Letter to the Editor Open Access
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Feb 19, 2025; 15(2): 99299
Published online Feb 19, 2025. doi: 10.5498/wjp.v15.i2.99299
Improving the outcome in leukemia patients by controlling subthreshold depression and cancer-related fatigue
Fa-Yang Xiang, Xin-Ke Li, College of Medical Informatics, Chongqing Medical University, Chongqing 400016, China
ORCID number: Xin-Ke Li (0000-0002-8777-744X).
Author contributions: Xiang FY designed the overall concept and outline of the manuscript, and wrote the first draft; Li XK wrote and edited the manuscript and reviewed the literature; all authors reviewed and approved the final version of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xin-Ke Li, PhD, Associate Professor, Postdoc, College of Medical Informatics, Chongqing Medical University, No. 1 Medical School Road, Chongqing 400016, China. lixinke@cqmu.edu.cn
Received: July 19, 2024
Revised: November 29, 2024
Accepted: December 13, 2024
Published online: February 19, 2025
Processing time: 179 Days and 4.6 Hours

Abstract

Patients with leukemia often suffer from the combined effects of cancer-related fatigue (CRF) and subthreshold depression, which mutually exacerbate each other in a vicious cycle. In this editorial, we comment on the article by Liu et al, published in the World Journal of Psychiatry. We further elucidate the profound impact of subthreshold depressive symptoms on the experience of CRF and complications in patients with leukemia. This editorial highlights the importance of early identification and treatment of subclinical depression, and advocates for a multidisciplinary and integrated treatment approach that includes social support, psychological interventions, and individualized treatment plans. Future research needs to explore the biological mechanisms underlying the interaction between the two to develop more effective prevention and treatment strategies.

Key Words: Subthreshold depression; Leukemia; Cancer-related fatigue; Early intervention

Core Tip: This editorial focuses on the relationship and impact of leukemia, subthreshold depression, and cancer-related fatigue (CRF), and provides insights for subsequent clinical care and individualized interventions for patients with leukemia. In addition, it offers reflections on the direction of research in subthreshold depression and CRF.



TO THE EDITOR

Leukemia is a malignant hematologic disorder marked by the abnormal proliferation of blood cells, significantly affecting patients both physically and psychologically. Advances in cancer treatment have markedly improved survival rates; however, these therapies also introduce various side effects and adverse reactions. Cancer-related fatigue (CRF) is one of the most prevalent and debilitating consequences of anticancer treatment. It is characterized by persistent exhaustion, weakness, and a lack of energy, which are unrelieved by rest or sleep[1]. CRF often serves as an early indicator of malignancy, with up to 40% of patients reporting fatigue at diagnosis. Additionally, it affects up to 90% of patients undergoing radiotherapy and 80% undergoing chemotherapy[2]. This fatigue is not solely attributable to cancer but is frequently exacerbated by concurrent psychological conditions, such as subthreshold depression.

Subthreshold depression, or minor depression, is frequently underdiagnosed and undertreated due to its subtle symptomatology[3]. Although less severe than major depression, subthreshold depression has the potential to progress into a full-blown depressive disorder if left unaddressed, highlighting the importance of early intervention[4]. Investigating the interplay between subthreshold depressive symptoms and CRF in leukemia patients is essential for developing holistic treatment strategies that address both the physical and psychological dimensions of cancer care.

Interaction between CRF and subclinical depression

CRF is a multifaceted phenomenon that impairs patients' physical, emotional, and cognitive functioning. Epidemiological studies reveal that subthreshold depression affects between 5% and 24% of the general population, a prevalence higher than that of major depression[5]. Leukemia patients with co-occurring subthreshold depression report more severe fatigue, which compromises their ability to perform daily activities and adhere to treatment regimens. Several factors have been identified as risk factors for CRF, including advanced age, concurrent radiation therapy, pain, and low hemoglobin levels[6]. Additionally, depression is associated with alterations in autonomic nervous system function and neurotransmitter dysregulation, leading to reduced levels of key neurotransmitters such as dopamine and serotonin. Furthermore, cancer-related cytokines and inflammatory stimuli contribute to changes in basal ganglia neural activity and elevate levels of inflammatory mediators, including IL-6 and TNF-α, which are implicated in the pathophysiology of fatigue[7].

The interplay between subthreshold depression and fatigue often creates a vicious cycle, where depressive symptoms exacerbate fatigue, and the resultant fatigue further intensifies depressive symptoms. This cycle is difficult to disrupt without targeted intervention. While evidence suggests a strong link between mental health and cancer, the potential impact of effectively treating depression on leukemia outcomes remains unclear. Additionally, chronic inflammation and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis are common pathophysiological features across several conditions, including depression, leukemia, and cardiovascular dysfunction[8]. For example, excessive cortisol secretion due to HPA axis dysfunction can exacerbate metabolic imbalances and mitochondrial damage, thereby worsening fatigue and psychological distress.

Leukemia patients often experience a range of complications during treatment, including infections, anemia, neurological impairments, and cardiovascular issues such as heart failure[9]. Fatigue is a common symptom of heart failure, resulting from reduced cerebral perfusion and an imbalance between oxygen supply and demand, which impairs brain function[10]. Inadequate oxygen delivery further disrupts mitochondrial function, exacerbating physical and psychological fatigue. Additionally, heart failure is frequently associated with anemia, leading to low hemoglobin levels, which are recognized as a significant risk factor for CRF[6]. This suggests that heart failure may not only act as a secondary complication in leukemia-related CRF but may also independently contribute to its progression. Furthermore, chemotherapy-induced inflammation and neuroendocrine responses may intensify this cycle, promoting a feedback loop where CRF and depressive symptoms become increasingly intertwined. Such a complex interplay underscores the need for a comprehensive, multidisciplinary approach to manage both the underlying conditions and their associated symptoms effectively.

Clinical nursing and personalization of interventions for patients with leukemia

Given the high prevalence of CRF in leukemia patients with comorbid subthreshold depression, traditional models of care are insufficient to meet their complex treatment needs. Exploring social support networks, encompassing medical care, psychological support, and involvement from family, friends, and support groups, is essential to mitigating the psychological burden of cancer[11]. Technological innovations, including virtual reality and mobile health applications, offer promising avenues for delivering psychological interventions and monitoring patient progress[12]. For leukemia patients with subthreshold depression, regular physical exercise has been shown to enhance physical health, regulate mood through neurotransmitter release, and reduce fatigue[13]. In addition to exercise, complementary approaches such as cognitive behavioral therapy and pharmacological treatments can be integrated to address the multifaceted nature of the patient's condition.

In addition to leukemia, depression is also a common comorbidity in various other cancers. Given the high prevalence of CRF and subthreshold depression among cancer patients, the treatment strategies outlined in this paper may apply to other malignancies. Depression significantly intensifies both the physical and emotional burden of cancer, irrespective of the specific malignancy. Therefore, early identification and intervention of depressive symptoms—through multidisciplinary care and personalized treatment approaches—can improve both psychological well-being and physical outcomes, not only in leukemia but also in patients with other cancers. Further research is necessary to refine these strategies, tailoring them to the distinct needs of different cancer populations, with attention to factors such as cancer type, treatment regimens, and individual patient characteristics.

Further research

Future research should explore the biological mechanisms underlying the interaction between subthreshold depression and CRF. Investigating the roles of inflammatory markers, neuroendocrine alterations, and genetic factors could provide valuable insights into this interplay and identify potential therapeutic targets. Incorporating routine psychological assessments into cancer care could facilitate the early detection of depressive symptoms, potentially alleviating CRF and improving patient outcomes. Longitudinal studies are essential to assess the long-term effects of early psychological and physical interventions on CRF and overall survival in leukemia patients. Such studies would provide crucial data to refine best practices in long-term patient management. Moreover, understanding the mechanisms behind common adverse effects of leukemia therapies is critical for developing targeted preventive and therapeutic strategies.

CONCLUSION

Subthreshold depression imposes a significant burden on leukemia patients. Effective treatment of leukemia should extend beyond addressing the disease itself to include the patient’s mental health. Early, individualized interventions are essential to prevent and alleviate CRF, improving both psychological well-being and overall outcomes.

Footnotes

Provenance and peer review: Invited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Psychiatry

Country of origin: China

Peer-review report’s classification

Scientific Quality: Grade C, Grade C

Novelty: Grade B, Grade B

Creativity or Innovation: Grade B, Grade B

Scientific Significance: Grade B, Grade B

P-Reviewer: Ajmal M; Tudoran C S-Editor: Liu H L-Editor: Wang TQ P-Editor: Yu HG

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