Biomarkers for bipolar disorder? Researchers consider heat shock proteins

Naveed Saleh, MD, MS, for MDLinx | August 03, 2018

Heat shock proteins CPN10, CPN60, and CPN70 could serve as biomarkers for bipolar disorder (BD), according to a new study published in Medicine. Furthermore, CPN60 serum levels could serve as a biomarker to indicate which BD patients have disturbed activity of the hypothalamic-pituitary-adrenal (HPA) axis.

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“Our findings in this preliminary study suggest that HSP potentially might be useful as a biomarker of [bipolar disorder] and for distinguishing [bipolar disorder] patients with abnormal HPA axis activity from patients with normal HPA axis activity,” the authors wrote.

“An association has been observed between BD and abnormal activity of the hypothalamic-pituitary-adrenal (HPA) axis, which plays an important role in the response to stress, although the role of HPA axis activity abnormalities in the pathophysiology of BD remains unclear,” wrote the authors, led by Yuhang Cheng, MD, The National Clinical Research Center for Mental Disorders and Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing. Results of a recent meta-analysis uncovered a significant link between BD and both cortisol (CORT) and adrenocorticotropic hormone (ACTH).

Heat shock proteins (HSPs), or molecular chaperones, help control cellular homeostasis during periods of stress. Heat shock transcription factors are triggered secondary to stress and induce the transcription of HSPs. The best-studied HSPs are CPN10 (ie, HSP10), CPN60 (ie, HSP60), and CPN70 (ie, HSP70).

“Originally, it was believed that HSP only had intracellular functions, but evidence has been accumulating that they also have extracellular functions,” the authors wrote. In addition to contributing to the folding of proteins, HSPs may also contribute to immune function.

The role of HSPs as related to BD has been suggested by researchers conducting animal and clinical studies. A previous study leveraged various methods to analyze lymphocytes from patients with BD and healthy controls. The results suggested that the increased interaction between glucocorticoid receptor and HSP70 in patients with BD—as well as other observations—may provide insight for understanding the role of these factors in BD pathogenesis.

Several studies have indicated that HSP is involved in BD pathogenesis. Consequently, HSPs could serve as biomarkers for BD. This is a game-changer, as there are currently no BD biomarkers. In the current study, investigators screened HSP candidates as potential in vivo biomarkers in patients with both BD and BD with abnormal HPA activity.

In this current case-control study, Dr. Cheng and colleagues recruited 100 patients aged 18 to 55 years with BD, as well as 94 healthy controls who fell within the same age range. In total, 33 of 100 BD patients exhibited abnormal HPA axis activity. The team drew blood samples and employed chemiluminescence, mass spectrometry, and flow cytometry to determine levels of CPN10, CPN60, and CPN70.

The team examined associations among CPN10, CPN60, CPN70, ACTH, and CORT using the Spearman rank correlation, with P < 0.05 considered statistically significant. The statistics were two-sided.

Notably, CPN10, CPN60, and CPN70 data were gathered from different populations. For CPN60 and CPN70, data were obtained from 59 BD patients and 59 controls. But for CPN10, data were gathered from 41 BD patients and 35 controls.

Controls harbored significantly higher levels of CPN10 when compared with those of BD patients (P=0.036). However, CPN60 (P=0.009) and CPN70 (P < 0.001) levels in controls were significantly decreased vs those of BD patients.

With regard to relationships between normal and abnormal HPA activity, CPN60 levels in the BD group were noted to be significantly less only in the abnormal HPA axis group vs CPN60 levels of the BD group that exhibited HPA axis levels within normal limits (P=0.002).

The team observed that CPN60 levels were negatively associated with ACTH levels in patients with bipolar depression, as well as in patients with bipolar hypomania; CPN70 levels were positively associated with ACTH levels in the same patients.

The authors conceded that one limitation of the present study was that they failed to compare baseline demographic characteristics between BD patients and controls.

“Our findings in this preliminary study suggest that HSP potentially might be useful as a biomarker of BD and for distinguishing BD patients with abnormal HPA axis activity from BD patients with normal HPA axis activity,” the authors wrote. “Our results may eventually be useful for making an earlier diagnosis and therefore being able to initiate treatment for BD earlier.”

This study was funded by the Capital Medical Research Development Found of China.

To read more about this study, click here

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