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Background <p>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.</p> Objective <p>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).</p> Methods <p>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.</p> Results <p>Elevated PRL prevalence was highest in females aged 18–45 (71.5%). PRL negatively correlated with clozapine use in males (<i>P</i> &lt; 0.001), with lower median levels in users vs. non-users (374.40 vs. 529.10 mIU/L, <i>P</i> &lt; 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 <i>P</i> &lt; 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.</p> Conclusion <p>The PRL demonstrates inverse, age-specific associations with clozapine use in male SSD patients, suggesting potential as a stratification biomarker for treatment resistance.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月25日

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  • Dan Qi,
  • Wenjie Sun,
  • Meijuan Li,
  • Tongxin Li,
  • Jing Ma,
  • Di Liu,
  • Minghui Li,
  • Chenghao Lu,
  • Xinxu Wang,
  • Yeqing Dong,
  • Shaobing Li,
  • Yanzhe Li,
  • Jie Li,
  • Shen Li,
  • Nannan Liu

摘要

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.