Anxiety and Depression Screening of Youth in Pediatric Pulmonary Hypertension Clinic: A Multi‐Center, Cross‐Sectional Study

Authors: Claire Parker, Elise Whalen, Michael A. Smith, Jasmine Becerra, Leah Stevens, Catherine M. Avitabile, Anna Brown, Michelle Cash, Emma Olson Jackson, Julia McSweeney, Kathleen Miller‐Reed, Janette T. Reyes, Cathy Sheppard, Mary P. Mullen

Abstract

Children with chronic diseases, including pulmonary hypertension (PH), have an increased risk of anxiety and depression (AD), impacting mental health (MH), and quality of life (QoL). We sought to characterize the prevalence of AD in pediatric PH and identify associated factors. We developed a prospective cross‐sectional study with 10 Pediatric Pulmonary Hypertension Network (PPHNet) centers. Eligible subjects aged 12–21, diagnosed with PH, and English or Spanish speaking, completed validated AD screening questionnaires during routine outpatient clinic visits. Caregivers provided socioeconomic status (SES) data and MH history via survey. Patient demographics and clinical characteristics were analyzed using standard descriptive statistics. Eighty‐eight patients were enrolled (female = 54, 61%). Forty‐six (51.7%) identified at least mild symptoms of AD. Females were more likely to report AD than males (OR 2.67, 95% CI 1.11–6.61, p = 0.030). There were no significant associations between AD and PH severity, MH history, family dynamics, SES status, race, or ethnicity. Twenty‐seven of those patients (58.7%) received MH education/counseling by MH professionals; ten (21.7%) were referred to MH providers, and nine patients (19.6%) were assessed for suicide safety. Adolescents with PH have a high prevalence of AD. Female patients had increased AD compared to male patients; no other predictors were linked to the prevalence of AD. Routine AD screening should be integrated into outpatient PH clinic visits with a focus on psychosocial support for young females diagnosed with PH.

Introduction

Recent global initiatives have increasingly focused on mental health (MH) awareness in diverse environments, including workplaces and schools, underscoring its critical importance. The World Health Organization (WHO) stresses the importance of safeguarding MH, with a focus on prevention efforts, which is especially vital for children [1]. Pediatric MH is a priority health concern as recent studies suggest a nearly twofold increase in MH disorders such as anxiety and depression (AD) among adolescents since the beginning of the COVID‐19 pandemic [2, 3]. Children with chronic diseases, including those with pulmonary hypertension (PH), are at an even higher risk for developing AD [4].

PH is a rare lung disease with significant morbidity and mortality. PH is a progressive disease with symptoms of breathlessness, decreased endurance, and right‐sided heart failure that affects activities of daily living and quality of life (QoL). Despite recent improvements in long‐term outcomes for PH patients, optimizing QoL remains essential [5]. Key studies have reported that patients diagnosed with PH experience lower QoL scores compared to other life‐threatening conditions, emphasizing the need for targeted interventions [5, 6, 7].

Studies in adult PH have highlighted the prevalence and impact of AD, emphasizing the importance of early detection and the global trend of clinicians underestimating these conditions among clinicians [8, 9]. These findings are consistent with broader research indicating that individuals with chronic illnesses including children, are more likely to suffer from AD [10]. Unrecognized AD can impair QoL and exacerbate further decline in physical functioning [11]. Therefore, targeted psychological interventions are recommended to enhance emotional well‐being and QoL for patients with PH [12]. The 2022 European Society of Cardiology/European Respiratory Society guidelines for the diagnosis and treatment of PH support the increased use of AD screening tools for adult PH patients to provide appropriate psychosocial referrals [13]. These recommendations parallel those supported by the Cystic Fibrosis (CF) Foundation for CF patients, another group of adolescents with chronic disease in whom psychological symptoms have been shown to impact lung function, body mass index, medical treatment adherence, and hospitalization rates [14].

To understand pediatric PH provider perspectives of AD in this population, Parker et al. surveyed 36 providers from 13 North American PH centers [15]. The survey revealed that while providers recognized the importance of MH screening and were aware of AD among their patients, their programs lacked a standardized assessment process and access to MH services. Barriers to screening were identified and included unfamiliarity with screening tools and discomfort in addressing MH issues among PH care providers.

The present study is the first aimed at characterizing the prevalence of AD and identifying associated factors in the pediatric PH population across major pediatric PH centers in North America.

Methods

Members of the Advanced Practice Provider Initiative (APPI), a subgroup of the Pediatric Pulmonary Hypertension Network (PPHNet), developed this multi‐center study. A central IRB was established at the University of California, San Francisco (UCSF) with participation from 10 PPHNet centers (Texas Children's Hospital (TCH), Boston Children's Hospital, Children's Hospital of Colorado, Children's Hospital of Philadelphia, Cincinnati Children's Hospital, Seattle Children's Hospital, Stollery Children's Hospital, The Hospital for Sick Children, and Vanderbilt Children's Hospital). A centralized REDCap database was created for data collection.

Patients were recruited through convenience sampling during routine PH follow‐up in outpatient clinics, with consent obtained on‐site to facilitate immediate support if needed. Inclusion criteria were current diagnosis of PH in World Symposium on Pulmonary Hypertension (WSPH) Diagnostic Groups 1–5 as per established clinical criteria, ages 12–21 years at the time of consent, ability to provide assent to participation, enrollment in the outpatient setting, ability to speak either Spanish or English and ability to complete the Patient Health Questionaire‐9A (PHQ‐9A)/Patient Health Questionaire‐9 (PHQ‐9) or Generalized Anxiety Disorder (GAD‐7) questionnaires without assistance. Pregnant women were excluded.

Study activities including questionnaire completion occurred before the visit with the PH provider. Once the patient and parent provided assent/consent, the patient was given either the PHQ‐9A or PHQ‐9 as appropriate for age, and the GAD‐7 to complete in privacy. The PHQ‐9, PHQ‐9(A), and the GAD‐7 are screening tools derived from the larger Patient Health Questionnaire (PHQ), a self‐administered screening tool to assess five of the most common MH disorders. These screening tools were selected due to their validated effectiveness in the target age group and their availability in both English and Spanish [16, 17]. The study coordinator scored screening tools in the clinic and provided scores to the PH provider. Utilizing the study algorithm, the provider intervened as appropriate (Figure 1).

A survey was given to the parent or child's primary caregiver to collect additional data including the child's date of birth, gender, race/ethnicity, any known history of a MH diagnosis, family demographics including educational level, financial information such as total household income and insurance, school attendance, and accommodations, as well as the impact of COVID‐19 on the household. This survey was accessible via QR code and could be completed on a mobile device in clinic. Additional patient PH health‐related data was collected through a retrospective chart review by the study coordinator.

Data were collected from June 2022 through October 2023. UCSF and TCH managed the REDCap database and provided statistical analysis of the results. Patient demographics and clinical characteristics were summarized using standard descriptive statistics. Continuous variables were first assessed graphically for normality and mean/standard deviation were reported for normally distributed continuous variables and median/interquartile range were reported for skewed distributions. Odds ratios (OR) for the binary outcome of AD were determined for select predictors using univariate logistic regression models. Predictors were selected a priori based on their perceived clinical relevance and potential for association with AD. Each predictor was entered into a separate model to estimate crude odds ratios with 95% confidence intervals (CIs) and corresponding p‐values. All statistical analyses were performed in R [18].

Results

Eighty‐eight subjects were enrolled in the study (female = 54, 61%). The mean age of the patients was 15.8 years (range 12–21 years). Non‐Hispanic white patients comprised 55.7% of the total study population. Eighty‐four percent of the subjects were from WSPH Group 1, followed by 11.4% from WSPH Group 3. Most subjects were WSPH Functional Class I–II (85.2%), while 14.8% were WSPH Functional Class III–IV. Over half (51.1%) were on triple PH therapy with a phosphodiesterase‐5 inhibitor, endothelin receptor antagonist, and prostacyclin. At least 25% of the study population were on a continuous prostacyclin (intravenous or subcutaneous treprostinil) (Table 1).

Twenty‐six percent of patients had at least one existing MH diagnosis, including anxiety, depression, obsessive‐compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), and posttraumatic stress disorder (PTSD), with notable variations in treatment and support. Eight (9.5%) of those patients were on medications for their MH diagnosis. There was an established relationship with a counselor/therapist, psychologist, psychiatrist, or other MH professional in 44.5% (39) of the total cohort. A palliative care service was involved with 23.9% of the subjects (Table 2).

PHQ‐9/PHQ‐9(A) and GAD‐7 scoring revealed that over half of the subjects (n = 46; 51.7%) displayed at least mild symptoms of anxiety or depression. Approximately 42% (n = 37) exhibited at least mild symptoms of depression, and 45.5% (n = 40) exhibited at least mild symptoms of anxiety (Table 3). To evaluate factors associated with AD amongst the study population, we examined PH clinical, MH, and socioeconomic metrics with univariate statistical analysis (Figure 2). There were no associations between an increased prevalence of AD and PH severity, MH history, family dynamics, SES status, race, or ethnicity. Females were more likely to report AD as compared to their male counterparts (OR 2.67, 95% CI 1.11–6.61, p = 0.030), which is consistent with other AD prevalence literature.

All 46 patients with elevated PHQ9(A) and GAD‐7 received at least one additional MH intervention. Of the 46 subjects, 27 (58.7%) had a social worker or designated MH professional to provide direct counseling and education, 10 subjects (21.7%) were referred for psychotherapy, and 9 subjects (19.6%) were assessed for suicide safety and subsequently referred to psychotherapy (Table 4).

Discussion

This cross‐sectional study examining a multicenter cohort of patients from leading pediatric PH centers underscores the importance of further exploring the MH impacts on health‐related QoL and health behaviors, including adherence to treatment plans and stress response. We found a high prevalence of AD, which affected significantly more female adolescents with PH. Screening for AD within our outpatient clinics led to a significant amount of MH referrals.

Gender Differences

In our convenience sample composed predominantly of females, females reported AD more often and with greater severity than males based on AD screening scores. This aligns with research showing higher AD rates in healthy adolescent females, influenced by gender roles and developmental factors [19, 20]. Bussotti and Sommaruga also highlighted the prevalence of mental disorders, particularly AD, in female PH patients from the Registry to Evaluate Early and Long‐term Pulmonary Arterial Hypertension Disease Management (REVEAL Registry), noting a global tendency for clinicians to underestimate these conditions [9].

The literature on gender differences in adolescents with PH is limited, though adult studies provide relevant insights. Adolescent females, now of childbearing potential, are learning about the increased risks associated with pregnancy and maternal mortality of women with PH [21, 22]. Yee et al. explored sexual health and sexual QoL among adult female PH patients, revealing concerns about intimate relationships, body image, and self‐esteem, often exacerbated by their condition [23]. Many of the subjects had fear of maintaining intimate relationships and worry about the burden of PH placed on their partner. Most participants noted a decline in self‐esteem and poor body image related to their treprostinil infusion, oxygen use, and/or weight gain related to PH [23]. This suggests that similar challenges may affect adolescent females with PH, though the full impact on MH remains unclear.

Given the higher prevalence of AD among females in our study and the adult literature, we recommend further study of targeted AD screening and women's health interventions for females with PH. Efforts could include allocated research funding to explore issues facing women with PH such as reproductive health, awareness campaigns, and enhanced MH resources. Further research is needed to understand the differences between female PH patients and healthy cohorts and to identify factors influencing AD severity. Additionally, potentially protective factors that may lead to less AD in males with PH should be explored. However, our findings suggest that males with PH had higher AD scores compared to their healthy peers, suggesting screening should not be limited to females alone.

Associated Predictors

In this population, there is concern regarding the impact of reduced physical functioning on the patient's PH and their ability to engage in meaningful activities and fulfill roles they view as important. Psychosocial development in the adolescent years is typically reflective of a need for greater independence and control. Teens with PH face specific challenges related to their illness, such as limitations in completing daily activities independently and reduced mobility. The use of drug therapy, including continuous infusion pumps for prostacyclin, comes with significant effects. Patients and families are educated about the critical nature of maintaining medication adherence to avoid severe consequences including disease worsening.

Frequent absences from school due to illness, hospitalization, or medical appointments are common in this population. We attempted to capture various metrics, expecting that factors such as increased hospitalizations or worsening functional class (which assesses the severity of disease‐related symptoms and their impact on daily activities) might indicate a higher risk for the development of AD. However, none of these metrics were identified as significantly associated with AD, except for gender, which is a non‐modifiable potential associated factor.

This suggests that disease severity alone is not a reliable predictor of AD in teens with PH in this sample. Simply having PH is the associated factor for AD, regardless of treatment or severity. Implementing standardized screening practices in outpatient PH clinic may be necessary to ensure no teen with AD goes undetected and untreated, which could lead to decreased quality of life and worsened AD long‐term.

Limitations

Our study faced limitations including a relatively small sample size, potential participation bias, and lack of a control group. Adolescents without significant AD may have been more willing to participate and complete a questionnaire. Those with AD may opt‐out to avoid parental or caregiver involvement or knowledge. Additionally, the presence of parents or caregivers during AD questionnaire completion introduces potential bias. Consequently, our data may either underrepresent or overrepresent the overall prevalence.

Compared to PPHNet registry data, which represents the patient population at PPHNet centers, our cohort had a higher proportion of female subjects (61.4% vs. 48.7%) and a greater percentage of WSPH Group 1 patients (84.1% vs. 41.7%) [23]. It should be noted that PPHNet registry data includes pediatric patients of all ages, whereas our study focused on an age range of 12–21 years. Additionally, there was no comparable data on functional class or medications due to differences in data collection. This limits generalizability to the larger pediatric PH population.

We also attempted to compare our data to post‐pandemic AD populations for context. This study was among the few in the literature focusing on understanding AD prevalence in the pediatric PH cohort, thus limiting comparisons primarily to adult PH populations and other chronic diseases.

Implications for Practice

AD can potentially influence the child's stress response and their resilience likely varies. The findings underscore the urgent need for universal AD screening in adolescents with PH given a lack of clear association despite evaluating for various metrics. This approach ensures equal opportunities for MH education and psychology referral when necessary. Integrating AD questionnaires into pediatric registries, alongside existing QoL tools, can enhance comprehensive patient assessments and facilitate timely interventions.

Currently, MH screening is typically deferred to the patient's primary care provider or pediatrician, although adolescents with PH often have more frequent interactions with their PH clinician. Stronger relationships between patients and PH clinicians can foster open discussions about MH, leading to more effective therapeutic interventions. While PH center structures vary by program, centers interested in implementing universal screening should establish plans for managing positive screens and accessing appropriate referral networks.

Future study is needed to explore the gender differences observed, with higher odds of experiencing AD among females than males. A larger study with more extensive sample size exploring AD prevalence in this population could provide meaningful insights to risk profiles. Adult studies have assessed AD prevalence alongside factors such as resiliency and coping, which should be considered in children with PH as well.

Conclusion

This study found that adolescents with PH have a high prevalence of AD. More than 50% of participants showed symptoms of at least mild anxiety and or depression, highlighting the urgent need for targeted MH support in this population. This rate was found to be consistent with trends in comparable chronic disease populations. Particularly in young women, targeted screening and low threshold for psychology referral is recommended to better support QoL and psychosocial impacts of disease. We recommend establishing support groups for adolescents and young women with PH and conducting further research to better understand and address the specific needs of this subpopulation.

Additionally, non‐profit organizations could play a significant role by facilitating overall MH awareness campaigns, providing educational resources, and creating targeted support programs for adolescents with PH. Collaboration with healthcare providers to ensure comprehensive care, including MH services, could also enhance outcomes. Studies are needed to explore gender‐specific differences relative to the general population and to develop interventions tailored to the psychosocial needs of female adolescents with PH. This comprehensive approach aims to improve the overall well‐being and QoL for youth facing the challenges of PH.

Author Contributions

All authors contributed to the design, data analysis, and or manuscript preparation.

Ethics Statement

All study sites received IRB approval as per known human subjects research standards.

Conflicts of Interest

The authors declare no conflicts of interest.