Risk Prediction Performance of Blood Biomarkers for Bipolar Disorder With Psychotic Symptoms

NI Zijun, YIN Junping, WANG Xiaoying, ZHOU Yuting, MO Xian, SUN Lu, ZHANG Wei

Abstract

Objective 

 To investigate biological markers associated with psychotic symptoms in patients with bipolar disorder (BD) based on electronic medical records of patients, and to develop an interpretable risk prediction model that supports the identification of high-risk individuals and that facilitates decision-making for providing clinical intervention in a timely manner.

Methods 

 A total of 2352 patients diagnosed with BD and admitted to West China Hospital, Sichuan University were enrolled using the electronic medical records system of the hospital. The participants were divided into two subgroups, the bipolar disorder depression (BDD) group and the bipolar disorder mania (BDM) group. The logistic regression algorithm was used to train and validate the prediction model, and interpretability methods were used to analyze the contribution of each feature to individuals and the effect of the features on specific target prediction decisions.

Results 

 The logistic regression model demonstrated robust predictive performance across the BD, BDD, and BDM cohorts, with areas under the curve (AUC) of the receiver operating characteristic curves always exceeding 81.6%. The core predictive features included platelet distribution width (PDW), fibrinogen (FIB), platelet large cell ratio (P-LCR), activated partial thromboplastin time (APTT), prothrombin time (PT), and triglyceride (TG). The logistic regression model exhibited strong interpretability and was combined with nomograms for intuitive risk quantification and individualized prediction.

Conclusion 

 The logistic regression model enables rapid and simple screening of BD patients with psychotic symptoms. Distinct patterns of changes observed in blood biomarkers of BDD and BDM subgroups enrich the understanding of the underlying pathophysiological mechanisms and highlight the importance of considering subtypes in the intervention and management of patients.

 

Keywords: Bipolar disorder, Machine learning, Prediction model, Biomarkers


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References


PERKES I. Serious mental illness? Categorical measurement for health service systems. Aust N Z J Psychiatry, 2023, 57(12): 1505-1507. doi: 10. 1177/00048674231214872.

DU Y, LI X D, FU D W. The diagnostic value of serum TBARS, NGF, BDNF in bipolar disorder and their relation-ship with different clinical phases. Journal of Molecular Diagnostics and Therapy, 2025, 17(4): 692-695. doi: 10.19930/j.cnki.jmdt.2025.04.047.

De AZEVEDO CARDOSO T, KOCHHAR S, TOROUS J, et al. Digital tools to facilitate the detection and treatment of bipolar disorder: key developments and future directions. JMIR Ment Health, 2024, 11: e58631. doi: 10.2196/58631.

GBD 2019 Mental Disorders Collaborators. Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Psychiatry, 2022, 9(2): 137-150. doi: 10.1016/S2215-0366(21)00395-3.

ARIAS D, SAXENA S, VERGUET S. Quantifying the global burden of mental disorders and their economic value. EClinicalMedicine, 2022, 54: 101675. doi: 10.1016/j.eclinm.2022.101675.

HUANG Y, LI Y, PAN H, et al. Global, regional, and national burden of neurological disorders in 204 countries and territories worldwide. J Glob Health, 2023, 13: 04160. doi: 10.7189/jogh.13.04160.

LAI J, LI S, WEI C, et al. Mapping the global, regional and national burden of bipolar disorder from 1990 to 2019: trend analysis on the Global Burden of Disease Study 2019. Br J Psychiatry, 2024, 224(2): 36-46. doi: 10.1192/bjp.2023.127.

CHAKRABARTI S, SINGH N. Psychotic symptoms in bipolar disorder and their impact on the illness: a systematic review. World J Psychiatry, 2022, 12(9): 1204-1232. doi: 10.5498/wjp.v12.i9.1204.

AMINOFF S R, ONYEKA I N, ØDEGAARD M, et al. Lifetime and point prevalence of psychotic symptoms in adults with bipolar disorders: a systematic review and meta-analysis. Psychol Med, 2022, 52(13): 2413-2425. doi: 10.1017/S003329172200201X.

KLOIBER S, ROSENBLAT J D, HUSAIN M I, et al. Neurodevelopmental pathways in bipolar disorder. Neurosci Biobehav Rev, 2020, 112: 213-226. doi: 10.1016/j.neubiorev.2020.02.005.

BAENA-OQUENDO S, VALENCIA J G, VARGAS C, et al. Neuropsychological aspects of bipolar disorder . Rev Colomb Psiquiatr (Engl Ed), 2021: S0034-7450(20)30092-5. doi: 10.1016/j.rcp.2020.08.003.

MULLINS N, FORSTNER A J, O'CONNELL K S, et al. Genome-wide association study of more than 40, 000 bipolar disorder cases provides new insights into the underlying biology. Nat Genet, 2021, 53(6): 817-829. doi: 10.1038/s41588-021-00857-4.

HEURICH M, FÖCKING M, MONGAN D, et al. Dysregulation of complement and coagulation pathways: emerging mechanisms in the development of psychosis. Mol Psychiatry, 2022, 27(1): 127-140. doi: 10. 1038/s41380-021-01197-9.

SANTA CRUZ E C, ZANDONADI F D S, FONTES W, et al. A pilot study indicating the dysregulation of the complement and coagulation cascades in treated schizophrenia and bipolar disorder patients. Biochim Biophys Acta Proteins Proteom, 2021, 1869(8): 140657. doi: 10.1016/j. bbapap.2021.140657.

ZHU X, LI R, ZHU Y, et al. Changes in inflammatory biomarkers in patients with schizophrenia: a 3-year retrospective study. Neuropsychiatr Dis Treat, 2023, 19: 1597-1604. doi: 10.2147/NDT.S411028.

ARRANZ B, SANCHEZ M, GARRIGA M, et al. Differential serum acute-phase biomarker profile in schizophrenia and bipolar disorder. Eur Psychiatr, 2016, 33(S1): S96. doi: 10.1016/j.eurpsy.2016.01.067.

WANG J, ZHAO Y L, XIAO W H, et al. Comparision in hematological inflammatory markers and brain-derived neurotrophic factor in patients with schizophrenia and those with bipolar disorder. Journal of Clinical Medicine in Practice, 2021, 25(22): 74-77. doi: 10.7619/jcmp.20212571

CHEN F, XIE G P, ZHANG Z J. Correlation between serum homocysteine, C -reactive protein, procalci-tonin levels and depression degree in patients with bipolar disorder andunipolar depressive. China Modern Medicine, 2025, 32(4): 52-55. doi: 10.3969/j.issn.1674-4721.2025.04.11.

MONGAN D, CANNON M, COTTER D R. COVID-19, hypercoagulation and what it could mean for patients with psychotic disorders. Brain Behav Immun, 2020, 88: 9-10. doi: 10.1016/j.bbi.2020.05.067.

WYSOKIŃSKI A, SZCZEPOCKA E. Platelet parameters (PLT, MPV, P-LCR) in patients with schizophrenia, unipolar depression and bipolar disorder. Psychiatry Res, 2016, 237: 238-245. doi: 10.1016/j.psychres.2016.01.034.

ZHU T, LIU X, WANG J, et al. Explainable machine-learning algorithms to differentiate bipolar disorder from major depressive disorder using self-reported symptoms, vital signs, and blood-based markers. Comput Methods Programs Biomed, 2023, 240: 107723. doi: 10.1016/j.cmpb.2023. 107723.

MONTAZERI M, MONTAZERI M, BAHAADINBEIGY K, et al. Application of machine learning methods in predicting schizophrenia and bipolar disorders: a systematic review. Health Sci Rep, 2023, 6(1): e962. doi: 10.1002/hsr2.962.

NAGY Á, DOMBI J, FÜLEP M P, et al. The actigraphy-based identification of premorbid latent liability of schizophrenia and bipolar disorder. Sensors (Basel), 2023, 23(2): 958. doi: 10.3390/s23020958. TIAN S,

ZHU R, CHEN Z, et al. Prediction of suicidality in bipolar disorder using variability of intrinsic brain activity and machine learning. Hum Brain Mapp, 2023, 44(7): 2767-2777. doi: 10.1002/hbm.26243.

MIKOLAS P, MARXEN M, RIEDEL P, et al. Prediction of estimated risk for bipolar disorder using machine learning and structural MRI features. Psychol Med, 2024, 54(2): 278-288. doi: 10.1017/S0033291723001319.

LIN C E, CHUNG C H, CHEN L F, et al. Increased risk for venous thromboembolism among patients with concurrent depressive, bipolar, and schizophrenic disorders. Gen Hosp Psychiatry, 2019, 61: 34-40. doi: 10.1016/j.genhosppsych.2019.10.003.

NIELSEN R E, BANNER J, JENSEN S E. Cardiovascular disease in patients with severe mental illness. Nat Rev Cardiol, 2021, 18(2): 136-145. doi: 10.1038/s41569-020-00463-7.

ZHENG C, LIU H, TU W, et al. Hypercoagulable state in patients with schizophrenia: different effects of acute and chronic antipsychotic medications . Ther Adv Psychopharmacol, 2023, 13: 20451253231200257. doi: 10.1177/20451253231200257.

ALBALAWI A. Deep venous thrombosis and hyponatremia associated with citalopram use for behavioral symptoms in Parkinson's disease: a case report. BMC Geriatr, 2023, 23(1): 344. doi: 10.1186/s12877-023-04057-z.

CHEN Z, WANG J, CARRU C, et al. Meta-analysis of peripheral mean platelet volume in patients with mental disorders: comparisons in depression, anxiety, bipolar disorder, and schizophrenia. Brain Behav, 2023, 13(11): e3240. doi: 10.1002/brb3.3240.

ZHANG Z, LI H, WENG H, et al. Genome-wide association analyses identified novel susceptibility loci for pulmonary embolism among Han Chinese population. BMC Med, 2023, 21(1): 153. doi: 10.1186/s12916-023-02844-4.

DICKENS A M, SEN P, KEMPTON M J, et al. Dysregulated lipid metabolism precedes onset of psychosis. Biol Psychiatry, 2021, 89(3): 288-297. doi: 10.1016/j.biopsych.2020.07.012.

EDINOFF A N, RAVEENDRAN K, COLON M A, et al. Selective serotonin reuptake inhibitors and associated bleeding risks: a narrative and clinical review. Health Psychol Res, 2022, 10(4): 39580. doi: 10.52965/ 001c.39580.

WEI Y, FENG J, MA J, et al. Characteristics of platelet-associated parameters and their predictive values in Chinese patients with affective disorders. BMC Psychiatry, 2022, 22(1): 150. doi: 10.1186/s12888-022-03775-9.

SLEURS D, SPERANZA M, ETAIN B, et al. Functioning and neurocognition in very early and early-life onset bipolar disorders: the moderating role of bipolar disorder type. Eur Child Adolesc Psychiatry, 2024, 33(11): 4029-4041. doi: 10.1007/s00787-024-02372-3.


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