Lack of relationship between posttraumatic stress disorder and coronary atherosclerotic burden among twin veterans from the Vietnam era.

Tumor-associated depression (TAD) is a prevalent pathological emotional response observed in cancer patients, particularly during diagnosis and early surgical treatment. It is characterized by diminished interest, fatigue, pessimism, self-blame, and suicidal ideation. Unlike general depressive disorders, TAD arises from tumor invasion, treatment-related damage, and psychological stress, with symptom severity fluctuating alongside disease progression. Compared with major depressive disorder (MDD), TAD has a distinct oncological etiology and is closely linked to organic changes, whereas MDD lacks organic triggers and is primarily defined by low mood and anhedonia. TAD also differs from psychotic depression, as it is not accompanied by psychotic symptoms such as delusions, and its onset is driven by tumor-induced neuroendocrine disturbances rather than primary cognitive dysfunction. Importantly, a bidirectional relationship exists: depression accelerates tumor progression through hypercortisolemia and immune suppression, while tumor-derived inflammatory mediators further exacerbate depressive symptoms, forming a vicious cycle. Epidemiological evidence indicates that depression is highly prevalent among cancer patients, with rates estimated at 20 %-50 %, representing a three- to fivefold increase compared with the general population. In advanced cancer, the prevalence rises further, reaching 30 %-50 %. For instance, among patients with hormone-sensitive malignancies such as ovarian or breast cancer, approximately 25 % experience at least mild depressive symptoms, while 12 % present with moderate to severe depression[]. It is report that approximately 20 %-25 % of cancer patients suffer from comorbid depression[]. Studies have demonstrated that depression can increase cancer mortality by 23 %-83 %[]. Their negative mental state and increased inflammatory factors may affect anti-tumor immunity. Meanwhile, depressive symptoms significantly reduce patients' quality of life and lead to a decrease in treatment adherence by as much as 30 %-40 %, which directly impacts treatment effectiveness and prognosis[]. Similarly, high rates of depression have been reported in prostate, cervical, and endometrial cancer[]. Beyond its psychological burden, chronic stress and depression exert profound biological effects, contributing to tumor initiation and progression by accelerating precancerous lesions, enhancing tumor growth, angiogenesis, invasion, and metastasis[,]. Similarly, preclinical studies have demonstrated that severe negative emotional responses to cancer diagnosis and treatment accelerate disease progression and are strongly associated with unfavorable clinical outcomes[]. Conversely, positive emotional responses, such as optimism and perceived social support, have been shown to slow disease progression and are associated with improved survival outcomes in cancer patients. In recent years, researchers have sought to elucidate the biological mechanisms underlying these observations through experimental studies. Although studies conducted over the past three decades have documented interactions between psychological stress and malignant tissues, the precise mechanisms by which depression contributes to tumor initiation and progression have remained unclear. Recent evidence, however, indicates that chronic stress, frequently associated with depression, modulates the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenocortical (HPA) axis, leading to the release of neurotransmitters and glucocorticoids (GCs). These catecholamines and GCs promote tumor development and progression by regulating multiple signaling cascades through interactions with adrenergic receptors (ARs) and glucocorticoid receptors (GRs) expressed on various tumor and immune cell types[,]. Recent studies suggest that these stress-related mediators and their corresponding receptors not only enhance the proliferative and invasive capacities of tumor cells but also alter tumor biology by reshaping the tumor microenvironment (TME)[,]. For instance, numerous studies have reported that tumors commonly exhibit an accumulation of stress-related mediators with strong immunosuppressive and pro-inflammatory properties[, , ]. Furthermore, emerging evidence indicates that tumor growth and survival depend, at least in part, on the development and infiltration of nerve fibers within the TME[]. This mechanism further involves the secretion of neurotransmitters, such as acetylcholine and catecholamines, into the tumor stroma, where they interact with their corresponding receptors on stromal and cancer cells. Indeed, depression or chronic stress may not directly induce nerve development, but they appear to act as critical contributors to nerve remodeling within the TME. Therefore, the coexistence of multiple tumor-promoting and immune escape mechanisms often limits the effectiveness of immunotherapy and conventional treatment strategies in cancer patien