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. 2025 Dec 25;26(1):76.
doi: 10.1186/s12888-025-07726-y.

Elevated prolactin and association with treatment resistance indicators in first-hospitalized schizophrenia spectrum disorders: a real-world cohort study

Dan Qi  1   2   3 , Wenjie Sun  1   2   4 , Meijuan Li  1   5 , Tongxin Li  1   2 , Jing Ma  6 , Di Liu  6 , Minghui Li  1 , Chenghao Lu  1   2 , Xinxu Wang  1   2 , Yeqing Dong  1   2 , Shaobing Li  1   2 , Yanzhe Li  1   2 , Jie Li  7 , Shen Li  8   9 , Nannan Liu  10   11
Affiliations

Elevated prolactin and association with treatment resistance indicators in first-hospitalized schizophrenia spectrum disorders: a real-world cohort study

Dan Qi et al. BMC Psychiatry. .

Abstract

Background: Hyperprolactinemia frequently occurs during antipsychotic treatment but is also observed in antipsychotic-naïve schizophrenia patients. The relationship between prolactin (PRL) and treatment resistance remains underexplored in real-world populations.

Objective: To characterize age-/sex-stratified PRL distribution in first-hospitalized schizophrenia spectrum disorder (SSD) patients and examine associations with treatment resistance proxies (clozapine use/rehospitalization).

Methods: We analyzed 4,103 first-hospitalized SSD patients using real-world data. PRL levels were stratified by age/sex. Binary logistic regression evaluated PRL-clozapine/rehospitalization associations with confounder adjustment. ROC analysis assessed PRL's discriminative capacity for clozapine use.

Results: Elevated PRL prevalence was highest in females aged 18-45 (71.5%). PRL negatively correlated with clozapine use in males (P < 0.001), with lower median levels in users vs. non-users (374.40 vs. 529.10 mIU/L, P < 0.001). This persisted in males aged 18-45 (434.90 vs. 558.60 mIU/L) and ≥ 55 years (308.60 vs. 583.30 mIU/L) (both P < 0.01). In males ≥ 55, each 1 mIU/L PRL increase reduced clozapine use probability by 0.2% (aOR = 0.998, 95%CI:0.997-1.000). ROC analysis showed moderate discriminative capacity (AUC = 0.72, sensitivity 78.6%, specificity 39.4%). No significant associations occurred in females or for rehospitalization.

Conclusion: The PRL demonstrates inverse, age-specific associations with clozapine use in male SSD patients, suggesting potential as a stratification biomarker for treatment resistance.

Keywords: Clozapine; First-hospitalized patients; Real-world data; Schizophrenia spectrum disorders; Serum prolactin; Sex differences.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: All procedures involving human participants were conducted in accordance with the ethical standards of the institutional research committee and the principles of the Declaration of Helsinki. All data were de-identified and encrypted to ensure patient privacy and data security throughout transmission, management, and analysis. The study was approved by the Institutional Review Board (IRB) of Tianjin Anding Hospital, and informed consent was waived due to the de-identified nature of the dataset. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Study population flowchart. EHR: the Electronic Health Records. SSD: schizophrenia spectrum disorders. PRL: prolactin. MECT: Modified electroconvulsive therapy
Fig. 2
Fig. 2
Overall distribution of prolactin Levels
Fig. 3
Fig. 3
ROC curve of prolactin levels and clozapine use
See this image and copyright information in PMC

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