Association of hemoglobin-to-red blood cell distribution width ratio and depression: a cross sectional study

doi:10.21203/rs.3.rs-2571242/v1

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Research Article

Association of hemoglobin-to-red blood cell distribution width ratio and depression: a cross sectional study

https://doi.org/10.21203/rs.3.rs-2571242/v1

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Objectives

We aimed to explore the association between hemoglobin-to-red blood cell distribution width ratio (HRR) and the depression.

Methods

Depression, general characteristics, life style, medical history, drug use, blood indicators were extracted from the National Health and Nutrition Examination Survey 2005–2018 to assess the relationship between HRR and depression. Two sample kolmogorove-smirnov test, chi-square test, spearman correlation, multiple linear regression and the receiver operating characteristic (ROC) curve were analysed.

Results

31784 participants were included and the incidence rate of depression was 9.05%. HRR was significant lower in low depression group and positive associated with depression(P < 0.05). Multiple linear regression showed that HRR was associated with depression after adjusted for general characteristics, life style, medical history, drug use and blood indicators (P < 0.05). The cutoff value of HRR for depression is 1.090 and the Youden index, sensitivity, and specificity of HRR to depression is higher than hemoglobin (Hb) and red blood cell distribution width ratio (RDW).

Conclusions

HRR, powerful than Hb or RDW, is an independent risk factor for depression. Clinicians should focus on the HRR to improve depression.

depression

hemoglobin-to-red blood cell distribution width ratio

hemoglobin

red blood cell distribution width ratio

Depression is one of the leading mental illnesses and disability worldwide[1, 2], which affecting approximately 280 million people and associated with premature mortality from other illnesses[3, 4] and suicide[5, 6]. These unfortunate observations underscore the need to identify the mechanism of depression.

Hemoglobin-to-red blood cell distribution width ratio (HRR), calculated by dividing hemoglobin (Hb) by red blood cell distribution width ratio (RDW), is a novel marker of inflammation proposed by Sun et al[7]. Lower level of HRR has been proved to be related with many adverse consequences such as poor prognosis, disease progression, and lower disease-free survival time[8–11]. More importantly, inflammatory processes have been implicated in the pathophysiology of depression[12, 13], and HRR is a novel marker of inflammation. Thus, the relationship of HRR and depression is not clear.

Hb, abundantly present in red blood cell (RBC) or erythrocyte is an oxygen carrying protein that gives the characteristic red color to our blood[14, 15] and is the most commonly used biochemical parameter in diagnosing anemia in blood now[16, 17]. Studies showed that lower Hb level is relate to depression performance and the influence mechanism is not clear yet[18–20].

RDW, a parameter that reflects the heterogeneity of circulating erythrocyte volume, is routinely calculated according to RBC volume and mean corpuscular volume (MCV)[21, 22] and elevated RDW indicates heterogeneous size of RBC, as known as anisocytosis[22]. RDW in combination with MCV can be used for the differential diagnosis of anemia[23]. Increased RDW has been proved to be associated with high incidence of many diseases such as diabetes[10, 24], colorectal diaeases[25], cardiovascular disease[26, 27], stroke[28], chronic health conditions[29], and improved the mortality[30, 31]. Of note, study reveals that higher RDW levels at were found to be correlated with depression and the influence mechanism is also not clear yet.

In short, the inflammatory processes have been implicated in the pathophysiology of depression and HRR is a novel marker of inflammation. Also, HRR was calculated by dividing Hb by RDW and Hb and RDW were all associated with depression. Based on the above two points, we have reason to believe that there HRR may be related to depression and we will explore the relationship between HRR and depression in this study.

Participants

This was a cross-sectional study extracted from the National Health and Nutrition Examination Survey (NHANES) database from 2005 to 2018 which was performed by the National Center for Health Statistics (NCHS) and approved by the NCHS Institutional Review Board. All informed consents has been obtained from eligible participants before collecting data. All data can be found on the website (https://wwwn.cdc.gov/nchs/nhanes/Default. aspx).

People with information including depression, general characteristics, life style characteristics, medical history and drug use, and blood indicators were included. A total of 40184 individuals participated in the NHANES from 2005 to 2018, participants with the missing data of depression and those younger than 20 and older than 79 were excluded. Therefore, this study contained a total of 31784 participants aged 20 to 79 (15581 men and 16203 women) (Fig. 1).

Depression Performance Assessment

Patient Health Questionnaire (PHQ-9), a 9-item screening instrument that asked the frequency of depressive symptoms in the past two weeks, were tested to measure the depressive symptom[32]. The total score of PHQ-9 was 0 ~ 27 points, of which 0 ~ 9 points was no depression, 10 points or more was depression[33].

General characteristics

The demographic information extracted from the NHANES database include age, gender, body mass index(BMI), race, education level, marital status, monthly family income.

Life style characteristics

The life style characteristics extracted from the NHANES database include smoke cigarettes, alcoholic drinks(1 year), sleep hours(weekdays or workdays), had trouble sleeping, minutes of sedentary activity a day, hours watch TV or videos past 30 days, working hours last week, usually work 35 or more hours per week, healthy diet.

Medical history and drug use

The medical history and drug use information extracted from the NHANES database include have diabetes, taking insulin, taking hypoglycemic drugs, had high blood pressure, taking prescription for hypertension, have high cholesterol level, taking prescription for high cholesterol, had coronary heart disease, had a stroke, had a thyroid problem, have asthma, had chronic bronchitis, number of prescription medicines taken.

Blood indicators

The blood indicators information extracted from the NHANES database include C-reactive protein(CRP, mg/dL), white blood cell count (WBC, 1000 cells/uL), lymphocyte number (1000 cells/uL), monocyte number (1000 cells/uL), segmented neutrophils number (1000 cell/uL), red blood cell count (RBC, million cells/uL), Hb (g/dL), RDW (%), HRR, platelet count (1000 cells/uL), glycohemoglobin (%), folate (nmol/L), total cholesterol(mmol/L), fasting glucose (mg/dL), insulin (uU/mL), alanine aminotransferase(ALT, U/L), albumin (g/dL), aspartate aminotransferase(AST, U/L), blood urea nitrogen (BUN, mmol/L), creatinine (umol/L), iron, refigerated (ug/dL), potassium (mmol/L), sodium (mmol/L), total bilirubin (mg/dL), total calcium (mg/dL), triglycerides (mg/dL), uric acid (mg/dL).

Statistical Analyses

Data was analyzed with the software SPSS 24.0 and MedCalc. All data in this study were tested by single sample Kolmogorove-Smirnov test for normality and homogeneity of variances. Data, still non-normal distribution after transformation, were be analyzed as non normal data. Non-normally distributed continuous variables were presented as medians (interquartile ranges, IQRs) and two sample Kolmogorove-Smirnov test was used to compare the levels between ttwo group. Percentage and Chi-square test were used to present and test different group categorical variables. Spearman correlation and multiple linear regression analyses was used to assess the association between HRR and depression. ROC analysis were used to determine the cut-off values of HRR for depression.

Demographics characteristics and depression

2875 individuals were evaluated to be depression and the incidence rate were 9.05%. There were significant differences between non-depression and depression group in gender, BMI, race, education level, marital status and annual family income(P < 0.05). Those who reported depression performance were more likely to be women, have low education level, have low annual family income and have bad marital status(Table 1).

Table 1

General characteristics
	Non-depression	Depression	Z/χ²	P
Age	47(33, 61)	49(36, 60)	-1.184	0.236
Gender			198.728	0.000
Men	14532(50.27)	1049(36.49)
Women	14377(49.73)	1826(63.51)
BMI	28.08(24.41, 32.70)	30.00(25.21, 35.22)	6.187	0.000
Race			72.250	0.000
Mexican American	4778(16.53)	442(15.37)
Other Hispanic	2762(9.55)	377(13.11)
Non-Hispanic White	11685(40.42)	1187(41.29)
Non-Hispanic Black	6402(22.15)	654(22.75)
Other Race - Including Multi-Racial	3282(11.35)	215(7.48)
Education Level			408.214	0.000
Less Than 9th Grade	2662(9.21)	403(14.03)
9-11th Grade (Includes 12th grade with no diploma)	3868(13.39)	607(21.14)
High School Grad/GED or Equivalent	6599(22.84)	698(24.30)
Some College or AA degree	8680(30.04)	872(30.36)
College Graduate or above	7082(24.51)	292(10.17)
Marital Status			446.658	0.000
Married	15479(53.58)	1020(35.50)
Widowed	1468(5.08)	219(7.62)
Divorced	3074(10.64)	511(17.79)
Separated	926(3.21)	205(7.14)
Never married	5454(18.88)	622(21.65)
Living with partner	2491(8.62)	296(10.30)
Annual Family Income	7(5, 11)	5(3, 7)	11.272	0.000

Life style characteristics

There were significant differences between non-depression and depression group in smoke cigarettes, alcoholic drinks(1 year), sleep hours(weekdays or workdays), had trouble sleeping, minutes of sedentary activity a day, hours watch TV or videos past 30 days, working hours last week, healthy diet(P < 0.05). Those who reported depression performance were more likely to smoking, drink alcohol, have less sleep, had trouble sleeping, sedentary, eating unhealthy and watching TV or videos or working for a long time(Table 2).

Table 2

Life style characteristics
	Non-depression	Depression	Z/χ²	P
Smoke cigarettes			223.384	0.000
Every day	4680(37.36)	966(55.71)
Some days	1141(9.11)	147(8.48)
Not at all	6707(53.54)	621(35.81)
Alcoholic drinks(1 year)	6(2, 12)	6(3, 15)	3.701	0.000
Sleep hours(weekdays or workdays)	7(6, 8)	6.5(5, 8)	-14.903	0.000
Had trouble sleeping			1763.865	0.000
Yes	6469(22.38)	1674(58.25)
No	22431(77.62)	1200(41.75)
Minutes of sedentary activity a day	300(180, 480)	360(180, 480)	-2.863	0.004
Hours watch TV or videos past 30 days			287.609	0.000
Do not watch TV or videos	1806(11.22)	188(12.63)
Less than 1 hour	2032(12.62)	140(9.40)
1 hour	2730(16.95)	177(11.89)
2 hours	4233(26.29)	270(18.13)
3 hours	2722(16.90)	235(15.78)
4 hours	2230(13.85)	435(29.21)
5 hours or more	349(2.17)	44(2.96)
Working hours last week	40(35, 48)	40(30, 45)	2.322	0.000
Usually work 35 or more hours per week			0.010	0.922
Yes	1800(38.59)	129(38.86)
No	2865(61.41)	203(61.14)
Healthy diet			1137.079	0.000
Excellent	2438(8.44)	119(4.14)
Very good	6054(20.95)	269(9.36)
Good	12139(42.01)	927(32.27)
Fair	6806(23.55)	1055(36.72)
Poor	1458(5.05)	503(17.51)

Medical history and drug use characteristics

There were significant differences between non-depression and depression group in whether have diabetes, taking insulin, had high blood pressure, taking prescription for hypertension, have high cholesterol level, had coronary heart disease, had a stroke, had a thyroid problem, have asthma, had chronic bronchitis, number of prescription medicines taken(P < 0.05). Those who reported depression performance were more likely to have diabetes, high blood pressure, high cholesterol level, coronary heart disease, stroke, thyroid problem, asthma, chronic bronchitis and taking insulin, prescription for hypertension and taken too many prescription medicines (Table 3).

Table 3

Medical history and drug use characteristics
	Non-depression	Depression	Z/χ²	P
Have diabetes			158.430	0.000
Yes	3388(11.99)	567(20.32)
No	24871(88.01)	2224(79.68)
Taking insulin			71.759	0.000
Yes	933(3.23)	181(6.30)
No	27972(96.77)	2694(93.70)
Taking hypoglycemic drugs			0.080	0.778
Yes	2036(46.52)	324(47.09)
No	2341(53.48)	364(52.91)
Had high blood pressure			231.622	0.000
Yes	9465(32.78)	1346(46.90)
No	19407(67.22)	1524(53.10)
Taking prescription for hypertension			8.771	0.003
Yes	7085(86.62)	966(83.42)
No	1094(13.38)	192(16.58)
Have high cholesterol level			108.399	0.000
Yes	9033(36.27)	1150(46.92)
No	15875(63.73)	1301(53.08)
Taking prescription for high cholesterol			1.168	0.280
Yes	4909(77.12)	630(75.45)
No	1456(22.88)	205(24.55)
Had coronary heart disease			72.460	0.000
Yes	876(3.03)	172(6.02)
No	27969(96.97)	2684(93.98)
Had a stroke			203.544	0.000
Yes	774(2.68)	216(7.54)
No	28106(97.32)	2650(92.46)
Had a thyroid problem			139.974	0.000
Yes	2550(8.83)	446(15.62)
No	26317(91.17)	2409(84.38)
Have asthma			244.222	0.000
Yes	3991(13.82)	709(24.67)
No	24896(86.18)	2165(75.33)
Had chronic bronchitis			485.149	0.000
Yes	1423(4.93)	431(15.05)
No	27439(95.07)	2432(84.95)
Number of prescription medicines taken	3(1, 5)	4(2, 7)	10.424	0.000

Blood indicators characteristics

There were significant differences between non-depression and depression group in CRP, WBC, lymphocyte numbe, monocyte number, segmented neutrophils number, RBC, Hb, RDW, HRR, platelet count, glycohemoglobin, folate, fasting glucose, insulin, ALT, albumin, AST, BUN, creatinine, iron, refigerated, sodium, total bilirubin, total calcium, triglycerides, uric acid(P < 0.05). Those who reported depression performance were more likely having higher level of CRP, WBC, segmented neutrophils number, RDW, platelet count, glycohemoglobin, and lower level of RBC, Hb, HRR, folate(Table 4).

Table 4

Blood indicator characteristics
	Non-depression	Depression	Z	P
CRP(mg/dL)	0.20(0.08, 0.46)	0.3(0.11, 0.67)	-8.560	0.000
WBC (1000 cells/uL)	6.90(5.70, 8.40)	7.40(6.00, 9.10)	-11.108	0.000
Lymphocyte number (1000 cells/uL)	2.10(1.70, 2.60)	2.10(1.70, 2.70)	-5.604	0.000
Monocyte number (1000 cells/uL)	0.50(0.40, 0.70)	0.50(0.40, 0.70)	-3.000	0.000
Segmented neutrophils number (1000 cell/uL)	4.00(3.10, 5.10)	4.40(3.20, 5.70)	-10.548	0.000
RBC(million cells/uL)	4.68(4.36, 5.03)	4.61(4.28, 4.95)	-8.089	0.000
Hb(g/dL)	14.10(13.10, 15.20)	13.90(12.80, 14.90)	-8.595	0.000
RDW (%)	13.00(12.50, 13.70)	13.30(12.60, 14.10)	-11.111	0.000
HRR	1.09(0.99, 1.19)	1.05(0.94, 1.16)	-11.999	0.000
Platelet count (1000 cells/uL)	241.00(205.00, 285.00)	250.00(209.00, 295.00)	-6.098	0.000
Glycohemoglobin (%)	5.50(5.20, 5.80)	5.60(5.30, 6.00)	-7.171	0.000
Folate (nmol/L)	33.90(23.50, 49.30)	31.50(21.65, 47.90)	-4.456	0.000
Total Cholesterol( mmol/L)	4.91(4.27, 5.66)	4.97(4.27, 5.74)	-1.878	0.060
Fasting Glucose (mg/dL)	100.00(93.00, 110.00)	102.00(94.00, 115.00)	2.412	0.000
Insulin (uU/mL)	10.06(6.32,16.34)	11.51(6.91, 20.11)	2.666	0.000
ALT (U/L)	21.00(16.00, 29.00)	20.00(15.00, 28.00)	1.669	0.008
Albumin (g/dL)	4.20(4.00, 4.50)	4.10(3.90, 4.40)	5.941	0.000
AST (U/L)	23.00(19.00, 27.00)	22.00(18.00, 27.00)	2.743	0.000
Blood urea nitrogen (mmol/L)	4.28(3.57, 5.71)	4.28(3.21, 5.36)	3.493	0.000
Creatinine (umol/L)	75.14(62.76, 88.40)	71.60(61.88, 85.75)	3.812	0.000
Iron, refigerated (ug/dL)	81.00(61.00, 105.00)	75.00(54.00, 100.00)	4.108	0.000
Potassium (mmol/L)	4.00(3.79, 4.20)	4.00(3.74, 4.20)	0.736	0.651
Sodium (mmol/L)	139.00(138.00, 141.00)	139.00(138.00, 141.00)	1.661	0.008
Total bilirubin (mg/dL)	0.60(0.50, 0.80)	0.60(0.40, 0.70)	4.860	0.000
Total calcium (mg/dL)	9.40(9.20, 9.60)	9.40(9.10, 9.60)	1.739	0.005
Triglycerides (mg/dL)	121.00(80.00, 187.00)	137.00(88.00, 208.00)	4.011	0.000
Uric acid (mg/dL)	5.30(4.40, 6.30)	5.20(4.30, 6.20)	2.239	0.000

HRR and depression

Spearman correlation showed that HRR were inversely associated with the score of depression (P < 0.05, Table 5).

Table 5

Correlation analysis of HRR, RDW, Hb and depression
		HRR	RDW	Hb
Depression	r	-0.106	0.077	-0.094
	P	0.000	0.000	0.000

Linear regression and multiple linear regression model showed that higher HRR were associated with lower depression score (P < 0.05). After adjustment for general characteristics(gender, BMI, race, education level, marital status, total annual family income), life style( smoke cigarettes, sleep hours, had trouble sleeping, hours watch TV or videos past 30 days, healthy diet), medical history, drug use(have diabetes, taking insulin, had high blood pressure, have high cholesterol level, had coronary heart disease, had a stroke, had a thyroid problem, have asthma, had chronic bronchitis) and blood indicators(WBC, CRP, uric acid), the relationship between HRR and cognition remain statistically significant(P < 0.05, Table 6).

Table 6

Multiple linear regression analysis of serum HRR concentration with depression from NHANES 2005–2018
	β	t	P value
Model1	-2.671	-18.339	0.000
Model2	-0.047	-6.310	0.000
Model3	-0.054	-4.330	0.000
Model4	-0.031	-2.298	0.022
Model5	-0.118	-2.613	0.009
Model 1: Crude.
Model 2: Adjusted for general characteristics: gender, BMI, race, education level, marital status, total annual family income.
Model3: Model 2 + adjusted for life style: smoke cigarettes, sleep hours, had trouble sleeping, hours watch TV or videos past 30 days, healthy diet.
Model4: Model 3 + adjusted for medical history and drug use: have diabetes, taking insulin, had high blood pressure, have high cholesterol level, had coronary heart disease, had a stroke, had a thyroid problem, have asthma, had chronic bronchitis
Model5: Model 4 + adjusted for blood indicators: WBC, CRP, Uric acid

The ROC analysis showed that the optimal cut-off value of HRR for depression is 1.090. The AUC for HRR was 0.569 and the youden index of HRR were 0.1113 which were higher than the Hb and RDW. All of these results were statistically significant (P < 0.05, Table 7).

Table 7

Optimal cut-off values for peripheral blood Hb, RDW, and HRR for depression
Items	AUC	Youden index	Sensitivity	Specificity	Optimal cut-off values
Hb	0.549	0.07456	49.11	58.34	13.80
RDW	0.564	0.09875	43.32	66.56	13.40
HRR	0.569	0.1113	61.10	50.03	1.090

Our study showed that the incidence rate of depression performance was 9.05%, which is consistent with the research results of Koire A etal[34].

Also we first identified an association between HRR and depression and there were several main outcomes of this study. First, our results showed that HRR levels were significantly lower in depression group than non-depression group. Second, HRR was significantly positive associated with depression. Third, low level of HRR could be an independent risk factor for depression which was more powerful than Hb or RDW alone. Forth the optimal cut-off value of HRR for depression is 1.090 which means that HRR less than 1.090 may increase the incidence of depression.

The mechanism of the impact of HRR on depression is still unclear. Studies have showed that inflammatory processes have been implicated in the pathophysiology of depression[12, 35] and HRR is a novel marker of inflammation[7]. In all, we have reason to believe that inflammation is likely a critical disease modifier, which can promote susceptibility to depression[12]. Regardless of whether it is secondary to early life trauma, a more acute stress response, microbiome alterations, a genetic diathesis, or a combination of these and other factors[12], controlling inflammation might provide an overall therapeutic benefit. Thus, the specific mechanism of the effect of HRR on depression may be related to inflammation, and this needs more research to explore.

Also, low level of HRR causing depression may be related to a decrease in Hb. Hb was lower in depression group than the non-depression group and this is consistent with study of Shinsuke Hidese[36]. Vulser etal also showed that, Hb has a significant and robust association between depression[20]. In addition, Fenglian Xu showed that depression was associated with anaemia in women before and after birth and treating or preventing anaemia may help to prevent postnatal depression[37]. Therefore, the impact of HRR on depression may be related to Hb, and more research is needed to explore the identified impact mechanism.

As the same, low level of HRR causing depression may not only related to the decrease in Hb, but also the increase in RDW. Level of RDW was higher in the depression group than the non-depression group in our study which is consistent with other research results. Yaqiang Li et al showed that RDW is closely related to inflammatory-related disease markers and higher RDW levels at admission were found to be correlated with post-stroke depression 3 months after stroke[38]. Fatih Demircan et al[39] also showed that hematological inflammatory markers might be useful parameters that can be used in patients with depression for coronary artery disease risk and specifically, RDW seem to be more hopeful. Therefore, the impact of HRR on depression may be also related to RDW, and as the same, more research also needed to explore the identified impact mechanism.

Hb and RDW are both important components of HRR, and the relationship between Hb, RDW and depression in participants has been confirmed. However, considering the high Youden index, high sensitivity, and high specificity of HRR to depression than Hb and RDW, HRR may be a more reliable parameter to depression.

Our results showed that HRR levels were significantly lower in depression group than non-depression group and low level of HRR could be an independent risk factor for depression which was more powerful than Hb or RDW alone. And, HRR less than 1.090 may increase the incidence of depression. However, the mechanism of the effect of HRR on depression is not clear, and a lot of research is needed to explore.

There are some limitations in the our study. First, since all participants aged 80 or above in the database all showed 80 years old, in order to ensure the accuracy of the study, only participants aged 20–79 years are selected for our study. In the future, we can explore the impact of HRR on depression aged 80 or above. Second, this was a cross-sectional study that can only represent an association between HRR and cognition, but not a cause-and-effect relationship. In the future, we can continue a further follow-up study to identify the causal relationship between HRR and depression.

Despite those limitations in our study, we also has some strengths. First, we provided a view to a new potential marker which is inexpensive and easily accessible from the blood indicators for predicting the depression. Second, we excrated data from the NHANES which all indicators are collected in strict accordance with the standards, with less bias and more authentic data.

HRR Hemoglobin-to-red blood cell distribution width ratio

NHANES National Health and Nutrition Examination Survey

ROC Receiver operating characteristic

Hb Hemoglobin

RDW Red blood cell distribution width ratio

RBC Red blood cell

MCV Corpuscular volume

NCHS National Center for Health Statistics

PHQ-9 Patient Health Questionnaire

BMI Body mass index

CRP C-reactive protein

WBC White blood cell count

RBC Red blood cell count

ALT Alanine aminotransferase

AST Aspartate aminotransferase

BUN Blood urea nitrogen

CRediT authorship contribution statement

Lijuan Xi: Visualization, Supervision, Conceptualization, Data curation, Writing - original draft, Writing - review & editing. Jiajie Zhou: Visualization, Supervision, Conceptualization, Data curation, Writing - review & editing. Peirong Xu: Visualization, Supervision, Conceptualization, Writing - review & editing. Yanzhang: Visualization, Supervision, Writing - review & editing. Pingting Zhu: Visualization, Supervision, Conceptualization, Data curation, Writing - review & editing. Jiayuan Tu: Visualization, Supervision, Writing - review & editing. Qiannan Sun: Visualization, Supervision, Writing - review & editing. Fang Fang: Visualization, Supervision, Conceptualization, Data curation, Writing - review & editing.

Declaration of Competing Interest

All authors declare that they have no conflicts of interest regarding this study.

Funding: This work was financially supported by grants from 2022 Open Topics of the "Care Fund" Program of Jiangsu Provincial Key Laboratory of Zoonology (HX2206）

Acknowledgement:The authors extend their thanks and appreciation to the participants in the NHANES database survey.

Availability of data and materials: All informed consents has been obtained from eligible participants before collecting data. All data can be found on the website (https://wwwn.cdc.gov /nchs/nhanes/Default. aspx).

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Association of hemoglobin-to-red blood cell distribution width ratio and depression: a cross sectional study

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Abstract

Objectives

Methods

Results

Conclusions

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Introduction

Materials And Methods

Participants

Depression Performance Assessment

General characteristics

Life style characteristics

Medical history and drug use

Blood indicators

Statistical Analyses

Results

Demographics characteristics and depression

Life style characteristics

Medical history and drug use characteristics

Blood indicators characteristics

HRR and depression

Discussion

Conclusion

Abbreviations

Declarations

Declaration of Competing Interest

References

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