Psychosomatics 40:5-17, February 1999
© 1999 The Academy of Psychosomatic Medine
Depression in Pediatric Chronic Illness
A Diathesis-Stress Model
Patrick Burke, M.B., B.C.H., Ph.D., and
Melanie Elliott, B.A.
Received August 20, 1997; revised May 8, 1998; accepted May 18, 1998. From the Department of Psychiatry, University of Arizona Health Sciences Center, Tucson, Arizona. Address correspondence and reprint requests to Dr. Burke, Department of Psychiatry, University of Arizona Health Sciences Center, P.O. Box 245002, Tucson, AZ 85724–5002. e-mail: burke{at}u.arizona.edu
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ABSTRACT
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Depression in pediatric chronic illness has been receiving increasing attention in recent years. Studies to date have typically focused on characteristics of illness as the major determinants of the development of depression, but characteristics of the child have received less attention. This review suggests that a diathesis-stress model can be a fruitful heuristic that would incorporate illness characteristics and attributes of the child and environmental effects in an overall framework to guide future research and treatment.
Key Words: Depression • Children • Stress
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INTRODUCTION
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Depression is a frequent and significant complication of chronic illness in adults that greatly increases medical morbidity as well as the cost of medical care.1 Although epidemiologic studies2–6 show that the risk of psychological disorder is substantially increased in children who have a chronic illness, until recently, relatively few studies specifically addressed depression in pediatric illness. Depression in children and adolescents is associated with significant impairment in social and family relationship as well as increased risk of suicide,7 and depression in chronically ill children may be equally significant. For example, depression has been linked to increased mortality in asthma,8,9 increased risk of retinopathy in juvenile diabetes,10 and increased risk of recurrence of depression in female adolescent diabetics.11,12 On the other hand, there is evidence that chronic illness may have a positive rather than a negative impact on many children.13 Therefore, differentiating which chronically ill children are most likely to become depressed and the circumstances and factors that contribute to the depression become important questions, which if answered would greatly facilitate the assessment and treatment of depression in this population.
From a theoretical and practical standpoint, whether or not pediatric illnesses differ from one another in their psychological consequences is important to understanding the relationship of depression to pediatric illness.14,15 It appears that specific characteristics of the illness as well as factors common to all illnesses are important in determining if an ill child will develop psychological symptoms, but it is not clear which illness characteristics are most influential.14,16,17 One of the few consistent findings is that children with a brain-related illness have more psychological or behavior disorders than do children with other illnesses.18–20 Characteristics of the child not associated with health status are also important determinants of psychological status in pediatric illness but have received relatively little attention.18 In addition, there is a broad literature attesting to the importance of environmental factors and life events in childhood depression.21
To address the relationship of depression to pediatric illness, a model is needed that considers illness parameters, characteristics of the child, and environmental factors. The model must also account for the fact that not all children with a chronic illness become depressed. These requirements may be met by diathesis-stress models of psychopathology that were developed to explain how some, but not all, individuals exposed to risk develop a disorder.22,23 Diathesis-stress models state that each individual has a particular set of vulnerabilities that when activated by stress lead to the emergence of a disorder.22,23 The vulnerabilities may be defined as inherited or acquired characteristics of functioning that render an individual susceptible to environmental stressors24 and arise from the influence of multiple risk factors, including biological, demographic, family, and social influences.22,24 Stressors may be formative and increase the individual's vulnerability, or may act as a precipitant, triggering the onset of maladjustment or psychopathology.24
While a diathesis-stress model of depression in adults with chronic pain has been proposed,25 this framework has not yet been used to study depression in children with chronic illness.
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I. DIATHESIS-STRESS MODELS OF DEPRESSION
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Current diathesis-stress models of depression emphasize social, cognitive, and biological vulnerability factors.22,26,27 Perris,27 for example, proposes that cultural, biological, psychological, and social factors interact to increase susceptibility to depression through the formation of negative cognitive schemata.28 Each individual is hypothesized to be uniquely susceptible to particular events that can activate the negative cognitions and lead to depression. Brown and colleagues26,29 propose that vulnerability factors (e.g., low self-esteem or lack of intimate ties) render an individual susceptible to depression and provoking factors such as loss, separation, or family discord precipitate depression in vulnerable subjects. In some individuals, interpersonal or achievement-oriented negative events may be necessary to activate the negative cognitions leading to depression.30 Recent cognitive–behavioral models suggest that a negative attributional style increases susceptibility to depression following exposure to uncontrollable negative events.31,32 Behavioral models of depression suggest that depression results from decreases in response-contingent positive reinforcement arising from a shift in the balance of positive and negative reinforcement.33 These cognitive–behavioral and behavioral models of depression can be conceptualized in terms of a diathesis-stress framework.25 Biological vulnerability could result from inherited defects in neurohormonal systems regulating the response to stress34,35 or from sensitization resulting from damage to neurohormonal systems by early experience.30 Depression could result if negative experiences were to activate the dysregulated neurohormonal system.30 Thus, diathesis-stress models identify a range of possible biological, social, and cultural risk factors and family processes that create individual vulnerabilities to depression that may manifest in social, cognitive, and biological domains.
While most diathesis-stress models address depression in adults, there is a growing literature on vulnerability models of depression in youth.36 For example, insecure attachment and impaired ability to regulate affect during a child's early years have been identified as a key link to depression,37 particularly chronic or recurrent forms of depression.30 These vulnerabilities arise from the interaction of the characteristics of the child (e.g., genotype, physical attributes, temperament) and attributes of the attachment figure (e.g., parental behavior and maternal attachment history).37 Attachment difficulties lead to negative self-schemata, negative affect, and impaired ability to regulate affect, putting the individual at risk for depression in the presence of environmental stressors.37 Another influential line of inquiry suggests that perceived competence and peer and parental support are key risk factors for depression in adolescents,38 acting through their influence on self-worth, affect, and hopelessness.
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II. DIATHESIS-STRESS MODELS AND DEPRESSION IN PEDIATRIC ILLNESS
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Depression in pediatric chronic illness can be conceptualized as the outcome of the interactions among the child's vulnerabilities for depression, the characteristics of the illness, and environmental stressors or life events. We propose, in line with current models,22,27,29 that the diathesis for depression has biological, cognitive, and social dimensions. The biological vulnerabilities may include genetic predisposition to depression, temperament, and female gender. Cognitive/affective vulnerabilities may include low self-esteem, a negative attributional style, external locus of control, and ineffective coping strategies. The social/behavioral component may include insecure attachment and poor peer relationships. In the proposed model, the illness is viewed as a stressor that could increase vulnerability to other stressors, or precipitate depression alone or in combination with other stressors. The importance of characteristics of the illness in depression will lie in how particular features of the illness interact with the child's vulnerabilities and other stressors. While it may be assumed that vulnerabilities are uniformly distributed across illnesses, and thus, the prevalence of depression should be the same across illnesses,25 certain illness characteristics or parameters may be more salient for depression depending on how they interact with vulnerabilities. Pertinent aspects of the illness include biological characteristics (e.g., neurologically related illnesses) and characteristics of the illness that have social implications (e.g., cosmetic effects, decreased mobility). The biological characteristics of the different pediatric illnesses would be predicted to interact with the diathesis in different ways. For example, individuals with an endocrine or immune disorder may be at greater risk because the biology of their illness may bear an integral relationship to the biology of depression.34 Thus, if an individual with vulnerability in the brain systems that regulate or influence mood develops an illness whose etiology or treatment directly affects the same systems, then the likelihood of depression would increase. Aspects of illness that have personal/social implications (e.g., bodily changes leading to a sense of loss or perceived inadequacy) could be critical. Children with a negative attributional style or low self-esteem would be more likely to become depressed as they attempt to cope with the illness, due to the influence of these vulnerabilities on the child's perception of the illness, response to the illness, and subsequent coping strategies. Illnesses that decrease mobility or produce fatigue leading to decreased activity would be particularly salient and could result in depression through reduction in response-contingent reinforcement.33 Chronic pain associated with illness could also lead to depression, as has been examined in adults.25 In addition, the risk of depression would increase when significant life events occur along with the illness (e.g., change of school, parental divorce, or changes in the economic state of the family). Specific characteristics of life events have been linked to depression22 and include the severity and type of event. Losses and exits from the social domain or affiliate or achievement-related events also appear to be especially salient for depression. Thus, features of illness, which lead to such consequences, could result in depression.
If the strength of the diathesis is low (i.e., the child has few or no vulnerabilities for depression), then depression is likely to develop only if aspects of the illness are particularly salient for depression (e.g., a central nervous system disorder involving brain systems regulating mood). If the individual is at high risk for depression because of the presence of multiple vulnerabilities, then a minor illness might be a sufficient stressor to induce depression. On the other hand, a child with good self-esteem, confident outlook, and good peer and family relationshipships could surmount the challenge of the illness and evidence psychological growth.
Support for a diathesis-stress model requires 1) evidence that depression is more prevalent in children with pediatric illness than in the general pediatric population; 2) examination of the role played by accepted risk factors for depression (e.g., demographic factors and family psychiatric history); 3) evidence for cognitive, social, and biological vulnerabilities for depression; and 4) examination of the role played by stressors or life events.
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III. DEPRESSION IN PEDIATRIC ILLNESS
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A. Incidence and Prevalence of Depression in Children With Chronic Illness
A number of methodological issues complicate research on depression in youth. Subjects are frequently drawn from tertiary-care settings, where comorbidity is likely, raters often cannot be blind to the medical diagnosis, and samples are frequently small and unrepresentative. Moreover, the signs and symptoms of the medical illness frequently overlap with those of depression, making diagnosis difficult.39,40–42 In addition to these methodological difficulties, there are important issues about the methods used to assess and diagnose depression in youth. Structured and semistructured interviews can yield current and lifetime diagnoses, but rating scales only measure current symptoms and cannot render a diagnosis. Interviews have become the accepted standard for diagnosis, but there are concerns about the reliability and validity of the interviews and the degree of agreement among informants (see review43). In view of the different levels of information obtained by the two methods, interview-based and rating scale-based studies must be considered separately.
1. Interview Data on Prevalence.
In a series of studies of children and adolescent patients, Kashani and colleagues used a semistructured interview and introduced methodologic refinements, such as interviewers being blind to diagnosis, 1-month minimum duration of symptoms, and exclusion of overlapping symptoms of depression and illness.44–46 The researchers reported depression in 7% of the acute pediatric inpatients,46 in 23% of the patients admitted for a planned orthopedic procedure,47 and in 13% of the cardiology clinic outpatients.45 Another study reported depression in 15% of the severely asthmatic adolescents admitted to a tertiary-care asthma center.48 In contrast, none of a group of 26 adolescents with asthma selected as a control group for adolescents with temporal lobe epilepsy (TLE) randomly selected from a clinic were depressed (only one adolescent with TLE was depressed).49 Two studies conducted on burn units revealed rates of current depressive symptoms or depressive disorder from 12% to 13%.50,51 A study of 35 pediatric cancer outpatients44 reported 6 subjects (17%) had major depression.
High lifetime rates of depression but not anxiety disorders were reported in children and adolescents with inflammatory bowel disease (IBD) (i.e., Crohn's disease or ulcerative colitis).52 Interestingly, the lifetime prevalence of depression was greater in IBD (27%) than in cystic fibrosis (11.5%). The prevalence of current depression, however, was lower in both IBD (11%) and cystic fibrosis (4%). Greater current prevalence (20%–25%) was reported in two other studies of IBD.53,54 The number of subjects studied, however, was small, and in one of the studies, the prevalence of depression was the same as the prevalence in physically healthy children, children with diabetes (5%), or children with recurrent headaches.54 In another study of preadolescent children with cystic fibrosis, 9% had major depression.55
2. Interview Data on Incidence.
Few studies have examined depression among children newly diagnosed with a chronic illness. In a study of 74 children with newly diagnosed diabetes evaluated 3 months after diagnosis,56 12% had an adjustment disorder with depressed mood and 4% had major depression. In a 10-year follow-up of 92 diabetic children, 27.5% experienced an episode of major depression.12 Another study reported that 5 of 36 children (14%) evaluated within 1 month of diagnosis of IBD had major depression.57
3. Rating-Scale Data on Prevalence.
Many studies using self-report instruments report little difference in depressive symptoms between ill children and control groups. In one study, scores of acute and chronically ill hospitalized adolescents did not differ from a control group of adolescents drawn from a local school.58 Other studies reported no difference between the depression scores of children with cystic fibrosis, asthma, or sickle cell disease and control subjects.59,60 In another study, parent-rated, but not child-rated, depression scores were higher in the asthmatic subjects, compared with the children with diabetes or cancer, or healthy children.61 However, one study62 of sickle cell disease, asthma, diabetes, and normal control subjects found that 65% of the index patients had depression scores in the moderate-to-severe range, compared with 13% of the control subjects. Similarly, a second study63 reported that the children with sickle cell disease had higher scores than the children who were evaluated but found not to have the disease. In a third study,64 the children with either Crohn's disease or ulcerative colitis scored higher than the healthy control subjects, but the former's scores were the same as those of children with functional abdominal pain. Studies often report little difference between depression scores of cancer patients in particular and those of healthy control subjects.65–67 One possible explanation for the relatively low scores is that the children with cancer may have denied symptoms.67 The denial-repressor hypothesis was supported in two recent studies of cancer patients in which the depression scores of the patients were lower than the scores of the healthy control subjects, but the patients scored higher on measures of repression.68,69
4. Summary and Discussion of Prevalence and Incidence Studies.
These studies suggest that 5%–23% of ill children and adolescents met criteria for major depression. Of children evaluated within 1 to 3 months of diagnosis, 4%–14% had major depression. Studies using rating scales yielded mixed results, some reporting increased depression in the ill children and others showing no difference between the ill children and control groups. Most studies only reported depression present at the time of evaluation and thus underestimate the prevalence of depression occurring over the course of illness.52 As a reference point to these findings in pediatric illness, one-third of all youth experience depressed affect at any one point in time, and the point prevalence of major depression is 1%–3% for physically healthy adolescents and is lower for preadolescents.70
Evidence from interview-based studies suggests that there is an increased prevalence of depression in pediatric illness compared with physically healthy children, but the evidence to date is unclear as to whether the prevalence of depression differs across illnesses. Our review of diagnostic interview-based studies suggests that severe asthma, IBD, and diabetes may have specifically elevated rates of depression. IBD also ranked highly in a recent meta-analysis of studies of adjustment problems in chronic illness, but the number of subjects studied to date is relatively small.14 Moreover, a recent review suggested that the risk of depression may be increased in sickle cell disease in addition to asthma, but not in cancer, cystic fibrosis, or diabetes.16 Overall, however, there are too few studies of a limited number of illnesses to indicate whether particular illnesses have more or less risk of depression in pediatric patients.
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IV. RISK FACTORS ASSOCIATED WITH VULNERABILITY FOR DEPRESSION IN CHILDREN WITH A CHRONIC ILLNESS
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The vulnerabilities fundamental in diathesis-stress models of depression are hypothesized to arise from multiple risk factors.22,24 Age, gender, and family psychiatric history, especially family history of depression, are among the most prominent variables identified as vulnerability-producing risk factors in childhood.7 Family history of depression could exert influence at a biological–genetic level or by leading to cognitive or social–behavioral vulnerabilities.
A. Demographic Variables
Among physically healthy youth, adolescents are more likely than pre-adolescents to become depressed, and the rates are higher for female adolescents than for male adolescents.71 According to a recent review, most studies have found no relationship between age and depression among children with a chronic illness.16 However, there are suggestions that depression is more common in older than in younger subjects.44,45 A similar conclusion was drawn in the case of gender differences, although a number of studies report at least trends for more depression in females.16 However, in one recent study, adolescent females with diabetes had a risk for recurrent depression nine times greater than that of males with diabetes.11 In an epidemiologic survey of chronically ill adolescents, depressive symptoms and suicidal ideation were also increased in the females compared with the control subjects.72 In a recent study of cancer patients, although group depression scores were the same as in a healthy control group, a significant minority (especially the females) had increased depression scores.73 In a study of IBD and cystic fibrosis, while there was no difference in prevalence of depression in the males and females with IBD, depression was found only in the female adolescents with cystic fibrosis.52 Methodologic problems may account for the inconsistencies. In most studies, the number of depressed subjects is small, and cross-sectional and rating scale studies are likely to underestimate the true prevalence of depression in a particular illness. Other factors are also important. Whether mothers or fathers are the informants influences determinations of children's adjustment to illness.74 In a study of burn-injured adolescents and young adults, gender differences became apparent when perceived social support was taken into account. Girls who perceived high social support, particularly from friends, showed less depression than boys with comparable burn injuries.75 In summary, review of demographic variables suggest that female adolescents with a chronic illness are at greater risk of depression than male adolescents, and depression may be more likely in older subjects. Key moderating factors, however, include informant status and social support.
B. Family Psychiatric History
Family psychiatric history has received some attention in chronically ill pediatric patients as a risk factor for depression. Of 100 consecutive admissions for an elective orthopedic procedure, emotional and adjustment problems were identified in the parents of 20 of 23 children who were depressed.47 Of 100 children acutely admitted to the hospital,46 significantly more depressed than nondepressed children had a parental history of depression. In the children with newly diagnosed IBD, the mothers of depressed subjects were more likely to have a lifetime history of depression, as determined by semistructured interview, than the mothers of nondepressed children.57,76 In children treated with phenobarbital for seizure disorders,77 depression was observed only in those children who had first-degree relatives who had major depression, as determined by the family history-research diagnostic criteria (FH-RDC) method.78 In a study48 of 62 adolescents hospitalized with severe asthma, the lifetime prevalence of affective disorders, also determined by the FH-RDC method, was significantly higher in the first-degree relatives of index patients than the published norms78 for the first-degree relatives of a non-ill group and were comparable to prevalence rates in a depressed group. Moreover, the lifetime rates of anxiety disorders were not significantly elevated in the relatives of the asthma group. The authors suggest that there may be a genetic link between severe asthma and depression in children. However, high lifetime rates of depression have also been reported in the mothers of children with IBD and in the mothers of children with cystic fibrosis.57 In this study, 51% of the 72 mothers of children with IBD and 41% of the 44 mothers of children with cystic fibrosis had a lifetime history of depression. In the case of IBD, the first episode of depression in most mothers occurred well before the child was diagnosed, indicating that maternal depression did not result from the diagnosis of a chronic illness in the child. Moreover, in a longitudinal study of 92 children with diabetes,12 while initial maternal psychopathology increased the risk of psychiatric disorder in the children, maternal depression was a specific risk factor for depression in the 27.5% of children who became depressed. In contrast, two studies found no correlation between maternal depressive symptoms derived from rating scales and depressive symptoms in children with diabetes79 or IBD.54 Thus, taking methodologic issues into consideration, family history of depression appears to be an important risk factor for depression in pediatric chronic illness.
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V. VULNERABILITY FACTORS AND DEPRESSION IN CHILDREN WITH CHRONIC ILLNESS
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This section reviews three categories of vulnerability factors: cognitive attributes, social/behavioral attributes, and biological factors that are considered important in childhood depression.
A. Cognitive Attributes
Certain cognitive attributes are central to diathesis-stress and cognitive–behavioral models of depression. Among those studied in pediatric illness to date are attributional style, self-esteem, and locus of control.
1. Attributional Style.
There is considerable evidence that attributional style (i.e., how an individual accounts for the causes of positive and negative events) is related to depression following exposure to uncontrollable negative events.31,32 Hopelessness and depression are positively associated with the tendency to make internal, stable, and global attributions for negative events.80 A few studies have examined attributional style in pediatric illness. One study81 examined attributional style and depression scale scores in 50 10- to 16-year-old children with diabetes of at least 1-year duration and who were free of a psychiatric disorder. An overall score of the tendency to attribute negative events to internal, stable, and global causes was positively correlated with depressive symptoms. In a study of 96 7- to 16-year-olds with either diabetes (n=27), leukemia (n=37), or sickle cell syndrome (n=32), attributional style also predicted self-reported depressive symptoms.82 In a study of 86 outpatients with cancer (7 to 18 years old), depression was predicted by a depressive attributional style as well as by an avoidant coping style and low social competence.83
2. Self-Esteem.
In a recent review, self-esteem was lower in the chronically ill children than in the healthy children, but not when the studies reported careful matching or comparisons with norms.14 In one study, self-worth was lower in the asthmatic children than in the children with diabetes or cancer, or healthy children.61 There were 25 subjects per group, and the subjects had been ill for at least 6 months, attended an outpatient clinic, and did not have a sibling or parent with a chronic illness. Lower self-worth was correlated with increased depression scores in the asthmatic children. In a second study,84 self-worth in 56 consecutively referred children with cystic fibrosis did not differ from self-worth in 56 children matched for age, gender, and race drawn from a pediatric walk-in clinic. However, self-worth was lower in the 45 children (7 to 12 years old) with cystic fibrosis who demonstrated poor behavioral adjustment, compared with those who were who were well-adjusted.55 In a study of 61 epileptic children and 91 diabetic children (8 to 15 years old), overall adjustment was also correlated with self-esteem. Self-esteem was lower in the children with epilepsy than in the diabetes group, and the relationship between low self-esteem and adjustment was stronger in the epilepsy group. Depression in 193 consecutively referred diabetic adolescents was also correlated with lower self-esteem and with poorer treatment adherence.85 Low self-esteem was also correlated with depression scale scores in 80 consecutively referred adolescents with sickle cell disease (n=20), asthma (n=40), or diabetes (n=20).86 In this study, the subjects had been ill for at least 2 years and hospitalized at least twice in the preceding year. Self-esteem was also lower in the chronically ill children than in a random sample of healthy children matched for age and gender drawn from a local school. In another study,54 self-esteem was lower in a county-wide sample of 20 children (7 to 18 years old) with IBD, compared with the healthy control subjects, and was significantly correlated with depressive symptoms. Finally, in a study60 of 138 child (8 to 16 years old) survivors of cancer and 92 control subjects, while self-esteem was within the norms for the scale used, the subjects who had severe late effects had lower self-esteem and higher depression scale scores than those with less severe effects.
3. Locus of Control.
Children's beliefs regarding locus of control mediate and moderate the relationship between stress and psychological symptoms.87 However, investigations of locus of control in pediatric chronic illness have produced mixed results, and few data exist that have specifically examined locus of control and depression in pediatric illness. Children with a chronic illness tend to attribute control of their health to chance and powerful external influences.88 For example, in a study of 20 children (7 to 18 years old), the IBD patients had a more external locus of control than did the diabetic children or healthy control subjects.89 However, the correlation between locus of control and psychiatric disorder was low in the children with IBD. In contrast, in another study of 17 children (7 to 14 years old), those with IBD had a greater internal locus of control than did the children with asthma, and the former had similar profiles to the children with cystic fibrosis.90 In this study, psychiatric disturbance, as determined by interview, was related to an external locus of control. Health locus of control was not related to overall measures of behavioral adjustment in 45 children (7 to 12 years old) with cystic fibrosis.55 In a study66 of 138 child survivors of cancer (8 to 16 years old), those with severe late effects had more depressive symptoms and a more external locus of control than the subjects with less severe effects. The subjects in general had an external locus of control but were within the norms for the scale.
Thus, there is some evidence that chronically ill children with an external locus of control are more likely than those with an internal locus of control to show evidence of psychiatric disorder. To date, the specific relationship between locus of control and depression has not been explored in-depth. One reason for the mixed results regarding locus of control and adjustment in chronically ill children may be that locus of control is usually measured as a bipolar, unidimensional (internal vs. external) construct, and this may be too limiting. A multidimensional approach (e.g., internal, powerful others, and unknown locus of control) may be more useful.91 Recent research suggests that unknown controls (i.e., no knowledge as to why the events occur) for both positive and negative events mediate the relationship between stress and psychological symptoms in children.87 Furthermore, children manifesting unknown control tend to have higher depression scores.92 However, a multidimensional approach to locus of control has not been applied to date to depression in pediatric chronic illness.
B. Social–Behavioral Attributes
Social–behavioral attributes have received minimal attention in the study of depression in pediatric illness. Attachment difficulties represent one aspect of social–behavioral functioning that have been correlated with an increased vulnerability to depression.93 In a study53 of children with IBD, a high proportion of the mothers (13 of 15) were insecurely attached. Eleven of the 15 children had at least 1 psychiatric diagnosis, with an increased prevalence of separation anxiety and depression. The authors suggest that the increase in psychopathology in their sample may be associated with vulnerable attachment in the mother. No studies to date have reported the prevalence of insecure attachment in children with chronic illness, and the relationship between attachment and depression in chronically ill children remains unstudied. In addition, other social–behavioral attributes such as social skills have not been studied specifically in relationship to depression in pediatric chronic illness. Social competence and an avoidant coping style were, however, identified as predictors of depression in children with cancer.83
C. Biological Factors
Biological vulnerability may manifest in a number of ways. Family history of depression is clearly a risk factor for depression in chronically ill children and could exert effects through biological–genetic mechanisms as well as through cognitive–behavioral mechanisms. Review of research to date also indicates that certain medications are associated with mood changes in pediatric illness,77,94 and the effects may be influenced by a family history of depression. For example, major depression, as determined by semistructured interview, occurred significantly more often in 15 children with epilepsy (6 to 16 years old) treated with phenobarbital than in a comparable group of 24 treated with tegretol,77 and depression occurred only in those children who had first-degree relatives with major depression. In another study,94 32 hospitalized, severely asthmatic children (8 to 16 years old) were given pulsed high- or low-dose prednisone in a counterbalanced design, and depressive symptoms were significantly more prominent in the high-dose condition. It would be of interest to know if the effect was conditional on family history of depression. There is also evidence that central serotonin synthesis may be implicated in depression in gastrointestinal disorders. Significantly lower plasma tryptophan levels and a lower ratio of plasma tryptophan to large neutral amino acids have been reported in the untreated children with coeliac disease, compared with the treated children.95 Both measures were lower in coeliac disease than in the normal subjects. The lowest levels were found in the children with behavioral problems, particularly mood disturbance, which suggests that central serotonin synthesis is impaired in coeliac disease and may be related to mood disturbance. The authors95 suggest that this may also be true of other gastrointestinal diseases.
D. Summary
The evidence suggests that the vulnerabilities linked to childhood depression are present in and are associated with the development of depression in chronically ill children. In particular, low self-esteem and negative attributional style are associated with depression in pediatric chronic illness. While an external locus of control is associated with poor adjustment to illness, the relationship of depression to locus of control remains to be elucidated. Social–behavioral attributes have received little attention to date. There is suggestive evidence supporting a role for biological vulnerability, perhaps mediated by a family history of depression.
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VI. ILLNESS PARAMETERS AND DEPRESSION
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In a diathesis-stress model of depression in pediatric illness, the illness can be viewed as a stressor that precipitates depression or increases vulnerability to other stressors. The importance of illness characteristics as risk factors will lie in how particular features of the illness interact with the child's vulnerabilities. Thus, illness parameters viewed in isolation can only yield limited information regarding depression. The illness can be viewed as a complex of features, each of which is salient for depression to the degree that the features interact with the vulnerabilities. However, attempts to date to understand the relationship of illness characteristics and psychological adjustment to pediatric illness have typically focused on aspects of illness in isolation and at best have produced equivocal results.14 Moreover, only a limited number of illness parameters have been considered. These include severity of illness, number of hospitalizations or relapse, course of illness, and the effects of the medications used to treat the illness.
1. Severity of Illness
Illness severity is a complex construct that includes three categories of elements: physiological or morphological severity, functional severity, and burden of illness.96 Physiologic or morphologic severity (impairment) is measured by laboratory tests or anatomical reports, whereas functional severity (disability) reflects the impact of the illness on the individual's ability to perform age-appropriate tasks and is assessed in a variety of ways, including school absence. Physiologic or morphologic status may proceed to functional impairment or disability,96 which is a person-based construct mediated by attributes of the individual (e.g., vulnerabilities). Disability could result from self-imposed constraints and distorted beliefs and may be an important link to depression in chronic illness.25
In general, recent reviews suggest that severity of illness is not related to depression in pediatric illness.16 For example, number of hospitalizations and relapses as indices of severity has been examined in a few studies. One study reported no association between psychiatric functioning and number of hospital admissions or other medical variables related to renal disease.97 Depression scores were also not correlated with number of hospitalizations, remission, relapse status, or number of relapses in adolescents with cancer,65 although number of hospitalizations was correlated with depressive symptoms in pre-adolescents. In contrast, another study reported that number of hospital admissions did not differentiate the depressed from the nondepressed children with cancer.44 However, there are some interesting exceptions. In one study of newly diagnosed children with IBD, those who were depressed at diagnosis were less severely ill than those who were not depressed.57,97 Interestingly, the depressed children also had a maternal history of depression, compared with the nondepressed children. One possibility is that these children had more vulnerabilities arising from maternal depression. In an earlier study of juvenile rheumatoid arthritis,98 disturbances in mood were also more prominent in the less severely ill children.
Other studies suggest that vulnerabilities are important mediators of the impact of illness. Cancer survivors who experienced restrictions in activities or severe cosmetic changes showed more depression than the survivors who did not share these experiences or effects.99 Decreased perceived physical appearance was also related to depressive symptoms in the children with newly diagnosed cancer, and the relationship was mediated by decreased self-esteem.100 In a study examining functional status and depressive symptoms in children with asthma, diabetes or cancer, and healthy children,61 the asthmatic children reported more depression than the children with other illnesses or the healthy children. Functional status was thought to mediate the association between affective symptoms and asthma, but not an association between cancer and decreased school attendance.
In an interesting recent study101 of adolescents with IBD, negative affectivity (a composite of depression and anxiety) was positively correlated with a subjective measure of severity of illness (i.e., functional impairment), but not with erythrocyte sedimentation rate, an objective measure of disease activity. Expressed hostility, however, was inversely related to sedimentation rate. The authors suggest that depression and anxiety did not vary with the disease process itself but with the adolescent's perception and reporting of symptoms and dysfunction. Furthermore, negative life events were positively correlated with negative affectivity, but not with IBD illness measures. These findings are consistent with a diathesis-stress model by suggesting that attributes of the individual mediate the link between impairment and disability. Disability, in turn, may lead to depression, and the effects of life events may be mediated through affective vulnerabilities.
2. Course of the Illness
Some studies56,57 have shown that depressive symptoms are common as early as 1 to 3 months following diagnosis of pediatric illness and that 4%–14% of children are clinically depressed at that time. The first year of illness was the highest risk period for depression in a 10-year prospective longitudinal study of juvenile diabetes.12 The emergence of depression early in the course of the illness is consistent with a diathesis-stress model. In contrast, other authors observed that no increase in psychological symptoms was found following diagnosis or that short-lived psychological symptoms emerged at the onset of illness.44,97 Others report that the duration of treatment did not differentiate the depressed from the nondepressed children with orthopedic problems or renal failure,47,97 nor were total depression scores correlated with time since diagnosis in the children with cancer.65 In the children observed over the first 6 years after diagnosis of diabetes, those who had high initial depression scores showed consistently higher scores over the course of their illness, and those with low initial scores showed slightly elevated scores later in the course of their illness.79
3. Medication
Little information is available on the relationship between type of medication prescribed to treat the chronic illness and resulting depression in pediatric patients. As presented earlier, however, one study reported that children with epilepsy treated with phenobarbital had a significantly higher prevalence of depression than comparable children treated with carbamazepam.77 In a follow-up study, the depression did not remit or decline as long as phenobarbital was continued.102 Moreover, as noted earlier, the effect occurred in the children with a family history of depression. Another study reported that severely asthmatic children exhibited more depression and anxiety when they were given high, compared with low, doses of prednisone,67 although the severity of depression did not reach clinical levels.
4. Other Parameters
Whether an illness is fatal or has a decreased life expectancy does not appear to be a critical variable for depression judging from the prevalence (described earlier) of depression in cancer and cystic fibrosis. There are insufficient data on other variables that might be important, such as age of onset, pain status, and predictability of episodes, to allow an assessment of their impact.
D. Summary and Discussion
Although the data on illness parameters and depression are relatively scant, there is evidence that parameters of the illness may be important risk factors for depression, but the effects may be mediated by the individual's vulnerabilities and contingent on risk factors such as family history of depression. With regard to severity, a critical distinction is that between morphologic/physiologic impairment and functional impairment or disability. Impairment may proceed to disability and in turn to depression as a function of the individual's vulnerabilities (e.g., low self-esteem).
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VII. STRESS/LIFE EVENTS IN CHILDREN WITH CHRONIC ILLNESS AND DEPRESSION
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Two major components make up diathesis-stress models: 1) the diathesis or set of vulnerabilities and 2) the life events or stressors that activate the diathesis. This section summarizes the results of studies that have examined the relationship between stressful life events and depression in chronically ill children.
An early study reported that among children hospitalized for orthopedic procedures, at least one stressful event was reported in the case of the children who were depressed, whereas recent stressful events were rare in the children who were not depressed.47 According to parental report, the most common stressor was the child's illness, followed by marital discord resulting from financial pressures. Another study of children admitted to a hospital with an acute illness reported that 86% of the children who were depressed had experienced the loss or separation from a significant adult figure because of death, chronic illness, or desertion.46 A study of children newly diagnosed with IBD indicated that the families of depressed children experienced significantly more life events and reported more conflict than the families of nondepressed children.57,76 In addition, the children treated with phenobarbital for seizure disorders who were found to be depressed had experienced more stressful life events and more family conflict in the past year than those who were not depressed.77 These studies used diagnostic interviews to diagnose depression. In contrast, studies using rating scales to measure depressive symptoms have reported mixed findings. Depression scores based on rating scales were highly correlated with total life events in adolescents with cancer but were only weakly correlated with total life events in the children with cancer. In both groups, depressive symptoms were correlated with negative life events, but a cross-lag panel analysis of this relationship suggested the relationship was not a causal one.65 Another study reported that depressive symptoms were not related to negative life events in the adolescents with severe illness.62 In a study of hospitalized adolescents, it was reported that undesirable life events were correlated with depression in acutely, but not chronically, ill youth. Overall, however, depression scores of these children did not differ from those of healthy control subjects.58
Despite the mixed results, interview-based studies, in particular, suggest that psychosocial factors related to life stress and family conflicts are key factors in the development of depression in pediatric chronic illness.
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VII. DISCUSSION
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In this review, we illustrate why a diathesis-stress model could be used to organize the literature on depression in chronic pediatric illness. We suggested that depression in pediatric chronic illness can be conceptualized as the outcome of the interactions among the child's vulnerabilities for depression, the characteristics of the illness, and environmental stresses or life events. Our review suggests that key elements of a diathesis-stress model of depression in pediatric illness can be supported by the evidence. Although relatively few studies of chronically ill children have specifically examined vulnerability factors thought to be important for childhood depression, there is evidence that a negative attributional style and low self-esteem, two key cognitive vulnerability factors, are linked to depression in pediatric illness. With regard to risk factors associated with vulnerability, depression is most likely to develop in children with chronic illness who have a family history of depression, and female gender may also be a risk factor. Finally, depression is most likely to be identified in those children with chronic illnesses who have experienced recent or past negative life events.
The diathesis-stress model has both research and clinical implications.25 Key directions for research include establishing the prevalence of vulnerability factors, followed by longitudinal studies aimed at determining how many children with these vulnerabilities develop depressed mood or depressive disorders over the course of illness. Important questions include which vulnerabilities or combinations of vulnerabilities are most predictive of depression. Key cognitive processes to be studied include attributional style and negative cognitive schemata. A second fruitful line of inquiry consistent with a diathesis stress model could be the study of perceived competency with peers, and peer and parental support in chronically ill adolescents.38 A third fruitful direction could examine attachment status and temperament as vulnerability factors. For example, illness occurring in insecurely attached children could be predicted to contribute to depression. Characteristics of the illness need to be examined in relation to such vulnerabilities to determine which are the most salient for depression and to identify the combinations of illness characteristics and vulnerabilities that best predict depression. Key illness parameters include severity, age at diagnosis, duration of illness, predictability of course or episodes, and association with pain. Severity can be categorized in terms of physical impairment, functional impairment, and burden of care,96 each examined in relation to vulnerabilities.
The diathesis-stress model also has clinical relevance. Assessment should include consideration of the child's vulnerabilities as well as the risk factors contributing to the vulnerabilities. This assessment should include the child's developmental, social, and family psychosocial and psychiatric history. Viewing the illness as a multidimensional stressor that interacts with vulnerabilities allows the clinician to consider aspects of the illness that adversely interact with particular vulnerabilities in individual children. For example, unpredictable exacerbations of illness in a child with a negative attributional style or disfiguring illness in a child with low self-esteem are situations likely to lead to depression. Treatment might then be organized around cognitive restructuring, development of effective coping strategies, and social skill building.
The diathesis-stress model can provide a framework to integrate characteristics of the child, features of the illness, and the child's social and developmental history in a way that can enhance clinical practice as well as advance research.
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FOOTNOTES
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The authors thank Velma Dobson, Ph.D., and Rachel Fleissner, M.D., for helpful comments on previous drafts of the manuscript.
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ABSTRACT
INTRODUCTION
