Chronic Stress in Bipolar Disorders Across the Different Clinical States: Roles of HPA Axis and Personality

Abstract

Introduction

Chronic stress has been linked to the pathophysiology of bipolar disorder (BD); however, the underlying mechanism remains unclear. In BD patients, hypothalamic-pituitary-adrenal (HPA) axis activity is associated with stress. This study aimed to examine the relationship between HPA axis activity and BD symptoms in various clinical states, as well as how personality influences the process.

Methods

This study investigated the differences in HPA axis activity among four BD states. We enrolled 813 BD patients in an 8-week longitudinal study to examine the relationship between HPA axis activity and symptom trajectories using dynamic temporal warping (DTW) analysis and an unsupervised machine learning technique. Furthermore, using mediation analyses, the relationship between the HPA axis, personality, and BD symptoms was investigated.

Results

Analysis of variance (ANOVA) analysis showed that glucocorticoid cortisol (CORT) and adrenocorticotropin (ACTH) did not differ significantly among the four clinical states of BD. The DTW integrating clustering analysis revealed that the two clusters were optimal, with cluster 1 characterized by severe manic symptoms, which then improved, and cluster 2, characterized by milder manic severity, which also improved. The two clusters showed different ACTH levels (t = 2.289, p = 0.022), and logistic regression analysis revealed a slight positive association between ACTH levels and cluster 1. Furthermore, the mediation analysis indicated that ACTH influences curative efficacy via conscientiousness (βc =0.103, p=0.001).

Discussion

In conclusion, we found that a higher level of ACTH is associated with severe manic symptoms, indicating a chronic stress response in BD patients. Additionally, the ACTH levels affect short-term BD curative efficacy via the mediation of conscientiousness, providing a psychotherapeutic strategy direction for BD.

Keywords:

• bipolar disorder
• hypothalamic–pituitary–adrenal axis
• personality
• dynamic time warping analysis
• mediation analysis

Abbreviations

BD, bipolar disorders; HPA, hypothalamic–pituitary–adrenal; CORT, glucocorticoid cortisol; ACTH, adrenocorticotropin; NEO-FFI, NEO Five-Factor Inventory; MADRS, Montgomery Asberg Depression Rating Scale; YMRS, Young Mania Rating Scale; CGI, Clinical Global Impression; DTW, dynamic time warping.

Data Sharing Statement

We guarantee the authenticity of the data, but do not disclose the data, if necessary, you can email [email protected] to obtain the data.

Ethics Approval

The study conformed to the principles of the Declaration of Helsinki and was approved by the Institutional Ethics Board of the Chinese Clinical Trial Registry (The registration number is ChiECTR-20180187).

Acknowledgment

We gratefully acknowledge the participants of this study for generously donating their time. We would like to thank the research staff for their dedication to this project.

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.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This work was supported by the West China Psychiatric Association, China. Grant ID: WCPASX-2016. It provided the fund for the investigation, editing and the subject’s allowance.