Salivary glutathione in bipolar disorder: A pilot study
Introduction
Easily accessible biomarkers could be of great value in the diagnosis and management of mood disorders. Oxidative stress has been implicated in the pathophysiology of bipolar disorder and several measures of this process, often utilising enzymes measured in blood, have been explored in bipolar patients (Berk et al., 2011, Rosa et al., 2014).
Glutathione (GSH) is a major endogenous free radicle scavenger, and its lessened availability can increase vulnerability to cellular oxidative stress (Berk et al., 2011). A number of studies have measured GSH concentrations in blood and brain in patients with bipolar disorder but the findings have been somewhat inconsistent. For example, GSH levels in blood plasma and red cells have been reported both as being lowered and unchanged (Raffa et al., 2012, Rosa et al., 2014, Tunçel et al., 2015). Limited post-mortem work has found lowered GSH in cerebral cortex from bipolar patients (Gawryluk et al., 2011), though this has not been confirmed in magnetic resonance spectroscopy studies which are able to measure GSH concentrations in the living brain (Lagopoulos et al., 2013, Godlewska et al., 2014).
Recently we have described a novel method of analysing GSH in saliva using an enzyme kinetic assay (see Ngamchuea et al., 2016a, Ngamchuea et al., 2017). The determination is rapid and accurate and the stability of GSH in saliva is greater than in plasma due to decreased GSH degradation (Ngamchuea et al., 2016b, Ngamchuea et al., 2017). Salivary GSH therefore offers the possibility of an easily accessible biomarker for bipolar patients. The aim of the present study was to carry out a pilot study examining GSH levels in saliva in patients with bipolar disorder compared to a group of healthy controls.
Section snippets
Study setting
Participants with bipolar disorder were patients of the Oxford Health NHS Foundation Trust who were identified by their clinical teams as not being acutely unwell. They were approached by research facilitators attached to clinical teams and asked if they would like to participate in the study which involved a clinical assessment and the donation of a saliva sample. Healthy control participants were recruited by advertisement. All participants gave full, written informed consent to the study
Demographic data
Patients and controls were well matched for age and gender (Table 1). Twelve of the patients met DSM-5 criteria for Bipolar 1 disorder, the remainder had Bipolar 2 disorder. Most patients were mildly symptomatic in terms of depressive symptomatology on the HAM-D, though none met criteria for Major Depressive Episode. There was no significant manic symptomatology as detected on the YMRS. As often reported, smoking was more frequent in the bipolar patients than controls (Table 1).
GSH values
GSH, GSSG and
Discussion
In this pilot study of salivary GSH in bipolar patients, we found raised salivary levels of GSH and its oxidised form GSSG compared to healthy controls. However the ratio of GSH:GSSG was unchanged. Since the latter has been suggested to represent a measure of oxidative status (Berk et al., 2011), our results suggest that in saliva at least there does not appear to be evidence for acute oxidative stress in medicated bipolar patients in a relatively euthymic state.
The increase in salivary GSH and
Strengths and limitations
The strength of the study is its novel and rapid measurement of GSH in saliva in bipolar patients. The limitations include the small sample size and the fact that the patients were medicated.
Conclusions
Assay for salivary glutathione measurements in bipolar patients was simple and feasible, allowing easy, swift and non-invasive testing of both GSH and GSSG. The finding of increased GSH and GSSG in bipolar patients was statistically significant, but unexpected and requires replication. It is possible that saliva GSH is not representative of GSH levels in tissues more directly related to the pathophysiology of bipolar disorder, for example the central nervous system. Nevertheless, salivary GSH
Author statement
PJC and RGC conceived the idea for the study and determined the methodology involved. KN carried out the assays and, with PJC, analysed the results and wrote the first draft of the manuscript. CB-M supervised the assays and contributed to study design. ALS also contributed to study design and managed the GCP aspects of the study. CW and BRG recruited and assessed the participants and collected the samples. All authors approved the final version of the manuscript.
Role of funding source
The study was funded by the Oxford University Departments of Chemistry and Psychiatry. The authors also acknowledge support from the NIHR Oxford Cognitive Health Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.
Acknowledgement
We thank the participants for taking part in the study.
Conflict of interest statement
The authors declare no conflict of interest related to the present work.
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