Diagnostic Value of Serum SHBG，NCAM and CCL2 Levels in Cognitive Dysfunction in First-episode Patients with Schizophrenia

Zhaogui CHEN; Yanhui MOU; Jingci CHEN; Zhi QUAN; Jingsi CHEN

Article Contents

Article Navigation > Journal of Kunming Medical University > 2026 > Corrected proof

Zhaogui CHEN, Yanhui MOU, Jingci CHEN, Zhi QUAN, Jingsi CHEN. Diagnostic Value of Serum SHBG，NCAM and CCL2 Levels in Cognitive Dysfunction in First-episode Patients with Schizophrenia[J]. Journal of Kunming Medical University.

Citation:

PDF( 685 KB)

Diagnostic Value of Serum SHBG，NCAM and CCL2 Levels in Cognitive Dysfunction in First-episode Patients with Schizophrenia

1.
Department of Psychiatry，Yulin City Veterans' Hospital （Yulin Fourth People's Hospital），Yulin Guangxi 537000
2.
Department of Oncology，The First People’s Hospital of Yulin，Yulin Guangxi 537000，China

Received Date: 2025-12-05
Available Online: 2026-03-19

Abstract

Abstract

Objective To explore the diagnostic value of the levels of serum sex hormone-binding globulin （SHBG）, neural cell adhesion molecule （NCAM）, and C-C motif chemokine ligand 2 （CCL2） in cognitive dysfunction among patients with first-episode schizophrenia （FES）. Methods A total of 125 FES patients treated between July 2023 and June 2025 were selected as the study group, and 132 healthy volunteers who underwent physical examination in Yulin City Veterans' Hospital（Yulin City Fourth People's Hospital） during the same period were selected as the control group. The study group was further divided into a non-dysfunction group （n = 72） and a dysfunction group （n = 53） based on whether cognitive dysfunction occurred. Serum levels of SHBG, NCAM, and CCL2 were detected using ELISA. The Positive and Negative Syndrome Scale （PANSS） was used to assess the severity of schizophrenia, the Montreal Cognitive Assessment （MoCA） was used to assess the presence of cognitive dysfunction, and the MATRICS Consensus Cognitive Battery （MCCB） score was used to assess the degree of cognitive impairment. Pearson correlation analysis was used to analyze the correlations between the levels of SHBG, NCAM, and CCL2 and the PANSS score and MCCB scores. The ROC curve was used to analyze the diagnostic value of SHBG, NCAM, and CCL2 for cognitive dysfunction in FES patients, and the Z-test was used to compare the differences in the area under the curve （AUC）. Results Compared with the control group, the study group had higher SHBG and CCL2 levels and lower NCAM levels （P < 0.05）. Compared with the non-dysfunction group, the dysfunction group had higher SHBG and CCL2 levels and lower NCAM levels （P < 0.05）. Compared with the non-dysfunction group, the dysfunction group had higher PANSS scores （positive symptoms, negative symptoms, general psychopathology, and total score） and lower MCCB scores （social cognition, reasoning and problem-solving ability, visual learning, verbal learning, working memory, attention/vigilance, information processing speed, and total score）（P < 0.05）. In the dysfunction group, serum SHBG and CCL2 levels were positively correlated with each item and total score of PANSS and negatively correlated with each item and total score of MCCB, while NCAM levels were negatively correlated with each item and total score of PANSS and positively correlated with each item and total score of MCCB （P < 0.05）. The AUC for combined diagnosis of cognitive dysfunction in FES patients using SHBG, NCAM, and CCL2 was 0.955, which was superior to individual diagnoses（0.795, 0.814, 0.824）（P < 0.05）. Conclusion FES patients have elevated SHBG and CCL2 levels and reduced NCAM levels. These three markers are correlated with disease severity and cognitive impairment severity. Combined diagnosis has certain clinical significance and provides a data foundation for clinical diagnosis and related drug development.
- First-episode schizophrenia,
- Sex hormone-binding globulin,
- Neural cell adhesion molecule,
- C-C motif chemokine ligand 2,
- Cognitive dysfunction,
- Diagnostic value

FullText(HTML)

References(27)

References

[1]	Hung C C, Lin C H, Lane H Y. Cystine/glutamate antiporter in schizophrenia: From molecular mechanism to novel biomarker and treatment[J]. Int J Mol Sci, 2021, 22(18): 9718. doi: 10.3390/ijms22189718
[2]	Takeda T, Umehara H, Matsumoto Y, et al. Schizophrenia and cognitive dysfunction[J]. J Med Invest, 2024, 71(3.4): 205-209. doi: 10.2152/jmi.71.205
[3]	Xu W, Su B J, Shen X N, et al. Plasma sex hormone-binding globulin predicts neurodegeneration and clinical progression in prodromal Alzheimer's disease[J]. Aging, 2020, 12(14): 14528-14541. doi: 10.18632/aging.103497
[4]	Ou M, Du Z, Jiang Y, et al. Causal relationship between schizophrenia and sex hormone binding globulin: A Mendelian randomization study[J]. Schizophr Res, 2024, 267: 528-533. doi: 10.1016/j.schres.2023.09.030
[5]	Khlidj Y, Haireche M A. Schizophrenia as autoimmune disease: Involvement of anti-NCAM antibodies[J]. J Psychiatr Res, 2023, 161: 333-341. doi: 10.1016/j.jpsychires.2023.03.030
[6]	Keshri N, Nandeesha H, Rajappa M, et al. Relationship between neural cell adhesion molecule-1 and cognitive functioning in schizophrenia spectrum disorder[J]. Indian J Clin Biochem, 2022, 37(4): 494-498. doi: 10.1007/s12291-020-00937-y
[7]	Guo H, Hu W C, Xian H, et al. CCL2 potentiates inflammation pain and related anxiety-like behavior through NMDA signaling in anterior cingulate cortex[J]. Mol Neurobiol, 2024, 61(8): 4976-4991. doi: 10.1007/s12035-023-03881-z
[8]	Ermakov E A, Mednova I A, Boiko A S, et al. Chemokine dysregulation and neuroinflammation in schizophrenia: A systematic review[J]. Int J Mol Sci, 2023, 24(3): 2215. doi: 10.3390/ijms24032215
[9]	CSNP精神病性障碍研究联盟全体成员, 张天宏. 中国精神病临床高危综合征早期识别和干预——CSNP精神病性障碍研究联盟专家共识(2020版)[J]. 中国神经精神疾病杂志, 2020, 46(4): 193-199.
[10]	Hieronymus F, Correll C U, Østergaard S D. Initial severity of the Positive and Negative Syndrome Scale (PANSS)-30, its main subscales plus the PANSS-6, and the relationship to subsequent improvement and trial dropout: A pooled participant-level analysis of 18 placebo-controlled risperidone and paliperidone trials[J]. Transl Psychiatry, 2023, 13(1): 191. doi: 10.1038/s41398-023-02491-6
[11]	Carlew A R, Smith E E, Goette W, et al. Montreal Cognitive Assessment (MoCA) scores in medically compromised patients: A scoping review[J]. Health Psychol, 2021, 40(10): 717-726. doi: 10.1037/hea0001138.supp
[12]	Ding Y, Hou W, Wang C, et al. Longitudinal changes in cognitive function in early psychosis: A meta-analysis with the MATRICS consensus cognitive battery (MCCB)[J]. Schizophr Res, 2024, 270: 349-357. doi: 10.1016/j.schres.2024.06.048
[13]	Touskova T P, Bob P, Pec O, et al. Dissociative symptoms in schizophrenia spectrum disorders: Historical links and future research perspectives[J]. Schizophr Res, 2022, 248: 206-207. doi: 10.1016/j.schres.2022.09.006
[14]	Arango C, Buitelaar J K, Correll C U, et al. The transition from adolescence to adulthood in patients with schizophrenia: Challenges, opportunities and recommendations[J]. Eur Neuropsychopharmacol, 2022, 59: 45-55. doi: 10.1016/j.euroneuro.2022.04.005
[15]	Wu Q, Wang X, Wang Y, et al. Developments in biological mechanisms and treatments for negative symptoms and cognitive dysfunction of schizophrenia[J]. Neurosci Bull, 2021, 37(11): 1609-1624. doi: 10.1007/s12264-021-00740-6
[16]	Priol A C, Denis L, Boulanger G, et al. Detection of morphological abnormalities in schizophrenia: An important step to identify associated genetic disorders or etiologic subtypes[J]. Int J Mol Sci, 2021, 22(17): 9464. doi: 10.3390/ijms22179464
[17]	Ma H, Chen Y. Examining the causal relationship between sex hormone-binding globulin (SHBG) and infertility: A Mendelian randomization study[J]. PLoS One, 2024, 19(6): e0304216. doi: 10.1371/journal.pone.0304216
[18]	Zhao F, Li B, Yang W, et al. Brain-immune interaction mechanisms: Implications for cognitive dysfunction in psychiatric disorders[J]. Cell Prolif, 2022, 55(10): e13295. doi: 10.1111/cpr.13295
[19]	Del Campo M, Pijnenburg Y A L, Chen-Plotkin A, et al. Sex hormone-binding globulin (SHBG) in cerebrospinal fluid does not discriminate between the main FTLD pathological subtypes but correlates with cognitive decline in FTLD tauopathies[J]. Biomolecules, 2021, 11(10): 1484. doi: 10.3390/biom11101484
[20]	Xu Y, Qian X, Zhang M, et al. Correlations of cognitive function with serum levels of homocysteine, sex hormone binding globulin, and leptin in patients with schizophrenia[J]. Pak J Med Sci, 2024, 40(10): 2319-2323. doi: 10.12669/pjms.40.10.8923
[21]	Duncan B W, Murphy K E, Maness P F. Molecular mechanisms of L1 and NCAM adhesion molecules in synaptic pruning, plasticity, and stabilization[J]. Front Cell Dev Biol, 2021, 9: 625340. doi: 10.3389/fcell.2021.625340
[22]	Shiwaku H, Katayama S, Kondo K, et al. Autoantibodies against NCAM1 from patients with schizophrenia cause schizophrenia-related behavior and changes in synapses in mice[J]. Cell Rep Med, 2022, 3(4): 100597. doi: 10.1016/j.xcrm.2022.100597
[23]	Boiko A S, Mednova I A, Kornetova E G, et al. Cell adhesion molecules in schizophrenia patients with metabolic syndrome[J]. Metabolites, 2023, 13(3): 376. doi: 10.3390/metabo13030376
[24]	Du S, Wu S, Feng X, et al. A nerve injury-specific long noncoding RNA promotes neuropathic pain by increasing CCL2 expression[J]. J Clin Invest, 2022, 132(13): e153563. doi: 10.1172/JCI153563
[25]	Zhu X, Meng J, Han C, et al. CCL2-mediated inflammatory pathogenesis underlies high myopia-related anxiety[J]. Cell Discov, 2023, 9(1): 94. doi: 10.1038/s41421-023-00588-2
[26]	Klaus F, Mitchell K, Liou S C, et al. Chemokine MCP1 is associated with cognitive flexibility in schizophrenia: A preliminary analysis[J]. J Psychiatr Res, 2021, 138: 139-145. doi: 10.1016/j.jpsychires.2021.04.007
[27]	Targum S D, Murphy C, Breier A, et al. Site-independent confirmation of primary site-based PANSS ratings in a schizophrenia trial[J]. J Psychiatr Res, 2021, 144: 241-246. doi: 10.1016/j.jpsychires.2021.10.027

Relative Articles(20)

Relative Articles

[1]	Yuzhen ZHAO, Yingyan MA, Lili HE. Analysis of the Value of Serum Testosterone，Sex Hormone-binding Globulin and Vitamin D Levels in Predicting Gestational Diabetes Mellitus Complicated by Polycystic Ovary Syndrome. Journal of Kunming Medical University,
[2]	Xing HE, Fang YANG, Siyang LI, Yi LI, Yan WANG. Relationship between Serum β2-MG，1，5-AG，GLP-1 and Islet Function in Diabetic Patients and Their Predictive Value for Comorbid Cognitive Impairment. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20260312
[3]	Xiaoyan WANG, Xinrui WAN, Shitao XU, Wei CHEN, Hongyan MAO, Lin WANG, Zhiqiang MA. Analysis of Serum Biomarkers in Patients with Pulmonary Tuberculosis Complicated by Invasive Pulmonary Aspergillosis. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20250320
[4]	Qinghua YI, Juan XU, Ailian LI, Linyun TIAN, Dongli SANG, Jing XIONG, Chang DENG. Association between Body Mass Index and Cognitive Impairment in the Elderly in Guandu District of Kunming City. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20241019
[5]	Yi HUANG, Yongjian HUANG, Ling MAI, Ting LUO. Relationship between TGF-β/Smads Signaling Pathway and Cognitive Dysfunction in Patients with Aneurysmal Subarachnoid Hemorrhage. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20240319
[6]	Jibo QU, Ling ZHU, Binghui HOU, Song BAI, Anmu XIE. Early Predictive Value of Lymphocyte Subsets for Cognitive Dysfunction in Cerebral Ischemia-reperfusion Injury. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20241218
[7]	Liqiang LAN, Jing LI, Qingbo REN. Value Evaluation of New Markers AFP-L3 and PIVKAⅡ in the Diagnosis of Liver Cancer. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20230705
[8]	Xiaopei LV, Shuai YUAN. The Effect of Butylphthalide on Cognitive Dysfunction after the Stroke Caused by Cerebral Small Vessel Disease and Its Effect on Cerebral Blood Perfusion. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20230922
[9]	Cuiling WU, Hongyi LIU, Yuan FAN, Jiarui LIU. Research Progress in Pathogenesis of Diabetic Encephalopathy. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20220733
[10]	Xin WU, Pin-fei ZOU, Min HUANG. Diagnostic Value of Guidewire Localization of Breast Mass Based on High-frequency Ultrasound Guidance in Breast Lesions. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20220216
[11]	Yuan YANG, Li-jia PENG, Lan-qing PU, Jun-jie LI, Jian-lin SHAO, Xin YANG. Application of Propofol Combined with Dexmedetomidine or Midazolam in Painless Gastrointestinal Endoscopy in the Elderly. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20210221
[12]	Yan-ping LI, Yi ZENG, Xiao-lin DONG, Huan WEI, Qing-yun LI, Ming-shun AN, Li-ping ZHAN, Jian-hui LI, Gang WU, Yang LI, Jing-hui LI. Related Factors Affecting Adverse Events of Symptomatic Carotid Artery Stenosis. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20210717
[13]	Xian LI, Chang-liang JI, Shu-e ZENG, Shu-yun YANG, Hao-qi YANG, Ya-ting HOU. A Comparative Study of the Cognitive Function in Patients with Different Degrees of Depression. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20201226
[14]	Zhang Jin Zhi , Zhang Xiao , Liu Zhen Zhen . . Journal of Kunming Medical University,
[15]	Li Yun Ling , Bao Tian Hao , Zhang Ya Zhou , Tian Wei Meng , Mao Wen Wen , Hu Xiao Yun , Li Hua , Gu Jun . . Journal of Kunming Medical University,
[16]	Jia Liang . The Diagnostic Value of Plasma Fibrinogen and D-dimer for the Progressive Stroke. Journal of Kunming Medical University,
[17]	Lei Yu . . Journal of Kunming Medical University,
[18]	Ao Lei . . Journal of Kunming Medical University,
[19]	Wang Xiao Peng . . Journal of Kunming Medical University,
[20]	Liu Shu Qing . . Journal of Kunming Medical University,