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Journal of Pediatric Psychology logoLink to Journal of Pediatric Psychology
. 2022 Jun 14;47(10):1185–1194. doi: 10.1093/jpepsy/jsac052

Physical Symptoms, Distress, and Functional Disability in Youth With Chronic Orthostatic Intolerance

Michele S Tsai Owens 1, Bridget K Biggs 2,✉, Amy C Fahrenkamp 3, Jennifer Geske 4, Deanna R Hofschulte 5, Cynthia Harbeck-Weber 6, Philip R Fischer 7,8,9
PMCID: PMC9960074  PMID: 35699566

Abstract

Objective

Youth with chronic orthostatic intolerance (OI) can experience significant physical, social, and academic functional debilitation. Previous studies have indicated associations among symptom severity, psychosocial factors, and functional disability. However, empirically tested models explaining how different medical and psychosocial factors may contribute to functional disability are lacking. The current cross-sectional study aimed to evaluate mediation, moderation, and additive models of the effect of physical symptoms and psychological distress on functional disability.

Methods

One hundred and sixty-five youth (13–22 years old) undergoing medical evaluation of chronic OI symptoms completed measures of autonomic dysfunction symptom severity, depressive and anxiety symptoms, and functional disability. Models were evaluated using tests of indirect effects and linear and logistic regression analyses.

Results

Results supported the mediation and additive effects models for depressive symptoms. Mediation, moderation, and additive models for hypothesized effects of anxiety symptoms were not supported.

Conclusions

Results provide preliminary support for models in which OI symptoms affect functional debility via their effects on mood and in which depressive symptoms have unique and additive effects on functioning. Findings lay the foundation for longitudinal and experimental evaluation of biopsychosocial models of functional disability in youth with chronic OI and related conditions. Implications include the importance of a biopsychosocial conceptualization of OI symptoms and debility as a complex interplay of factors rather than as a purely physiological or psychological process.

Keywords: adolescents, anxiety, chronic illness, depression, emerging/young adults, psychosocial functioning

Introduction

Youth with orthostatic intolerance (OI) struggle with a range of symptoms associated with upright posture that improves with supine positioning. These include syncope/near syncope, lightheadedness, headache, fatigue, weakness, visual changes, cognitive difficulties, abdominal distress, and exercise intolerance. Individuals with chronic OI experience symptoms for at least 3 months, and symptom severity and the presence of various signs may be consistent with different types of autonomic dysfunction (AD) such as postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), or postural vasovagal syncope (VVS; Stewart et al., 2018). The prevalence of chronic OI among the U.S. population has been estimated at >500,000 (Robertson, 1999), though the exact prevalence is not known as OI symptoms are not routinely screened. Chronic OI conditions are increasingly being identified in youth, as symptom onset often occurs during adolescence (Stewart et al., 2018). Individuals with chronic OI may experience significant functional limitations (McTate & Weiss, 2016), which in youth can include disruptions in academic engagement and/or performance, engagement in extracurricular activities, engagement in physical activities, and peer and family relationships (Anderson et al., 2012). A few reports have implicated symptom severity and psychosocial factors in determining the level of functional impairment (Benrud-Larson et al., 2002; Kizilbash et al., 2014). One of the limitations of the nascent literature on functional disability among affected individuals is the lack of empirically supported models explaining how medical and psychosocial factors contribute to functional disability.

The extant literature on chronic pain and functional impairment may serve as a useful guide for hypothesis generation and testing to better understand factors influencing functional impairment among youth with chronic OI. The literature on chronic OI and related conditions indicates comorbidity and etiological overlap with chronic pain conditions (Johnson et al., 2010) and recommends similar treatment approaches (Kizilbash et al., 2014). The biopsychosocial model of pediatric chronic pain is widely accepted (Miró et al., 2007) and empirically tested (Liossi & Howard, 2016). This model conceptualizes chronic pain as a multifactorial construct manifesting from a complex interplay of biological, psychological, and social factors. In particular, both anxiety and depression are frequent in youth with chronic pain and contribute to increased functional disability (Cohen et al., 2010; Kashikar-Zuck et al., 2001).

Pediatric research guided by the biopsychosocial model of chronic pain has demonstrated correlations of pain severity and disability with a number of proposed precipitating and intervening factors, including psychological distress (Liossi & Howard, 2016), typically examining these factors in isolation rather in conjunction (McKillop & Banez, 2016). Studies examining the interrelationship of factors including psychological distress suggest several possible models. Studies of pediatric patients with pain have supported models of depression as a mediator of the association between pain intensity and school functioning (Logan et al., 2009) and as carrying an indirect association between family functioning and functional disability (Kaczynski et al., 2016). Another study supported anxiety as a partial mediator between stress and abdominal pain (White & Farrell, 2006). Psychosocial factors may also moderate the relation between symptom severity and functional impairment. Studies in pediatric chronic pain have demonstrated that the degree to which symptoms relate to functional impairment depends on psychological and parental/family factors such as the degree of worry (Simons et al., 2012), perceived self-worth (Guite et al., 2007), and the family environment (disruptive or adaptive; Logan & Scharff, 2005). In one of the few longitudinal studies relevant to the current study, Valrie and colleagues (2021) found that positive affect mediated the relationship between sleep quality and pain severity, and negative affect moderated that same relationship. Finally, it is also possible that psychosocial factors and pain have unique, additive effects on functional disability.

Although scholars claim the biopsychosocial model of chronic pain is applicable to chronic OI and related conditions (Junghans-Rutelonis et al., 2019), few studies have tested the model empirically. Two published studies have demonstrated bivariate associations of functional disability with number of OI symptoms, pain severity, depressive symptoms, anxiety symptoms, and pain catastrophizing among pediatric patients with OI and chronic pain (Kritzberger et al., 2011; McTate & Weiss, 2016). Despite the congruence of these findings with the biopsychosocial model for chronic pain, the interplay between physical symptom severity and psychological distress in determining disability has yet to be studied in a comprehensive model of functional impairment related to OI.

Given the variety of models present in the chronic pain literature and the limited empirical literature investigating psychological distress and chronic OI, the current study aimed to evaluate three models of the effect of physical symptoms and psychological distress on functional disability among youth with chronic OI: (a) a mediation model in which anxiety/depression symptoms explain the association between OI symptom severity and functioning, (b) a moderation model in which the association depends on the degree of anxiety/depression symptoms, and (c) an additive model in which OI, anxiety, and depression symptoms have independent, cumulative effects on functioning (Figure 1). The study tested the proposed models with a sample of youth seeking diagnostic evaluation for OI symptoms in a cross-sectional design as a foundational step toward more controlled, resource-intensive research.

Figure 1.

Figure 1.

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Conceptual models for effects of symptom severity and psychological distress on functional impairment among youth with chronic orthostatic intolerance.

Methods

Procedures

Figure 2 summarizes study recruitment and enrollment of youth seeking evaluation through the Mayo Clinic Pediatric Diagnostic & Referral Clinic (PDRC) between September 11, 2017 and December 31, 2018. Eligible individuals were 13–22 years old who were evaluated for and diagnosed with a chronic OI condition; exclusion criteria included inability to complete research questionnaires in English independently and having a documented disability. Previous diagnosis of AD was removed as an exclusion criterion on October 30, 2017, due to a high percentage of patients seeking a second opinion. Nonclinical research team members identified patients potentially eligible for the study by prescreening PDRC calendars and prompting PDRC clinicians to confirm eligibility criteria and invite eligible patients to participate during the initial clinic visit. Youth who met criteria and expressed interest completed the informed consent/assent process with the study coordinator and the study survey via secure online survey (paper option also offered). Participants received a small monetary remuneration for completing study measures. Researchers abstracted OI-related diagnoses and treatment recommendations from electronic health records and excluded 14 youths without a relevant diagnosis for the current analyses. The Institutional Review Board of Mayo Clinic approved the study procedures.

Figure 2.

Figure 2.

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Enrollment flow diagram. Note.  aExclusion criterion removed on October 30, 2017.

Participants

Of the 165 total study participants, 154 were adolescents aged 13–17 years and 11 were young adults aged 18–22 years (age of overall sample: M = 15.7, SD = 1.4). The majority were female, White, and currently enrolled in formal education (Table I). Participants reported missing, on average, nearly a third of school days in the current academic year (M = 32.3%, SD = 26.6%, min–max = 0.0–100.0%) and about a quarter of days in the previous year (M = 27.4%, SD = 22.7%, min–max = 0.0–99.0%). Overall, participants’ parents were well-educated (n = 108, 65.5% with bachelor’s or higher degree). Clinician-assigned diagnoses in the medical record were as follows: 66 (40.0%) with chronic OI, 61 (37.0%) with POTS, 34 (20.6%) with AD, 2 (1.2%) with OH, and 2 (1.2%) with VVS.

Table I.

Sample Demographic and Educational Characteristics (n = 165)

Characteristic n %
Gender
 Female 143 86.7
 Male 18 10.9
 Transgender female – –
 Transgender male 2 1.2
 Other 2 1.2
Race
 White 143 86.7
 American Indian 2 1.2
 Asian 2 1.2
 Black/African American 1 0.6
 Middle Eastern/North African 1 0.6
 Pacific Islanders – –
 Bi-/multiracial 10 6.1
 Did not answer 6 3.6
Ethnicity
 Hispanic 9 5.5
Educational level
 7th grade 7 4.2
 8th grade 15 9.1
 9th grade 23 13.9
 10th grade 45 27.3
 11th grade 40 24.2
 12th grade 26 15.8
 Postsecondary year 1 2 1.2
 Postsecondary year 2 1 0.6
 Postsecondary year 3 1 0.6
 Not currently enrolleda 5 3.0
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Note. aOne individual did not complete high school and four graduated from high school.

Measures

Demographic and Educational Information

Participants self-reported gender identity, age, race, ethnicity, and parents’/guardians’ highest educational level achieved. Participants also reported their current educational level and approximate percentage of school days missed in the previous and current academic years.

AD Symptoms

The Composite Autonomic Symptom Score 31 (COMPASS 31) is an abbreviated (31-item) measure of AD symptom severity in six domains: OI, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor. For each domain, participants answered a yes/no question indicating the presence or absence of the symptom (e.g., feeling dizzy with positional changes for OI) in the last month and, if answered affirmatively, responded to additional questions to indicate the frequency and severity of the symptoms. Following scoring guidelines, item scores were summed within each domain, each domain raw score was multiplied by the recommended weight (weights were 4.0, 0.83, 2.1, 0.89, 1.1, and 0.33, respectively), and the resulting domain scores were summed into a composite score that can range from 0 to 100, with higher scores indicating greater symptom severity. The COMPASS 31 has been validated in individuals with POTS and healthy controls (Rea et al., 2017; Sletten et al., 2012). Internal consistency in this study sample was α = .88.

Emotional Distress

Participants completed the Center for Epidemiological Studies Depression Scale for Children (CES-DC; Fendrich et al., 1990) and the Spence Children’s Anxiety Scale (SCAS; Spence et al., 2003) as indicators of psychological distress in the last month. The CES-DC is a 20-item depression screener with total scores ranging from 0 to 60, with higher scores indicating greater symptomatology. The internal consistency of the CES-DC in the current study sample was α = .92. The SCAS is a 44-item measure assessing anxiety symptoms related to social phobia, separation anxiety, panic/agoraphobia, obsessive-compulsive disorder, generalized anxiety, and physical injury fears. Total scores based on 38 scored items range from 0 to 114, with higher scores indicating greater symptomatology. The internal consistency in this study sample was α = .95.

Functional Impairment

Participants completed the Functional Disability Inventory (FDI; Walker & Greene, 1991), a modified version of the Child Sheehan Disability Scale (CSDS; Whiteside, 2009), and a single item about perceived ability to attend school as indicators of functional disability. The FDI is a 15-item measure assessing illness-related limitations on activities of daily living among pediatric patients. Total scores range from 0 to 60, with higher scores indicating greater disability. Internal consistency (in this study sample, Cronbach’s α = .89), validity, and sensitivity to treatment are strongly supported (Claar & Walker, 2006; Walker & Greene, 1991). The FDI has been used to classify levels of disability (e.g., 0–12 no/minimal disability, 13–29 moderate disability, ≥30 severe disability) in youth with chronic pain (Kashikar-Zuck et al., 2011) and POTS (Bruce et al., 2016). The CSDS is a 3-item measure assessing the extent to which a child’s anxiety interferes with school, social, and family functioning. Respondents rate each item on an 11-point Likert scale (0 = not at all, 10 = very, very much). Total scores range from 0 to 30. The validity of the CSDS is supported through small-to-moderate correlations with other measures of symptom-related disability and its incremental ability to distinguish youth with anxiety disorders from a community sample beyond the contribution of anxiety symptoms (Whiteside, 2009). For this study, the item stems were modified to replace “fears and worries” with reference to a participant’s AD symptoms. Neither the original CSDS nor this modified version specified a recall period. Internal consistency of this modified CSDS was α = .75. Participants also responded to an item about school functioning: “What effect do your health problems/symptoms usually have on your ability to attend school?” (response options: “I am unable to attend school due to symptoms,” “I can only attend school when symptom-free,” “I attend school with much difficulty due to symptoms,” “I manage to attend school in spite of symptoms,” or “Symptoms do not affect my school attendance”). For analyses, school attendance was a two-category variable: attends: last two response options and difficulty attending: first two response options.

Data Analyses

Descriptive statistics are presented as mean and standard deviation or N (%). Pearson correlations, analyses of variance (ANOVAs), and χ2 analyses tested bivariate relationships among demographic and study variables to inform the development of multivariable models. Multivariable regression analyses tested moderation and additive effects models. Procedures recommended by Preacher and Hayes (2004) tested the three models of indirect effects for each combination of predictors (COMPASS 31), mediators (CES-DC, SCAS), and outcome variables (FDI, CSDS, symptom interference with school attendance). Bias-corrected confidence intervals were based on 1,000 bootstrap samples. The sample provided sufficient power for multivariable models and tests of mediation, as 165 participants allows for detection of a mediation effect (at power = 0.80) for models including small (0.13) or greater coefficients associated with the effect of the independent variable on the mediator and the effect of the mediator on the dependent variable adjusted for the independent variable (Fritz & MacKinnon, 2007). Statistical analyses were conducted using SAS software (version 9.4; Cary, NC). Data are available on request.

Results

Preliminary Descriptive and Bivariate Analyses

Table II summarizes scores on the self-report measures of AD symptoms, psychological distress, and functional disability. Mean AD symptom severity was comparable to prior studies of youth with POTS (Rea et al., 2017). Most participants (78.2%) scored above the suggested CES-D cutoff score of 15 (Fendrich et al., 1990). SCAS scores were similar to those of youth with anxiety disorders (Whiteside & Brown, 2008). FDI scores fell in the moderate range, and CSDS scores were similar to clinical samples (Whiteside, 2009). Many participants reported difficulty attending school due to symptoms.

Table II.

Sample Clinical and Functional Characteristics (n=165)

Measure M SD Min Max
AD symptoms (COMPASS 31) 41.1 13.4 7.7 76.6
Depressive symptoms (CES-DC) 24.8 12.6 1.0 53.0
Anxiety symptoms (SCAS) 31.3 20.4 2.0 111.0
Functional disability (FDI) 25.9 10.9 0.0 49.0
Symptom interference with functioning (CSDS) 16.1 7.2 0.0 30.0
Effect of health difficulties on ability to attend school N %
 Unable to attend school due to symptoms 30 18.6
 Can only attend school when symptom-free 17 10.6
 Attend school with much difficulty due to symptoms 59 36.7
 Manage to attend school in spite of symptoms 52 32.3
 Symptoms do not affect school attendance 3 1.9
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Note. COMPASS 31 = Composite Autonomic Symptom Score 31; CES-DC = Center for Epidemiological Studies Depression Scale for Children; SCAS = Spence Children’s Anxiety Scale; FDI = Functional Disability Inventory; CSDS = (modified) Child Sheehan Disability Scale; AD = autonomic dysfunction.

Bivariate correlational analyses indicated AD, depression, and anxiety symptoms were positively associated with functional disability (Table III). ANOVAs indicated no significant associations of school attendance with age or symptom severity. There were no significant bivariate relationships of demographic variables (age, gender, race, or ethnicity) with study variables.

Table III.

Bivariate Correlations Among Study Measures and Participant Age

2 3 4 5 6
1. Age .10 −.05 −.04 .01 .06
2. AD symptoms (COMPASS 31) .48** .44** .57** .29**
3. Depressive symptoms (CES-DC) .78** .46** .39**
4. Anxiety symptoms (SCAS) .35** .23**
5. Functional disability (FDI) .67**
6. Symptom interference (CSDS)
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Note. **p < .01. AD = autonomic dysfunction; CES-DC = Center for Epidemiological Studies Depression Scale for Children; SCAS = Spence Children’s Anxiety Scale; FDI = Functional Disability Inventory; CSDS = Child Sheehan Disability Scale.

Evaluation of Mediation, Moderation, and Additive Effects

Table IV summarizes tests of mediation/indirect effects models for the FDI and CSDS. Results of Model 1 supported the hypothesized indirect effect of AD symptom severity via depressive symptoms on functional disability as measured by the FDI. The direct effect remained significant, supporting a partial mediation model. Model 2 results supported the hypothesized indirect effect of AD symptom severity via depression symptoms on functional disability as measured by the CSDS. The direct effect was not significant when depressive symptoms were included in the model, suggesting mediation. Results did not support indirect effects models of AD symptom severity on functional disability via anxiety symptom severity.

Table IV.

Evaluation of Indirect Effects of Autonomic Dysfunction Symptom Severity on Functional Disability via Psychological Distress

Model/path β SE 95% CI % Mediated
Model 1: M = CES-DC, Y = FDI 21.9
 AD symptoms—Depressive symptoms (a) 0.45 0.06 0.32, 0.58
 Depressive symptoms—FDI (b) 0.39 0.06 0.28, 0.51
 Total effect AD symptoms—FDI (c) 0.46 0.05 0.35, 0.57
 Direct effect AD symptoms—FDI (c’) 0.36 0.06 0.24, 0.47
 Indirect effect (ab) 0.10 0.03 0.05, 0.16
Model 2: M = CES-DC, Y = CSDS 58.4
 AD symptoms—Depressive symptoms (a) 0.45 0.06 0.32, 0.58
 Depressive symptoms—CSDS (b) 0.22 0.04 0.14, 0.30
 Total effect AD symptoms—CSDS (c) 0.16 0.04 0.08, 0.24
 Direct effect AD symptoms—CSDS (c’) 0.07 0.05 −0.02, 0.14
 Indirect effect (ab) 0.09 0.03 0.05, 0.15
Model 3: M = SCAS, Y = FDI 9.7
 AD symptoms—Anxiety symptoms (a) 0.67 0.11 0.46, 0.88
 Anxiety symptoms—FDI (b) 0.19 0.04 0.11, 0.26
 Total effect AD symptoms—FDI (c) 0.45 0.05 0.35, 0.56
 Direct effect AD symptoms—FDI (c’) 0.41 0.06 0.30, 0.54
 Indirect effect (ab) 0.04 0.03 −0.01, 0.10
Model 4: M = SCAS, Y = CSDS 21.8
 AD symptoms—Anxiety symptoms (a) 0.67 0.11 0.46, 0.88
 Anxiety symptoms—CSDS (b) 0.08 0.03 0.03, 0.13
 Total effect AD symptoms—CSDS (c) 0.15 0.04 0.07, 0.23
 Direct effect AD symptoms—CSDS (c’) 0.12 0.05 0.03, 0.21
 Indirect effect (ab) 0.03 0.02 0.00, 0.08
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Note. Bolded indirect effect values indicate significant mediation (i.e., 95% confidence interval did not contain zero for Models 1–2, 4–5). Please see Figure 1A for depiction of mediation model paths. COMPASS 31 = Composite Autonomic Symptom Score 31; CES-DC = Center for Epidemiological Studies Depression Scale for Children; SCAS = Spence Children’s Anxiety Scale; FDI = Functional Disability Inventory; CSDS = (modified) Child Sheehan Disability Scale; School = ability to attend school; AD = autonomic dysfunction.

Regression analyses testing additive and moderation models for functional impairment measured by the FDI and CSDS resulted in no significant interaction terms, indicating no support for moderation models. Regression analyses with interaction terms removed (Table V) supported the overall additive effects model for AD symptoms, depressive symptoms, and anxiety on functional disability measured by the FDI. AD symptoms and depressive symptoms were significantly and uniquely associated with FDI scores. The overall model for CSDS scores was significant, with only depressive symptoms uniquely associated with CSDS scores.

Table V.

Evaluation of Additive Effects of AD Symptom Severity and Psychological Distress on Functional Disability

Regression models β SE T p F df p R 2 Adj. R2
Model 1: Y = FDI 32.27 164 <.001 .38 .36
 AD symptoms (COMPASS 31) 0.38 0.06 6.55 <.001
 Depressive symptoms (CES-DC) 0.27 0.09 2.99 .003
 Anxiety symptoms (SCAS) −0.05 0.05 −0.94 .350
Model 2: Y = CSDS 11.90 164 <.001 .18 .17
 AD symptoms (COMPASS 31) 0.08 0.04 1.78 .077
 Depressive symptoms (CES-DC) 0.27 0.07 4.09 <.001
 Anxiety symptoms (SCAS) −0.07 0.04 −1.79 .075
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Note. COMPASS 31 = Composite Autonomic Symptom Score 31; CES-DC = Center for Epidemiological Studies Depression Scale for Children; SCAS = Spence Children’s Anxiety Scale; FDI = Functional Disability Inventory; CSDS = (modified) Child Sheehan Disability Scale; AD = autonomic dysfunction.

Discussion

Psychological distress has been implicated conceptually as an important driver of functional disability among youth with chronic OI and related conditions. The current study leads necessary research testing integrated models of how physical symptoms and psychological distress may explain functional impairment among youth with chronic OI symptoms. Findings from this cross-sectional study provide preliminary support for mediation and additive models for depressive symptoms. That is, results were consistent with a conceptualization of AD symptoms influencing functional impairment through their impact on young people’s mood and were also consistent with a conceptualization of AD and depressive symptoms as having unique and additive effects on functional impairment. These findings are consistent with chronic stress models of depression linking emergence of depressive symptoms to the experience of stressors (Hammen, 2005) and the literature demonstrating increased risk for depressive symptoms among youth with chronic medical conditions, particularly among youth with chronic pain and chronic fatigue (Pinquart & Shen, 2011). Considering the prevalence of depressive disorders and subclinical depressive symptoms among youth in general (Mojtabai et al., 2016) and the potential effects of stress related to chronic symptoms and disability, the findings of this study emphasize the importance of considering depressive symptoms in the assessment and treatment of chronic OI and related conditions in youth.

While anxiety symptoms had significant bivariate relationships with AD symptom severity and functional disability, study findings did not support mediation models for anxiety nor did they support moderation and additive models when AD symptom severity and depressive symptoms were simultaneously considered. This may be related to the overlap between physiologic symptoms of anxiety and OI symptoms (e.g., heart rate changes, dizziness). It is possible that other forms of anxious distress, rather than symptoms of anxiety disorders, may be more relevant to AD symptom-related disability in youth. For example, pain catastrophizing is implicated in the fear-avoidance model of chronic pain and has been empirically linked to functional disability among individuals with chronic pain (Asmundson et al., 2012; Leeuw et al., 2007). The potential role of catastrophic interpretations of AD symptoms in functional disability should be investigated in youth with chronic OI.

The lack of support for moderation models in this study should not exclude future exploration of moderation models for other psychosocial variables in determining functional impairment due to chronic OI. That is, other factors may influence whether or the degree to which chronic physical symptoms lead to impairment, as appears to be the case for family environment in determining the degree of functional impairment associated with pediatric chronic pain (Guite et al., 2007).

Limitations

Findings from this study should be interpreted in the context of several limitations. Longitudinal studies are needed to address limitations in the cross-sectional design to determine whether the presumed direction of relationships in these models is supported (Maxwell et al., 2011). The study sample included patients seeking tertiary care with, on average, moderate symptom-related functional disability. OI symptoms, emotional distress, and functioning may present differently in nonclinical, epidemiologic samples. Consistent with previously reported characteristics of youth and adults with chronic OI conditions (Johnson et al., 2010; Stewart et al., 2018), the sample comprised a majority of White, female participants. Study results may not adequately reflect the experiences of males or individuals identifying with gender, racial, or ethnic minoritized groups. The possibility of self-selection bias may also limit generalizability of findings, as 31% of patients invited to participate in this study did not enroll.

Implications and Future Directions

Findings from this initial evaluation of models of functional disability in youth with chronic OI warn against viewing these youths’ functional challenges through either a purely biomedical or a purely psychological perspective. While certainly some symptoms of depression (e.g., fatigue, poor sleep, poor appetite) overlap with AD symptoms, our results indicate that individuals’ experience of depressive symptoms has a significant effect on their functioning that is unique from the effect of AD symptoms. Study results are also clear that depressive symptoms do not fully account for the effect of AD symptoms on functional disability, arguing against viewing these patients’ debilitation as psychosomatic. Unfortunately, in our clinical experience, a number of youth with chronic OI conditions have reported that in seeking medical care for their AD symptoms, their symptoms had been attributed to psychological factors (e.g., “It’s all in your head.” “Nothing is medically wrong—you’re just depressed.”). This study’s findings emphasize the need for integrated medical and psychosocial evaluation of youth presenting with debilitating AD symptoms, treatment targeting AD symptom management, and referral behavioral health services to assess and treat relevant psychological needs.

Future studies to further develop biopsychosocial models of functional disability should test the generalizability of these models to the range of youth with chronic OI conditions and assess the contributions of additional psychosocial factors such as symptom catastrophizing and parental factors. Specifically, models of functional disability should be assessed among youth with chronic OI seeking care in a range of medical settings (including primary care); potential gender and racial/ethnic differences should be evaluated; and the contributions of cognitive, family, and social factors to multiple domains of functioning should be assessed. Additionally, longitudinal studies are needed to address limitations in cross-sectional designs and to examine the relationships among changes in AD symptoms, psychosocial factors, and functional debilitation over time (Maxwell et al., 2011). Intervention studies could also shed light on direction of effects by studying, for example, whether depressive symptoms improve following improvement of AD symptoms resulting from treatment. Results of these studies would assist medical providers in identifying when psychosocial interventions should be recommended along with fluid, exercise, and pharmacologic interventions for chronic OI as well as the specific targets of the psychosocial interventions (e.g., affective, cognitive, family functioning).

Funding

This work was supported by the Greg and Beth Wahl Research Fund and the Small Grants Program of the Mayo Clinic Department of Psychiatry & Psychology, which is funded by the National Center for Advancing Translational Sciences at the National Institutes of Health (grant number UL1TR000135).

Conflicts of interest: None declared.

Contributor Information

Michele S Tsai Owens, Department of Psychiatry, Indiana University School of Medicine, USA.

Bridget K Biggs, Department of Psychiatry and Psychology, Mayo Clinic, USA.

Amy C Fahrenkamp, Pain, Palliative Care, and Integrative Medicine Department, Children’s Hospitals and Clinics of Minnesota, USA.

Jennifer Geske, Department of Quantitative Health Sciences, Mayo Clinic, USA.

Deanna R Hofschulte, Department of Psychiatry and Psychology, Mayo Clinic, USA.

Cynthia Harbeck-Weber, Department of Psychiatry and Psychology, Mayo Clinic, USA.

Philip R Fischer, Department of Pediatric and Adolescent Medicine, Mayo Clinic, USA; Department of Pediatrics, Sheikh Shakhbout Medical City, United Arab Emirates; Khalifa University, United Arab Emirates.

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