethics approval and consent to participate

The study was approved by the Ethics Committee of Shanghai University of Medicine and Health Sciences and these methods were implement in accordance with the principles of the Declaration of Helsinki. All of the participants provided the informed consent prior to enrollment in the study.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Al-Nashri F, Almutary H. Impact of anxiety and depression on the quality of life of haemodialysis patients. J Clin Nurs. 2022; 31(1-2):220-230.
Semaan V, Noureddine S, Farhood L. Prevalence of depression and anxiety in end-stage renal disease: A survey of patients undergoing hemodialysis. Appl Nurs Res. 2018; 43:80-85.
Farrokhi F, Abedi N, Beyene J, Kurdyak P, Jassal SV. Association between depression and mortality in patients receiving long-term dialysis: a systematic review and meta-analysis. Am J Kidney Dis. 2014; 63(4):623-635.
Schouten RW, Haverkamp GL, Loosman WL, Chandie Shaw PK, van Ittersum FJ, Smets YFC, Vleming LJ, Dekker FW, Honig A, Siegert CEH. Anxiety Symptoms, Mortality, and Hospitalization in Patients Receiving Maintenance Dialysis: A Cohort Study. Am J Kidney Dis. 2019; 74(2):158-166.
Johnson S, Dwyer A. Patient perceived barriers to treatment of depression and anxiety in hemodialysis patients. Clin Nephrol. 2008; 69(3):201-206.
Zhang S, Liu SX, Wu QJ, Wang ZH, Liu H, Xiao P, Lu Y, Dong C, Meng QM. Association between handgrip strength and depressive symptoms in patients undergoing hemodialysis: a cross-sectional study from a single Chinese center. BMC Psychiatry. 2024; 24(1):182.
Pignataro P, Dicarlo M, Suriano C, Sanesi L, Zerlotin R, Storlino G, Oranger A, Zecca C, Dell'Abate MT, Mori G et al. Once-Daily Subcutaneous Irisin Administration Mitigates Depression- and Anxiety-like Behavior in Young Mice. Int J Mol Sci. 2023; 24(7).
Chen LK, Woo J, Assantachai P, Auyeung TW, Chou MY, Iijima K, Jang HC, Kang L, Kim M, Kim S et al. Asian Working Group for Sarcopenia: 2019 Consensus Update on Sarcopenia Diagnosis and Treatment. J Am Med Dir Assoc. 2020; 21(3):300-307 e302.
Isoyama N, Qureshi AR, Avesani CM, Lindholm B, Barany P, Heimburger O, Cederholm T, Stenvinkel P, Carrero JJ. Comparative associations of muscle mass and muscle strength with mortality in dialysis patients. Clin J Am Soc Nephrol. 2014; 9(10):1720-1728.
Li Z, Tong X, Ma Y, Bao T, Yue J. Prevalence of depression in patients with sarcopenia and correlation between the two diseases: systematic review and meta-analysis. J Cachexia Sarcopenia Muscle. 2022; 13(1):128-144.
Zhang Y, Song Y, Miao Y, Liu Y, Han D. The causal relationship of depression, anxiety, and neuroticism with main indicators of sarcopenia: A Mendelian randomization study. Int J Geriatr Psychiatry. 2023; 38(7):e5980.
Kurita N, Wakita T, Fujimoto S, Yanagi M, Koitabashi K, Suzuki T, Yazawa M, Kawarazaki H, Shibagaki Y, Ishibashi Y. Hopelessness and Depression Predict Sarcopenia in Advanced CKD and Dialysis: A Multicenter Cohort Study. J Nutr Health Aging. 2021; 25(5):593-599.
Kim JK, Choi SR, Choi MJ, Kim SG, Lee YK, Noh JW, Kim HJ, Song YR. Prevalence of and factors associated with sarcopenia in elderly patients with end-stage renal disease. Clin Nutr. 2014; 33(1):64-68.
Khoury R, Ghantous Z, Ibrahim R, Ghossoub E, Madaghjian P, Karam E, Karam G, Fares N, Karam S. Anxiety, depression and post-traumatic stress disorder in patients on hemodialysis in the setting of the pandemic, inflation, and the Beirut blast: a cross-sectional study. BMC Psychiatry. 2023; 23(1):284.
Noh HM, Park YS. Handgrip strength, dynapenia, and mental health in older Koreans. Sci Rep. 2020; 10(1):4004.
Carvalho AF, Maes M, Solmi M, Brunoni AR, Lange S, Husain MI, Kurdyak P, Rehm J, Koyanagi A. Is dynapenia associated with the onset and persistence of depressive and anxiety symptoms among older adults? Findings from the Irish longitudinal study on ageing. Aging Ment Health. 2021; 25(3):468-475.
Venant V, Pouget M, Lahaye C, Gentes E, Pereira B, Lambert C, Debarges J, Domingues-Faria C, Palmier-Forestier C, Farigon N et al. Depression Severity as a Risk Factor of Sarcopenic Obesity in Morbidly Obese Patients. J Nutr Health Aging. 2019; 23(8):761-767.
Liu H, Song B, Jin J, Liu Y, Wen X, Cheng S, Nicholas S, Maitland E, Wu X, Zhu D. Length of Stay, Hospital Costs and Mortality Associated With Comorbidity According to the Charlson Comorbidity Index in Immobile Patients After Ischemic Stroke in China: A National Study. Int J Health Policy Manag. 2021.
Bassett DR, Jr. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003; 35(8):1396.
Chen X, Han P, Song P, Zhao Y, Zhang H, Niu J, Yu C, Ding W, Zhao J, Zhang L et al. Mediating Effects of Malnutrition on the Relationship between Depressive Symptoms Clusters and Muscle Function Rather than Muscle Mass in Older Hemodialysis Patients. J Nutr Health Aging. 2022; 26(5):461-468.
Marcelli D, Usvyat LA, Kotanko P, Bayh I, Canaud B, Etter M, Gatti E, Grassmann A, Wang Y, Marelli C et al. Body composition and survival in dialysis patients: results from an international cohort study. Clin J Am Soc Nephrol. 2015; 10(7):1192-1200.
Manini TM, Clark BC. Dynapenia and aging: an update. J Gerontol A Biol Sci Med Sci. 2012; 67(1):28-40.
Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, Martin FC, Michel JP, Rolland Y, Schneider SM et al. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing. 2010; 39(4):412-423.
Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001; 16(9):606-613.
Levis B, Benedetti A, Thombs BD, Collaboration DESD. Accuracy of Patient Health Questionnaire-9 (PHQ-9) for screening to detect major depression: individual participant data meta-analysis. BMJ. 2019; 365:l1476.
Spitzer RL, Kroenke K, Williams JB, Lowe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006; 166(10):1092-1097.
Plummer F, Manea L, Trepel D, McMillan D. Screening for anxiety disorders with the GAD-7 and GAD-2: a systematic review and diagnostic metaanalysis. Gen Hosp Psychiatry. 2016; 39:24-31.
Dang LT, Luong TC, Nguyen DH, Hoang TA, Nguyen HT, Nguyen HC, Duong TH, Tran TT, Pham LV, Ngo TV et al. The Associations of Suspected COVID-19 Symptoms with Anxiety and Depression as Modified by Hemodialysis Dietary Knowledge: A Multi-Dialysis Center Study. Nutrients. 2022; 14(12).
King-Wing Ma T, Kam-Tao Li P. Depression in dialysis patients. Nephrology (Carlton). 2016; 21(8):639-646.
Murtagh FE, Addington-Hall J, Higginson IJ. The prevalence of symptoms in end-stage renal disease: a systematic review. Adv Chronic Kidney Dis. 2007; 14(1):82-99.
Watnick S, Wang PL, Demadura T, Ganzini L. Validation of 2 depression screening tools in dialysis patients. Am J Kidney Dis. 2005; 46(5):919-924.
Nguyen TTN, Liang SY, Liu CY, Chien CH. Self-care self-efficacy and depression associated with quality of life among patients undergoing hemodialysis in Vietnam. PLoS One. 2022; 17(6):e0270100.
Kroenke K, Spitzer RL, Williams JB, Monahan PO, Lowe B. Anxiety disorders in primary care: prevalence, impairment, comorbidity, and detection. Ann Intern Med. 2007; 146(5):317-325.
Kim S, Choi JY, Moon S, Park DH, Kwak HB, Kang JH. Roles of myokines in exercise-induced improvement of neuropsychiatric function. Pflugers Arch. 2019; 471(3):491-505.
Sen S, Duman R, Sanacora G. Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biol Psychiatry. 2008; 64(6):527-532.
Tu WJ, Qiu HC, Liu Q, Li X, Zhao JZ, Zeng X. Decreased level of irisin, a skeletal muscle cell-derived myokine, is associated with post-stroke depression in the ischemic stroke population. J Neuroinflammation. 2018; 15(1):133.
Osimo EF, Baxter LJ, Lewis G, Jones PB, Khandaker GM. Prevalence of low-grade inflammation in depression: a systematic review and meta-analysis of CRP levels. Psychol Med. 2019; 49(12):1958-1970.
Westbury LD, Fuggle NR, Syddall HE, Duggal NA, Shaw SC, Maslin K, Dennison EM, Lord JM, Cooper C. Relationships Between Markers of Inflammation and Muscle Mass, Strength and Function: Findings from the Hertfordshire Cohort Study. Calcif Tissue Int. 2018; 102(3):287-295.
Vezzoli A, Mrakic-Sposta S, Montorsi M, Porcelli S, Vago P, Cereda F, Longo S, Maggio M, Narici M. Moderate Intensity Resistive Training Reduces Oxidative Stress and Improves Muscle Mass and Function in Older Individuals. Antioxidants (Basel). 2019; 8(10).
Gordon BR, McDowell CP, Hallgren M, Meyer JD, Lyons M, Herring MP. Association of Efficacy of Resistance Exercise Training With Depressive Symptoms: Meta-analysis and Meta-regression Analysis of Randomized Clinical Trials. JAMA Psychiatry. 2018; 75(6):566-576.
De Spiegeleer A, Beckwee D, Bautmans I, Petrovic M, Sarcopenia Guidelines Development group of the Belgian Society of G, Geriatrics. Pharmacological Interventions to Improve Muscle Mass, Muscle Strength and Physical Performance in Older People: An Umbrella Review of Systematic Reviews and Meta-analyses. Drugs Aging. 2018; 35(8):719-734.

Table 1. Baseline Characteristics of Study Participants According to the Presence of Depression and Anxiety.
Variables	Non-depression	Depression	P value	Non-anxiety	Anxiety	P value
	(n=914)	(n=160)		(n=989)	(n=85)
Age (y)	60.8±12.5	64.5±12.2	0.001	61.3±12.7	62.2±10.6	0.478
Male (%)	571(62.5)	105(65.6)	0.446	628(63.5)	48(56.5)	0.198
Dry weight (kg)	63.06±12.72	61.85±13.24	0.271	63.04±12.89	61.09±11.60	0.179
BMI (kg/m2)	23.35±3.83	23.23±3.96	0.721	23.35±3.87	23.11±3.67	0.574
SMI (kg/m2)	7.06±1.24	6.89±1.25	0.098	7.04±1.24	6.93±1.29	0.430
Muscle strength (kg)	25.49±8.77	22.34±8.20	<0.001	25.17±8.77	23.28±8.47	0.056
Gait speed (m/s)	1.02±0.29	0.82±0.32	<0.001	1.00±0.30	0.93±0.32	0.039
Vintage (months)	43.1(19.5,93.4)	34.1(12.7,73.3)	0.080	43.0(18.3,91.4)	36.1(12.0,72.0)	0.337
Widowed (%)	70(7.7)	11(6.9)	0.322	73(7.4)	8(9.4)	0.186
Living alone (%)	50(5.5)	7(4.4)	0.559	56(5.7)	1(1.2)	0.076
Education (%)			0.022			0.111
Less than high school	204(22.3)	49(30.6)		227(23.0)	26(30.6)
High school or higher school	710(77.7)	111(69.4)		762(77.0)	59(69.4)
Dringking (%)	11(1.2)	1(0.6)	0.158	11(1.1)	1(1.2)	0.296
Smoking (%)	208(22.8)	29(18.1)	0.159	223(22.6)	14(16.5)	0.373
PHQ-9	3.07±2.77	14.10±3.96	<0.001	4.01±4.16	12.94±5.68	<0.001
GAD-7	1.14±2.23	6.34±5.79	<0.001	1.06±1.84	11.86±3.58	<0.001
MIS	4.17±2.93	5.59±3.53	<0.001	4.34±3.05	4.87±3.28	0.127
IPAQ (Met-min/wk)	1386(523,3066)	693(0,1533)	<0.001	1386(462,3008)	693(119,2079)	0.016
Number of medications (n)	4.43±2.41	4.96±2.76	0.014	4.49±2.43	4.80±2.96	0.269
CCI	3.92±1.70	4.76±1.95	<0.001	4.03±1.75	4.24±1.93	0.310
Laboratory parameters
Hemoglobin (g/dL)	110.44±16.11	109.22±17.85	0.387	110.09±16.40	112.31±16.02	0.208
Albumin (g/L)	39.37±3.84	38.50±4.20	0.009	39.31±3.89	38.51±4.02	0.007
PTH(pg/dL)	346.45±313.11	343.45±316.48	0.913	343.90±308.98	370.76±363.06	0.451
Calcium (mg/dL)	2.26±0.25	2.25±0.25	0.527	2.26±0.25	2.29±0.25	0.478
Phosphorus (mg/dL)	1.98±0.66	1.99±0.62	0.745	1.97±0.65	2.02±0.66	0.593
Kt/v	1.37±0.34	1.31±0.31	0.040	1.36±0.34	1.34±0.32	0.670

BMI, body mass index; SMI, muscle mass index; PHQ-9, patient health questionnaire-9; GAD-7, Generalized Anxiety Disorder Scale; MIS, malnutrition inflammation score; IPAQ, international physical activity questionnaire; Met-min/wk, metabolic equivalent task minutes per week; CCI, Charlson Comorbidity Index; PTH, parathyroid hormone; Kt/V , fractional clearance index for urea.

Table 2. Baseline subject characteristics according to categories of sarcopenia and dynapenia.
Variables	Sarcopenia	Dynapenia	Presarcoepnia	Robust	P value
	(n=211)	(n=267)	(n=100)	(n=496)
Age (y)	69.5±10.5	64.3±11.1a	59.0±11.6a,b	56.8±12.1a,b	<0.001
Male (%)	129(61.1)	158(59.2)	58(58.0)	331(66.7)	0.111
Dry weight (kg)	53.14±7.98	65.56±11.05a	53.59±7.77b	67.46±12.96a,b,c	<0.001
BMI (kg/m2)	21.06±2.91	24.60±3.83a	20.24±2.36b	24.25±3.70a,c	<0.001
SMI (kg/m2)	5.80±0.76	7.31±1.02a	6.02±0.72b	7.61±1.09a,b,c	<0.001
Muscle strength (kg)	18.0±5.94	18.97±5.05	27.18±6.00a,b	30.82±7.41a,b,c	<0.001
Gait speed (m/s)	0.79±0.32	0.89±0.28a	1.15±0.19a,b	1.11±0.25a,b	<0.001
Vintage (months)	45.8(20.0,113.1)	37.4(13.8,91.4)	57.3(28.0,106.3)	39.7(19.0,78.1)a,c	0.007
Widowed (%)	25(11.8)	27(10.1)	4(4.0)	25(5.0)	0.003
Living alone (%)	10(4.7)	21(7.9)	4(4.0)	22(4.4)	0.190
Education (%)					<0.001
Less than high school	71(33.6)	67(25.1)	22(22.0)	93(18.8)
High school or higher school	140(66.4)	200(74.9)	78(78.0)	403(81.3)
Dringking (%)	2(1.0)	4(1.5)	2(2.0)	4(0.8)	0.472
Smoking (%)	28(13.3)	50(18.7)	28(28.0)	131(26.4)	0.001
Depression (%)	41(19.4)	61(22.8)	14(14.0)	44(8.9)	<0.001
Anxiety (%)	22(10.4)	28(10.5)	6(6.0)	29(5.8)	0.053
MIS	5.75±3.42	4.87±3.28a	4.11±2.27a,b	3.60±2.67a,b	<0.001
IPAQ (Met-min/wk)	693(0,1619)	693(179,2639)	1990(693,3439)a	1485(693,3707)a,b	<0.001
Number of medications (n)	4.57±2.56	4.72±2.50	4.27±2.49	4.42±2.42	0.309
CCI	4.59±1.85	4.37±1.88	3.57±1.39a,b	3.74±1.63a,b	<0.001
Laboratory parameters
Hemoglobin (g/dL)	110.37±15.84	109.55±15.87	116.07±17.16a,b	109.43±16.52c	0.002
Albumin (g/L)	38.24±3.62	38.63±3.94	40.61±4.04a,b	39.73±3.84a,b,c	<0.001
PTH(pg/dL)	291.52±275.44	356.39±346.05a	326.57±298.49	367.43±311.09a	0.027
Calcium (mg/dL)	2.24±0.27	2.26±0.23	2.28±0.25	2.26±0.25	0.590
Phosphorus (mg/dL)	1.90±0.65	1.96±0.66	1.93±0.63	2.03±0.64a	0.063
Kt/v	1.48±0.31	1.34±0.39a	1.44±0.26b	1.31±0.32a,c	<0.001

BMI, body mass index; SMI, muscle mass index; MIS, malnutrition inflammation score; IPAQ, international physical activity questionnaire; Met-min/wk, metabolic equivalent task minutes per week; CCI, Charlson Comorbidity Index; PTH, parathyroid hormone; Kt/V , fractional clearance index for urea.

Table 3. Multivariate analyses of factors linked to the presence of depression.
	Multivariate Analysis
	Odds ratio	95%CI	P value
Sarcopenia	1.76	1.06-2.93	0.030
Dynapenia	2.20	1.41-3.44	0.001
Presarcopenia	1.84	0.95-3.57	0.070
Robust	1.00	Reference
MIS	1.10	1.04-1.16	0.001
CCI	1.19	1.08-1.31	<0.001
Kt/v	0.50	0.27-0.93	0.027

MIS, malnutrition inflammation score; CCI, Charlson Comorbidity Index; Kt/V , fractional clearance index for urea; CI, confidence interval.

No competing interests reported.

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Sarcopenia and dynapenia are associated with depression rather than anxiety in Chinese hemodialysis patients

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Introduction

Methods

Study design and participants

Covariates

Definition of sarcopenia, dynapenia, and presarcopenia

Assessment of depression

Assessment of anxiety

Statistical analysis

Results

Characteristics of the patients for depression and anxiety

Characteristics of the patients for sarcopenia, dynapenia and presarcopenia

Multivariate analyses of factors associated with the presence of depression

Discussion

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