Where Psyche Meets Soma in Asthma

January 1, 2002

Asthma is a serious health condition that can be exacerbated by emotional triggers. Furthermore, depression in these patients can affect treatment compliance, thus worsening prognosis. What role does psychiatry play in treating these patients?

Nemo Psychologus Nisi Physiologus -- Johannes Mueller

Recognition of the relationship between psyche and soma dates back to antiquity and is captured in written records and historical accounts. Galen, in the first century CE, was reported to have written that the condition of intermittent obstruction of breathing (now called asthma) was secondary to secretions dripping into the lung from the brain. This was arguably among the earliest accounts of the important link between mind and body in medical illness. Indeed, asthma is considered by many to be the prototype of psychosomatic illness. Maimonides, circa 1190 CE, wrote in his Book of Asthma:

When in mental anguish, fear, mourning or distress...his agitation affects the respiratory organs and he can not exercise them at will...The cure of such conditions lies not in food recipes, neither in drugs alone, nor in regular medical advice...psychological methods are a greater help.

Current literature documents negative effects of stress and emotion on asthma. However, there is controversy as to whether emotions and stress adversely influence asthma directly or by exacerbating poor treatment adherence. The purpose of this article is to elaborate pathways of connection between psyche and soma in asthma, placing emphasis on empirical support and rationale for psychophysiologic mechanisms underlying the impact of stress and emotions on asthma.

Definition and Pathogenesis

The National Heart, Lung, and Blood Institute (NHLBI) defines asthma as a chronic inflammatory disorder of the airways, in which bronchial hyper-reactivity causes recurrent episodes of wheezing, breathlessness, chest tightness and cough associated with airflow obstruction that is reversible (NHLBI, 1997). The pathogenesis underlying asthma is best understood as a genetically predetermined vulnerability of the airway to a complex set of interactions involving inflammatory mediators (cytokines and chemokines), effector cells (e.g., eosinophils, T cells) and the (autonomic) nervous system (Middleton et al., 1998). Pharmacologic treatment of asthma is directed both at anti-inflammatory (immune/allergic) and bronchodilator (neural) pathways.

Many diverse stimuli can trigger asthma symptoms including allergens, infections, exercise, cold air and emotions. More than one stimulus may trigger an asthma attack, and it is often difficult to identify with certainty the specific stimuli that triggered symptoms (NHLBI, 1997). An individual's susceptibility to asthma triggers may change in the course of maturation or in response to life circumstances.

Asthma is known to have a strong genetic predisposition. Children with one asthmatic parent have approximately a 20% chance of developing the disease, while those with two asthmatic parents have nearly a 50% risk. Risk factors for the phenotypic expression of asthma in children with genetic loading include early exposure to viral infections, highly allergenic substances and emotional stress in the family (Mrazek et al., 1991).

Morbidity and Mortality

Asthma is one of the most common chronic diseases of childhood, affecting 4.8 million children in the United States (NHLBI, 1997). Among children with chronic medical conditions, asthma is the most common cause for hospitalization and school absence (Newacheck and Halfon, 2000). Asthma is more prevalent in adolescent males than females and in African American children than Caucasians. Asthma prevalence, morbidity and mortality have been increasing over the past two decades, despite new effective medical regimens (Weitzman et al., 1992).

The reasons for these increases are unclear. However, increased exposure to emotional stress in the environment must be considered among other causes (Wright and Steinbach, 2001).

Although asthma mortality in children rarely occurs, it is nonetheless a problem of serious concern. Depressive emotions and family turmoil play heavily into the risk pool for death from asthma. In a case-controlled, retrospective study of children who died from asthma, we found that feelings of depression, hopelessness and despair; poor family functioning; and heightened sensitivity to separation and loss characterized children who died as compared to those who survived a life-threatening asthma attack (Miller and Strunk, 1989).

It is also likely that poor treatment adherence is a factor affecting asthma morbidity and mortality (Strunk et al., 1985). Adherence comprises at least three major components: 1) medication management; 2) avoidance of substances or situations known to trigger exacerbations; and 3) maintenance of good physical health, e.g., diet and exercise. Despite the clear association between poor adherence and poor asthma health, the relationship is imperfect, indicating that other factors also must be taken into account. We found that poor emotional functioning of asthmatic patients and families and childhood depression are associated with poor medical adherence (B.D.M., unpublished data). This finding is particularly worrisome given a meta-analytic review of 60 studies showing that children with asthma were at greater risk for developing depressive symptoms, even as compared to children with other chronic illnesses such as cancer, cystic fibrosis and diabetes mellitus (Bennett, 1994).

Depression and Asthma

There is evidence from animal and human studies indicating that emotional states of depression and hopelessness produce a physiological state that would foster airway constriction in asthma. Reite and colleagues (1978) monitored heart rate (HR), respiration and basal body temperature (BBT) using biotelemetry implants in infant primates who were separated from their mothers. Initially, the infants showed marked behavioral arousal, searching and protest behavior, which was accompanied by marked increase in HR and BBT, i.e., a sympathetic nervous system outpouring. On the third day, these animals exhibited behavioral changes including postural collapse, withdrawal and sad facies -- all signs of depression, hopelessness and despair. Accompanying physiologic changes included deceleration in HR, increase in HR variability, fall in BBT and irregular respirations, marking an autonomic shift to parasympathetic/vagal influence on the cardio-respiratory system. Research on human infants has replicated the primate findings (Izard, 1991; McCabe and Schneiderman, 1985).

The link between depression and airway function is supported by the findings of Sugihara et al. (1965) and Meares et al. (1971) who found a positive effect of amitriptyline (Elavil) on lung function in patients with chronic asthma. Furthermore, Avni and Bruderman (1969) found that intravenous infusion of amitriptyline produced bronchodilation and inhibition of bronchoconstriction in intact anesthetized dogs.

Calling upon my clinical experience in treating children with asthma and building on these and other human and animal research findings, I put forward the Autonomic Nervous System (ANS) Dysregulation Model of Emotional Influence on Asthma, which proposes that depressed, despairing or hopeless emotional states are associated with ANS dysregulation such that a cholinergic (parasympathetic nervous system [PNS]/vagal) bias potentiates cholinergically (PNS/vagal) mediated airway constriction, thus giving rise to a psychophysiologically vulnerable asthmatic state (Miller, 1987).

Recent discoveries on the interaction of the autonomic nervous, endocrine and immune systems provide a compelling argument for a mediating role of the hypothalamic-pituitary-adrenal (HPA) axis in neuro-immune pathways by which emotions influence asthma. Depression also has been implicated in alterations in immune function (Herbert and Cohen, 1993). Gold et al. (1995) have identified specific depressive conditions in which the HPA axis is hyporeactive, thus causing hypofunction of the hypothalamic corticotropin-releasing hormone neurons, which, in failing to modulate the immune inflammatory process, could give rise to increased inflammatory manifestations (Sternberg et al., 1989). In another avenue of research, Buske-Kirschbaum et al. (1997) found that children known to suffer from atopic dermatitis or from asthma have blunted HPA response to laboratory-induced stress. These researchers propose that the children's lower HPA function may make them susceptible to allergies by rendering their inflammatory response system disinhibited.

Taken together, the depression research and these HPA atopic findings suggest the potential for hopelessness/depression to be pathogenic in the allergic/inflammatory mechanisms' underlying airway compromise in asthma. Based on these findings and rationale, the ANS model has been recently expanded to include a depression-HPA-immune pathway (Figure).

Empirical Support

We began testing the ANS model using a laboratory-based, experimental paradigm that was designed to evoke psychophysiologic responses in children with asthma (Miller and Wood, 1994). Twenty-four children with moderate to severe asthma had their heart rate, respiration and oxygen saturation (pulmonary function) continuously monitored while watching a videotape of the movie E.T. The Extra-Terrestrial. Four movie scenes were targeted for analysis: the opening credits (emotionally neutral), an E.T. death scene (sad/hopeless), a scene where E.T. revives (happy/excited) and a separation/reunion scene where E.T. goes home (mixed sad/happy). Increased heart rate variability was found to be associated with increased emotional reactivity, decreased FEV1 (forced expiratory volume in one second) following the movie and increased airway reactivity to methacholine. Further findings demonstrated that, in the context of this movie, the sad/hopeless scene was associated with greater heart rate variability (an index of vagal activation) and pulmonary instability as compared to happy and neutral scenes, with intermediate results for the mixed happy/sad scene (Miller and Wood, 1997, 1994). These findings are in support of a cholinergic/vagal mechanism mediating the impact of emotions on airway function.

In a follow-up laboratory study of 22 children with asthma (ages 8 to 16; 11 male), we found that the child's triangulation in parent conflict, insecure parent-child relatedness and self-report of hopelessness all were associated with heightened vagal activation (Wood et al., 2000).

Current studies underway in our laboratory are exploring the emotion-HPA-immune pathway of the ANS model, along with emotion-ANS pathways.

Clinical Considerations

The proposed model of psychophysiologic mechanisms and supporting empirical evidence suggest certain conclusions regarding the clinical approach to psychiatric and psychosocial management of asthma in children. Identification of children with asthma at greatest risk for morbidity and mortality is essential. We know that emotional states of hopelessness and despair, depression, chronic or intense emotional stress, separation and loss, and poor family functioning are all psychosocial risk factors in childhood asthma. These risk factors can be elicited by careful history taking, and family members and primary care providers can be alerted to be on the lookout for them as well.

Once such a child has been identified, intervention should be focused in the relevant areas of risk (Miller and Wood, 1991). Individual and family psychotherapy may be helpful in reducing stress or treating depression. Antidepressant medications may be helpful in conjunction with psychologic therapies (Miller and Wood, 1995). Although concern has been raised about the use of tricyclic antidepressants along with other medicines used to treat asthma (Wamboldt et al., 1997), I find that TCAs may have an added benefit because of their direct anticholinergic effects. However, side effects need to be carefully monitored. The selective serotonin reuptake inhibitors also may be used to treat depression and anxiety. Heavily sedating medications, however, may augment vagal effects and thereby compromise airway function and should be used with extreme caution, if at all, in treating psychiatric symptoms in asthma.

The most important consideration in treating a child or adult with asthma is to be cognizant of stressful life events and situations, quality of family relationships, and emotional status of the individual patient. In treating such patients, it is important to be prepared to coordinate biologic, psychologic and family intervention when indicated and to collaborate knowledgeably and respectfully with the treating physician.

References:

References


1.

Avni J, Bruderman I (1969), The effect of amitriptyline on pulmonary ventilation and the mechanics of breathing. Psychopharmacologia 14(3):184-192.

2.

Bennett DS (1994), Depression among children with chronic medical problems: a meta-analysis. J Pediatr Psychol 19(2):149-169.

3.

Buske-Kirschbaum A, Jobst S, Psych D et al. (1997), Attenuated free cortisol response to psychosocial stress in children with atopic dermatitis. Psychosom Med 59(4):419-426.

4.

Gold PW, Licinio J, Wong ML, Chrousos GP (1995), Corticotropin releasing hormone in the pathophysiology of melancholic and atypical depression and in the mechanism of action of antidepressant drugs. Ann N Y Acad Sci 771:716-729.

5.

Herbert TB, Cohen S (1993), Depression and immunity: a meta-analytic review. Psychol Bull 113(3):472-486.

6.

Izard CE (1991), The Psychology of Emotions. New York: Plenum Press.

7.

McCabe PM, Schneiderman N (1985), Psychophysiological reactions to stress. In: Behavioral Medicine: The Biopsychosocial Approach, Schneiderman N, Tapp JT, eds. Hillsdale, N.J.: Lawrence Erlbaum Associates.

8.

Meares RA, Mills JE, Horvath TB et al. (1971), Amitriptyline and asthma. Med J Aust 2(1):25-28.

9.

Middleton E Jr, Reed CE, Ellis EF et al., eds. (1998), Allergy: Principles and Practice, 5th ed. St. Louis: Mosby.

10.

Miller BD (1987), Depression and asthma: a potentially lethal mixture. J Allergy Clin Immunol 80(3 pt 2):481-486.

11.

Miller BD, Strunk RC (1989), Circumstances surrounding the deaths of children due to asthma. A case-control study. Am J Dis Child 143(11):1294-1299 [see comment].

12.

Miller BD, Wood BL (1991), Childhood asthma in interaction with family, school, and peer systems: a developmental model for primary care. J Asthma 28(6):405-414 [see comment pp401-403].

13.

Miller BD, Wood BL (1994), Psychophysiologic reactivity in asthmatic children: a cholinergically mediated confluence of pathways. J Am Acad Child Adolesc Psychiatry 33(9):1236-1245.

14.

Miller BD, Wood BL (1995), "Psychophysiologic reactivity" in asthmatic children: a new perspective on emotionally triggered asthma. Pediatric Asthma Allergy and Immunology 9:133-142.

15.

Miller BD, Wood BL (1997), Influence of specific emotional states on autonomic reactivity and pulmonary function in asthmatic children. J Am Acad Child Adolesc Psychiatry 36(5):669-677.

16.

Mrazek DA, Klinnert MD, Mrazek P, Macey T (1991), Early asthma onset: consideration of parenting issues. J Am Acad Child Adolesc Psychiatry 30(2):277-282.

17.

Newacheck PW, Halfon N (2000), Prevalence, impact, and trends in childhood disability due to asthma. Arch Pediatr Adolesc Med 154(3):287-293.

18.

NHLBI (1997), Expert Panel Report 2. Guidelines for the Diagnosis and Management of Asthma. NIH Publication No. 97-4051. Bethesda, Md.: National Heart, Lung, and Blood Institute.

19.

Reite M, Short R, Kaufman IC et al. (1978), Heart rate and body temperature in separated monkey infants. Biol Psychiatry 13(1):91-105.

20.

Sternberg EM, Young WS 3rd, Bernardini R et al. (1989), A central nervous system defect in biosynthesis of corticotropin-releasing hormone is associated with susceptibility to streptococcal cell wall-induced arthritis in Lewis rats. Proc Natl Acad Sci U S A 86(12):4771-4775.

21.

Strunk RC, Mrazek DA, Fuhrmann GS, LaBrecque JF (1985), Physiologic and psychological characteristics associated with deaths due to asthma in childhood. A case-controlled study. JAMA 254(9):1193-1198.

22.

Sugihara H, Ishihara K, Noguchi H (1965), Clinical experience with amitriptyline (tryptanol) in the treatment of bronchial asthma. Ann Allergy 23(9):422-429.

23.

Wamboldt MZ, Yancey AG Jr, Roesler TA (1997), Cardiovascular effects of tricyclic antidepressants in childhood asthma: a case series and review. J Child Adolesc Psychopharmacol 7(1):45-64.

24.

Weitzman M, Gortmaker SL, Sobol AM, Perrin JM (1992), Recent trends in the prevalence and severity of childhood asthma. JAMA 268(19):2673-2677 [see comment].

25.

Wood BL, Klebba KB, Miller BD (2000), Evolving the biobehavioral family model: the fit of attachment. Fam Process 39(3):319-344.

26.

Wright RJ, Steinbach SF (2001), Violence: an unrecognized environmental exposure that may contribute to greater asthma morbidity in high risk inner-city populations. Environ Health Perspect 109(10):1085-1089.