Alterations in blood proteins in the prodromal stage of bipolar II disorders

Dong Yeon Park,Se Hyun Kim,Dohyun Han,Kyooseob Ha,Myungjae Baik,Eun Young Kim,Hyunsuk Shin,Tae Young Lee,Jun Soo Kwon,Jayoun Kim,Sungwon Roh,Sang Jin Rhee,Hee Yeon Jung,Yunna Lee,Minah Kim,Yong Min Ahn,Hyunju Lee,Hyeyoon Kim,Junhee Lee

doi:10.1038/s41598-022-07160-0

Abstract

Although early intervention may help prevent the progression of bipolar disorder, there are some controversies over early pharmacological intervention. In this study, we recruited 40 subjects in the prodromal stage of BD-II (BP), according to bipolar at-risk state criteria. We compared the expression of their plasma proteins with that of 48 BD-II and 75 healthy control (HC) to identify markers that could be detected in a high-risk state. The multiple reaction monitoring method was used to measure target peptide levels with high accuracy. A total of 26 significant peptides were identified through analysis of variance with multiple comparisons, of which 19 were differentially expressed in the BP group when compared to the BD-II and HC groups. Two proteins were overexpressed in the BP group; and were related to pro-inflammation and impaired neurotransmission. The other under-expressed peptides in the BP group were related to blood coagulation, immune reactions, lipid metabolism, and the synaptic plasticity. In this study, significant markers observed in the BP group have been reported in patients with psychiatric disorders. Overall, the results suggest that the pathophysiological changes included in BD-II had already occurred with BP, thus justifying early pharmacological treatment to prevent disease progression.

Highlights

Bipolar disorders (BDs) pose a higher risk of functional impairment or irreversible change as their courses become chronic
This study focused on recruiting subjects in a high risk state who were difficult to diagnose in terms of whether they were affected by depressive disorder or bipolar II disorder with respect to disease prognosis, and those who showed subthreshold hypomanic, depressive or cyclothymic symptoms but did not meet the diagnostic criteria at that time
It is necessary to measure these variations simultaneously to ensure diagnostic accuracy. By applying this analytic technique, we aimed to identify changes in several blood protein markers that are characteristically observed in high-risk groups by comparing BD-II and healthy control (HC) patients

Summary

Introduction

Bipolar disorders (BDs) pose a higher risk of functional impairment or irreversible change as their courses become chronic. This study focused on recruiting subjects in a high risk state who were difficult to diagnose in terms of whether they were affected by depressive disorder or bipolar II disorder with respect to disease prognosis, and those who showed subthreshold hypomanic, depressive or cyclothymic symptoms but did not meet the diagnostic criteria at that time. Biochemical changes, which could reflect disease progression in BDs, have been reported via altered gene expression[18], such as increased pro-inflammatory cytokines, oxidative stress, and cellular mitochondria dysfunction[19–21] Some of these biochemical markers have been found to be associated with disease severity, regardless of the polarity of the subject’s mood state, and have recovered after remission or t reatment[19]. By applying this analytic technique, we aimed to identify changes in several blood protein markers that are characteristically observed in high-risk groups by comparing BD-II and HC patients

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