Mauro Giovanni Carta
Antonio Egidio Nardi- 1Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
- 2LABPR – Panic and Respiration Laboratory (LABPR), Institute of Psychiatry (IPUB), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
1 Introduction: cancer and its association with depressive disorder
The comorbidity between chronic illnesses and depression is well known to all psychiatrists working in general hospitals. A large body of research indicates a bidirectional relationship: each condition can exacerbate the other, leading to worse outcomes compared to conditions without comorbidity (1–7). At first glance, the comorbidity between depression and cancer may seem comparable to that seen in other chronic conditions. Yet, a more nuanced reality emerges.
First, this is a phenomenon of considerable scope; however, it is not a distinctive characteristic of cancer (8). According to authoritative large cohort studies, reviews, and meta-analyses, the prevalence of major depressive disorder among people with cancer is estimated within a broad range but is reasonably around 10–15%, varying according to cancer type and the diagnostic tools used (9–11), which is roughly three to four times the rate observed in the general population (12, 13). However, this prevalence is lower than that observed in conditions such as myocardial infarction, in which up to one in three individuals experiences depression (14–16), or diabetes, where approximately one in five individuals is affected (17–20).
Research on cancer stage as a predictor of depression has produced contradictory findings. Some studies report an association between depression and advanced or terminal stages of cancer (21); however, systematic reviews indicate that although advanced or metastatic disease often correlates with a higher burden of depressive symptoms, the effect is modest as a direct determinant and less consistent than psychological or social variables, such as a history of previous depressive episodes or the presence of concurrent stressors (22–24). Observational studies and meta-analyses suggest that depressive symptoms are more frequent during active treatment phases, but findings are heterogeneous and frequently confounded by multiple factors (22, 25).
Based on the current literature, chemotherapy agents and oncological drugs can be broadly classified into high- and moderate-risk categories with respect to depressive disorders. High-risk agents include interferon-α, for which the strongest evidence regarding depression risk derives mainly from non-oncological studies (26, 27), and corticosteroids used in combination therapies, which are associated with an increased risk of mania and mixed states during treatment and depressive episodes following discontinuation (28–30). Agents considered to carry a moderate risk include platinum-based compounds (31), taxanes (32), hormonal therapies for prostate and breast cancer (33, 34), and methotrexate (35).
2 Cancer, depressive episodes and quality of life
The apparently lower frequency of the association between cancer and depression compared to what is observed in other chronic diseases does not diminish the importance of comorbidity; rather, the specificity of the depression/cancer relationship becomes evident when the connection between cancer and quality of life is analyzed. A study by our group measured the impact of cancer on quality of life in a consecutive sample of 150 individuals with solid tumors and compared it with the impact of other chronic diseases on quality of life in standardized case-controls studies (21). The research surprisingly revealed that not only is the impact of solid tumors on quality of life no greater than that of other chronic diseases, but also that diseases with a less fatal outcome, such as multiple sclerosis (36) and even fibromyalgia (37), compromise quality of life on average more than solid tumors. The impact was calculated as the difference in the score obtained on the SF-12 scale by individuals with the condition in question, compared to a sample of the same age and sex drawn from the database of an epidemiological study on the well-being of the general Italian population (38). Therefore, all the studies cited by Aviles Gonzales et al. (21) were conducted using a case-control design with controls matched by sex and age to cases, drawn each time from the same database (21). Obviously, some solid tumors have a greater impact than others. In the cited study, the sample comes consecutively from the two regional reference centers in Sardinia, so the proportion of the different tumors is approximately the same as that present in the community.
The relatively low impact (compared to other diseases) of cancer on quality of life might be explained by the fact that, today, suffering from an oncological condition is probably less stigmatizing than it was a few decades ago (39–41), and that treatments and prognosis have improved, including for symptoms such as pain and/or functional disability (42–44). We are increasingly hearing entrepreneurs, politicians, and ordinary citizens speak openly in the media about their experiences after a cancer diagnosis, whereas only a few years ago this was kept secret. Difficulties persist for those who experience ongoing symptoms or live in sociocultural contexts in which stigma is still present. But, paradoxically, despite the relatively high prevalence, one of the greatest challenges concerns depressive disorder. In fact, the same study that highlighted the relatively low impact of cancer on the quality of life of those affected (21) also calculated how the onset of a depressive episode can further reduce the quality of life in people with cancer, and how this compares with other chronic diseases. In other words, we measured the difference in the SF-12 score between those who have cancer or another chronic illness without depression and those who have the same illness but also present depression. It emerges that, in the case of solid tumors, comorbidity with depression reduces quality of life by an average of 10 SF-12 points, which is about three times more than what is observed in other chronic conditions. In cancer, even if the frequency of depression is not very high, when depression is present as a comorbidity, the impact is devastating. The interest of the study by Aviles-Gonzales and colleagues lies in the fact that the comparison between cancer and other chronic diseases was conducted using the same methodology and a shared database derived from a national community survey, allowing the generation of age- and sex-matched control groups for each condition. More broadly, however, the negative impact of depression on cancer outcomes and quality of life is well established in the international literature (45–50).
Living with cancer requires maintaining a delicate balance that hinges, on one hand, on renewed hope for survival made possible by improved treatments, and, on the other, on the acceptance of life’s end as a real possibility, albeit one moderated by therapeutic advances and hope. The onset of a depressive episode can profoundly disrupt this balance, often more severely than in other medical conditions. The combined effects of pain, functional impairment, and stigma, worsened by depression, may lead to a significant loss of hope. In such circumstances, the end of life may appear as inevitable and catastrophic, while the prospect of survival may be perceived instead as a source of anxiety, associated with fears of disability and external dependency.
3 Some questions that require answers
The dramatic impact of depressive disorders on quality of life raises significant questions for both research and clinical practice.
1. Is the impact of depressive comorbidity so substantial that it may lead to a worsening of disease progression and even premature death?
2. What mechanisms can be investigated?
3. Is there a bidirectional relationship, namely, can depression increase the risk of cancer?
4. Can depression prevention and early intervention improve outcomes?
We will attempt to propose some answers based on current knowledge. Even in cancer, depression is associated with disease worsening and increased risk of death. A landmark meta-analysis unequivocally revealed, across a large sample of studies, that a diagnosis of depression is linked to a higher mortality rate. This holds true whether depression emerges before or after the cancer diagnosis (51). Subsequent studies have confirmed these findings. In the case of depression–cancer comorbidity, the risk of mortality (compared with individuals with cancer but without depression) is approximately 1.5; however, when mortality not directly related to cancer is also included (for instance, suicide), the risk exceeds 2 (52–55).
Robust evidence found the consequences that depression can exert during the progression of cancer, and how these consequences may serve as mediating factors leading to premature death. For the sake of simplicity, we distinguish between psychosocial and behavioral consequences on the one hand, and biological, somatic consequences on the other; from a psychosomatic perspective, this distinction is artificial, yet we adopt it for clarity.
Among the former, it has been demonstrated that depression leads to poor adherence to treatment (53, 56–58). Depression also reduces energy and motivation, which may result in malnutrition, a sedentary lifestyle, and consequently a general weakening of the organism (55, 59, 60). Individuals with depressive disorders may increase their consumption of alcohol, tobacco, or other risky behaviors (61–63). The loss of social support can further worsen psychological well-being and disease management (64–66).
Among so-called somatic consequences, the most significant of which are:
● Alterations of the immune system. Depression may impair immune function, reducing the body’s ability to fight cancer cells (67–69).
● Depression is also associated with elevated levels of inflammatory cytokines, which may promote cancer progression (70–73).
● Depression can disrupt cortisol secretion, negatively affecting the stress response and potentially stimulating tumor growth (74–76).
● Depression can also alter sleep-wake rhythms, resulting in imbalances in several metabolic functions and in the biorhythms of neurotransmitter secretion that influence tumor progression (76, 77).
As can be seen, rather than a clear distinction between psychosocial and somatic consequences, it would be more accurate to speak of two different perspectives from which to observe the same psychosomatic impact.
4, An indefinite border between spirituality and psychosomatics. Could death wish in depression develop in parallel with the mechanisms responsible for regulating tumor cells?
The themes of death and depression suggest a psychosomatic perspective that does not exclude a spiritual dimension. It is therefore legitimate to ask whether death wish associated with depression might develop in parallel with the mechanisms responsible for regulating tumor cells. While this question may be relevant from a spiritual standpoint, it also opens the possibility of exploring pathogenic processes. Consequently, one might ask whether, in the absence of an initial tumor, depression, through its physiological effects and the accompanying death wish, could facilitate the onset of cancer. This remains a hypothesis, but it may offer a fruitful direction for both clinical and theoretical investigation.
It’s now widely understood that even people suffering from depression (initially without cancer) are also at increased risk of developing cancer (78–81). The risk is higher in prostate (82–84), breast (85, 86), and lung cancers (87–89). In this framework, we shouldn’t overlook the risk factors produced or amplified by depression, which may act as mediators. This has been well demonstrated in lung cancer, which may represent a model. However, in other cancers, risk factors common to depression and cancer are emerging, particularly breast and prostate cancer, which may represent another model.
4 Two different models
The association between depression and lung cancer weakens after adjusting the data for factors such as tobacco use, suggesting that lifestyle (influenced by depression) may play an important mediating role. In this case, it can be stated that the increase in smoking associated with depression is the main cause of the higher incidence of lung cancer among individuals with depression (90). This same model could be useful to explain the depression–cancer association in other organs/anatomical sites. For example, in the Emilia Romagna cohort (91), an elevated risk was also observed for stomach and pancreatic cancer. It would be interesting to investigate whether alcohol consumption plays a similar role in these tumors.
Regarding the second model, an example can be drawn from the fact that mood disorders (92–94), as well as prostate (95, 96) and breast cancer (97, 98), are influenced by light pollution, which disrupts melatonin rhythms, with consequences for circadian hormonal patterns and for the balance between stimulating neurosteroids (estrogens and testosterone) and stabilizing neurosteroids (progestins and their derivatives), in favor of the former (99, 100). Other research findings suggest that a genetic predisposition to mood disorders may be associated with a genetic risk for breast cancer (101). These data do not challenge the hypotheses concerning the impact of light pollution on both conditions (it is perhaps a sensitivity to rhythm dysregulation that is inherited). However, the underlying biological mechanisms deserve further investigation.
5 Light pollution, rhythms, and neurotransmitters: does serotonin have a role?
Dorsal raphe neurons, which produce serotonin, display rhythmic electrical activity linked to the sleep–wake cycle (102, 103). Serotonin is a wakefulness-associated neurotransmitter and promotes cell proliferation. This has also been demonstrated in normal, non-cancerous cells (such as epithelial, intestinal, and stam cells) (104, 105). Serotonin may exert a pro-oncogenic role in various types of cancer (106). Some examples include Serotonin stimulates the proliferation of breast cancer cells, which in turn can also produce serotonin themselves (107, 108); Serotonin enhances prostate cancer cell proliferation through the 5-HT1A or 5-HT2B receptors (109). Intestinal serotonin (produced by enterochromaffin cells) has been linked to colon cancer cell proliferation (110). A role for the stress response has also been hypothesized along of a brain-gut axis (111, 112).
Given these premises, it is legitimate to ask whether serotonergic antidepressants may represent a risk factor. Considering all cancer types as a whole, current data suggest that the use of serotonergic medications is not associated with a significant increase in cancer risk, although the available studies are not methodologically robust (113–115). However, when specifically addressing breast cancer, serious concerns arise. A study involving 23,669 breast cancer patients found that SSRI users had higher breast cancer–specific mortality (HR = 1.27; 95% CI 1.16–1.40), which was even higher among long-term SSRI users (HR = 1.54; 95% CI 1.03–2.29). In this case as well, the co-occurrence of depression, although accounted for in the statistical analysis, still leaves room for interpretative ambiguity (116).
6 Social support and fear of death
The data presented highlight the importance of psychosocial interventions in preventing the development of depression. A study conducted by our group found that strong psychological and spiritual support, as well as a supportive network of friends, were associated with optimal adherence to cancer treatments and better clinical outcomes (53). Psychosocial interventions and a good social networks are also protective factors against the onset of depressive episodes (117, 118). When antidepressant use was necessary, research on non-cancer depression, showed that psychosocial interventions were associated with lower dosages and shorter treatment durations (119, 120). Therefore, support, even from a single person with whom to share fears and concerns, can play a crucial role, in fact consistent with research on perceived social support in oncology, the perceived availability of at least one emotionally available significant other with whom patients can openly share their fears and concerns functions as an important protective factor against depressive symptoms in people living with cancer (121–123). Even the simple possibility of sharing the fear of death can be a protective factor for both the person suffering from cancer and the caregiver (124, 125).
This concept has also been elegantly expressed through art. In Giovan Battista Caracciolo’s renowned painting Christ in the Garden of Gethsemane (https://www.meisterdrucke.ie/fine-art-prints/Giovanni-Battista-Caracciolo/1014752/Christ-on-the-Mount-of-Olives.html), “Battistello” portrays the precise moment in which Christ experiences anguish and fear in the face of imminent death, while simultaneously receiving consolation from an angel. As the Gospel of Luke states: “Then an angel appeared to him from heaven and strengthened him” (Luke 22:43). The painting thus conveys two essential elements: on the one hand, the fear of death, restored to its profoundly human dimension; on the other, the presence of someone, the angel, who consoles, shares that fear, and thereby makes it possible to accept it.
To prevent a person with cancer from being aware of the possibility of death, and to deny them dialogue and the sharing of fears, can exacerbate the fear of death as an individual burden that must be concealed rather than shared. Silence intensifies anxiety, obscures awareness of improved treatments, and relegates the possibility of death to a solitary, terrifying event. This suggests that, even in the context of cancer, the possibility of death should not be denied or regarded as inexpressible, provided that the individual wishes to confide. Yet one must ask: does the contemporary world foster loneliness and isolation in the face of death?
7 The denial of the awareness of death in contemporary culture
The denial of awareness of death in contemporary culture has attracted the attention of numerous philosophers, sociologists, and intellectuals. According to Philippe Ariès (126), in the modern world death has become a taboo, “invisible,” concealed. In contemporary society, death is suppressed as a social occurrence and delegated to healthcare institutions (126). Michel Foucault argues that modern societies exercise control over life in order to neutralize death as a lived and shared experience, a process he defines as biopolitical power (2008). As a consequence, death is “medicalized” and becomes a technical moment rather than an existential or spiritual one (127).
Zygmunt Bauman adds that in consumer society, death is perceived as an individual failure—something embarrassing that must be hidden (1992). Death no longer carries public meaning; it is reduced to a private, often solitary matter (128). Edgar Morin on “The man and the death” (129) contends that, within contemporary culture, the denial of death generates anxiety, which transforms into an obsession with youth and health, now perceived as synonymous with media-driven beauty.
Prohibiting awareness of the possibility of death in cancer patients, refusing dialogue about it, may ultimately reinforce the fear of death as a personal affront that must be concealed rather than shared.
Death, as a social fact, feared yet regarded as an essential element of life, and from whose fear one may find comfort, lies at the roots of our Mediterranean and Latin cultures. When Georges Duby recounts the life of William “the Marshal,” the quintessential medieval knight, the narrative begins with his death (130). For the medieval man, imbued with a religious and spiritual worldview, life was fundamentally a preparation for death.
Similarly, in Islamic ethical-religious literature—particularly within Sufi thought—earthly life is understood as a preparation (fitna) for the hereafter (akhira) (131).
Even atheist or agnostic philosophers such as Sartre (132)Cioran (133), and Camus (134) developed the theme of death as a search for the meaning of life, or as a form of existential contemplation. “To die proudly when it is no longer possible to live proudly” reflects an exacerbation of individualism, yet it also implies a need for social testimony.
The COVID-19 pandemic demonstrated how, within Mediterranean societies, the prohibition of funeral rites was associated with an increased risk of depression among relatives of the deceased. demonstrating in this way how the sociality of death can be an essential moment in the metabolization of mourning (135).
Despite the media bombardment that denies death as an individual value and a social event (as well as the social importance of death and life), this vision has not yet fully taken root in our cultures. The experience of cancer can be lived with reasonable hope thanks to the successes of science, but it also requires reflection that can give meaning to life, not only because the fear of possible death is modulated by hope, but also because of the social significance of the disease, consistent with our cultural roots. Those who have already lived this experience (healthcare workers or caregivers) can more easily be a point of reference for those who are going through.
8 A summary with practical suggestions from this complex perspective
Prevention of depressive episodes is essential: attention should be paid to signs of stress and to dysregulation of social rhythms; sometimes the alteration of the sleep–wake cycle alone may serve as an early warning signal. Providing accurate information to patients and their caregivers is equally important. A crucial aspect is also the organization of services and the provision of comprehensive care—too often individuals are left on their own to navigate clinical examinations, specialist imaging, and other procedures.
Emotional support plays a significant role. Support groups, including self-help groups, may be valuable, particularly (though not exclusively) for individuals who feel isolated or lack a social network. It may be beneficial to have someone with whom, due to cultural or spiritual proximity, it is easier to discuss these issues.
If a depressive episode is diagnosed, it is important to keep in mind that several forms of psychotherapy are effective. Pharmacotherapy should not be avoided when necessary; however, the most appropriate medications should be carefully evaluated, and, whenever possible, treatment duration should not be unnecessarily prolonged (as previously discussed with regard to serotonin). For this reason, psychotherapy or other interventions that may help shorten the duration of pharmacological treatment are essential. It must be borne in mind that depression is a multifactorial disorder and therefore requires diversified therapeutic approaches, not limited to psychopharmacological treatment alone; moreover, effective non-pharmacological interventions have also been tested and shown to be beneficial in oncology settings (136–139).
This reading has considered (the treatment and prevention of) the disease as a social event, both in terms of the importance of the specific cultural context as a place of care and a tool for treatment, and as a social mediator for prevention (105-142). This does not deny the relevance of disease in a globalized context, nor does it contrast this with an awareness of the role of technology and,science but rather, it integrates technology into cultural contexts.
Author contributions
MGC: Methodology, Conceptualization, Supervision, Funding acquisition, Formal analysis, Writing – original draft. AEN: Writing – original draft, Supervision, Conceptualization, Investigation.
Funding
The author(s) declared that financial support was received for this work and/or its publication. Regione Sardegna Project QR (form improving the quality of Care in Mental Health).
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The handling editor SMD declared a past co-authorship with the author MGC.
Generative AI statement
The author(s) declared that generative AI was not used in the creation of this manuscript.
Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
1. Katon WJ. Epidemiology and treatment of depression in patients with chronic medical illness. Dialogues Clin Neurosci. (2011) 13:7–23. doi: 10.31887/DCNS.2011.13.1/wkaton
2. Berk M, Köhler-Forsberg O, Turner M, Penninx BWJH, Wrobel A, Firth J, et al. Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management. World Psychiatry. (2023) 22:366–87. doi: 10.1002/wps.21110
3. Herrera PA, Campos-Romero S, Szabo W, Martínez P, Guajardo V, and Rojas G. Understanding the relationship between depression and chronic diseases such as diabetes and hypertension: A grounded theory study. Int J Environ Res Public Health. (2021) 18:12130. doi: 10.3390/ijerph182212130
4. Moussavi S, Chatterji S, Verdes E, Tandon A, Patel V, and Ustun B. Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet. (2007) 370:851–8. doi: 10.1016/S0140-6736(07)61415-9
5. Read JR, Sharpe L, Modini M, and Dear BF. Multimorbidity and depression: A systematic review and meta-analysis. J Affect Disord. (2017) 221:36–46. doi: 10.1016/j.jad.2017.06.009
6. Handajani YS, Schroeder-Butterfill E, Hogervorst E, Turana Y, and Hengky A. Multimorbidity and depression increase prevalence of frailty of community-dwelling Indonesian older adults: Indonesia care networks study. Int J Prev Med. (2024) 15:69. doi: 10.4103/ijpvm.ijpvm_160_23
7. Kim H, Kim SH, and Cho YJ. Combined effects of depression and chronic disease on the risk of mortality: the korean longitudinal study of aging (2006-2016). J Korean Med Sci. (2021) 36:e99. doi: 10.3346/jkms.2021.36.e99
8. Bortolato B, Hyphantis TN, Valpione S, Perini G, Maes M, Morris G, et al. Depression in cancer: The many biobehavioral pathways driving tumor progression. Cancer Treat Rev. (2017) 52:58–70. doi: 10.1016/j.ctrv.2016.11.004
9. Linden W, Vodermaier A, Mackenzie R, and Greig D. Anxiety and depression after cancer diagnosis: prevalence rates by cancer type, gender, and age. J Affect Disord. (2012) 141:343–51. doi: 10.1016/j.jad.2012.03.025
10. Smith HR. Depression in cancer patients: Pathogenesis, implications and treatment (Review). Oncol Lett. (2015) 9:1509–14. doi: 10.3892/ol.2015.2944
11. Krebber AM, Buffart LM, Kleijn G, Riepma IC, de Bree R, Leemans CR, et al. Prevalence of depression in cancer patients: a meta-analysis of diagnostic interviews and self-report instruments. Psychooncology. (2014) 23:121–30. doi: 10.1002/pon.3409
12. Horwath E, Cohen RS, and Weissman MM. Epidemiology of depressive and anxiety disorders. In: Tsuang MT and Tohen M, editors. Textbook in psychiatric epidemiology, 2nd ed. Wiley-Liss, New York, NY (2002). p. 389–426.
13. Kasyanov E, Yakovleva Y, Khobeysh M, Gerasimchuk E, and Mazo G. Lifetime prevalence of recurrent and persistent depression: A scoping review of epidemiological studies. Clin Pract Epidemiol Ment Health. (2025) 21:e17450179372815. doi: 10.2174/0117450179372815250516102324
14. Wium-Andersen MK, Wium-Andersen IK, Prescott EIB, Overvad K, Jørgensen MB, and Osler M. An attempt to explain the bidirectional association between ischaemic heart disease, stroke and depression: a cohort and meta-analytic approach. Br J Psychiatry. (2020) 217:434–41. doi: 10.1192/bjp.2019.130
15. Ogunmoroti O, Osibogun O, Spatz ES, Okunrintemi V, Mathews L, Ndumele CE, et al. A systematic review of the bidirectional relationship between depressive symptoms and cardiovascular health. Prev Med. (2022) 154:106891. doi: 10.1016/j.ypmed.2021.106891
16. Bobo WV, Ryu E, Petterson TM, Lackore K, Cheng Y, Liu H, et al. Bi-directional association between depression and HF: An electronic health records-based cohort study. J Comorb. (2020) 10:2235042X20984059. doi: 10.1177/2235042X20984059
17. Zhao F, Pan A, Yang X, Meng R, Ye Y, Wang Y, et al. Bidirectional association between depressive symptoms and type 2 diabetes mellitus: The China Health and Retirement Longitudinal Study. J Diabetes Complications. (2019) 33:107387. doi: 10.1016/j.jdiacomp.2019.05.018
18. Meng R, Liu N, Yu C, Pan X, Lv J, Guo Y, et al. Association between major depressive episode and risk of type 2 diabetes: A large prospective cohort study in Chinese adults. J Affect Disord. (2018) 234:59–66. doi: 10.1016/j.jad.2018.02.052
19. Alzoubi A, Abunaser R, Khassawneh A, Alfaqih M, Khasawneh A, and Abdo N. The bidirectional relationship between diabetes and depression: A literature review. Korean J Fam Med. (2018) 39:137–46. doi: 10.4082/kjfm.2018.39.3.137
20. Beran M, Muzambi R, Geraets A, Albertorio-Diaz JR, Adriaanse MC, Iversen MM, et al. The bidirectional longitudinal association between depressive symptoms and HbA1c: A systematic review and meta-analysis. Diabetes Med. (2022) 39:e14671. doi: 10.1111/dme.14671
21. Aviles Gonzalez CI, Angermeyer M, Deiana L, Loi C, Murgia E, Holzinger A, et al. The Quality of Life of People with Solid Cancer is Less Worse than Other Diseases with better Prognosis, Except in the Presence of Depression. Clin Pract Epidemiol Ment Health. (2021) 17:315–23. doi: 10.2174/1745017902117010315.2021
22. Riedl D and Schüßler G. Factors associated with and risk factors for depression in cancer patients - A systematic literature review. Transl Oncol. (2022) 16:101328. doi: 10.1016/j.tranon.2021.101328
23. Grassi L, Caruso R, Riba MB, Lloyd-Williams M, Kissane D, Rodin G, et al. Anxiety and depression in adult cancer patients: ESMO Clinical Practice Guideline. ESMO Open. (2023) 8:101155. doi: 10.1016/j.esmoop.2023.101155
24. Rodríguez-González A, Velasco-Durántez V, Cruz-Castellanos P, Hernández R, Fernández-Montes A, Jiménez-Fonseca P, et al. Mental adjustment, functional status, and depression in advanced cancer patients. Int J Environ Res Public Health. (2023) 20:3015. doi: 10.3390/ijerph20043015
25. Singer S, Das-Munshi J, and Brähler E. Prevalence of mental health conditions in cancer patients in acute care–a meta-analysis. Ann Oncol. (2010) 21:925–30. doi: 10.1093/annonc/mdp515
26. MaChado MO, Oriolo G, Bortolato B, Köhler CA, Maes M, Solmi M, et al. Biological mechanisms of depression following treatment with interferon for chronic hepatitis C: A critical systematic review. J Affect Disord. (2017) 209:235–45. doi: 10.1016/j.jad.2016.11.039
27. Ehret M and Sobieraj DM. Prevention of interferon-alpha-associated depression with antidepressant medications in patients with hepatitis C virus: a systematic review and meta-analysis. Int J Clin Pract. (2014) 68:255–61. doi: 10.1111/ijcp.12268
28. Faggiano A, Mazzilli R, Natalicchio A, Adinolfi V, Argentiero A, Danesi R, et al. Corticosteroids in oncology: Use, overuse, indications, contraindications. An Italian Association of Medical Oncology (AIOM)/ Italian Association of Medical Diabetologists (AMD)/ Italian Society of Endocrinology (SIE)/ Italian Society of Pharmacology (SIF) multidisciplinary consensus position paper. Crit Rev Oncol Hematol. (2022) 180:103826. doi: 10.1016/j.critrevonc.2022.103826
29. De Bock M and Sienaert P. Corticosteroids and mania: A systematic review. World J Biol Psychiatry. (2024) 25:161–74. doi: 10.1080/15622975.2024.2312572
30. Koning ACAM, van der Meulen M, Schaap D, Satoer DD, Vinkers CH, van Rossum EFC, et al. Neuropsychiatric adverse effects of synthetic glucocorticoids: A systematic review and meta-analysis. J Clin Endocrinol Metab. (2024) 109:e1442–51. doi: 10.1210/clinem/dgad701
31. Vaishnav B and Mondkar SN. Impact of platinum-based versus other chemotherapies on health-related quality of life and hospital anxiety and depression scale in patients with Malignancies in a tertiary center in western India. Ann Afr Med. (2025). doi: 10.4103/aam.aam_128_25
32. Ibrahim EY, Domenicano I, Nyhan K, Elfil M, Mougalian SS, Cartmel B, et al. Cognitive effects and depression associated with taxane-based chemotherapy in breast cancer survivors: A meta-analysis. Front Oncol. (2021) 11:642382. doi: 10.3389/fonc.2021.642382
33. Nead KT, Sinha S, Yang DD, and Nguyen PL. Association of androgen deprivation therapy and depression in the treatment of prostate cancer: A systematic review and meta-analysis. Urol Oncol. (2017) 35:664.e1–9. doi: 10.1016/j.urolonc.2017.07.016
34. Qazi SU, Altaf Z, Zafar M, Tariq MA, Khalid A, Kaleem A, et al. Development of depression in patients using androgen deprivation therapy: A systemic review and meta-analysis. Prostate. (2024) 84:525–38. doi: 10.1002/pros.24676
35. Van Lint JA, Bakker T, Ten Klooster PM, van Puijenbroek EP, Vonkeman HE, and Jessurun NT. Neuropsychiatric adverse drug reactions associated with low dose methotrexate in rheumatoid arthritis patients. Expert Opin Drug Saf. (2022) 21:417–23. doi: 10.1080/14740338.2022.2003328
36. Carta MG, Aguglia E, Balestrieri M, Calabrese JR, Caraci F, Dell'Osso L, et al. The lifetime prevalence of bipolar disorders and the use of antidepressant drugs in bipolar depression in Italy. J Affect Disord. (2012) 136:775–80. doi: 10.1016/j.jad.2011.09.041
37. Carta MG, Moro MF, Pinna FL, Testa G, Cacace E, Ruggiero V, et al. The impact of fibromyalgia syndrome and the role of comorbidity with mood and post-traumatic stress disorder in worsening the quality of life. Int J Soc Psychiatry. (2018) 64:647–55. doi: 10.1177/0020764018795211
38. Carta MG, Moro MF, Lorefice L, Picardi A, Trincas G, Fenu G, et al. Multiple sclerosis and bipolar disorders: the burden of comorbidity and its consequences on quality of life. J Affect Disord. (2014) 167:192–7. doi: 10.1016/j.jad.2014.05.024
39. Xu J, Li Q, Gao Z, Ji P, Ji Q, Song M, et al. Impact of cancer-related fatigue on quality of life in patients with cancer: multiple mediating roles of psychological coherence and stigma. BMC Cancer. (2025) 25:64. doi: 10.1186/s12885-025-13468-7
40. Ernst J, Mehnert A, Dietz A, Hornemann B, and Esser P. Perceived stigmatization and its impact on quality of life - results from a large register-based study including breast, colon, prostate and lung cancer patients. BMC Cancer. (2017) 17:741. doi: 10.1186/s12885-017-3742-2
41. Zamanian H, Amini-Tehrani M, Jalali Z, Daryaafzoon M, Ramezani F, Malek N, et al. Stigma and quality of life in women with breast cancer: mediation and moderation model of social support, sense of coherence, and coping strategies. Front Psychol. (2022) 13:657992. doi: 10.3389/fpsyg.2022.657992
42. Shrestha A, Martin C, Burton M, Walters S, Collins K, and Wyld L. Quality of life versus length of life considerations in cancer patients: A systematic literature review. Psychooncology. (2019) 28:1367–80. doi: 10.1002/pon.5054
43. Poço Gonçalves J, Veiga D, and Araújo A. Chronic pain, functionality and quality of life in cancer survivors. Br J Pain. (2021) 15:401–10. doi: 10.1177/2049463720972730
44. Ehrhardt MJ, Krull KR, Bhakta N, Liu Q, Yasui Y, Robison LL, et al. Improving quality and quantity of life for childhood cancer survivors globally in the twenty-first century. Nat Rev Clin Oncol. (2023) 20:678–96. doi: 10.1038/s41571-023-00802-w
45. Caruso R, Nanni MG, Riba M, Sabato S, Mitchell AJ, Croce E, et al. Depressive spectrum disorders in cancer: prevalence, risk factors and screening for depression: a critical review. Acta Oncol. (2017) 56:146–55. doi: 10.1080/0284186X.2016.1266090
46. Geue K, Brähler E, Faller H, Härter M, Schulz H, Weis J, et al. Prevalence of mental disorders and psychosocial distress in German adolescent and young adult cancer patients (AYA). Psychooncology. (2018) 27:1802–9. doi: 10.1002/pon.4730
47. Yen YC, Huang CY, Chan HW, Wang YY, Changchien TC, Wang DW, et al. Longitudinal association of universal screening and treatment for major depressive disorder with survival in cancer patients. J Pers Med. (2022) 12:1213. doi: 10.3390/jpm12081213
48. Akechi T, Mishiro I, and Fujimoto S. Risk of major depressive disorder in adolescent and young adult cancer patients in Japan. Psychooncology. (2022) 31:929–37. doi: 10.1002/pon.5881
49. Ohi K. Shared genetic correlation and causal association between major depressive disorder and breast cancer. BMC Med. (2023) 6:203. doi: 10.1186/s12916-023-02905-8
50. Osmani V, Hörner L, Klug SJ, and Tanaka LF. Prevalence and risk of psychological distress, anxiety and depression in adolescent and young adult (AYA) cancer survivors: A systematic review and meta-analysis. Cancer Med. (2023) 12:18354–67. doi: 10.1002/cam4.6435
51. Pinquart M and Duberstein PR. Depression and cancer mortality: a meta-analysis. Psychol Med. (2010) 40:1797–810. doi: 10.1017/S0033291709992285
52. Ko A, Kim K, Sik Son J, Park HY, and Park SM. Association of pre-existing depression with all-cause, cancer-related, and noncancer-related mortality among 5-year cancer survivors: a population-based cohort study. Sci Rep. (2019) 9:18334. doi: 10.1038/s41598-019-54677-y
53. Sancassiani F, Mulas O, Madeddu C, Massa E, La Nasa G, Caocci G, et al. Adherence to treatment in patients with solid and hematological cancers. Could spiritual and psychological support facilitate optimal adherence? WCRJ. (2023) 10:e2727. doi: 10.32113/wcrj_202312_2727
54. Lan A, Li H, Shen M, Li D, Shu D, Liu Y, et al. Association of depressive symptoms and sleep disturbances with survival among US adult cancer survivors. BMC Med. (2024) 22:225. doi: 10.1186/s12916-024-03451-7
55. Li Z, Yu C, Hao J, Shu Y, Li J, Zhang J, et al. Joint association of depressive symptoms and dietary patterns with mortality among US cancer survivors: a population-based study. BMC Cancer. (2025) 25:566. doi: 10.1186/s12885-025-13945-z
56. Mausbach BT, Schwab RB, and Irwin SA. Depression as a predictor of adherence to adjuvant endocrine therapy (AET) in women with breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat. (2015) 152:239–46. doi: 10.1007/s10549-015-3471-7
57. de Souza BF, de Moraes JA, Inocenti A, dos Santos MA, Silva AE, and Miasso AI. Women with breast cancer taking chemotherapy: depression symptoms and treatment adherence. Rev Lat Am Enfermagem. (2014) 22:866–73. doi: 10.1590/0104-1169.3564.2491
58. Chabrier M, Bezy O, Mouret M, Bay J, and Jalenques I. Impact of depressive disorders on adherence to oral anti-cancer treatment. Rev Bull Cancer. (2013) 100:1017–22. doi: 10.1684/bdc.2013.1824
59. Yao P, Zhong Y, and Wei Z. Association between sedentary behavior, depressive symptoms, and the risk of all-cause and cause-specific mortality among U.S. Cancer survivors BMC Cancer. (2025) 25:570. doi: 10.1186/s12885-025-13578-2
60. Jin D, Lv T, Zhang C, and Hu Y. Joint association of dietary live microbe intake and depression with cancer survivor in US adults: evidence from NHANES. BMC Cancer. (2025) 25:487. doi: 10.1186/s12885-025-13699-8
61. Duffy SA, Ronis DL, Valenstein M, Lambert MT, Fowler KE, Gregory L, et al. A tailored smoking, alcohol, and depression intervention for head and neck cancer patients. Cancer Epidemiol Biomarkers Prev. (2006) 15:2203–8. doi: 10.1158/1055-9965.EPI-05-0880
62. McCarter K, Baker AL, Britton B, Wolfenden L, Wratten C, Bauer J, et al. Smoking, drinking, and depression: comorbidity in head and neck cancer patients undergoing radiotherapy. Cancer Med. (2018) 7:2382–90. doi: 10.1002/cam4.1497
63. Trudel-Fitzgerald C, Zevon ES, Kawachi I, Tucker-Seeley RD, and Kubzansky LD. Depression, smoking, and lung cancer risk over 24 years among women. Psychol Med. (2022) 52:2510–9. doi: 10.1017/S0033291720004390
64. Hermann M, Goerling U, Hearing C, Mehnert-Theuerkauf A, Hornemann B, Hövel P, et al. Social support, depression and anxiety in cancer patient-relative dyads in early survivorship: an actor-partner interdependence modeling approach. Psychooncology. (2024) 33:e70038. doi: 10.1002/pon.70038
65. Wondimagegnehu A, Abebe W, Abraha A, and Teferra S. Depression and social support among breast cancer patients in Addis Ababa, Ethiopia. BMC Cancer. (2019). doi: 10.1186/s12885-019-6007-4
66. Marzorati C, Voskanyan V, Sala D, Grasso R, Borgogni F, Pietrobon R, et al. Psychosocial factors associated with quality of life in cancer patients undergoing treatment: an umbrella review. Health Qual Life Outcomes. (2025) 23:31. doi: 10.1186/s12955-025-02357-z
67. Spiegel D and Giese-Davis J. Depression and cancer: mechanisms and disease progression. Biol Psychiatry Biol Psychiatry. (2003) 54:269–82. doi: 10.1016/S0006-3223(03)00566-3
68. Reiche EM, Morimoto HK, and Nunes SM. Stress and depression-induced immune dysfunction: implications for the development and progression of cancer. Int Rev Psychiatry. (2005) 17:515–27. doi: 10.1080/02646830500382102
69. Sephton SE, Dhabhar FS, Keuroghlian AS, Giese-Davis J, McEwen BS, Ionan AC, et al. Depression, cortisol, and suppressed cell-mediated immunity in metastatic breast cancer. Brain Behav Immun. (2009) 23:1148–55. doi: 10.1016/j.bbi.2009.07.007
70. Sotelo JL, Musselman D, and Nemeroff C. The biology of depression in cancer and the relationship between depression and cancer progression. Int Rev Psychiatry. (2014) 26:16–30. doi: 10.3109/09540261.2013.875891
71. Bouchard LC, Antoni MH, Blomberg BB, Stagl JM, Gudenkauf LM, Jutagir DR, et al. Postsurgical depressive symptoms and proinflammatory cytokine elevations in women undergoing primary treatment for breast cancer. Psychosom Med. (2016) 78:26–37. doi: 10.1097/PSY.0000000000000261
72. Panjwani AA, Aguiar S, Gascon B, Brooks DG, and Li M. Biomarker opportunities in the treatment of cancer-related depression. Trends Mol Med. (2022) 28:1050–69. doi: 10.1016/j.molmed.2022.10.003
73. Parlindungan F, Hidayat R, Ariane A, and Shatri H. Association between proinflammatory cytokines and anxiety and depression symptoms in rheumatoid arthritis patients: A cross-sectional study. Clin Pract Epidemiol Ment Health. (2023) 19:e174501792304261. doi: 10.2174/17450179-v19-e230510-2022-34
74. Kanter NG, Cohen-Woods S, Balfour DA, Burt MG, Waterman AL, and Koczwara B. Hypothalamic-pituitary-adrenal axis dysfunction in people with cancer: A systematic review. Cancer Med. (2024) 13:e70366. doi: 10.1002/cam4.70366
75. Dong J, Du J, Liu R, Zhang Y, Wang X, Li H, et al. Depressive disorder affects TME and hormonal changes promoting tumour deterioration development. Immunology. (2025) 175:403–18. doi: 10.1111/imm.13933
76. George MY, Abdel Mageed SS, Mansour DE, and Fawzi SF. The cortisol axis and psychiatric disorders: an updated review. Pharmacol Rep. (2025) 77:1573–99. doi: 10.1007/s43440-025-00782-x
77. Saptadip S and Debasis B. An intricate relationship between circadian rhythm dysfunction and psychiatric diseases. Explor Neurosci. (2024) 3:321–51. doi: 10.37349/en.2024.00053
78. Oerlemans ME, van den Akker M, Schuurman AG, Kellen E, and Buntinx F. A meta-analysis on depression and subsequent cancer risk. Clin Pract Epidemiol Ment Health. (2007) 3:29. doi: 10.1186/1745-0179-3-29
79. Wang YH, Li J, Shi JF, Que JY, Liu JJ, Lappin JM, et al. Depression and anxiety in relation to cancer incidence and mortality: a systematic review and meta-analysis of cohort studies. Mol Psychiatry. (2020) 25:1487–99. doi: 10.1038/s41380-019-0595-x
80. Mössinger H and Kostev K. Depression is associated with an increased risk of subsequent cancer diagnosis: A retrospective cohort study with 235,404. Patients Brain Sci. (2023) 13:302. doi: 10.3390/brainsci13020302
81. Grassi L, Stivanello E, Belvederi Murri M, Cruciata M, Muscettola A, Perlangeli V, et al. Major depression and mortality from cancer: a 10-year Italian study. Eur Psychiatry. (2025) 4:1–21. doi: 10.1192/j.eurpsy.2025.10048
82. Chhatre S, Gallo JJ, Guzzo T, Morales KH, Newman DK, Vapiwala N, et al. Trajectory of depression among prostate cancer patients: A secondary analysis of a randomized controlled trial. Cancers. (2023) 15:2124. doi: 10.3390/cancers15072124
83. Fervaha G, Izard JP, Tripp DA, Aghel N, Shayegan B, Klotz L, et al. Psychological morbidity associated with prostate cancer: Rates and predictors of depression in the RADICAL PC study. Can Urol Assoc J. (2021) 15:181–6. doi: 10.5489/cuaj.6912
84. Crump C, Stattin P, Brooks JD, Sundquist J, Sieh W, and Sundquist K. Mortality risks associated with depression in men with prostate cancer. Eur Urol Oncol. (2024) 7:1411–9. doi: 10.1016/j.euo.2024.03.012
85. Yang H, Brand JS, Fang F, Chiesa F, Johansson AL, Hall P, et al. Time-dependent risk of depression, anxiety, and stress-related disorders in patients with invasive and in situ breast cancer. Int J Cancer. (2017) 140:841–52. doi: 10.1002/ijc.30514
86. Carreira H, Williams R, Funston G, Stanway S, and Bhaskaran K. Associations between breast cancer survivorship and adverse mental health outcomes: A matched population-based cohort study in the United Kingdom. PloS Med. (2021) 18:e1003504. doi: 10.1371/journal.pmed.1003504
87. Hopwood P and Stephens RJ. Depression in patients with lung cancer: prevalence and risk factors derived from quality-of-life data. J Clin Oncol. (2000) 18:893–903. doi: 10.1200/JCO.2000.18.4.893
88. Yan X, Chen X, and Zhang P. Prevalence and risk factors of depression in patients with lung cancer: protocol for a systematic review and meta-analysis. BMJ Open. (2019) 9:e028994. doi: 10.1136/bmjopen-2019-028994
89. Hung CI, Lee C, Huang HY, Tsai YT, Chen TJ, Liu CJ, et al. Incidence and risk factors of depression after diagnosis of lung cancer: A nationwide population-based study. Med (Baltimore). (2017) 96:e6864. doi: 10.1097/MD.0000000000006864
90. van Tuijl LA, Basten M, Pan KY, Vermeulen R, Portengen L, de Graeff A, et al. Depression, anxiety, and the risk of cancer: An individual participant data meta-analysis. Cancer. (2023) 129:3287–99. doi: 10.1002/cncr.34853
91. Grassi L, Stivanello E, Belvederi Murri M, Perlangeli V, Pandolfi P, Carnevali F, et al. Mortality from cancer in people with severe mental disorders in Emilia Romagna Region, Italy. Psychooncology. (2021) 30:2039–51. doi: 10.1002/pon.5805
92. Paksarian D, Rudolph KE, Stapp EK, Dunster GP, He J, Mennitt D, et al. Association of outdoor artificial light at night with mental disorders and sleep patterns among US adolescents. JAMA Psychiatry. (2020) 77:1266–75. doi: 10.1001/jamapsychiatry.2020
93. Tancredi S, Urbano T, and Vinceti M. Artificial light at night and risk of mental disorders: A systematic review. Sci Total Environ. (2022) 833:155185. doi: 10.1016/j.scitotenv.2022.155185
94. Menculini G, Cirimbilli F, Raspa V, Scopetta F, Cinesi G, Chieppa AG, et al. Insights into the effect of light pollution on mental health: focus on affective disorders-A narrative review. Brain Sci. (2024) 14:802. doi: 10.3390/brainsci14080802
95. Smolensky MH, Sackett-Lundeen LL, and Portaluppi F. Nocturnal light pollution and underexposure to daytime sunlight: Complementary mechanisms of circadian disruption and related diseases. Chronobiol Int. (2015) 32:1029–48. doi: 10.3109/07420528.2015.1072002
96. Chowdhury-Paulino IM, Hart JE, James P, Iyer HS, Wilt GE, Booker BD, et al. Association between outdoor light at night and prostate cancer in the health professionals follow-up study. Cancer Epidemiol Biomarkers Prev. (2023) 32:1444–50. doi: 10.1158/1055-9965.EPI-23-0208
97. Sweeney MR, Nichols HB, Jones RR, Olshan AF, Keil AP, Engel LS, et al. Light at night and the risk of breast cancer: Findings from the Sister study. Environ Int. (2022) 169:107495. doi: 10.1016/j.envint.2022.107495
98. Luo Z, Liu Z, Chen H, Liu Y, Tang N, and Li H. Light at night exposure and risk of breast cancer: a meta-analysis of observational studies. Front Public Health. (2023) 11:1276290. doi: 10.3389/fpubh.2023.1276290
99. Russart KLG and Nelson RJ. Light at night as an environmental endocrine disruptor. Physiol Behav. (2018) 190:82–9. doi: 10.1016/j.physbeh.2017.08.029
100. Hardoy MC, Serra M, Carta MG, Contu P, Pisu MG, and Biggio G. Increased neuroactive steroid concentrations in women with bipolar disorder or major depressive disorder. J Clin Psychopharmacol. (2006) 26:379–84. doi: 10.1097/01.jcp.0000229483.52955.ec
101. Ren Q, Luo F, Ge S, and Chen P. Major depression disorder may causally associate with the increased breast cancer risk: Evidence from two-sample mendelian randomization analyses. Cancer Med. (2023) 12:1984–96. doi: 10.1002/cam4.5043
102. Urbain N, Creamer K, and Debonnel G. Electrophysiological diversity of the dorsal raphe cells across the sleep-wake cycle of the rat. J Physiol. (2006) 573:679–95. doi: 10.1113/jphysiol.2006.108514
103. Kocsis B, Varga V, Dahan L, and Sik A. Serotonergic neuron diversity: identification of raphe neurons with discharges time-locked to the hippocampal theta rhythm. Proc Natl Acad Sci U S A. (2006) 103:1059–64. doi: 10.1073/pnas.0508360103
104. Shah PA, Park CJ, Shaughnessy MP, and Cowles RA. Serotonin as a mitogen in the gastrointestinal tract: revisiting a familiar molecule in a new role. Cell Mol Gastroenterol Hepatol. (2021) 12:1093–104. doi: 10.1016/j.jcmgh.2021.05.008
105. Benninghoff J, Gritti A, Rizzi M, Lamorte G, Schloesser RJ, Schmitt A, et al. Serotonin depletion hampers survival and proliferation in neurospheres derived from adult neural stem cells. Neuropsychopharmacology. (2010) 35:893–903. doi: 10.1038/npp.2009.181
106. Sarrouilhe D, Clarhaut J, Defamie N, and Mesnil M. Serotonin and cancer: what is the link? Curr Mol Med. (2015) 15:62–77. doi: 10.2174/1566524015666150114113411
107. Jayachandran P, Battaglin F, Strelez C, Lenz A, Algaze S, Soni S, et al. Breast cancer and neurotransmitters: emerging insights on mechanisms and therapeutic directions. Oncogene. (2023) 42:627–37. doi: 10.1038/s41388-022-02584-4
108. Gwynne WD, Shakeel MS, Girgis-Gabardo A, and Hassell JA. The role of serotonin in breast cancer stem cells. Molecules. (2021) 26:3171. doi: 10.3390/molecules26113171
109. Siddiqui EJ, Shabbir M, Mikhailidis DP, Thompson CS, and Mumtaz FH. The role of serotonin (5-hydroxytryptamine1A and 1B) receptors in prostate cancer cell proliferation. J Urol. (2006) 176:1648–53. doi: 10.1016/j.juro.2006.06.087
110. Yu H, Qu T, Yang J, and Dai Q. Serotonin acts through YAP to promote cell proliferation: mechanism and implication in colorectal cancer progression. Cell Commun Signal. (2023) 21:75. doi: 10.1186/s12964-023-01096-2
111. Di YZ, Han B, and Di J. Role of the brain-gut axis in gastrointestinal cancer. World J Clin Cases. (2019) 7:1554–70. doi: 10.12998/wjcc.v7.i13.1554
112. Chen L, Huang S, Wu X, He W, and Song M. Serotonin signalling in cancer: Emerging mechanisms and therapeutic opportunities. Clin Transl Med. (2024) 14:e1750. doi: 10.1002/ctm2.1750
113. Ma Y, He J, Li CY, Liu FB, Wang YG, and Song FJ. Effect of antidepressants use on cancer morbidity and mortality: A propensity score-matched longitudinal cohort study. J Affect Disord. (2025) 387:119554. doi: 10.1016/j.jad.2025.119554
114. Liu Y, Chen VC, and Lu M. The association between selective serotonin reuptake inhibitors (SSRIs) use and the risk of bladder cancer: A nationwide population-based cohort study. Cancers (Basel). (2020) 12:1184. doi: 10.3390/cancers12051184
115. Chen L, Li X, Li C, and Zou C. Antidepressant use and colorectal cancer morbidity and mortality: A dose-response meta analysis. Med (Baltimore). (2020) 99:e20185. doi: 10.1097/MD.0000000000020185
116. Busby J, Mills K, Zhang SD, Liberante FG, and Cardwell CR. Selective serotonin reuptake inhibitor use and breast cancer survival: a population-based cohort study. Breast Cancer Res. (2018) 20:4. doi: 10.1186/s13058-017-0928-0
117. Buntrock C, Harrer M, and Sprenger AA. Psychological interventions to prevent the onset of major depression in adults: a systematic review and individual participant data meta-analysis. Lancet Psychiatry. (2024) 11:990–1001. doi: 10.1016/S2215-0366(24)00316-X
118. Gariépy G, Honkaniemi H, and Quesnel-Vallée A. Social support and protection from depression: systematic review of current findings in Western countries. Br J Psychiatry. (2016) 209:284–93. doi: 10.1192/bjp.bp.115.169094
119. Breedvelt JJF, Brouwer ME, Harrer M, Semkovska M, Ebert DD, Cuijpers P, et al. Psychological interventions as an alternative and add-on to antidepressant medication to prevent depressive relapse: systematic review and meta-analysis. Br J Psychiatry. (2021) 219:538–45. doi: 10.1192/bjp.2020.198
120. Breedvelt JJF, Warren FC, and Segal Z. Continuation of antidepressants vs sequential psychological interventions to prevent relapse in depression: an individual participant data meta-analysis. JAMA Psychiatry. (2021) 78:868–75. doi: 10.1001/jamapsychiatry.2021.0823
121. Ng CG, Mohamed S, and See MH. Anxiety, depression, perceived social support and quality of life in Malaysian breast cancer patients: a 1-year prospective study. Health Qual Life Outcomes. (2015) 13:205. doi: 10.1186/s12955-015-0401-7
122. Naseri N and Taleghani F. Social support and depression in Iranian cancer patients: the role of demographic variables. J Caring Sci. (2018) 7:143–7. doi: 10.15171/jcs.2018.023
123. Zamanian H, Amini-Tehrani M, and Jalali Z. Perceived social support, coping strategies, anxiety and depression among women with breast cancer: evaluation of a mediation model. Eur J Oncol Nurs. (2021) 50:101892. doi: 10.1016/j.ejon.2020.101892
124. An E, Wennberg E, and Nissim R. Death talk and relief of death-related distress in patients with advanced cancer. BMJ Support Palliat Care. (2020) 10:e19. doi: 10.1136/bmjspcare-2016-001277
125. Haaksman M, Ham L, Brom L, Baars A, van Basten JP, van den Borne BEEM, et al. Open communication between patients and relatives about illness & death in advanced cancer-results of the eQuiPe Study. Support Care Cancer. (2024) 32:214. doi: 10.1007/s00520-024-08379-5
126. Ariès P. Western Attitudes toward Death: From the Middle Ages to the Present. Baltimore: Johns Hopkins University Press (1974).
127. Foucault M. The Birth of Biopolitics: Lectures at the Collège de France 1978–79. New York: Palgrave Macmillan (2008).
128. Bauman Z. Mortality, Immortality and Other Life Strategies. Stanford: Stanford University Press (1992).
131. Al-Ghazālī. The Remembrance of Death and the Afterlife. Cambridge: Islamic Texts Society (1989).
135. Carta MG, Kovess V, Aissa A, Larnaout A, Zgueb Y, Alnasser LA, et al. Depression during the COVID pandemic in La Manouba Governorate, Tunisia: A community survey. Int J Soc Psychiatry. (2024) 70:1128–37. doi: 10.1177/00207640241264678
136. Osborn RL, Demoncada AC, and Feuerstein M. Psychosocial interventions for depression, anxiety, and quality of life in cancer survivors: meta-analyses. Int J Psychiatry Med. (2006) 36:13–34. doi: 10.2190/EUFN-RV1K-Y3TR-FK0L
137. Faller H, Schuler M, Richard M, Heckl U, Weis J, and Küffner R. Effects of psycho-oncologic interventions on emotional distress and quality of life in adult patients with cancer: systematic review and meta-analysis. J Clin Oncol. (2013) 31:782–93. doi: 10.1200/JCO.2011.40.8922
138. Zainal NZ, Booth S, and Huppert FA. The efficacy of mindfulness-based stress reduction on mental health of breast cancer patients: a meta-analysis. Psychooncology. (2013) 22:1457–65. doi: 10.1002/pon.3171
139. Yin P, Liu L, Gao N, Huai Y, Dong Y, Jin Q, et al. Non-pharmaceutical interventions for depressive symptoms in patients with breast cancer: protocol for a systematic review and network meta-analysis. BMJ Open. (2024) 14:e081281. doi: 10.1136/bmjopen-2023-081281
140. Carta MG, Tondo L, Balestrieri M, Caraci F, Dell'osso L, Di Sciascio G, et al. Sub-threshold depression and antidepressants use in a community sample: searching anxiety and finding bipolar disorder. BMC Psychiatry. (2011) 11:164. doi: 10.1186/1471-244X-11-164
141. Mitchell AJ, Chan M, Bhatti H, Halton M, Grassi L, Johansen C, et al. Prevalence of depression, anxiety, and adjustment disorder in oncological, haematological, and palliative-care settings: a meta-analysis of 94 interview-based studies. Lancet Oncol. (2011) 12:160–74. doi: 10.1016/S1470-2045(11)70002-X
Keywords: cancer, depressive disorders, mental pain, precision medicine, spirituality
Citation: Carta MG and Nardi AE (2026) Psychosomatics at the threshold: cancer, mood disorders, and the mental pain of death — where precision medicine meets spirituality. Front. Psychiatry 17:1751310. doi: 10.3389/fpsyt.2026.1751310
Received: 21 November 2025; Accepted: 26 January 2026;
Published: 10 February 2026.
Edited by:
Serdar M. Dursun, University of Alberta, CanadaReviewed by:
Digdem Goverti, Kocaeli University Faculty of Medicine, TürkiyeCopyright © 2026 Carta and Nardi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Mauro Giovanni Carta, bWF1cm9nY2FydGFAZ21haWwuY29t