There are still pockets in the world where an attempted suicide is considered a crime. Picture this: a gentleman, carrying an unspeakable burden, attempts to end his life. He is then found alive; his physicians confirm that he is relatively well, and he is discharged. Before he even has time to gather his thoughts, he is being charged in court for the crime of attempted suicide. 

Such is the state of affairs with issues relating to mental health in many southeast Asian parts of the world. Attitudes are modernizing but are still slow to change; many people still think of anxiety and depression as “cop-outs,” an “abdication of responsibility,” and a selfish act. 

However, in Malaysia, where I reside, there was an outbreak of poverty during the worst of the COVID-19 pandemic. Social media users encouraged those without basic food supplies to raise a white flag in front of their homes as a means to ask for help, albeit indirectly. This season of profound turmoil in the country has put mental health in the forefront of many minds, and people are beginning to see that negative events (and not just a negative disposition) can trigger a breakdown in mental health. 

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“Anxiety, depression, and stress are identifiable emotional states in the face of the COVID-19 epidemic and they are found in almost half of our population, in different degrees of severity,” Pérez-Cano and colleagues wrote in Cirugía y Cirujanos. 

Understanding the Patient Experience in CAD

Scientists are increasingly recognizing the heavy mental health toll incurred the moment a diagnosis of a rare and chronic disease is made. In almost every study on the impact that rare disease has on health-related quality of life, researchers have found that the scale of its impact on psychological well-being is more widespread, and indeed more nuanced, than previously expected. 

This is illustrated by a study carried out by Broome and colleagues on the mental health impact on patients newly diagnosed with cold agglutinin disease (CAD). This study, published in PLoS ONE, sought to investigate the prevalence of anxiety and/or depression among those diagnosed with CAD. 

Studies indicate that patients with anemia are more likely to develop anxiety/depression, but there has not been any studies looking specifically into CAD, a subtype of anemia. Broome and her coauthors sought to identify the risk of medically attended anxiety and depression in individuals with CAD. 

Recruited participants must have had CAD as defined by the International Classification of Diseases (ICD) and been free from any history of anxiety and depression. To verify these diagnoses, the research team reviewed clinical notes of the attending physicians. Eight hundred fourteen recruited participants with CAD were matched with up to 10 comparison patients from the general population. 

Read more about CAD etiology 

The outcomes of anxiety and depression were broadly defined. Patients were said to have anxiety and/or depression if they received a diagnosis during the course of their disease according to ICD classifications. In addition, patients may have been on medication therapy or mention that they are on medication therapy; all these were taken into account.  

“CAD patients were at increased risk of medically attended anxiety and depression including outcomes of medication or therapy,” the authors of the study reported. “CAD patients were 1.7 times more likely to use prescription medications for anxiety and depression than comparisons.” 

Mental Health and Rare Disease

It is clear that mental health is an area of deep concern for patients struggling with a rare and chronic illness. In addition, Broome and colleagues opined that the relationship between mental and physical health is bidirectional, meaning that the emergence of mental illness can increase morbidity and mortality and drive up the overall cost of the illness. From a public health standpoint, this means increased healthcare resource utilization. 

There are theories suggesting that certain mechanisms of disease activity trigger pathways that make a patient vulnerable to anxiety or depression. For example, a study on hematological diseases mediated by the classical complement pathway found a high level of anxiety among the patient population studied. Could there be unexplored pathways that trigger the activation of stress and/or mental illness? 

”The exact role that complement activation plays in anxiety and depression is unknown,” the authors of the study wrote. “The potential mechanisms responsible for the concurrent anxiety and depression with chronic diseases are complex and multifaceted, and may involve an interplay of genetic, biological, psychosocial, and behavioral factors.” 

Read more about CAD treatment 

Indeed, this is a clarion call for further exploration into whether the mechanisms of disease activity play a role in triggering certain pathways that can eventually lead to mental disease. In the meantime, physicians would be wise to assume that the patients they see suffer from some form of psychological setback the moment they receive the diagnosis of a rare and chronic disease. 

The modern version of the Hippocratic Oath contains a poignant line about the awesome role of a physician; may it describe our posture today and always: 

“I will remember that I do not treat a fever chart, a cancerous growth, but a sick human being, whose illness may affect the person’s family and economic stability.”


Pérez-Cano HJ, Moreno-Murguía MB, Morales-López O, et al. Anxiety, depression, and stress in response to the coronavirus disease-19 pandemicCir Cir. 2020;88(5):562-568. doi:10.24875/CIRU.20000561

Broome CM, Hooda N, Su J, et al. Medically-attended anxiety and depression is increased among newly diagnosed patients with cold agglutinin disease: analysis of an integrated claim-clinical cohort in the United StatesPLoS One. 2022;17(12):e0276617. doi:10.1371/journal.pone.0276617