Asthma, Suicide Risk, and Psychiatric Comorbidity

In this month's issue, Kuo and colleagues (1) report that a current history of asthma and a greater number of respiratory symptoms were associated with a greater than twofold increase in subsequent suicide in a population-based study of over 160,000 high school students in Taiwan followed up in young adulthood. Asthma prevalence in young people has been increasing in the United States, with up to 10% of adolescents affected. Asthma is the sixth leading cause of death in children 5–14 years of age in the United States, and suicide is the third leading cause of death in adolescents. The study by Kuo et al. is the first to link asthma with completed suicide in young people. A previous large U.S. study of 5,692 adults showed a significant association between asthma and suicide ideation with (but not without) suicide attempts (2). This relationship was partially mediated by socioeconomic factors, health risk behaviors, and DSM-IV diagnoses of depression, alcohol abuse, and panic disorder.

A limitation of the study by Kuo et al. is the lack of measurement of depression or anxiety, at baseline or over time. The authors attempted to address this limitation with a sensitivity analysis that used prior data on the prevalence of comorbid depression in patients with asthma to estimate how baseline depression might influence estimates of the association of asthma and suicide. Although this analysis continued to show a significant association of asthma and suicide, measurement of depression at only one time point and lack of measurement of anxiety were still likely to result in underestimating the effect of comorbid psychiatric illness. However, there are several ways that asthma itself as well as comorbid anxiety and depression may increase the risk of subsequent suicide.

Asthma may interfere with normal development in youths by limiting participation and mastery in social and physical activities as well as by affecting self-esteem because of feeling different from other youths. Youths with asthma, atopic dermatitis, and allergic rhinitis also have two to five times the incidence of short stature, skeletal retardation, and delayed puberty compared with others, which also may affect childhood relationships and self-esteem. Parental overprotection because of concerns of the youth's vulnerability to asthmatic episodes may adversely affect normal development and lead to family conflict in adolescence. The high prevalence of psychiatric comorbidity in people with asthma may also adversely affect normal development.

Initial small case-control studies in the United States described an elevated prevalence of panic disorder in youths and adults with asthma. Subsequent larger population-based studies found an elevated prevalence of most DSM-IV depressive and anxiety disorders in youths and adults with asthma relative to comparison subjects (3). For instance, a large population-based study of 1,300 adolescents enrolled in a large health maintenance organization found that the prevalence of meeting criteria for one or more DSM-IV depressive and anxiety disorders was twice as high in youths with asthma relative to comparison subjects (16.3% versus 8.6%) after controlling for socioeconomic status, other medical comorbidity, and health risk behaviors (3). Recent population-based longitudinal studies that have examined the chronology of the development of asthma and psychiatric disorders have reported the relationships to be bidirectional: early development of respiratory symptoms and asthma is associated with a greater risk of depressive and anxiety disorders (4), and early development of psychiatric disorders is associated with a greater subsequent risk of asthma (5).

Several hypotheses have been proposed to explain the link between asthma and depressive and anxiety disorders. A cognitive explanation posits that longitudinal experience with respiratory diseases such as asthma may generate fearful or catastrophic beliefs about respiratory symptoms, which might in turn provoke separation anxiety and panic attacks in youths (6). Evidence that only asthmatic patients with high scores on a measure of the tendency to respond with fear to bodily sensations were likely to meet criteria for panic disorder is consistent with this theory (6). Asthma can be associated with near-death episodes, need for ventilation support, and other illness experiences, which could certainly influence the development of these frightening cognitions and anxiety disorders.

Biologic theories posit that repetitive experiences with hypoxia and hypercapnia may also sensitize neural circuits that control fear responses, such as neurons in the amygdala and locus ceruleus, to overreact to either subsequent episodes of hypoxia and hypercapnia due to asthma or to fearful perceptions of conditioned stimuli such as the sensation of breathlessness. Alternatively, both asthma and depressive and anxiety disorders may result from a shared genetic (e.g., instability of the autonomic nervous system) or environmental diatheses (e.g., chronic exposure to secondhand cigarette smoke or an abusive early environment). One recent large epidemiologic study found that early adversity and development of a depressive or anxiety disorder before age 21 independently increased the risk of developing asthma in adulthood (5). Other studies have found that high maternal anxiety levels in pregnancy and persistent maternal distress from birth to age 7 were associated with a significantly higher risk of asthma in children.

Physiologic studies of children with asthma and healthy comparison subjects have suggested that experimental stress modestly increases airway resistance in both case and control subjects. However, children with asthma begin with higher intrinsic airway resistance, so increases in resistance result in a higher absolute level of compromise relative to healthy comparison subjects. Studies have also shown that depression and psychological distress can dysregulate neuroimmunologic processes, which may worsen asthma control. The greater reactivity to life stressors often seen in patients with depressive and anxiety disorders may be associated with more frequent perturbations in airway resistance with common stressors, which may in turn stimulate neural circuits associated with fear responses.

The high level of comorbidity with depressive and anxiety disorders experienced by youths and adults with asthma may also markedly affect asthma symptom burden, functioning, and health risk behaviors. After controlling for socioeconomic status, asthma severity, and other medical comorbidities, recent studies showed that compared to youths with asthma alone, those with asthma and one or more comorbid depressive and anxiety disorders had a significantly higher number of asthma symptoms (7), had additive functional impairment in social, educational, and familial activities (8), and were more likely to be smokers (9). The increased prevalence of smoking is especially worrisome because smoking is a major risk factor in asthma medication failure and could contribute to greater asthma symptom burden and asthma-related physical impairment seen in youths with asthma and comorbid depressive and anxiety disorders.

One-year ambulatory medical costs have been found to be approximately 50% greater in youths with comorbid depression and asthma compared to those with asthma alone after controlling for socioeconomic factors, severity of asthma, and health risk behaviors. Despite the high comorbidity of depressive and anxiety disorders in youths with asthma and high medical utilization, less than half of youths with asthma and comorbid depressive and anxiety disorders have been found to have their mental health disorders accurately diagnosed by medical systems of care, and less than one-quarter received an evidence-based psychological or pharmacologic treatment (10). There is a public health need to enhance accurate diagnosis of mental health disorders in youths with asthma and other chronic medical conditions and to develop health services models to improve exposure to evidence-based treatments. In adults, collaborative care models have been shown to enhance depression quality of care and depression outcomes of patients with diabetes and heart disease, but thus far, limited research has been conducted with youths. The findings by Kuo et al. linking asthma to subsequent risk of suicide highlights the need for such research.