Abstract
Background
Multiple psychological factors and related comorbidities affect children with chronic pancreatitis (CP) or acute recurrent pancreatitis (ARP). We aimed to describe the frequency of psychological symptoms/diagnoses in children with CP/ARP and predict the severity of the disease burden based on these factors.
Methods
We retrospectively identified patients ages >=5 years with prior history of CP/ARP seen by a pediatric psychologist as part of their evaluation for total pancreatectomy with islet autotransplantation (TPIAT) at a single center. Symptoms of psychological disorders and prior psychological diagnoses were identified. Patients and their families completed pain questionnaires as part of clinical care. Demographic and pancreatic disease data were collected from electronic medical records.
Key Results
Of 105 children (mean age 12.1 ± 3.5 years, 54.3% females, 84.4% white), 37.1% had a psychological diagnosis [20.0% anxiety, 13.3% depression, 23.8% attention deficit hyperactivity disorder (ADHD), 4.8% post-traumatic stress disorder (PTSD)] while 86.7% displayed symptoms based on DSM-5 criteria (75.7% anxiety, 32.3% depression, 21.1% suicidal ideation, 40.2% panic). Regarding pain, 38.8% of patients reported daily abdominal pain, 24.3% weekly, 14.6% monthly, and 22.3% less than once per month. In the six months pre-psychology appointment, 70.9% used opioids in the inpatient setting, 25.7% used outpatient, and 45.2% were on a neuromodulator to control their pain. Median pain severity did not statistically differ by psychological diagnosis or symptoms (p=.16).
Conclusion
There was a high prevalence of psychological diagnoses/symptoms in patients with ARP/CP including suicidal ideation. This highlights the need for future prospective studies to explore the role of mental health in disease outcomes in children with CP or ARP.
Keywords: pancreatitis, psychological, anxiety, depression, suicidal ideation
Introduction:
Chronic pancreatitis (CP) or acute recurrent pancreatitis (ARP) can have a significant impact on a child’s quality of life.1 Per the International Study Group of Pediatric Pancreatitis: In Search for a Cure (INSPPIRE) criteria, CP is diagnosed in the presence of: (1) typical abdominal pain plus characteristic imaging findings or (2) exocrine insufficiency plus imaging findings or (3) endocrine insufficiency plus imaging findings. ARP is diagnosed as ≥two or more distinct episodes of AP with intervening return to baseline.2 The prevalence of CP in children is estimated to be 6 in 100,000.3
The burden of ARP and CP in children is significant, with studies showing 84.3% of these children report pancreatitis-related abdominal pain significantly affects their daily functioning.4 Constant pain is reported in 23.6% of children with ARP or CP.1 Children with CP and ARP report frequent pain, multiple hospitalizations and ER visits, endoscopic and surgical therapies, including total pancreatectomy with islet autotransplantation (TPIAT) and missed school, all of which impact their quality of life. 5 Currently there is limited research on the interplay between CPIARP and adverse mental health outcomes.
Psychological comorbidities are common among adults with CP or ARP. A study using data from the United States National Inpatient Sample found the prevalence of anxiety or depression in adults with CP to be 31 %.6 The prevalence of psychological comorbidities and/or symptoms of depression or anxiety in children with CP have not previously been evaluated.
The aims of this study were to 1) describe the frequency of psychological comorbidities in children with ARP or CP and 2) explore the association between the prevalence of psychological comorbidities in children with ARP or CP with their pain characteristics and use of analgesics.
Methods:
Clinical cohort:
This study identified patients ages 5 years and above with a prior history of CP or ARP who were seen by a pediatric psychologist at Cincinnati Children’s Hospital and Medical Center as part of their TPIAT multidisciplinary workup from April 2018 to May 2024. Exclusion criteria included patients less than 5 years old and those with significant developmental delays which would impair their ability to complete the pain rating scale As part of the TPIAT evaluation at Cincinnati Children’s Hospital and Medical Center (CCHMC), a multidisciplinary pain evaluation is completed by a pain physician and pediatric psychologist. Clinical documentation pertaining to the patient’s TPIAT workup was reviewed from pediatric psychology, pain management, and gastroenterology specialists for psychological comorbidities, pain history, and pancreatitis symptoms and treatment history, respectively. As part of the TPIAT evaluation, a multidisciplinary pain evaluation is completed by a pain physician and pediatric psychologist. Every patient presenting for a TPIAT evaluation is required to have an evaluation with a pediatric psychologist, irrespective of pre-existing diagnoses or clinical symptoms. Clinical documentation pertaining to the patient’s TPIAT workup was reviewed from pediatric psychology, pain management, and gastroenterology specialists for psychological comorbidities, pain history, and pancreatitis symptoms and treatment history, respectively. Demographic data was obtained from electronic medical records (EMR). All the notes screened occurred in the same weeklong time period, and no data was screened from the chart that was after those dates. This study was approved by the CCHMC Institutional Review Board.
Psychological and Pain Assessments:
The psychologists conducted health and behavior assessments based on the DSM-5 criteria to identify anxiety, depression, and panic disorders. Common symptoms for anxiety included worry that is difficult to control, restlessness or feeling on edge, being easily fatigued, difficulty concentrating or mind going blank, irritability, muscle tension, and sleep disturbance.7 Common symptoms for depression included depressed mood/sadness, diminished interest/please in activities significant changes in weight, insomnia/hypersomnia, psychomotor agitation/retardation, fatigue/loss of energy, irritability or history of suicidal ideation. 8 The psychologists working with the pancreas care team at CCHMC conducted health and behavior assessments rather than a psychological diagnostic interview. As a result, they only described symptoms of psychological disorders based on DSM-5 criteria and did not make a formal psychological diagnosis. Any psychological diagnoses reported for the patient were historical, and these historical diagnoses were reported in the psychologist’s evaluation note. Any symptoms of psychological diagnoses reported were collected during the clinical interview with a CCHMC psychologist.
At the Pancreas Care Center, pain team evaluations include a pain physician and a psychologist for the initial assessments and follow ups. Prior to the pediatric psychology appointment, patients or their caregivers completed the Numeric Rating Scale (NRS) pain questionnaire, rating their average pain, highest pain, lowest pain, and current pain based on the NRS pain scale. With this scale, zero represents no pain at all, while 10 represents the worst pain imaginable.9 The patient’s EMR was screened to collect this data. Finally, the EMR was screened for pain medication usage including neuropathic pain medications, inpatient only opioid use, and outpatient opioid use (<6 months from pediatric psychology appointment).
Following data collection, patients were grouped into the following cohorts: those with a psychological diagnosis or history of suicidal ideation, those with other psychological symptoms but no prior diagnosis, and those with neither a diagnosis nor symptoms (Figure 1). The descriptors previously described were then compared between groups to analyze for trends.
Figure 1: Distribution of Psychological Diagnoses and Symptoms in Children with Acute Recurrent and Chronic Pancreatitis -.
The distribution of patients based upon their psychological status. Those in the psychological diagnosis cohort had historical diagnoses of anxiety, depression, or post-traumatic stress disorder, while the rest of the patients were grouped based on their stated symptoms collected during their appointment with a pediatric clinical psychologist.
Statistical Methods:
Continuous measures were presented with either means (SD) or medians (Ql, Q3), while categorical metrics were reported as frequencies and percentages. Comparisons by diagnoses and symptoms groupings were evaluated using chi-square, ANOVA, or Kruskal-Wallis tests. A p-value < 0.05 was considered statistically significant. All analyses were conducted using SAS v9.4.
Results:
A total of 105 patients met the inclusion criteria. The mean age was 12.1 ± 3.5 years, 54.3% were female, mean BMI was 22.8 ± 6.6, and 84.4% were white. The age ranged from 5-21 years (Table 1). The prevalence of acute recurrent pancreatitis was 10.5% and the prevalence of chronic pancreatitis was 89.5% (Table 1). Regarding pain, 38.8% of patients reported daily abdominal pain, 24.3% had pain weekly, 14.6% had pain monthly, and 22.3% had pain less than monthly. The median duration of pain was 48 months (Table 2). 98% had abdominal pain (55.2% epigastric/upper abdominal, 15.2% periumbilical, 4.7% lower abdominal, 18.1% generalized, and 4.7% multiple locations), 80.9% had nausea, 46.7% vomiting, and 25.7% had weight loss (Table 3). 70.9% of patients used opioids inpatient in the past six months to control their pain, while 25.7% of patients used opioids outpatient in the past six months to control their pain (11.4% daily, 3.8% weekly, and 10.5% monthly), and 45.2% of patients were on a neuromodulator drug (including gabapentin, duloxetine, pregabalin, or amitriptyline) to control their pain (Table 2). For therapeutic interventions, 76.2% of patients underwent endoscopic retrograde cholangiopancreatography (ERCP) with interventions and 50.5% of patients later underwent TPIAT (Table 2).
Table 1:
Demographic Data and Psychological Characteristics
| N | 105 |
|
| |
| Age at appointment (years), mean (SD) | 12.1 (3.5) |
|
| |
| Sex | |
| Female | 54.3% (57) |
| Male | 45.7% (48) |
|
| |
| Race | |
| White | 84.4% (81) |
| African American | 8.3% (8) |
| Middle Eastern | 2.1% (2) |
| Asian | 1.0% (1) |
| Pacific Islander | 1.0% (1) |
| American Indian/Alaskan Native | 1.0% (1) |
| Multiple Races | 2.1% (2) |
|
| |
| Body Mass Index, mean (SD) | 22.8 (6.6) |
|
| |
| Body Mass Index Z-score, mean (SD) | 0.88 (1.13) |
|
| |
| Psychological Diagnosis,% (n) | 23.8% (25) |
|
| |
| Symptoms,% (n) | |
| Anxiety | 75.7% (78) |
| Depression | 32.3% (32) |
| Panic | 40.2% (39) |
| Suicidal Ideation | 21.2% (20) |
|
| |
| Diagnoses, % (n) | |
| ADHD | 23.8% (25) |
| Anxiety | 20.0% (21) |
| PTSD | 4.8% (5) |
| Depression | 13.3% (14) |
| Bipolar I or II | 0% (0) |
|
| |
| Psychological Diagnosis or Symptoms% (n) | 86.7% (91) |
ADHD: Attention-deficit/Hyperactivity Disorder, PTSD: Post Traumatic Stress Disorder
Those with only an ADHD diagnosis were excluded from the psychological diagnosis group
Table 2:
Pain Characteristics
| Frequency of Pain, % (n) | |
| Daily | 38.8% (40) |
| Weekly | 24.3% (25) |
| Monthly | 14.6% (15) |
| Less than monthly | 22.3% (23) 1 |
|
| |
| Type of Pain, % (n) | |
| Intermittent | 64.8% (68) |
| Constant | 35.2% (37) |
|
| |
| Severity of Pain, Median (Ql,Q3) | 3 (0,5) |
|
| |
| Inpatient Opioid Use, % (n) | 70.9% (73) |
|
| |
| Outpatient Opioid Use, % (n) | |
| None | 74.3% (78) |
| Once per week | 3.8% (4) |
| More than once per week | 11.4% (12) |
| Once per month | 10.5% (11) |
|
| |
| Duration of Pain (months), Median (Ql, Q3) | 48 (18, 84) |
|
| |
| Neuropathic Pain Medication Use, % (n) | 45.2% (47) |
|
| |
| ERCP with Interventions,% (n) | 76.2% (80) |
|
| |
| TPIAT, % (n) | 50.5% (53) |
ERCP: Endoscopic Retrograde Cholangiopancreatography, TPIAT: Total Pancreatectomy with Islet Autotransplantation
Table 3:
Demographics and Clinical Characteristics Among Cohorts
| Psychological Diagnosis | Psychological Symptoms | No Diagnosis or Symptoms | P-value | |
|---|---|---|---|---|
|
| ||||
| % (n) | 23.8% (25) | 61.0% (64) | 15.2% (16) | |
|
| ||||
| Age at appointment (years), mean (SD) | 13.3 (3.4) | 12.1 (3.5) | 10.3 (3.0) | 0.026 |
|
| ||||
| Sex | 0.29 | |||
| Female | 68.0% (17) | 50.0% (32) | 50.0% (8) | |
| Male | 32.0% (8) | 50.0% (32) | 50.0% (8) | |
|
| ||||
| Race | 0.37 | |||
| White | 91.3% (21) | 84.5% (49) | 73.3% (11) | |
| African American | 4.4% (1) | 8.6% (5) | 13.3% (2) | |
| Middle Eastern | 0% (0) | 3.5% (2) | 0% (0) | |
| Asian | 0% (0) | 0% (0) | 6.7% (1) | |
| Pacific Islander | 4.4% (1) | 0% (0) | 0% (0) | |
| American Indian/Alaskan | 0% (0) ( | 1.7% (1) | 0% (0) | |
| Native | 0% (0) | 1.7% (1) | 6.7% (1) | |
| Multiple Races | ||||
|
| ||||
| Body Mass Index, mean (SD) | 26.7 (7.6) | 21.6 (6.2) | 21.3 (4.1) | 0.002 |
|
| ||||
| Body Mass Index Z-score, mean (SD) | 1.34 (1.0) | 0.68 (1.2) | 1.00 (1.0) | 0.045 |
|
| ||||
| Pancreatitis Type, % (n) | 0.91 | |||
| Acute Recurrent | 8.0% (2) | 10.9% (7) | 12.5% (2) | |
| Chronic | 92.0% (23) | 89.1% (57) | 87.5% (14) | |
| Pain Location, % (n) | 0.81 | |||
| Periumbilical | 12.0% (3) | 12.9% (8) | 31.3% (5) | |
| Generalized | 24.0% (6) | 17.7% (11) | 12.5% (2) | |
| Epigastric/upper abdominal | 56.0% (14) | 56.5% (35) | 56.3% (9) | |
| Lower abdominal | 4.0% (1) | 6.5% (4) | 0% (0) | |
| Multiple | 4.0% (1) | 6.5% (4) | 0% (0) | |
|
| ||||
| Nausea, % (n) | 88.0% (22) | 87.3% (48) | 100.0% (15) | 0.47 I |
|
| ||||
| Vomiting, % (n) | 50.0% (12) | 48.2% (26) | 73.3% (11) | 0.21 I |
|
| ||||
| Weight Loss, % (n) | 25.0% (6) | 25.9% (15) | 40.0% (6) | 0.52 |
We found that 23.8% of the patients had a psychological diagnosis, with the most common being anxiety (20%), followed by depression (13.3%) and post-traumatic stress disorder (PTSD, 4.8%, Table 1). Patients with only attention deficit hyperactivity disorder (ADHD) diagnosis were excluded from the psychological diagnosis group during comparisons since it was not an internalizing disorder. Internalizing disorders are defined as those that tend to be composed of relative covert symptoms, many of which are cognitive, internal to the youngster, or relatively difficult to observe.10 In addition, 86.7% of patients displayed symptoms of psychological diagnoses based on DSM-5 criteria (75.7% anxiety, 32.3% depression, 21.1% suicidal ideation, and 40.2% panic, Table 1, Figure 2). Suicidal ideation would point to a diagnosis of depression. Hence, it was included in the first group of psychological diagnosis during group comparisons.
Figure 2: Overlap of Psychological Symptoms in Children with Acute Recurrent and Chronic Pancreatitis -.
A visual representation of the prevalence of psychological symptoms in the study cohort. Those endorsing symptoms of multiple psychological diagnoses are represented by the overlapping circles, to represent the patients in the cohort which were impacted in multiple domains.
Comparing the three cohorts of those with a pre-existing psychological diagnosis, those with psychological symptoms but no prior diagnosis, and those with neither a diagnosis nor symptoms, age (p=.026) and BMI (p=.002) statistically differed between groups with patients in the psychological diagnosis group being older and more obese (Table 3). Neuropathic pain medication use including gabapentin, duloxetine, pregabalin, or amitriptyline, significantly differed between groups with 68% usage among those with psychological diagnoses, 36.5% usage among those with psychological symptoms, and 43.8% usage among those with neither a diagnosis nor symptoms (p=.028, Table 3). No significant association was observed between pain frequency among the study groups (p=.21, Table 4).
Table 4:
Comparison of Pain Characteristics Among Cohorts
| Psychological Diagnosis | Psychological Symptoms | No Diagnosis or Symptoms | P-value | |
|---|---|---|---|---|
|
| ||||
| Frequency of Pain, % (n) | 0.21 | |||
| Daily | 54.2% (13) | 33.3% (21) | 37.5% (6) | |
| Weekly | 20.8% (5) | 27.0% (17) | 18.8% (3) | |
| Monthly | 0% (0) | 19.1% (12) | 18.8% (3) | |
| Less than monthly | 25.0% (6) | 20.6% (13) | 25.0% (4) | |
|
| ||||
| Severity of Pain, Median (Ql, Q3) | 4(1,6) | 2 (0, 4) | 2 (0, 5) | 0.16 |
|
| ||||
| Highest Pain Severity, Median (Ql, Q3) | 7 (4, 9) | 6 (2, 9) | 7(5,10) | 0.48 |
|
| ||||
| Outpatient Opioid Use, % (n) | 0.53 | |||
| None | 68.0% (17) | 78.1% (50) | 68.8% (11) | |
| Any | 32.0% (8) | 21.9% (14) | 31.3% (5) | |
|
| ||||
| Duration of Pain (months), median (Ql, Q3) | 60 (19, 96) | 36 (15,84) | 50 (20, 60) | 0.44 |
|
| ||||
| Neuropathic Pain Medication Use, % (n) | 68.0% (17) | 36.5% (23) | 43.8% (7) | 0.028 |
|
| ||||
| ERCP with interventions, % (n) | 80.0% (20) | 75.0% (48) | 75.0% (12) | 0.88 |
|
| ||||
| TPIAT, % (n) | 60.0% (15) | 46.9% (30) | 50.0% (8) | 0.54 |
Abbrevations: ERCP:Endoscopic Retrograde Cholangiopancreatography TPIAT: Total Pancreateectomy with Islet Autotransplantation
Discussion:
Our study reports a novel finding in the literature, describing psychological comorbidities in a sample of US children with ARP and CP. We found a high percentage of anxiety and depressive symptoms in children with ARP/CP. These symptoms could lead to worse pain and functional disability outcomes in this medically complex population.11 This is an important finding given that underlying psychiatric diagnoses and mood disorders have been shown to affect the efficacy and response to pain-focused psychology and return to function management12, and are known risk factors for on-going pain and disability, as well as continued mood disorders despite remission of pain, into adulthood.13
The prevalence of psychological diagnoses in the pediatric population is a growing concern. United States data collected through the National Health Interview Survey from 2021-2022 demonstrates that 10% of children ages 3-17 years old were diagnosed with anxiety, 4% of children had depression while 7% had other behavioral disorders.14 The patients in our study demonstrated higher rates of psychological diagnoses, with 20% anxiety and 13.3% diagnosed with depression. In children aged 6 to 12y, the prevalence of suicidal ideation was 7.5%15, while our cohort showed a prevalence of 21.1%.
Among US adolescents ages 12–17y in 2021-2022, 21% reported symptoms of anxiety in the past two weeks and 17% reported symptoms of depression in the past two weeks. 14 Our study found 86.7% of patients to display symptoms of psychological diagnoses based on DSM-5 criteria of the disorder (75.7% anxiety, 32.3% depression, and 40.2% panic).
Alarmingly, the patients in our study with CP or ARP had much higher rates of adverse psychological diagnoses than the general population, with most notably almost three times higher rates of suicidal ideation. We also found patients with a psychological diagnosis were older and had a higher BMI compared to the other two cohorts. Independently, both age and BMI have been previously shown to predispose someone to adverse mental health outcomes. 16 A study of almost 10,000 discrete hospitalizations for youth with chronic pancreatitis found that almost 20% had a psychological disorder. 17 This suggests that disease burden and pain could be contributing to the development of psychological symptoms in youth with CP or ARP. However, there is a significant gap in literature when it comes to reporting rates of psychological comorbidities in these youth, despite numerous studies for pediatric patients with other GI-pain based conditions, such as Inflammatory Bowel Disease.
When looking at 2022 data on psychological disorders in the adult population with ARP or CP, 18.2% of adults aged 18 years and older experienced any symptoms of anxiety and 21.4% symptoms of depression. 18 The severity of symptoms continued to differ by sociodemographic and geographic characteristics. The percentage of adults with mild, moderate, or severe symptoms of both anxiety and depression decreased with age and were higher among women than men. 1 8 In adults with CP the prevalence of anxiety was 20% and the prevalence of depression was 23.9%19, which is similar to the data found in our study. In 2023, a large study showed that even after a single episode of AP, adults had a higher rate of a psychological disorder compared to individuals who were hospitalized with another acute pain condition (i.e., appendicitis).20 The association between chronic pain in the setting of pancreatitis and psychological problems in adults is well-documented.
It is difficult to draw conclusions on CP in adults versus children, as the disease course of pediatric pancreatitis has not been investigated in children into adulthood, and the risk factors for developing CP or ARP in the two populations are starkly different.21 Risk factors for children include genetic mutations (CFTR, PRSSl, SPINKl, CTRC), obstructive, traumatic, infectious, and metabolic causes.21 Risk factors for adults include alcohol abuse, smoking, hypertriglyceridemia, gallstones, drugs, and abdominal trauma.22 Further investigation is needed to understand the progression of children with CP or ARP into adulthood and how the disease burden changes.
With regards to pain, current literature suggests that among children with CP or ARP, almost a quarter (23.6%) of children reported having constant pain, and 75.1% reported episodic pain, with only 1.5% of patients being prescribed opioids for outpatient use.1 In comparison, 35.2% of our cohort had constant pain, 64.8% had intermittent pain, and 25.7% were prescribed opioids for outpatient use in the previous six months. This again demonstrates the need for further investigation into the role that pain has in the quality of life and well-being of children with CP or ARP.
We were limited by the retrospective design and the cross-sectional nature of the study. This research was done at a single center, which introduces bias and can limit broad application of the findings in this research, re-enforcing the need for further investigation and research. Due to time constraints and purpose of clinical evaluation, a full psychological diagnostic interview could not be conducted to delineate if clinical mood disorders were present.
Higher rates of psychological symptoms and diagnoses in our cohort, compared to the 2021-2022 published data, may reflect the lingering impact of the COVID-19 pandemic on child and adolescent mental health, rather than solely attributed to pancreatic-associated pain and disability. 14 The impact of COVID-19 on psychological outcomes was hard to fully account for, and as such we were unable to completely assess the scope in which it may have impacted the results. The association between older age and higher likelihood of psychological diagnosis may be influenced by the link between progressive disease burden and psychological outcomes, potentially introducing a measurement bias. The patients’ pain ratings were subjective and sometimes were proxy-reported by the parents, both which led to a limited ability to interpret the pain ratings and a potential reporting bias. Accurate pain outcome assessments have been an ongoing issue in clinical pediatric CP trials as well. 23 Utilizing a validated pain questionnaire would better elicit any association of the presence of psychological symptoms on pain morb.1d.1ty. 24
Strengths of this study include a moderate sample size and the integration of multiple unique assessments, including pain assessments, medication usage, and multidisciplinary team assessments. This was done to ensure that readers were provided with a comprehensive view of the disease burden in children with ARP or CP.
To conclude, our study found a significant portion of patients with ARP and CP with underlying psychological comorbidities at our single center institution. These preliminary findings underscore the importance of mental health screenings in this population. Future larger multicenter, multi-countries, multi-ethnicity studies are needed to provide a global understanding of psychological comorbidities in ARP and CP. An increased awareness, systematic assessment and a multidisciplinary approach to treatment is required to improve the care of this medically complex population. Specifically, routine screening of depression and anxiety symptoms in youth who present to gastroenterologists could yield valuable information and facilitate appropriate treatment referrals.
Grants and financial support:
Dr. Santucci is supported by the NIH NIDDK K23DK135797. Dr. Abu-El-Haija is supported by the NIH 23DK118190, R03 DK13l 156.
Footnotes
Conflicts: Dr. Santucci is a consultant for Ironwood and a key opinion leader for Kate Farms and Gi Health Foundation. No other authors have any conflict of interest.
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