PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Pediatr Pulmonol. Author manuscript; available in PMC 2012 October 2.
Published in final edited form as:
PMCID: PMC3462584
NIHMSID: NIHMS291565

SCREENING FOR SYMPTOMS OF DEPRESSION AND ANXIETY IN ADOLESCENTS AND YOUNG ADULTS WITH CYSTIC FIBROSIS

Summary

Background

Although studies have assessed symptoms of depression and anxiety in individuals with cystic fibrosis (CF), few have been conducted since the advent of new medical treatments (e.g., nebulized antibiotics, ThAIRpy Vest). Study objectives were to: 1) document symptoms of depression and anxiety for adolescents and young adults with CF and compare with normative values, 2) examine the associations among depressive/anxiety symptoms and gender, age, lung function, and body mass index, and 3) determine the relations between adolescent and caregiver symptoms of depression and anxiety.

Methods

Patients and caregivers completed the Hospital Anxiety and Depression Scale (HADS) anytime (e.g. beginning or end) during routine CF clinic appointments.

Results

Participants included 59 adolescents/young adults with CF (Mage = 15.8 years, 54% female, 98% Caucasian, MFEV1 % predicted = 84.6) and caregivers of 40 adolescents. Although symptom scores were in the normative range for patients with CF (MDepression = 2.27 and MAnxiety = 5.59), 3% and 32% exhibited clinically elevated symptoms of depression and anxiety, respectively. Symptoms of depression and anxiety were significantly associated with age (r = 0.28, 0.36). Symptoms of depression and anxiety were also positively correlated (r = 0.48). Females endorsed higher anxiety symptoms than males. While adolescent and caregiver anxiety scores were not related, higher caregiver depressive symptoms were associated with older patient age and worse lung function.

Conclusions

Data from the current study suggest low levels of depressive symptoms and substantial levels of anxiety symptoms in adolescents and young adults with CF. Consistent with prior literature, depressive symptoms appear higher in older patients and are significantly associated with anxiety symptoms. Caregiver symptomology appears to be more affected by an adolescent’s health status, suggesting a need to screen caregivers when health begins to decline.

Keywords: depression, anxiety, psychosocial, gender, adolescents, young adults, caregivers

Introduction

Cystic fibrosis (CF) is a progressive, multi-system pulmonary disease, affecting approximately 30,000 individuals in the United States1. Living with CF, which requires adhering to a complex and time-consuming treatment regimen, affects health-related quality of life23 and places patients at increased risk for depression45. Depression is a common psychiatric diagnosis, with lifetime prevalence rates of 10% in adolescence6 and 16.6% in adults7. Prior studies, which have limitations, suggest that rates of depression in adolescents and adults with CF are significantly higher than those of the general population, ranging from 11–14.5%89 for youth and 29%–46%8,10 for adults. Furthermore, subclinical symptoms of depression (e.g. scores lower than clinical cut-offs for screening measures) have important implications and are associated with psychosocial dysfunction, functional impairment, and future episodes of major depression in the general population 11. However, little is known about the continuum of symptoms of depression for individuals with CF.

A recent report by the US Preventive Services Task Force (USPSTF) recommended the routine screening of adolescents for depression within primary care settings12. Given that CF teams often see patients with CF on a quarterly basis, it seems reasonable that this type of screening could be conducted within routine CF clinical care. The early screening and identification of depressive symptoms is important because studies have shown that age of onset is decreasing. Furthermore, once a depressive episode is experienced, the likelihood of relapse is high13, placing children and adolescents at increased risk throughout their lifetime. Depression also impedes adherence to medical regimens14, thereby potentially increasing morbidity in patients with CF. Similarly, increased depressive symptoms are associated with poorer lung function in children and adults with CF2,15. Thus, routine screening of depressive symptoms during clinical encounters could result in earlier detection, further assessment, and intervention.

Given the high comorbidity between depression and anxiety1619, assessment of anxiety symptoms is also important5. Some studies suggest normative levels of anxiety in adolescents15 and adults20 with CF, whereas others indicate clinical elevations8,21. Unlike depression, low/moderate levels of anxiety may serve as a protective factor for long-term health. Specifically, recent evidence suggests that adherence is higher for patients with CF exhibiting anxiety symptoms21. Given the USPSTF recommendations, one goal of the current study was to use a single screening measure to assess self-reported symptoms of depression and anxiety in patients with CF during routine clinic visits.

Limitations of prior studies of depression and anxiety in CF include use of measures/interviews that incorporated overlapping symptoms of depression and physical symptoms of CF (e.g., somatic items such as fatigue or loss of appetite)21, restricted age ranges, and assessments that occurred before the development of new CF therapies (e.g., ThAIRapy vest, inhaled antibiotics) in the United States 89. The latter point is especially salient because it is unclear how the additional burden of new treatments affects symptoms of depression and anxiety. For example, the initiation of inhaled antibiotics and mucolytics may increase treatment time by 20–30 minutes and decrease recreation22, which may lead to less interaction with peers. In contrast, treatment benefits could reduce physical symptoms and morbidity (e.g., pulmonary exacerbations), resulting in improved overall physical and psychological health.

Finally, mothers of children/adolescents with chronic illnesses are at increased risk for depression23 with high rates in caregivers of children with CF between birth and 18 years of age (e.g., 36–44%)24. Research has demonstrated that children of depressed caregivers are at increased risk for depression compared to children of non-depressed caregivers25. In addition, caregiver depressive symptoms have been linked to poor health outcomes for adolescents with other pediatric conditions, including asthma26 and diabetes27. These children are also more likely to exhibit broad psychosocial impairments in adulthood (e.g., anxiety)28. This intergenerational association of symptoms of depression and anxiety has not been studied in CF.

The objectives of this study were to: 1) document symptoms of depression and anxiety for individuals with CF (≥ 12 years) and compare with norms, 2) examine differences in symptoms of depression and anxiety by sex, age, and lung function, and 3) determine the association between adolescent and caregiver symptoms of depression and anxiety. Adolescents and young adults with CF were expected to report more symptoms of depression and anxiety compared to normative data. It was hypothesized that symptoms of depression and anxiety would be higher for individuals with more severe lung disease and for those who were older and female. Furthermore, a strong positive association was expected between patient- and caregiver-reported symptoms of depression and anxiety.

Methods and Materials

Participants and Procedure

Adolescents and young adults with CF (n=59) receiving outpatient care at Cincinnati Children’s Hospital Medical Center (CCHMC) CF Center participated in the current study. These data were part of a larger international study aimed at assessing depressive and anxious symptoms in youth and adults with CF and their caregivers (www.Tides-CF.org), for which CCHMC served as a pilot site to establish feasibility of study procedures. It is important to note that CCHMC data will not be included in the larger study results. Recruitment rate for this study was 95%. Demographic and medical data are presented in Table 1. This study was approved by the CCHMC Institutional Review Board.

Table 1
Demographic characteristics

A convenience sample of adolescents/young adults with CF and their caregivers who attended CF clinic visits between September 2006 to November 2008 were approached for study participation. The CF Team social worker obtained adult patient/caregiver informed consent and adolescent assent. Questionnaires were then independently completed by the adolescents/young adults and, when applicable, their caregivers at any time during their clinical encounter regardless of when they received their FEV1% (forced expiratory volume in 1 second) predicted results. Caregivers completed a demographic questionnaire and depression/anxiety screening measures, while adolescents/young adults completed one depression/anxiety screening measure. Questionnaires took approximately 15 minutes to complete and were scored upon completion. If moderate to severe symptoms were endorsed, mental health referrals were provided if desired. Health status indicators (e.g., FEV1% predicted, body mass index (BMI)) were extracted from medical records.

Measures

Hospital Anxiety and Depression Scale

The (HADS)29 – The HADS is a 14-item instrument which assesses the cognitive symptoms of depression and anxiety. This measure is specifically used with chronic illness samples to reduce the overlap of somatic symptoms of depression/anxiety with disease-related symptoms. The HADS has excellent reliability, validity, sensitivity and specificity in individuals with and without medical conditions. Current study coefficient alphas were 0.60 and 0.79 for patient symptoms of depression and anxiety, respectively. Participants were categorized as having clinically elevated symptoms based on established clinical cut-off scores of greater than 729. Scores between 0–7 represent normal symptom levels, 8–10 mild symptoms, 11–14 moderate symptoms, and 15–21 severe symptoms.

Health indicators

Forced expiratory volume predicted in one second (FEV1% predicted) was obtained from the medical chart and was based on Wang and Hankinson equations. Illness severity ratings were based on established cutoffs for FEV1 % predicted values: normal (≥ 90%), mild (70%–89%), moderate (40%–69%), and severe (≤ 39%) disease. Weight and height data were used to calculate body mass index (BMI in kg/m2).

Statistical Analyses

Descriptive data (e.g., means, standard deviations) were calculated for adolescent/young adults and caregiver HADS scores, as well as demographic and medical variables. Z-tests were conducted to compare HADS scores of adolescents/adults with CF to normative data for a healthy population30. Controlling for pulmonary functioning, one-way analysis of variance was used to examine sex differences on patient HADS scores. Pulmonary functioning was controlled for because prior studies have demonstrated gender differences in health outcomes 3132, as well as significant associations between pulmonary functioning and symptoms of depression 2. Finally, Pearson correlations were used to examine relations among patient depressive and anxious symptoms, age, pulmonary functioning, and caregiver symptoms of depression and anxiety. All analyses were conducted using SPSS 16.0.

Results

Descriptive Data and Normative Values

Descriptive data are presented in Table 1. Overall, means for both symptoms of depression and anxiety were within the normal range. Compared to normative data30, z-tests revealed fewer depressive symptom scores (z = −4.94, p < 0.0001) in individuals with CF and no significant differences in anxiety (z = −1.14, p = n.s.). Three percent of adolescents/young adults had clinically elevated depressive symptoms in the mild range (n=2) while 32% exhibited clinically elevated anxiety symptoms (Mild: 25%, n=15; Moderate: 5%, n=3; Severe: 2%, n=1).

Caregivers of adolescents also exhibited mean scores within the normal range for HADS depressive (z = −1.70, p = n.s.) and anxiety (z = 0.26, p = n.s.) symptom scores However, 10% had clinically elevated HADS depressive symptoms (Mild: 8%, n=3; Moderate: 2%, n=1; Severe: 0%), and 35% had clinically elevated HADS anxiety symptoms (Mild: 25%, n=10; Moderate: 8%, n=3; Severe: 2%, n=1).

Relations among patient HADS scores, demographic/health status variables, and caregiver HADS scores

Patient Depressive Symptoms

After controlling for FEV1 % predicted, no significant sex differences were found on the HADS depression scale (F (1, 56) = 0.49, p = n.s.; estimated marginal means: Mfemales = 2.47 vs. Mmales= 2.10). A significant correlation was observed between age and HADS depressive scores (r = 0.36; See Table 2). Patient HADS depressive scores were also significantly positively correlated with HADS anxiety scores (r = 0.48, See Table 2). Patient HADS depressive symptom scores were not associated BMI or caregiver HADS scores; however, a negative trend was noted with FEV1 % predicted.

Table 2
Correlations between patient HAD scores, caregiver HADS scores, demographic and health status variables

Patient Anxiety Symptoms

Significant sex differences were found for HADS anxiety scores (F (1, 56) = 7.34, p = 0.009: estimated marginal means: Mfemales= 6.92 vs. Mmales= 4.47), after controlling for FEV1% predicted. Age was also significantly correlated with HADS anxiety scores (r = 0.28, See Table 2). Patient HADS anxiety symptom scores were not associated with BMI, FEV1 % predicted, or caregiver HADS scores.

Caregiver symptoms of depression and anxiety

Caregiver HADS Depressive symptom scores were significantly associated with their adolescent’s age (r = 0.36) and pulmonary functioning (r = −0.52). Specifically, older adolescents and those with lower pulmonary functioning had caregivers with higher depressive symptoms. A negative trend was also noted between caregiver anxiety symptoms and FEV1 % predicted. A strong correlation was found between caregiver symptoms of depression and anxiety (r = 0.67; See Table 2).

Discussion

Results from this pilot study indicated low rates of depressive symptoms in adolescents and young adults with CF (3%). These rates are lower than previous studies and could be influenced by improved physical symptoms and psychological functioning (e.g., depressive symptoms) as a result of advances in CF treatment. The low prevalence rate of clinically elevated depressive symptoms precluded the ability to adequately examine relations with pulmonary functioning. However, the larger literature suggests a negative cumulative impact of both depressive symptoms and severe lung disease on daily functioning2. A positive trend was also noted for age, which is consistent with both the general depression67 and CF8 literature. Finally, prior studies examining depressive symptoms in CF have used measures that include somatic items that overlap with symptoms of CF, which likely contributes to prevalence discrepancies for adolescents/adults with CF. This may be a key reason that individuals in our sample reported lower HADS depressive symptoms. Furthermore, the finding that symptoms of depression were significantly lower than normative data was surprising. However we recognize that several key variables associated with symptoms of depression, were not accounted for in the current study and may help to explain this finding. For example, it is possible that our participants had high levels of social support, which could have served as a buffer for increased symptoms of depression 3334. This is an important area for future research.

In contrast to depressive symptoms, symptoms of anxiety in our sample were consistent with prior literature, with 32% reporting mild to severe symptoms. Prior literature has demonstrated there may be a healthy level of anxiety which promotes optimal adherence 21, suggesting that anxiety may play an adaptive role in disease management. This needs to be further explored in adolescent and young adult populations with CF. In contrast to the potential positive impact of anxiety on adherence, there is also evidence suggesting that anxiety precedes depression and that childhood anxiety predicts the onset of later episodes of major depression35. Thus, it may be that rates of anxiety in our sample are higher than that of depression because the latter has yet to develop. To answer this question of sequential (i.e., one disorder precedes the other) and cumulative (i.e., both disorders occur during one’s lifetime) comorbidity of anxiety and depression in CF, longitudinal prospective studies assessing these disorders are necessary. Regardless of the temporal relations between depression and anxiety and consistent with prior research1619, a significant association was found between symptoms of depression and anxiety in adolescents and young adults with CF.

Data from the extant literature suggest that depressive symptoms increase as patients with CF grow older. Although the ideal age to begin screening for depression is yet to be determined, these data suggest that screening is necessary. Screening for depression is warranted during adolescence since the prevalence increases during this developmental period when health status also typically begins to decline due to the progressive nature of the disease. This is also consistent with recent USPSTF recommendations regarding depression screening for adolescents in the general population12. Our data also revealed that females exhibit significantly higher levels of anxiety symptoms than males. This gender difference could be due to anxiety related to more frequent lung infections36 and decreased life expectancy for females compared to males31. Future research focused on the CF-specific factors that result in higher levels of anxiety in females with CF seems warranted.

Finally, results indicated that caregivers of adolescents with CF exhibited clinically-elevated depressive (10%) and anxiety (35%) symptoms, with a strong association noted between symptoms. While the relation between caregiver and adolescent symptoms of depression and anxiety was non-significant, it appears that the adolescent’s lung function and age were associated with caregiver depressive symptoms. Specifically, it is possible that concerns about their adolescent’s progressive illness and transition to adulthood may increase caregiver symptomology. This is especially salient during the adolescent-young adulthood developmental period where increases in autonomy and independence combined with decreased parental supervision of the treatment regimen37 may serve to exacerbate caregiver symptoms of depression and anxiety.

Several limitations of the current study are noteworthy. First, we did not control for the timing of questionnaire completion. It is possible that either the anticipation or awareness of current pulmonary functioning test results led to higher or lower symptom endorsement. Therefore, investigation of the impact of FEV1 % predicted results on the immediate reporting of symptoms in future studies is necessary. Second, longitudinal studies are needed as the cross-sectional nature of these data prohibits conclusions about causality and the long-term impact of symptoms. Finally, it is unclear whether the use of a somatic-symptom free measure (e.g., HADS) is the most appropriate for adolescents/young adults with CF. Research has suggested that due to disease and depressive symptom overlap, somatic items should be omitted 45. However, it is unclear whether physical symptoms of depression precede physical symptoms of CF or vice versa. Without longitudinal studies to clarify which occurs first, it remains unclear whether measures with (e.g., Beck Depression Inventory 38) or without somatic items are better for assessing depression. A recent study reported that depressive symptom levels did not differ when somatic items were included compared to when they were removed using the same instrument2.

In summary, adolescents and young adults with CF in this study reported low levels of symptoms of depression and anxiety. However, a subset of individuals with CF demonstrated clinically elevated symptoms that may be in need of intervention. This subsample, as well as caregivers with elevated symptoms of anxiety and depression would benefit from recommendations, such as further assessment and treatment for symptoms of depression 12 and anxiety. Thus, screening for symptoms of depression and anxiety appears warranted for patients with CF and caregivers of adolescents, especially as adolescents transition into adulthood.

Acknowledgments

Funding/Support: This work was supported by a T32 DK063929 grant from the National Institute of Diabetes & Digestive & Kidney Disease to Drs. Modi and Driscoll. It was also supported by a Cystic Fibrosis Foundation Grant to Alexandra Quittner, Ph.D. (PI) and Michael Schechter, M.D. (co-PI) for the larger study, The International Depression/Anxiety Epidemiological Study (TIDES).

We would like to extend our deepest appreciation to the adolescents, young adults, and caregivers who participated in this study. We would also like to thank the research assistants (Kara Caudell, Sarah Valentine, and Julie Koumoutsos) who were instrumental in entering and organizing the data. Finally, we would also like to thank the CF Team at Cincinnati Children’s Hospital Medical Center for their support.

Abbreviations

BMI
body mass index
CF
cystic fibrosis
FEV1
forced expiratory volume in 1 second
HADS
hospital anxiety and depression scale
USPSTF
US Preventive Services Task Force

Footnotes

A portion of this data was presented at the following conference:

Modi, A.C., Lemming, C., Driscoll, K., & Montag-Leifling, K. (October 2007). “Preliminary results of the national depression and anxiety screening study in two CF centers in Ohio,” Paper presented at the 21st Annual North American Cystic Fibrosis Conference, Anaheim, CA.

Conflict of Interest: No financial or other potential conflicts of interest exist for any of the authors. This work was conducted at Cincinnati Children’s Hospital Medical Center.

Contributor Information

Avani C. Modi, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, 3333 Burnet Ave. MLC 7039 (Adherence Center), Cincinnati, OH, 45229.

Kimberly A. Driscoll, Florida State University College of Medicine, Department of Medical Humanities & Social Sciences, Tallahassee, FL 32306-4300.

Karen Montag-Leifling, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, 3333 Burnet Ave. MLC 2021 (Pulmonary Medicine), Cincinnati, OH, 45229.

James D. Acton, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, 3333 Burnet Ave. MLC 2021 (Pulmonary Medicine), Cincinnati, OH, 45229.

References

1. Cystic Fibrosis Foundation. [Accessed on December 29, 2009];About Cystic Fibrosis. 2009 www.cff.org/AboutCF/
2. Riekert KA, Bartlett SJ, Boyle MP, Krishnan JA, Rand CS. The association between depression, lung function, and health-related quality of life among adults with cystic fibrosis. Chest. 2007;132(1):231–237. [PubMed]
3. Modi AC, Quittner AL. Validation of a disease-specific measure of health-related quality of life for children with cystic fibrosis. Journal of pediatric psychology. 2003;28(8):535–545. [PubMed]
4. Quittner AL, Barker DH, Snell C, Grimley ME, Marciel K, Cruz I. Prevalence and impact of depression in cystic fibrosis. Curr Opin Pulm Med. 2008;14(6):582–588. [PubMed]
5. Cruz I, Marciel KK, Quittner AL, Schechter MS. Anxiety and depression in cystic fibrosis. Semin Respir Crit Care Med. 2009;30(5):569–578. [PubMed]
6. Dubois DL, Felner RD, Bartels CL, Silverman MM. Stability of self-reported depressive symptoms in a community sample of children and adolescents. Journal of Clinical Child Psychology. 1995;24:386–396.
7. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):593–602. [PubMed]
8. Pearson DA, Pumariega AJ, Seilheimer DK. The development of psychiatric symptomatology in patients with cystic fibrosis. J Am Acad Child Adolesc Psychiatry. 1991;30(2):290–297. [PubMed]
9. Birmaher B, Ryan ND, Williamson DE, Brent DA, Kaufman J. Childhood and adolescent depression: a review of the past 10 years. Part II. J Am Acad Child Adolesc Psychiatry. 1996;35(12):1575–1583. [PubMed]
10. Burker EJ, Sedway J, Carone S. Psychological and educational factors: Better predictors of work status than FEV1 in adults with cystic fibrosis. Journal of Pediatric Pulmonology. 2004;38:413–418. [PubMed]
11. Lewinsohn PM, Solomon A, Seeley JR, Zeiss A. Clinical implications of “subthreshold” depressive symptoms. J Abnorm Psychol. 2000;109(2):345–351. [PubMed]
12. Williams SB, O’Connor EA, Eder M, Whitlock EP. Screening for child and adolescent depression in primary care settings: a systematic evidence review for the US Preventive Services Task Force. Pediatrics. 2009;123(4):e716–735. [PubMed]
13. Association AP. Diagnostic and Statistical Manual of Mental Disorders. 4. Washington DC: American Psychiatric Association; 2000.
14. Smith BA, Modi AC, Quittner AL, Wood B. Depression in children with cystic fibrosis and parent caregivers and its effects on adherence. Pediatric Pulmonology. under review. [PubMed]
15. Bregnballe V, Thastum M, Schiotz PO. Psychosocial problems in children with cystic fibrosis. Acta Paediatr. 2007;96(1):58–61. [PubMed]
16. Lewinsohn PM, Zinbarg R, Seeley JR, Lewinsohn M, Sack WH. Lifetime comorbidity among anxiety disorders and between anxiety disorders and other mental disorders in adolescents. J Anxiety Disord. 1997;11(4):377–394. [PubMed]
17. Angold A, Costello EJ. Depressive comorbidity in children and adolescents: empirical, theoretical, and methodological issues. Am J Psychiatry. 1993;150(12):1779–1791. [PubMed]
18. Brady EU, Kendall PC. Comorbidity of anxiety and depression in children and adolescents. Psychol Bull. 1992;111(2):244–255. [PubMed]
19. Rohde P, Lewinsohn PM, Seeley JR. Comorbidity of unipolar depression: II. Comorbidity with other mental disorders in adolescents and adults. J Abnorm Psychol. 1991;100(2):214–222. [PubMed]
20. Havermans T, Colpaert K, Dupont LJ. Quality of life in patients with Cystic Fibrosis: association with anxiety and depression. J Cyst Fibros. 2008;7(6):581–584. [PubMed]
21. White T, Miller J, Smith GL, McMahon WM. Adherence and psychopathology in children and adolescents with cystic fibrosis. Eur Child Adolesc Psychiatry. 2009;18(2):96–104. [PubMed]
22. Modi AC, Quittner AL. Utilizing computerized phone diary procedures to assess health behaviors in family and social contexts. Children’s Health Care. 2006;35:29–45.
23. Yilmaz O, Sogut A, Gulle S, Can D, Ertan P, Yuksel H. Sleep quality and depression-anxiety in mothers of children with two chronic respiratory diseases: asthma and cystic fibrosis. J Cyst Fibros. 2008;7(6):495–500. [PubMed]
24. Driscoll KA, Montag-Leifling K, Acton JD, Modi AC. Relations between depressive and anxious symptoms and quality of life in caregivers of children with cystic fibrosis. Pediatr Pulmonol. 2009;44(8):784–792. [PMC free article] [PubMed]
25. Beardslee WR, Keller MB, Seifer R, Lavori PW, Staley J, Podorefsky D, Shera D. Prediction of adolescent affective disorder: effects of prior parental affective disorders and child psychopathology. J Am Acad Child Adolesc Psychiatry. 1996;35(3):279–288. [PubMed]
26. Weil CM, Wade SL, Bauman LJ, Lynn H, Mitchell H, Lavigne J. The relationship between psychosocial factors and asthma morbidity in inner-city children with asthma. Pediatrics. 1999;104(6):1274–1280. [PubMed]
27. Cameron FJ, Northam EA, Ambler GR, Daneman D. Routine psychological screening in youth with type 1 diabetes and their parents: a notion whose time has come? Diabetes Care. 2007;30(10):2716–2724. [PubMed]
28. Weissman MM, Wickramaratne P, Nomura Y, Warner V, Pilowsky D, Verdeli H. Offspring of depressed parents: 20 years later. Am J Psychiatry. 2006;163(6):1001–1008. [PubMed]
29. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67(6):361–370. [PubMed]
30. Crawford JR, Henry JD, Crombie C, Taylor EP. Normative data for the HADS from a large non-clinical sample. Br J Clin Psychol. 2001;40(Pt 4):429–434. [PubMed]
31. Rosenfeld M, Davis R, FitzSimmons S, Pepe M, Ramsey B. Gender gap in cystic fibrosis mortality. Am J Epidemiol. 1997;145(9):794–803. [PubMed]
32. Liou TG, Adler FR, Fitzsimmons SC, Cahill BC, Hibbs JR, Marshall BC. Predictive 5-year survivorship model of cystic fibrosis. Am J Epidemiol. 2001;153(4):345–352. [PMC free article] [PubMed]
33. Kendler KS, Myers J, Prescott CA. Sex differences in the relationship between social support and risk for major depression: a longitudinal study of opposite-sex twin pairs. Am J Psychiatry. 2005;162(2):250–256. [PubMed]
34. Varni JW, Katz ER, Colegrove R, Jr, Dolgin M. Perceived social support and adjustment of children with newly diagnosed cancer. J Dev Behav Pediatr. 1994;15(1):20–26. [PubMed]
35. Parker G, Wilhelm K, Mitchell P, Austin MP, Roussos J, Gladstone G. The influence of anxiety as a risk to early onset major depression. J Affect Disord. 1999;52(1–3):11–17. [PubMed]
36. Block JK, Vandemheen KL, Tullis E, Fergusson D, Doucette S, Haase D, Berthiaume Y, Brown N, Wilcox P, Bye P, Bell S, Noseworthy M, Pedder L, Freitag A, Paterson N, Aaron SD. Predictors of pulmonary exacerbations in patients with cystic fibrosis infected with multi-resistant bacteria. Thorax. 2006;61(11):969–974. [PMC free article] [PubMed]
37. Modi AC, Marciel KK, Slater SK, Drotar D, Quittner AL. The influence of parental supervision on medical adherence in pre and late-adolescents with cystic fibrosis: Developmental shifts from early to late adolescence. Children’s Health Care. 2008;37(1):78–92.
38. Beck A, Steer R, Brown G. Manual for Beck Depression Inventory II (BDI-II) San Antonio: Psychology Corporation; 1996.