Heart rate variability parameters and youth depression: Exploring the role of the high-frequency band

doi:10.21203/rs.3.rs-3756868/v1

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Heart rate variability parameters and youth depression: Exploring the role of the high-frequency band

https://doi.org/10.21203/rs.3.rs-3756868/v1

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Background

We try to explore the association between depression symptoms and HRV parameters in youth, due to the Heart rate variability (HRV) has emerged as a potential physiological indicator for depression.

Methods

A total of 118 participants diagnosis with MDD and a healthy control group were recruited. HRV measurements were recorded using the Bodychecker, and an animal experiment was conducted to validate the clinical findings.

Results

Our results showed a significant association between youth depression symptoms and the high-frequency (HF) band of HRV in both clinical and animal data.

Conclusion

These findings suggested the potential of the HF band as a screening tool for youth depression.

Psychiatry

Heart rate variability

Youth depression

High-frequency band

Diagnosis tool

Given that the current diagnosis and assessment of depression primarily rely on symptomatology and scale assessments, which may lack accuracy in identifying depressed patients, heart rate variability (HRV) offers a dynamic parameter influenced significantly by the interaction between the human sympathetic nervous system (SNS) and the Vagus nerve. In recent years, HRV has emerged as a promising physiological indicator for depression and other mental health problem(1–6). In previous research, reduced HRV could related to depression(7) and reduced parasympathetic control(8). Consequently, researchers have hypothesized that lower HRV in patients may signify an elevated risk of depression(8, 9). At the same time, there is an association between HRV alters that lower HRV with more severe depressive symptoms (7, 10). What’s more, the higher frequency alteration was exhibited in patients who were hospitalized and could be a possible screening tool (11).

This study aimed to investigate the potential correlation between depression symptoms and HRV parameters, emphasizing the significance of the high-frequency (HF) band. Additionally, an animal model was employed to validate the clinical findings.

Participants

A total of 118 youth participants (mean age: 16.92 ± 3.126) were recruited from the Shanghai Pudong New Area Mental Health Center between April 2023 and June 2023. Our team conducted a controlled study of HRV based on a cohort of young adults with MDD using data from 118 patients with MDD (n = 86) and Healthy Control (HC, n = 32). The depression group met DSM-5 criteria for depression and had no history of brain damage, neurological degenerative diseases, or intellectual deficits. Ethical approval was obtained from the Shanghai Pudong New Area Mental Health Ethics Committee, and all participants provided written informed consent.

Equipment

HRV was assessed using the Bodychecker (Medicore) equipped with the MS-001 sensor model. Participants were instructed to wear the finger clips and sit in a quiet room for a standardized measurement duration of 2 minutes and 30 seconds. The HRV results were recorded using the equipment.

Animal experiment

Twenty male Sprague-Dawley rats weighing 180–200 g were purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd. (Beijing, China; Certificate No. SCXK (Jing) 2021-0006) and acclimated to a controlled environment for one week before the experiment.

The rats were divided into the Control group (n = 10) and the Model group (n = 10). The Model group was exposed to three different stressors (Supplementary Material). The Model group stressor: The rats were evenly divided into Control group and Model group (n = 10). Model group rats were exposed to three different stressors. In brief, they were first restrained for 2 h in a plastic cone. Immediately after, they were placed for 20 min for a forced-swim in a water tank (40 cm of depth, 25 ± 1°C). Following a 15 min recuperation period, rats were placed in a desiccator and exposed to diethyl ether vapor (Beijing Tongchang Fine Chemical Company, China) until they became anesthetized and unresponsive. In the end, they were immediately returned to their home cages.

At fourteen days following stress induction, all rats in both groups were anesthetized intraperitoneally with 2% Pentobarbital Sodium at a dosage of 0.28 mL per 100 g of body weight, and their electrocardiograph patterns were recorded using a multi-channel physiological signal acquisition and processing system (Chengdu Instrument Factory, China). HRV measurements in both groups were recorded for 1 min. The experiment received approval from the Institutional Animal Care and Use Committee, the Academy of Military Medical Sciences (Approval Code: IACUC- DWZX-2022-688).

Association between sex and depression

Our study results are presented in Table 1, providing descriptive data. Notably, all HRV measurements deviated from normal distribution due to the inherent baseline nature of the data. The control group (n = 32, 27.12%) did not contribute to the Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) scores. An analysis examining the relationship between sex and SDS/SAS scores yielded noticeable differences between females and males.

Association between HRV parameters and depression

HRV measurements revealed a significant association between depression levels and the HF band (F (3,114), p = 0.013) (Table 2, Fig. 1). This association was consistent even within the comorbidity group (F (2,115), p = 0.005) (Table 3). Through the independent samples t-test, the dataset was stratified into two distinct groups: a depression group and a control group, with a cutoff point set at 1. The results of this analysis mirrored the previous findings, with the HF band (p = 0.023) significantly distinguishing the control group from the depression group (Table 4).

Association between HRV parameters and depression in animal experiment

To corroborate the clinical findings, we utilized the Single Prolonged Stress (SPS)-induced depression and anxiety model in our animal experiment. On the 14th day, HRV was measured (Fig. 3). The results revealed a significant increase in the HF band (p = 0.0225) in the model group compared with that in the control group, aligning with the clinical findings (Fig. 2).

The independent t-test comparison revealed a significant difference between females and males in SDS/SAS scores, consistent with previous studies (12, 13). This finding supports the notion that females are at a higher risk of depression, which aligns with our study's sample composition, primarily consisting of young females, many of whom were in the pre-pubertal stage.

The observed difference between the depression group and the control group in HF could be attributed to the modulation of parasympathetic system by depression symptoms (14). Since HF serves as an indicator of parasympathetic modulation, a lower HF value indicates modulation resulting from abnormal parasympathetic function, which influences the pathological processes of various diseases, including MDD (15).

Supporting our findings, a recent meta-analysis (16) investigated children and adolescents (n = 2625) and consistently reported lower HF values in individuals with depression. Another study (17) has similarly revealed that depressed subjects exhibit lower HF values during rest conditions and show reduced inhibition during task conditions.

The results from the animal experiment are consistent with the clinical findings, where the control group exhibited higher HF values compared to the model group. Moreover, the clinical results indicated that the control group had higher HF values than the depression group, further demonstrating that lower HF values can distinguish the model group from the control group.

However, limitations, such as sample size variations, variations in stressors employed, and differences in HRV recording methodologies, may explain the divergent outcomes between the clinical and animal experiments. These limitations warrant further research to confirm and elucidate these findings.

The findings of our study indicate that the HF band can serve as a differentiating factor between the depression group and the control group in humans. This outcome was further supported by the results obtained from our animal experiments. The consistent findings across both human and animal data underscore the potential of the HF band as a screening tool for youth depression. These results provide valuable insights into the identification and characterization of youth depression in young individuals. The supportive evidence provided can potentially enhance future diagnostic approaches for youth depression, leading to a significant reduction in the misdiagnosis rate.

HRV, heart rate variability; HF, high-frequency; SDS, Self-Rating Depression Scale; SAS, Self-Rating Anxiety Scale; MDD, Major depressive disorder; SNS, sympathetic nervous system.

Ethics approval and consent to participate

Ethical approval was obtained from the Shanghai Pudong New Area Mental Health Ethics Committee, and all participants provided written informed consent. The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.” and “The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional guides on the care and use of laboratory animals.

Consent for publication

Not applicable

Availability of data and materials

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

Competing interests

The authors declare that they have no competing interests

Funding

This work was supported by Medical discipline Construction Project of Pudong Health Committee of Shanghai (Grant No.: PWZzb2022-09), and Medical discipline Construction Project of Pudong Health Committee of Shanghai (Grant No.: PWYgy2021-02), these fundings were received by Xiwang Fan

Authors' contributions

YZ carried out the data analysis and drafted the initial manuscript.
CL in charge of animal experiments.
BS, BL reviewed the manuscript for important intellectual content.
JX, YG, YS, and XF conceptualized and designed the study and critically revised the manuscript.

Acknowledgements

Not applicable

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Table 1 Descriptive Statistics

	N	Range	Minimum	Maximum	Mean		Std. Deviation	Variance	Skewness		Kurtosis
	Statistic	Statistic	Statistic	Statistic	Statistic	Std. Error	Statistic	Statistic	Statistic	Std. Error	Statistic	Std. Error
Age	118	13	11	24	16.92	.288	3.126	9.771	.351	.223	-.843	.442
SDS	86	35	53	88	72.02	.941	8.729	76.188	-.141	.260	-.639	.514
SAS	86	47	36	83	59.64	1.121	10.398	108.116	.289	.260	-.462	.514
TP	118	15765.14	70.11	15835.25	2890.185	267.3803	2904.494	8436084.25	2.159	.223	5.184	.442
VLF	118	12177.98	31.82	12209.79	1229.711	144.1473	1565.84029	2451855.828	3.818	.223	21.150	.442
LF	118	8665.04	25.53	8690.57	730.2974	112.7111	1224.35638	1499048.556	3.725	.223	17.740	.442
HF	118	4706.05	12.68	4718.73	502.8885	65.15254	707.73777	500892.753	3.013	.223	11.980	.442
LF/HF	118	8.46	.13	8.58	1.6565	.13241	1.43836	2.069	2.227	.223	5.936	.442
Sex	118	1	1	2	1.72	.041	.451	.203	-.995	.223	-1.029	.442
Valid N (listwise)	86

Table 2 One-way ANOVA difference between HRV parameters according to depression level

		Sum of Squares	df	Mean Square	F	Sig.
TP	Between Groups	8888024.028	3	2962674.676	0.345	0.793
TP	Within Groups	978133833.276	114	8580121.345
VLF	Between Groups	2607325.159	3	869108.386	0.349	0.790
VLF	Within Groups	284259806.714	114	2493507.076
LF	Between Groups	1648583.906	3	549527.969	0.361	0.782
LF	Within Groups	173740097.177	114	1524035.940
HF	Between Groups	5239345.018	3	1746448.339	3.731	0.013
HF	Within Groups	53365107.126	114	468114.975
LF_HF	Between Groups	7.577	3	2.526	1.228	0.303
LF_HF	Within Groups	234.482	114	2.057

Table 3 One-way ANOVA difference between HRV parameters according to comorbidity status

		Sum of Squares	df	Mean Square	F	Sig.
TP	Between Groups	9243584.180	2	4621792.090	0.544	0.582
TP	Within Groups	977778273.124	115	8502419.766
VLF	Between Groups	2237228.740	2	1118614.370	0.452	0.638
VLF	Within Groups	284629903.134	115	2475042.636
LF	Between Groups	6211950.308	2	3105975.154	2.111	0.126
LF	Within Groups	169176730.775	115	1471102.007
HF	Between Groups	5176738.164	2	2588369.082	5.571	0.005
HF	Within Groups	53427713.980	115	464588.817
LF_HF	Between Groups	5.569	2	2.784	1.354	0.262
LF_HF	Within Groups	236.490	115	2.056

Table 4 Independent Samples Test for Depression group and control group

		F	Sig.	t	df*	Sig. (2-tailed)	Mean Difference	Std. Error Difference	95% Confidence Interval of the Difference
		F	Sig.	t	df*	Sig. (2-tailed)	Mean Difference	Std. Error Difference	Lower	Upper
TP	Equal variances assumed	.326	.569	-.087	116	.931	-52.357	604	-1248.655	1143.942
TP	Equal variances not assumed			-.095	68.162	.924	-52.357	548.6	-1147.025	1042.312
VLF	Equal variances assumed	1.482	.226	.537	116	.592	174.631	325.229	-469.526	818.788
VLF	Equal variances not assumed			.633	80.369	.529	174.631	275.873	-374.334	723.596
LF	Equal variances assumed	1.220	.272	-.360	116	.720	-91.608	254.476	-595.629	412.413
LF	Equal variances not assumed			-.424	80.183	.673	-91.608	216.059	-521.563	338.347
HF	Equal variances assumed	5.292	.023	-3.345	116	.001	-470.138	140.559	-748.533	-191.742
HF	Equal variances not assumed			-3.027	46.692	.004	-470.138	155.331	-782.677	-157.599
LF/HF	Equal variances assumed	1.182	.279	1.435	116	.154	.425	.297	-.162	1.013
	Equal variances not assumed			1.541	64.436	.128	.425	.276	-.126	.977

Supplementary Material file is not available with this version.

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Version 1

posted

You are reading this latest preprint version

Heart rate variability parameters and youth depression: Exploring the role of the high-frequency band

Status:

Version 1

Abstract

Background

Methods

Results

Conclusion

Figures

Background

Methods

Participants

Equipment

Animal experiment

Results

Association between sex and depression

Association between HRV parameters and depression

Association between HRV parameters and depression in animal experiment

Discussion

Conclusion

Abbreviations

Declarations

References

Tables

Supplementary Material

Status:

Version 1