Higher Concentration of Adrenocorticotropic Hormone Predicts Post-Stroke Depression

Abstract

Background

Post-stroke depression (PSD) is the most common neuropsychiatric complication after stroke, seriously affecting the quality of survivors’ life. As one of the important causes of PSD, neuroendocrine mechanism has been widely studied in recent years. The main objective of this study was to investigate the relationship between adrenocorticotropic hormone (ACTH) on admission and PSD at 3 months.

Methods

This is a hospital-based prospective cohort study, which was conducted at three independent hospitals (Tongji Hospital, Wuhan First Hospital and Wuhan Central Hospital) between August 2018 and June 2019. A total of 768 ischemic stroke patients were finally eligible for analysis and categorized into equal tertiles according to the distribution of ACTH and the number of patients. The χ²-test, Mann–Whitney U-test and Kruskal–Wallis test were used to check for statistical significance. And restricted cubic spline (RCS) regression model was used to explore the non-linear relationship between continuous ACTH levels and PSD at 3 months.

Results

The optimal cut-off points of ACTH were as follows: (T1) 0.32–20.55 pg/mL, (T2) 20.56–39.79 pg/mL, (T3) 39.80–143.40 pg/mL. A total of 305 patients (39.7%) were diagnosed as PSD at 3 months follow-up. Significant differences were found between the PSD and non-PSD groups in ACTH concentration (P = 0.001). After adjustment for all conventional confounders, the odds ratios of PSD were 1.735 (95% CI = 1.176–2.560, P = 0.005) for the highest tertile of ACTH and 1.496 (95% CI = 1.019–2.194, P = 0.040) for the middle tertile of ACTH, as compared with the lowest tertile. In multiple-adjusted RCS regression, continuous ACTH showed saturation effect relation with PSD risk after 31.02 pg/mL (P for nonlinear = 0.0143).

Conclusion

Higher ACTH level on admission is a significant and independent biomarker to predict the development of PSD at 3 months follow-up. Besides, saturation effect was revealed even if the underlying mechanism is unclear. For stroke patients, doctors should pay attention to the baseline ACTH for screening high-risk PSD in clinical practice.

Keywords:

• neuroendocrinology
• HPA axis
• adrenocorticotropic hormone
• post-stroke depression
• restricted cubic spline
• saturation effect

Abbreviations

PSD, post-stroke depression; HPA, hypothalamic pituitary adrenal; CRH, corticotropin releasing hormone; ACTH, adrenocorticotropic hormone; GR, glucocorticoid receptor; HAMD-17, 17-item Hamilton Rating Scale for Depression; TNF-α, tumor necrosis factor-α; BDNF, brain-derived neurotrophic factor; BMI, body mass index; CHD, coronary heart disease; WBC, white blood count; NEU, neutrophil count; IL, interleukin; IFN, interferon; NIHSS, The National Institutes of Health Stroke Scale; BI, Barthel Index; mRS, modified Rankin Scale; RCS, restricted cubic spline.

Data Sharing Statement

The database used in the current study are available from the corresponding authors on reasonable request.

Ethics Approval and Consent to Participate

All patients involved in this study or their family members gave written informed consents according to the Declaration of Helsinki. The approval of the study for experiments was obtained from the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology (Approved No. of ethics committee: TJ-IRB20171108).

Acknowledgments

We would like to acknowledge all participants of this project and investigators for collecting data.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work. SZ and ZZ had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Disclosure

The authors report no conflicts of interest for this work nor concerning the materials or methods used in this study nor the findings specified in this paper.

Additional information

Funding

This work was financially supported by the National Key R&D Program of China (grant number 2017YFC1310000), Hubei Technological Innovation Special Fund (grant number 2019ACA132), and National Natural Science Fund of China (grant numbers 82101605, 82001218, and 82171465). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.