Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, typically diagnosed at an advanced stage. The identification of prodromal symptoms could support earlier detection. Among these, depression is frequently reported, raising the question of whether it may represent not only a reactive response but also a paraneoplastic manifestation. Methods: We conducted a narrative review of clinical, epidemiological and biological literature published between 1988 and 2025. Searches were performed in PubMed/MEDLINE, Scopus, and Web of Science using predefined keywords related to pancreatic cancer, depression, prodromal symptoms, cytokines, and the kynurenine pathway. Eligible studies included clinical cohorts, population-based analyses, biological investigations, and case reports exploring the temporal or mechanistic link between depression and PDAC. Results: A substantial proportion of patients (10–20%) exhibit depressive symptoms in the months preceding the clinical diagnosis of pancreatic cancer. In several cases, depression occurs independent of weight loss and new-onset diabetes. Biological evidence highlights the involvement of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), NF-κB signaling, and activation of the tryptophan–kynurenine pathway (IDO), suggesting a link between tumor-related processes and mood alterations. These mechanistic findings are actually hypothesis-generating, deriving mainly from small clinical cohorts and preclinical models. Clinically, depression is associated with reduced adherence to treatment, poorer quality of life, and shorter survival. However, no specific depressive phenotype has been identified. Conclusions: Depression may represent a potential prodromal symptom of pancreatic cancer, reflecting systemic biological processes as well as psychological reactions. Its utility as a standalone marker remains limited; future studies should integrate psychiatric, clinical and biological biomarker assessments to enhance early clinical diagnosis.
背景：胰腺导管腺癌（PDAC）是最致命的恶性肿瘤之一，通常在晚期才被诊断。识别前驱症状可能有助于早期发现。其中，抑郁症状常被报道，这引发了一个问题：抑郁是否不仅是一种反应性心理反应，也可能是一种副肿瘤性表现。 方法：我们对1988年至2025年间发表的临床、流行病学和生物学文献进行了叙述性综述。在PubMed/MEDLINE、Scopus和Web of Science数据库中，使用与胰腺癌、抑郁、前驱症状、细胞因子及犬尿氨酸通路相关的预设关键词进行检索。符合条件的研究包括临床队列研究、基于人群的分析、生物学研究以及探讨抑郁与PDAC时间或机制关联的病例报告。 结果：相当一部分患者（10–20%）在胰腺癌临床诊断前的数月内表现出抑郁症状。在多个病例中，抑郁的发生与体重减轻和新发糖尿病无关。生物学证据强调了促炎细胞因子（IL-6、IL-1β、TNF-α）、NF-κB信号通路以及色氨酸-犬尿氨酸通路（IDO）激活的参与，表明肿瘤相关过程与情绪改变之间存在联系。这些机制性发现目前主要基于小型临床队列和临床前模型，具有假设生成性质。临床上，抑郁与治疗依从性降低、生活质量下降以及生存期缩短相关。然而，尚未发现特定的抑郁表型。 结论：抑郁可能是胰腺癌的潜在前驱症状，反映了系统性生物学过程以及心理反应。其作为独立标志物的应用价值仍然有限；未来的研究应整合精神心理、临床和生物学标志物评估，以提升早期临床诊断能力。
Depression as a Prodromal Symptom of Pancreatic Cancer: A Narrative Review
肿瘤(癌症)患者之家