PHQ-9 scores for depression associated with high prevalence of thyroid disease in US adults: a cross-sectional study

doi:10.21203/rs.3.rs-2604468/v1

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PHQ-9 scores for depression associated with high prevalence of thyroid disease in US adults: a cross-sectional study

https://doi.org/10.21203/rs.3.rs-2604468/v1

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Objective

Thyroid disease is a very common disease in the world, but the risk factor is not fully clear about present. This study aims to assess the relationship between Patient Health Questionnaire-9 (PHQ-9) scores for depression and the prevalence of thyroid disease in United States (US) adults.

Methods

All samples of the study came from NHANES database from 2017–2020 pre-pandemic. Three different variable models were established; and the logistic regression analyses, generalized additive model, smoothed curve fitting, threshold effect analysis, subgroup analyses were used to assess the relationship between PHQ-9 scores for depression and the prevalence of thyroid disease.

Results

The results suggested that there is a positive relationship between PHQ-9 scores and the prevalence of thyroid disease, and the effect value was 1.0462(1.0311, 1.0615); each unit increase in PHQ-9 scores were associated with a 4.62% increase in the prevalence of thyroid disease. The threshold effect analysis found that log-likelihood ratio was P = 0.042, the inflection points K = 8. When the inflection points were less than 8, The incidence rate of thyroid disease increased by 7.15% for every one unit increase in PHQ-9 scores (P＜0.05); when K was greater than 8, the result was no significant difference. And the relationship between them was very stable according to subgroup analyses.

Conclusions

PHQ-9 scores for depression were positively associated with the prevalence of thyroid disease; the higher PHQ-9 scores of the minimal or mild depression in US adults, the prevalence of thyroid disease is higher; while there was no significant difference in moderately and severe depression adults. However, the causal relationship between the prevalence of thyroid disease and PHQ-9 scores for depression is not clear at present, further research is needed to explore.

PHQ-9 scores

depression

thyroid disease

prevalence

cross-sectional study

Thyroid disease is a very common disease in the world, which mainly includes hyperthyroidism, hypothyroidism, thyroid tumor, goiter and thyroiditis[1]. Thyroid disease may not only cause neck pain, neck enlargement, weight loss, fear of heat, excessive sweating, hand trembling, exophthalmos and other symptoms[2], but also may cause developmental delay, mental retardation[3], heart failure[4], hyperthyroidism crisis[5], and even death. At present, the prevalence of thyroid disease in the whole world is increasing every year, the cost of medical treatment for thyroid disease in US will estimate to be 3.5 billion dollars to 2030[6]. The increasing prevalence of thyroid disease will have a huge impact on the global economy and society. Therefore, it is very important to reduce the prevalence of thyroid disease. Currently. iodine deficiency[7] is considered an important causative factor of thyroid disease; but other risk factors are not fully clear and still need to be actively researched and explored.

Depression is a very common psychological disease, and there are approximately 340 million people worldwide currently suffering from depression. Depression has been the second cause of the global burden of disease[8]. Depression can not only cause depressed mood, poor concentration, reduced volitional activity, sleep disturbance and even suicide[9], It is also a risk factor of several systemic diseases, such as stroke [10], hypertension[11], diabetes[12], heart disease[13], functional bowel disease [14]. However, there are relatively few studies on the effect of depression to the prevalence of thyroid disease. Patient Health Questionnaire-9 is a questionnaire which contains a total of 9 depression related symptom questions, every question can be scored as 0 point, 1 point, 2 points, or 3 points[15](Table 1); the minimum score is 0 point and the maximum score are 27 points. It is currently the preferred screening tool for depression in US[16]. Therefore, we can explore the value of depression in the prevalence of thyroid disease among US adults by examining the relationship between PHO-9 scores and the prevalence of thyroid disease.

Table 1

PHQ-9 screening instrument for depression
Problems	Not at all	Several days	More than half the days	Nearly every day
Little interest or pleasure in doing things	0	1	2	3
Feeling down, depressed , or hopeless	0	1	2	3
Trouble falling or staying asleep, or sleeping much	0	1	2	3
Feeling tired or having little energy	0	1	2	3
Poor appetite or overeating	0	1	2	3
Feeling bad about yourself or that you are a failure or have let yourself or your family down	0	1	2	3
Trouble concentrating on things, such as reading the newspaper or watching television	0	1	2	3
Moving or speaking so slowly that other people could have noticed; or the opposite being so fidgety or restless that you have been moving around a lot more than usual	0	1	2	3
Thoughts that you would be better off dead or of hurting yourself in some way	0	1	2	3
PHQ-9 final scores were the sum of the nine question scores, The lowest score was 0 and the highest score was 27.

2.1 Study population

NHANES is a cross-sectional study based on the nutritional situation and physical status for children and adults in United States, which includes demographic data, questionnaire data, laboratory examination data and nutritional intake. The baseline information about all samples of this study was obtained from NHANES data onto 2017–2020 pre-pandemic; and a total of 15560 participants have completed questionnaire survey. In contrast, we only collected the information about people who explicitly answered whether they had thyroid disease in this study, and there were 7851 samples collected in this study at final. Detailed inclusion and exclusion criteria were in Fig. 1.

2.2 Data Collection

PHQ-9 scores were designed as an exposure variable. PHQ-9 is an important assessment tool for depression, it is completed by respondents entering the NHNAES mobile examining center (MEC). The questionnaire was scored by professionals, then they detailed recorded and calculated the final scores. The scoring rules were at Table 1. This questionnaire can assess the depressive status of participants in the last 2 weeks[17]. The prevalence of thyroid disease was designed as an outcome variable. It was also completed by participants at the MEC, the content of this questionnaire was "Has a doctor or other health professional ever told (you/SP} that (you/s/he} had another thyroid (thigh-roid) problem?", and the participants that clearly answered YES or NO were included in the study.

Then we established three different variable models to eliminate some potential con-founders that may have an effect on the relationship between PHQ-9 scores and the prevalence of thyroid disease. The covariates included in this study were energy intake (kcal), protein intake (gm), sex (male/female), age(years), fat intake (gm), glucose intake (gm), marital status (married/divorced/unmarried), education level, carbohydrate intake (gm), cholesterol intake (gm), race, BMI (kg/m²), ratio of family income to poverty (PIR), diabetes (yes/no), smoke status (yes/no), hypertension (yes/no), alcohol (yes/no), physical activity (vigorous/moderate/unclear), sleep disorders (hours); two 24- hour dietary recalls had to finish for all nutrition and energy data, and we used the average of nutrition and energy data for statistical analysis. All variables and samples data included in this study can be publicly available on the NAHANES website (www.cdc.gov/nchs/nhanes), and all participants have signed the relevant informed consent forms, which were reviewed and approved by the ethics committee; it doesn't need additional authorization and ethical review.

2.3 Statistical Methods

The samples data onto NHANES were obtained through complex, multilevel sampling; therefore, stratification, clustering, and sample weights should be used for all statistical analyses in this study. Categorical variables could be expressed by weighted surveys and 95% confidence intervals (CIs), and continuous variables could be expressed by weighted survey means and 95% CIs. All covariates were first checked and screened by covariant collinearity selection, and the covariates which VIF values greater than 5 were excluded. Then three different variable models were established. In Model 1, we did not adjust any covariates; in Model 2, we adjusted age, gender, marital status, sleep disorders, physical activity and diabetes; In Model 3, we adjusted all covariates in the study. Multiple logistic regression equations were used to analyze the relationship between PHQ-9 scores and the prevalence of thyroid disease in three different models separately. Then we divided continuous variables into three groups on average, and we completed the sensitivity analysis by converted the continuous variables into categorical variables. The relationship between the prevalence of thyroid disease and PHQ-9 scores was further explored by smoothing curve fitting and generalized additive model (GAM), and then log-likelihood ratio tests and inflection points were obtained using threshold and saturation effect models. Subgroup analyses were also performed for sleep disorders, physical activity, age, gender, diabetes, and marital status. P < 005 was considered to be statistically significant. All statistical analysis software used in this study was both R version (The R Foundation; http://www. R-project.org; version 4.2.0) and Empower Stats (www.empowerstats.net,X&Y solutions, Inc. Boston, Massachusetts).

The statistical baseline characteristics of the samples of this study were presented in Table 2. The sleep disorders of the thyroid disease group were 7.48(7.34,7.61), and 7.62 (7.58, 7.67) in the no thyroid disease group, the sleep disorders in the thyroid disease group were less than in the no disease group (P = 0.0302); PHQ-9 scores were 3.15 (3.01, 3.28) in the no thyroid disease group, and 4.31(3.80, 4.82) in the thyroid disease group; PHQ-9 scores were higher in the thyroid disease group (P = 0.0001). Meanwhile, the proportion of vigorous activities in the thyroid disease group was significantly lower(P < 0.0001); and the prevalence of hypertension and diabetes was higher in the thyroid disease group (all P < 0.0001).

Table 2

Baseline characteristics of participants, weighted.
Characteristic	No thyroid disease	Thyroid disease	P-value
Age (years)	38.11 (36.98 ,39.23)	37.09 (35.18 ,39.01)	0.2663
Ratio of family income to poverty	2.91 (2.79 ,3.02)	2.99 (2.81 ,3.16)	0.3943
BMI (kg/m²)	27.51 (27.18 ,27.84)	27.27 (26.53 ,28.00)	0.4882
PHQ-9 scores	3.15 (3.01 ,3.28)	4.31 (3.80 ,4.82)	0.0001
Sleep disorders (h)	7.62 (7.58 ,7.67)	7.48 (7.34 ,7.61)	0.0302
Protein (gm)	73.48 (72.12 ,74.83)	72.56 (70.20 ,74.92)	0.5243
Total fat (gm)	79.84 (78.77 ,80.90)	77.36 (73.66 ,81.06)	0.2612
Carbohydrate (gm)	228.10 (225.28 ,230.92)	225.31 (218.01 ,232.61)	0.4504
Total sugars (gm)	98.60 (97.15 ,100.06)	96.59 (91.97 ,101.21)	0.3920
Cholesterol (mg)	281.55 (275.49 ,287.61)	275.52 (249.71 ,301.34)	0.6867
Gender			0.3170
Male	49.82 (47.94 ,51.70)	45.78 (38.05 ,53.71)
Female	50.18 (48.30 ,52.06)	54.22 (46.29 ,61.95)
Race			0.9930
Mexican American	10.58 (8.00 ,13.86)	10.11 (6.67 ,15.05)
Other Hispanic	8.23 (6.77 ,9.97)	8.04 (5.76 ,11.12)
White	58.56 (52.72 ,64.17)	59.31 (52.57 ,65.72)
Black	12.46 (9.31 ,16.48)	11.99 (9.29 ,15.33)
Other Race	10.18 (8.40 ,12.28)	10.54 (7.56 ,14.53)
Marital status			0.1755
Married	45.80 (43.86 ,47.75)	44.73 (41.18 ,48.34)
Divorced	14.13 (12.72 ,15.66)	14.03 (11.44 ,17.10)
Never married	13.74 (12.00 ,15.68)	17.30 (13.81 ,21.45)
Others	26.33 (24.75 ,27.99)	23.93 (20.63 ,27.59)
Education Level			0.3261
Less than high school	8.15 (7.28 ,9.12)	6.40 (4.38 ,9.25)
High school	19.58 (17.61 ,21.71)	18.85 (13.05 ,26.43)
More than high school	45.86 (43.34 ,48.40)	50.75 (43.62 ,57.85)
Others	26.40 (24.79 ,28.09)	24.00 (20.69 ,27.66
Smoked			0.4598
YES	41.39 (39.83 ,42.97)	43.41 (37.87 ,49.12)
NO	58.61 (57.03 ,60.17)	56.59 (50.88 ,62.13)
Alcohol			0.0513
YES	91.24 (90.31 ,92.09)	88.41 (84.23 ,91.59)
NO	8.76 (7.91 ,9.69)	11.59 (8.41 ,15.77)
Hypertension			< 0.0001
YES	36.85 (35.19 ,38.54)	56.34 (50.84 ,61.69)
NO	63.15 (61.46 ,64.81)	43.66 (38.31 ,49.16)
Diabetes			< 0.0001
YES	13.46 (11.99 ,15.09)	24.52 (20.75 ,28.74)
NO	86.54 (84.91 ,88.01)	75.48 (71.26 ,79.25)
Physical activity			< 0.0001
Vigorous	28.38 (26.48 ,30.36)	18.30 (14.57 ,22.72)
Moderate	21.17 (19.87 ,22.53)	26.25 (22.14 ,30.82)
Unclear	50.45 (48.53 ,52.38)	55.46 (51.03 ,59.80)
For continuous variables: survey-weighted mean (95% CI), P-value was by survey-weighted linear regression.
For categorical variables: survey-weighted percentage (95% CI), P-value was by survey-weighted Chi-square test.

3.1 Modeling and sensitivity analysis

First, the covariate energy intake (VIF = 7.4) was excluded by covariant collinearity selection. Then, the relationship between PHQ-9 scores and the prevalence thyroid disease was constructed as three different variable models, and PHQ-9 scores were converted into categorical variables for sensitivity analysis (Table 3). The effect value of model 1 was 1.0527(1.0380, 1.0676), mode 2 was 1.0512(1.0363, 1.0662), and model 3 was 1.0462 (1.0311, 1.0615). Sensitivity analysis showed that the prevalence of thyroid disease increased 0.6946 multiple in the Tertile3 group (OR = 1.6946, (1.4337, 2.0030)). The results suggested that there is a positive relationship between PHQ-9 scores and the prevalence of thyroid disease, and the effect value was 1.0462(1.0311, 1.0615); each unit increase in PHQ-9 scores were associated with a 4.62% increase in the prevalence of thyroid disease.

Table 3

Analysis between PHQ-9 scores and the prevalence of thyroid disease.
Characteristic	Model 1 OR (95%CI)	Model 2 OR (95%CI)	Model 3 OR (95%CI)
PHQ-9 Score	1.0527 (1.0380, 1.0676)	1.0512 (1.0363, 1.0662)	1.0462 (1.0311, 1.0615)
Categories
Tertile1	1.0	1.0	1.0
Tertile2	1.2929 (1.0891, 1.5348)	1.2951 (1.0898, 1.5391)	1.2663 (1.0640, 1.5070)
Tertile3	1.7880 (1.5198, 2.1035)	1.7759 (1.5070, 2.0928)	1.6946 (1.4337, 2.0030)
Model 1 = no covariate was adjusted.
Model 2 = Model 1 + gender, age, marital status; sleep disorders; physical activity; diabetes.
Model 3 = Model 2+, race, education level, ratio of family income to poverty, BMI, smoked, alcohol, hypertension, protein, carbohydrate, total fat, total sugars, cholesterol, were adjusted.

3.2 Dose-response relationship between PHQ-9 scores and the prevalence of thyroid disease

The relationship between the prevalence of thyroid disease and PHQ-9 scores was further explored by GAM and smoothed curve fitting. The result found that the relationship between them was not a linear relationship. The threshold effect analysis found that log-likelihood ratio was P = 0.042, the inflection points K = 8. When the inflection points were less than 8, The incidence rate of thyroid disease increased by 7.15% for every one unit increase in PHQ-9 scores (P＜0.05); when K was greater than 8, the result was no significant difference (Fig. 2, Table 4). These results revealed that there was a positive curvilinear relationship between PHQ-9 scores and the prevalence of thyroid disease.

Table 4

Threshold effect analysis
Characteristic	OR (95%CI)	P
Linear model	1.0462 (1.0311, 1.0615)	< 0.0001
Curve model
K ≤ 8 effect 1	1.0715 (1.0427, 1.1011)	< 0.0001
K＞8 effect 2	1.0148 (0.9813, 1.0493)	0.3910
Log likelihood ratio 0.042, the inflection points (K = 8).

3.3 Subgroup Analysis

Subgroup analyses were performed for activity status, sleep disorders, age, dia betes, gender, and marital status; to further explore the robustness of the correlation between PHQ-9 scores and the prevalence of thyroid disease (Table 5). The results revealed that PHQ-9 scores were almost always positively correlated with the prevalence of thyroid disease in the activity status, sleep disorders, age, diabetes, gender, and marital status subgroups.

Table 5

Subgroup analysis between PHQ-9 scores and the prevalence of thyroid disease.
Characteristic	Model 1 OR (95%CI)	Model 2 OR (95%CI)	Model 3 OR (95%CI)
Subgroup analysis stratified by gender
Male	1.0547 (1.0339, 1.0759)	1.0531 (1.0322, 1.0745)	1.0470 (1.0257, 1.0688)
Female	1.0507 (1.0301, 1.0716)	1.0488 (1.0279, 1.0702)	1.0450 (1.0236, 1.0668)
Subgroup analysis stratified by age
20–40	1.0576 (1.0388, 1.0768)	1.0563 (1.0372, 1.0756)	1.0498 (1.0305, 1.0695)
41–60	1.0314 (0.9978, 1.0661) 0	1.0300 (0.9959, 1.0653)	1.0280 (0.9931, 1.0641)
61–80	1.0580 (1.0258, 1.0913)	1.0592 (1.0262, 1.0931)	1.0526 (1.0189, 1.0874)
Subgroup analysis stratified by race
Married	1.0415 (1.0160, 1.0677)	1.0410 (1.0151, 1.0675)	1.0396 (1.0132, 1.0667)
Divorced	1.0703 (1.0321, 1.1099)	1.0668 (1.0279, 1.1072)	1.0601 (1.0196, 1.1023)
Never married	1.0445 (1.0040, 1.0866)	1.0436 (1.0022, 1.0867)	1.0391 (0.9954, 1.0847)
Others	1.0586 (1.0355, 1.0823)	1.0580 (1.0345, 1.0820)	1.0512 (1.0274, 1.0757)
Subgroup analysis stratified by diabetes
YES	1.0438 (1.0150, 1.0735)	1.0466 (1.0172, 1.0768)	1.0432 (1.0129, 1.0743)
NO	1.0511 (1.0341, 1.0684)	1.0537 (1.0365, 1.0711)	1.0493 (1.0318, 1.0672)
Subgroup analysis stratified by physical activity
Vigorous	1.0247 (0.9902, 1.0604)	1.0228 (0.9879, 1.0589)	1.0132 (0.9775, 1.0503)
Moderate	1.0259 (0.9972, 1.0554)	1.0224 (0.9935, 1.0521)	1.0195 (0.9898, 1.0501)
Unclear	1.0792 (1.0591, 1.0997)	1.0756 (1.0553, 1.0963)	1.0706 (1.0500, 1.0916)
Subgroup analysis stratified by sleep disorders
<=6	1.0474 (1.0085, 1.0878)	1.0470 (1.0074, 1.0882)	1.0464 (1.0057, 1.0888)
> 6, <=8	1.0639 (1.0462, 1.0819)	1.0616 (1.0437, 1.0798)	1.0559 (1.0378, 1.0744)
> 8	1.0130 (0.9772, 1.0500)	1.0171 (0.9805, 1.0550)	1.0119 (0.9740, 1.0512)
Model 1 = no covariate was adjusted.
Model 2 = Model 1 + gender, age, marital status; sleep disorders; physical activity; diabetes.
Model 3 = Model 2+, race, education level, ratio of family income to poverty, BMI, smoked, alcohol, hypertension, protein, carbohydrate, total fat, total sugars, cholesterol, were adjusted.

The thyroid gland is the largest endocrine organ in the human body, it can affect the growth and development of body, metabolism by synthesizing and secret thyroid hormones[18]. Therefore, the thyroid gland plays a huge role in the endocrine system of the body. Currently, the prevalence of thyroid disease in the United States is as high as 5%[6], and the number of cases is increasing every year. The risk factor has been confirmed to be mainly related to iodine intake[19], but may also be related to other factors such as smoking[20], it still needs to be further explored. Analysis of the baseline data onto this study showed that sleep disorders and proportion of vigorous activity were lower in the thyroid disease group, while the prevalence of hypertension and diabetes was significantly higher in the thyroid disease group (all p < 0 0001). This indicates that the prevalence of thyroid disease may be related to sleep time, vigorous activity, hypertension, and diabetes. We also established three different variable models; and we found that PHQ-9 scores was positively associated with the prevalence of thyroid disease through multiple logistic regression equations and sensitivity analysis; the effect values were 1.0462 (1.0311, 1.0615). The prevalence of thyroid disease gradually increased to increasing PHQ-9 scores; it reveals that depression may be a risk factor of the prevalence of thyroid disease. We further explored the stability of this result using multiple subgroup analyses. It was found that PHQ-9 scores were almost always positively correlated with the prevalence of thyroid disease in the activity status, sleep disorders, age, diabetes gender, and marital status subgroups. These indicate that the relationship between PHQ-9 scores and the prevalence of thyroid disease is very stable. Meanwhile, we found that there was a positive curvilinear relationship between PHQ-9 scores and the incidence rate of thyroid disease through smoothed curve fitting and GAM analyses; and the threshold effect analysis found that log-likelihood ratio was P = 0.042, the inflection points K = 8. When the inflection points were less than 8, The incidence rate of thyroid disease increased by 7.15% for every one unit increase in PHQ-9 scores (P＜0.05); when K was greater than 8, the result was no significant difference.

The PHQ-9 is an important screening tool for depression in United States; it is scored by questionnaire, and higher PHQ-9 scores indicate more severe depression[21]. According to the score, MAURER[22] divided depression into minimal depression (1-4points), mild depression(5-9points), moderate depression (10-14points), moderately severe depression (15-19points), severe depression(20-27points). Thus, the higher PHQ-9 scores of the minimal and mild depression adults, the prevalence of thyroid disease is higher; while there was no significant difference in the prevalence of thyroid disease in moderately and severe depression adults. The relevant mechanism of action is not fully understood. The thyroid gland is an important target organ of the human endocrine system, which is mainly regulated by hypothalamic-pituitary-thyroid axis[23]. When the hypothalamic-pituitary-thyroid axis is affected or disturbed; thyroid function may become abnormal or disturbed, which may cause thyroid disease. And some studies[24, 25] have confirmed that depression can cause disorders of the hypothalamic-pituitary-thyroid axis. Therefore, we guess that the depression may induce thyroid disease by affecting the function of the hypothalamic-pituitary-thyroid axis. The exact mechanism of action is not fully understood and further exploratory studies are needed.

The advantage of this study is that all sample data were obtained from the NHANES public database in United States, which data is traceable, authentic, reliable, and nationally representative. Meanwhile, this study not only established several different variable models but also converted the independent variable into categorical variables for sensitivity analysis; the final results are more stable and reliable. The disadvantage is that this study is only a cross sectional study, but it cannot define the causal relationship between the prevalence of thyroid disease and depression. Further research is needed to explore. Secondly, the diagnosis of thyroid disease in this study was only based on patient questionnaires, but no relevant medical records or auxiliary examinations or test results were provided, which may lead to biased results.

PHQ-9 scores for depression were positively associated with the prevalence of thyroid disease, and the effect value was 1.0462 (1.0311, 1.0615). The higher PHQ-9 scores of the minimal or mild depression in US adults, the prevalence of thyroid disease is higher; while there was no significant difference in moderately and severe depression adults. Depression may be a risk factor of thyroid disease, maybe it can reduce the prevalence of thyroid disease among US adults through try hand to improve depression symptoms or reduce PHQ-9 scores of the minimal or mild depression adults. However, the causal relationship between the prevalence of thyroid disease and PHQ-9 scores for depression is not clear at present, further research is needed to explore.

Data availability statement

All samples of the study come from NAHANES database (www.cdc.gov/nchs/nhanes/).

Ethics statement

All NHANES protocols were implemented in accordance with the U.S. Department of Health and Human Services (HHS) Human Research Subject Protection Policy and were reviewed and standardized annually by the NCHS Research Ethics Review Committee. All participants in the survey have signed informed consent forms. It didn't need additional authorization and ethical review.

Author contributions

Study design and manuscript writing by LBZ, KQM; data collection by HSW, HC, data analysis by LBZ, TSC.

Funding

This study was no funding supported.

Acknowledgments

We thank all the workers and participants who have made contributions to NHANES. Consent for publication

Not applicable.

Conflict of interest

We declare that the study has no conflict of interest.

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No competing interests reported.

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Abstract

Objective

Methods

Results

Conclusions

Figures

1 Introduction

2 Methods

2.1 Study population

2.2 Data Collection

2.3 Statistical Methods

3 Results

3.1 Modeling and sensitivity analysis

3.2 Dose-response relationship between PHQ-9 scores and the prevalence of thyroid disease

3.3 Subgroup Analysis

4 Discussion

5 Summary

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1