Protein biomarkers for bipolar II disorder are correlated with affective cognitive performance

Abstract Background In our previous research, we identified five candidate proteins—Carbonic Anhydrase 1 (CA-1), Matrix Metallopeptidase 9 (MMP9), Peroxiredoxin 2 (PRDX2), Phenylalanyl-tRNA Synthetase Subunit Beta (FARSB), and Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)—as prospective biom...

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Main Authors: Sheng-Yu Lee, Sung-Chou Li, Tzu-Yun Wang, Ru-Band Lu, Liang-Jen Wang, Kuo-Wang Tsai
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Psychiatry
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Online Access:https://doi.org/10.1186/s12888-025-07104-8
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author Sheng-Yu Lee
Sung-Chou Li
Tzu-Yun Wang
Ru-Band Lu
Liang-Jen Wang
Kuo-Wang Tsai
author_facet Sheng-Yu Lee
Sung-Chou Li
Tzu-Yun Wang
Ru-Band Lu
Liang-Jen Wang
Kuo-Wang Tsai
author_sort Sheng-Yu Lee
collection DOAJ
description Abstract Background In our previous research, we identified five candidate proteins—Carbonic Anhydrase 1 (CA-1), Matrix Metallopeptidase 9 (MMP9), Peroxiredoxin 2 (PRDX2), Phenylalanyl-tRNA Synthetase Subunit Beta (FARSB), and Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)—as prospective biomarkers for bipolar II disorder (BD-II). In this study, we explored the relationships between these potential plasma proteins and cognitive performance in BD-II patients using the Brief Assessment of Cognition in Affective Disorders (BACA), a validated tool for assessing cognitive deficits in mood disorders. Methods One hundred and seventeen participants with BD-II and 41 controls participated in this study. Plasma concentrations of the aforementioned proteins were measured, and cognitive performance was evaluated using the BACA. Results Our findings indicated that the BD-II group scored significantly lower than the control group across several BACA subtests, including Digit Sequencing, Symbol Coding, Verbal Memory, and Verbal Fluency, and in overall composite scores and all subtests of the Affective Interference Test (AIT) and Emotion Inhibition Test (EIT). Notably, we observed significant correlations in the BD-II group between levels of CA-1 (r = -0.26, P = 0.005), FARSB (r = 0.399, P < 0.001), and MMP9 (r = 0.24, P = 0.008) with the AIT-Cued affective words subtest. In contrast, a significant correlation was found between the Symbol Coding task and PCSK9 levels (r = 0.35, P = 0.003) in the control group, but not in the BD-II group. Conclusion These findings offer new perspectives on the underlying mechanisms contributing to cognitive decline in individuals with BD-II.
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spelling doaj-art-fd2fb6d7f79b41b8bde862d210abbb532025-08-20T04:01:36ZengBMCBMC Psychiatry1471-244X2025-07-0125111310.1186/s12888-025-07104-8Protein biomarkers for bipolar II disorder are correlated with affective cognitive performanceSheng-Yu Lee0Sung-Chou Li1Tzu-Yun Wang2Ru-Band Lu3Liang-Jen Wang4Kuo-Wang Tsai5Department of Psychiatry, Kaohsiung Veterans General HospitalDepartment of Medical Education and Research, Kaohsiung Veterans General HospitalDepartment of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung UniversityDepartment of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung UniversityDepartment of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineDepartment of Research, Buddhist Tzu Chi Medical Foundation, Taipei Tzu Chi HospitalAbstract Background In our previous research, we identified five candidate proteins—Carbonic Anhydrase 1 (CA-1), Matrix Metallopeptidase 9 (MMP9), Peroxiredoxin 2 (PRDX2), Phenylalanyl-tRNA Synthetase Subunit Beta (FARSB), and Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)—as prospective biomarkers for bipolar II disorder (BD-II). In this study, we explored the relationships between these potential plasma proteins and cognitive performance in BD-II patients using the Brief Assessment of Cognition in Affective Disorders (BACA), a validated tool for assessing cognitive deficits in mood disorders. Methods One hundred and seventeen participants with BD-II and 41 controls participated in this study. Plasma concentrations of the aforementioned proteins were measured, and cognitive performance was evaluated using the BACA. Results Our findings indicated that the BD-II group scored significantly lower than the control group across several BACA subtests, including Digit Sequencing, Symbol Coding, Verbal Memory, and Verbal Fluency, and in overall composite scores and all subtests of the Affective Interference Test (AIT) and Emotion Inhibition Test (EIT). Notably, we observed significant correlations in the BD-II group between levels of CA-1 (r = -0.26, P = 0.005), FARSB (r = 0.399, P < 0.001), and MMP9 (r = 0.24, P = 0.008) with the AIT-Cued affective words subtest. In contrast, a significant correlation was found between the Symbol Coding task and PCSK9 levels (r = 0.35, P = 0.003) in the control group, but not in the BD-II group. Conclusion These findings offer new perspectives on the underlying mechanisms contributing to cognitive decline in individuals with BD-II.https://doi.org/10.1186/s12888-025-07104-8Bipolar II disorderProteinCognitive functionCorrelation
spellingShingle Sheng-Yu Lee
Sung-Chou Li
Tzu-Yun Wang
Ru-Band Lu
Liang-Jen Wang
Kuo-Wang Tsai
Protein biomarkers for bipolar II disorder are correlated with affective cognitive performance
BMC Psychiatry
Bipolar II disorder
Protein
Cognitive function
Correlation
title Protein biomarkers for bipolar II disorder are correlated with affective cognitive performance
title_full Protein biomarkers for bipolar II disorder are correlated with affective cognitive performance
title_fullStr Protein biomarkers for bipolar II disorder are correlated with affective cognitive performance
title_full_unstemmed Protein biomarkers for bipolar II disorder are correlated with affective cognitive performance
title_short Protein biomarkers for bipolar II disorder are correlated with affective cognitive performance
title_sort protein biomarkers for bipolar ii disorder are correlated with affective cognitive performance
topic Bipolar II disorder
Protein
Cognitive function
Correlation
url https://doi.org/10.1186/s12888-025-07104-8
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