Prevalence of Pediatric Acute-Onset Neuropsychiatric Syndrome and Associated Obsessive-Compulsive Symptoms in Youth with Avoidant/Restrictive Food Intake Disorder

Abstract

Objectives:

Individuals with both avoidant/restrictive food intake disorder (ARFID) and pediatric acute-onset neuropsychiatric syndrome (PANS) report restrictive eating. Inflammatory and immunological alterations may drive the onset of restrictive eating and comorbid obsessive-compulsive (OC) symptoms in PANS, while the etiology of restrictive eating in ARFID is unknown. Nevertheless, few studies have explored PANS and related OC symptoms among individuals with ARFID. We aimed to identify the frequency and nature of PANS and OC symptoms among those with full or subthreshold ARFID. We also explored associations between OC severity, ARFID profiles, and infection history.

Methods:

The study included 37 adolescents and young adults with subthreshold or full ARFID. We quantified the frequency of PANS/pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection symptoms and diagnoses, as well as OC symptoms and severity, in our ARFID sample. We analyzed associations between ARFID profiles and OC severity, along with the relationship between infection history and OC severity.

Results:

Two individuals (5%) met PANS criteria, and 17 (46%) reported lifetime mild–severe OC severity. The fear of aversive consequences profile was associated with a significant increase in log-transformed OC severity (β = 1.2, p = 0.04, adjusted R² = 0.10) after adjusting for sensory sensitivity, lack of interest, and body mass index z-score. We did not find any associations between OC severity and infection history.

Discussion:

In the first study to examine PANS and related symptoms among individuals with ARFID, we demonstrated salient overlap between PANS, OC symptoms, and ARFID. Further research is needed to examine the relationship between ARFID and PANS.

Keywords

feeding and eating disorders avoidant/restrictive food intake disorder ARFID obsessive-compulsive symptoms PANS restrictive eating infections sensory sensitivity fear of aversive consequences lack of interests

Introduction

Restrictive eating is a defining symptom of both anorexia nervosa (AN) and avoidant/restrictive food intake disorder (ARFID) (APA, 2022). Although lesser known, restrictive eating is also a core symptom of pediatric acute-onset neuropsychiatric syndrome (PANS), a postinfectious autoimmune neuropsychiatric disease characterized by the sudden onset or relapse of obsessive-compulsive disorder (OCD) and/or restrictive eating (Swedo et al., 2012). Youth with PANS present with a range of neuropsychiatric syndromes, including anxiety, emotional lability or depression, irritability/oppositional behavior, behavioral/developmental regression, deterioration of school or cognitive skills, sensory or motor abnormalities (e.g., tics), and somatic symptoms (e.g., sleep disruption, urinary symptoms; Calaprice et al., 2017; Frankovich et al., 2015; Gamucci et al., 2019; Gaughan et al., 2016; Gromark et al., 2019). While the restrictive eating behavior may present similarly in PANS and eating disorders, PANS is often linked to immunological or inflammatory conditions, such as H1N1 influenza, Epstein–Barr virus, and Borrelia burgdorferi (Lyme) disease. However, the PANS diagnosis is agnostic to infections due to the challenge of identifying a causal relationship between symptoms and specific infections (Caruso et al., 2000; Ercan et al., 2008; Fallon et al., 1998; Pavone et al., 2021). To date, only three studies have reported the prevalence of PANS within an eating disorders sample (Aman et al., 2022; Swedo et al., 2012; Toufexis et al., 2015) and only one study has specifically reported on ARFID (Aman et al., 2022).

PANS represents a clinical syndrome that is an expansion of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). Both PANS/PANDAS symptoms may follow a relapsing and remitting course, marked by “flare” periods where symptoms dramatically worsen for approximately 3–4 months (Brown et al., 2017). While PANDAS initially focused only on the abrupt onset of OCD and/or tics, clinical observations of the acute onset of restrictive eating behaviors promoted the inclusion of restrictive eating in PANS (Swedo et al., 2012). For example, several cases of children with PANS/PANDAS have described restrictive eating motivated by concerns of being overweight (Toufexis et al., 2015), sensory sensitivity (Toufexis et al., 2015), and fear of aversive consequences—such as fears of choking (Henry et al., 1999; Storch et al., 2004a; Toufexis et al., 2015), contamination (Storch et al., 2004a; Toufexis et al., 2015), vomiting (Toufexis et al., 2015), or allergic reaction (Toufexis et al., 2015). Although some cases involved co-occurring or subsequent body image concerns aligning more closely with AN, many have primarily described avoidant/restrictive eating behaviors (Toufexis et al., 2015), highlighting the potential overlap between PANS/PANDAS and ARFID (Strand et al., 2019). Notably, in the study examining PANS/PANDAS diagnoses among youth with eating disorders, only 23% (N = 23) were diagnosed with ARFID, with no detailed information on ARFID presentations available. Among the individuals with ARFID, 43% (N = 10) received a PANS diagnosis, with no PANDAS cases reported (Aman et al., 2022).

ARFID is an eating disorder characterized by extreme food avoidance due to sensory sensitivity, a lack of interest in food, and/or fear of aversive consequences that may occur with eating (American Psychiatric Association, 2022). The presentation of ARFID is heterogeneous, fitting a dimensional model, whereas individuals show heterogeneity in both symptom severity and profiles (Thomas et al., 2017). OCD, encompassing the core symptoms of PANS/PANDAS, is often comorbid with ARFID, with suggested rates of comorbidity from 3% to 20% (Cañas et al., 2021; Kambanis et al., 2020; Lieberman et al., 2019; Nitsch et al., 2023; Norris et al., 2021). Specifically, greater severity in the sensory sensitivity or the fear of aversive consequences profiles of ARFID is uniquely associated with up to triple the odds of OCD and related disorders (Kambanis et al., 2020). Although studies supported the association between ARFID and OCD (Fisher et al., 2014; Kambanis et al., 2020; Nicely et al., 2014; Norris et al., 2021), no study has investigated the associations between ARFID profiles and OC severity, which may highlight important insights into the nuances of ARFID presentations and inform more targeted interventions.

The primary goals of this study were to characterize OC severity, PANS/PANDAS diagnoses, and lifetime symptoms of OC and PANS/PANDAS within each ARFID profile among adolescents and young adults with full and subthreshold ARFID. We also aimed to examine unique associations between ARFID profiles and OC severity. Given the phenotypic overlap between OCD and individuals with the ARFID fear of aversive consequences profile (e.g., fear of choking or vomiting), we predicted that this profile would contribute to OC severity. Finally, we aimed to investigate the association between OC severity and past streptococcal pharyngitis as well as nonstreptococcal infections, hypothesizing that past infections would be significantly associated with OC severity.

Methods

Participants

Participants from a multidisciplinary study on the neurobiology of ARFID (National Institute of Mental Health R01MH108595) were invited to participate in a substudy exploring OC and PANS/PANDAS symptoms. Subjects were recruited for the parent study between July 2016 and January 2021 at Massachusetts General Hospital, Boston, USA, with Institutional Review Board approval. For the current substudy, participants were recruited from January 2020 to January 2021. Participants were sourced from both treatment settings (i.e., eating disorder clinics, adolescent medicine programs, hospital research programs) and nontreatment settings (i.e., social media, flyers, clinical research websites). Only individuals with full or subthreshold ARFID and without other significant current eating disorders were included. Detailed inclusion and exclusion criteria are available in the Supplementary Data; further details on the dataset have been published previously by our team (Kambanis et al., 2025). After excluding participants with missing data, the sample consisted of 37 participants. Thirty-three participants were available for analyses of OC severity because of the missing data in four participants. Demographic and clinical characteristics of the sample are summarized in Supplementary Table S1.

Procedure

We obtained written informed consent from all participants. We assessed ARFID profiles and severity at baseline using the Pica, ARFID, and Rumination Disorder Interview (PARDI; Bryant-Waugh et al., 2019). The PARDI is a semi-structured interview that assesses full versus subthreshold ARFID and provides a severity score for each Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) ARFID profile on a scale from 0 to 6, where higher scores indicate greater severity. Further details on full versus subthreshold ARFID diagnoses and ARFID profiles are available in the Supplementary Data. The PARDI has shown excellent psychometric properties (Bryant-Waugh et al., 2022; Cooper-Vince et al., 2022).

During a 2-year follow-up, we collected self-reports of lifetime OC symptoms and severity, probable diagnosis and symptoms of PANS/PANDAS, and infection history. We assessed OC symptoms and severity using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) for participants 18 years and older (Goodman et al., 1989a, 1989b) and the Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS) for those younger than 18 (Scahill et al., 1997). Both scales include a symptom checklist and a 10-item severity scale, with each item rated from 0 (None) to 4 (Extreme). The Y-BOCS and CY-BOCS have demonstrated satisfactory reliability and validity (Abramowitz and Deacon, 2006; Lewin et al., 2014; Scahill et al., 1997; Storch et al., 2004b).

We adapted the PANS/PANDAS self-report form from a previous study (Harris et al., 2021) and the 31-item PANS Symptom Rating Scale (Bernstein et al., 2024). To establish the diagnosis of PANDAS and evaluate immunological functions, we asked about the history of streptococcal pharyngitis, premature birth, Lyme disease, and nonstreptococcal infections, including Mycoplasma pneumoniae, tonsillitis, ear infections, and pneumonia. The PANS/PANDAS criteria featured in the questionnaire are aligned with the guidelines proposed by others (Swedo et al., 2012) and are informed by the diagnostic flowchart from the PANDAS Physicians Network (https://www.pandasppn.org/flowchart). Notably, the psychometric properties of the PANS/PANDAS questionnaires have not been validated, and there are currently no formal diagnostic interviews or self-report questionnaires specific to PANS/PANDAS. For the comprehensive PANS/PANDAS questionnaires and infection history form, please see the Supplementary Data.

Data analyses

For our first aim, we quantified the frequency and severity of OC symptoms, as well as PANS/PANDAS symptoms and diagnoses within each ARFID profile. For our second aim, because the OC severity score did not follow a normal distribution, we examined the association between OC severity and each ARFID profile using the Wilcoxon rank-sum test. We conducted linear regression to predict log-transformed OC severity, with the three ARFID profiles and body mass index (BMI) z-score as predictors. The BMI z-score was calculated based on age- and gender-adjusted Centers for Disease Control and Prevention growth charts (National Center for Health Statistics, 2024), allowing for standardized comparisons across youth. For individuals older than 20 years, the BMI z-score was calculated by comparing it to the 20-year-old cohort. To preclude multicollinearity within our regression model, we assessed associations among the three PARDI profiles and BMI z-score. For categorical measures of ARFID profiles, we used previously established clinical cutoffs (Cooper-Vince et al., 2022). Fisher’s exact test found no significant associations between categorical profiles of fear of aversive consequences and sensory sensitivity (p = 1), fear of aversive consequences and lack of interest (p = 0.404), or lack of interest and sensory sensitivity (p = 1). The Wilcoxon rank-sum test showed no significant associations between BMI z-score and any ARFID profile (lack of interest: p = 0.483; fear of aversive consequences: p = 0.328; sensory sensitivity: p = 0.316). Given these findings, our linear model incorporated all categorical ARFID profiles and BMI z-score as predictors. We further refined our model using stepwise selection based on the Akaike information criterion to determine the most predictive ARFID-related model for OC severity. For our third aim, we used the Wilcoxon rank-sum test to examine associations between OC severity and past streptococcal pharyngitis, as well as OC severity and any nonstreptococcal infections. All data analyses were conducted in R (R Core Team, 2023; Version 4.3.1, Inc., Boston, MA).

Results

Clinical features of the ARFID sample

Our study included 37 participants (median [IQR] age = 16.9 [14.1–21.9] years), with 20 (54.1%) females and 17 (45.9%) males. The participant pool was predominantly White (N = 34, 91.9%), with 8.1% (N = 3) identifying as multiracial. In addition, four (10.8%) participants identified as Hispanic/Latinx. The median BMI z-score for the group was −0.32 (IQR = −1.53 to 0.74). The sensory sensitivity subtype was the most common (N = 33, 89.2%), followed by lack of interest (N = 27, 73%), and fear of aversive consequences (N = 8, 21.6%). Four participants (10.8%) had subthreshold ARFID, while 33 (89.2%) were diagnosed with ARFID. Further demographic details and psychiatric comorbidities are provided in Supplementary Table S1.

Characterization of OC severity and PANS/PANDAS in our ARFID sample

Of the 37 participants, 17 (46%) reported mild-to-severe lifetime OC severity, with contamination obsessions being the most prevalent (N = 15, 40.5%), followed by checking compulsions (N = 14, 37.8%). Two participants (5.4%) met the criteria for probable PANS diagnosis. The most common PANS symptoms were general anxiety (N = 22, 59.5%) and depressed mood (N = 17, 45.9%), followed by social anxiety, panic attacks, and irritability (all N = 11, 29.7%). No participants had a positive PANDAS diagnosis. Table 1 shows the detailed frequencies of OC severity level, PANS/PANDAS diagnoses, and individual OC and PANS symptoms under each ARFID profile. Among the two subjects with a probable PANS diagnosis, one exhibited symptom aligning with the lack of interest profile, and both exhibited symptoms associated with the fear of aversive consequences and sensory sensitivity profiles.

Table 1.

Frequency of Obsessive-Compulsive Symptoms and Severity, Pediatric Acute-Onset Neuropsychiatric Syndrome Symptoms, Pediatric Acute-Onset Neuropsychiatric Syndrome/Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection Diagnosis, and Infection History by Avoidant/Restrictive Food Intake Disorder Profile

	Lack of interests (n = 27)	Sensory sensitivity (n = 33)	Fear of aversive consequences (n = 8)
OC symptoms
Washing/cleaning compulsions	9 (33%)^a	9 (27%)	3 (37%)
Checking compulsions	11 (40%)	11 (33%)	3 (37%)
Repeating compulsions	5 (18%)	5 (15%)	1 (12%)
Counting compulsions	5 (18%)	5 (15%)	1 (12%)
Arranging/symmetry compulsions	2 (7%)	3 (9%)	2 (25%)
Hoarding/saving compulsions	4 (14%)	5 (15%)	0 (0%)
Miscellaneous compulsions	13 (48%)	14 (42%)	5 (62%)
Aggressive obsessions	8 (29%)	7 (21%)	2 (25%)
Contamination obsessions	13 (48%)	14 (42%)	4 (50%)
Hoarding/saving obsessions	4 (14%)	4 (12%)	0 (0%)
Sexual obsessions	3 (11%)	4 (12%)	2 (25.0%)
Religious/moral obsessions	2 (7%)	3 (9%)	1 (12 %)
Health-related obsessions	8 (29%)	8 (24%)	5 (62%)
Miscellaneous obsessions	12 (44%)	12 (36%)	4 (50%)
OC severity
Subclinical	10 (37%)	14 (42%)	0 (0%)
Mild	5 (18%)	7 (21%)	3 (37%)
Moderate	6 (22%)	6 (18%)	2 (25%)
Severe	3 (11%)	3 (9%)	1 (12%)
Extreme	0 (0%)	0 (0%)	0 (0%)
Missing	3 (11%)	3 (9%)	2 (25%)
PANS symptoms
General anxiety	17 (63%)	19 (57%)	7 (87%)
Separation anxiety as a child	3 (11%)	4 (12%)	1 (12%)
Social anxiety	10 (37%)	9 (27%)	2 (25%)
Irrational fears	8 (29%)	8 (24%)	4 (50%)
Panic attacks	9 (33%)	9 (27%)	6 (75%)
Emotional liability	5 (18%)	5 (15%)	1 (12%)
Irritability	11 (40%)	10 (30%)	3 (37%)
Severe oppositional behaviors	1 (3%)	1 (3%)	0 (0%)
Depressed mood	15 (55%)	14 (42%)	6 (75%)
Behavioral or developmental regression as a child	2 (7%)	1 (3%)	0 (0%)
Deterioration in work/school performance as a child/adult	5 (18%)	5 (15%)	0 (0%)
Sensory or motor abnormalities	5 (18%)	5 (15%)	2 (25%)
Sleepwalking	0 (0%)	2 (6%)	1 (12%)
Challenges staying asleep or falling asleep	9 (33%)	8 (24%)	2 (25%)
Falling asleep during the day	2 (7%)	2 (6%)	0 (0%)
Enuresis	2 (7%)	2 (6%)	0 (0%)
Loss of bladder control	0 (0%)	0 (0%)	0 (0%)
PANS/PANDAS diagnosis
PANS diagnosis	1 (3%)	2 (6%)	2 (25%)
PANS diagnosis (no coincidence)^b	1 (3%)	3 (9%)	2 (25%)
PANDAS diagnosis	0 (0%)	0 (0%)	0 (0%)
Any positive diagnosis of streptococcal pharyngitis
Never	8 (29%)	9 (27%)	1 (12%)
>1 times	18 (66%)	23 (69%)	7 (87%)
Missing	1 (3%)	1 (3%)	0 (0%)
Associated conditions
Tonsillectomy/adenoidectomy	1 (3%)	1 (3%)	0 (0%)
Premature birth	2 (7%)	2 (6%)	0 (0%)
Lyme disease	2 (7%)	2 (6%)	1 (12%)
Any nonstreptococcal infections^c	16 (59%)	19 (57%)	4 (50%)

Percentages are based on the sample size of each ARFID profile.

Criterion of coincidence = endorsed the PANS symptoms coincided with the symptoms of picky eating.

Including Mycoplasma pneumoniae, tonsillitis, ear infections, and pneumonia.

OC, obsessive-compulsive; PANS, pediatric acute-onset neuropsychiatric syndrome; PANDAS, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection.

Associations between OC severity and ARFID profiles

Consistent with our hypothesis, we found a significant association between OC severity and the fear of aversive consequences profile (W = 122.5, p = 0.05, Fig. 1). However, there were no significant associations between OC severity and either the lack of interest profile (W = 149.5, p = 0.09) or the sensory sensitivity profile (W = 46.5, p = 0.95). In our regression model, the fear of aversive consequences profile was significantly associated with an increase in OC severity on the log scale (β = 1.24, p = 0.04) after adjusting for sensory sensitivity, lack of interest, and BMI z-score (adjusted R² = 0.10). Furthermore, stepwise model selection indicated that the lack of interest (β = 0.71, p = 0.16) and fear of aversive consequences (β = 1.16, p = 0.05) profiles together provided the most effective predictive linear model for OC severity (adjusted R² = 0.14).

FIG. 1.

Boxplots of OC severity by ARFID subtype. The y-axis represents OC severity scores, ranging from 0 to 40, with higher scores indicating greater severity. Note that due to missing data in OC severity, the boxplots are based on N = 33 subjects. ARFID, avoidant/restrictive food intake disorder; OC, obsessive-compulsive.

Associations between OC severity and infection history

Contrary to our hypothesis, we did not find any significant associations between OC severity and any past streptococcal pharyngitis episodes (W = 107.5, p = 0.88) or any nonstreptococcal infections (W = 123, p = 0.72).

Discussion

In our study, we observed a relatively high frequency of OC symptoms, especially with 41% of participants with full or subthreshold ARFID reporting contamination obsessions. In comparison, prevalence estimates of OC symptoms in the general population of adolescents range from 2% to 19%, varying by factors such as age and country of origin (Mathes et al., 2019). Moreover, consistent with our hypothesis, the fear of aversive consequences subtype of ARFID was significantly associated with increased OC severity. This specific ARFID subtype might share psychopathological mechanisms with OCD, wherein food avoidance serves as a mechanism to alleviate obsessive fears about food intake, such as fears of contamination. We also noted a high prevalence of PANS symptoms, especially general anxiety (60%). Interestingly, Toufexis et al. (2015) reported that 66% of their PANS pediatric sample exhibited food restrictions secondary to contamination fears. Our findings replicate and extend potential overlap in the shared psychopathologies of fear of aversive consequences in ARFID, OC, and PANS.

Surprisingly, only a small proportion of our participants (5%) met the criteria for a probable PANS diagnosis, with none qualifying for a PANDAS diagnosis. This prevalence is comparable to those found in studies of pediatric patients with related disorders, such as abrupt symptom onset in tic disorders (11%; Singer et al., 2000); PANS in a movement disorders clinic (1%; Kilbertus et al., 2014); and PANS/PANDAS in an outpatient OCD clinic (5%; Jaspers-Fayer et al., 2017). The relatively low prevalence of PANS in our sample could also be impacted by our inclusion of both young adult and subthreshold ARFID cases, which may not typically exhibit as pronounced PANS/PANDAS symptoms as pediatric cases. Contrary to past evidence (Leckman et al., 2011; Swedo et al., 1998), we did not find significant associations between infections and OC severity. This lack of association may be due in part to the reliance on self-reported infection history, making it difficult to confirm positive diagnoses of infectious diseases.

Conclusions

This is the first study to investigate the prevalence of PANS/PANDAS and OC symptoms in a sample diagnosed with full or subthreshold ARFID, and the first to investigate the unique association between ARFID profiles and OC severity. We demonstrated salient overlaps between PANS, OC symptoms, and ARFID. The shared psychopathology between the fear of aversive consequences subtype of ARFID, OC severity, and PANS demonstrates the potential to create transdiagnostic constructs that might benefit treatment endeavors. Nevertheless, our study is limited in our sample size, our heterogeneous sample that includes young adults and subthreshold ARFID, and low ethnic/racial diversity, with limited generalizability to greater populations. Further research is needed to characterize PANS/PANDAS prevalence in ARFID profiles in pediatric and adult samples and examine the relationships between ARFID, OCD, and PANS/PANDAS.

Clinical Significance

High rates of contamination-related OC symptoms in ARFID, particularly in the fear of aversive consequences profile, suggest clinicians should routinely assess for obsessive fears and compulsive avoidance. Our finiding reinforce the importance of incorporating exposure-based cognitive-behavioral strategies into ARFID treatment. Although PANS presentations were uncommon, the overlap among anxiety, OC symptoms, and restrictive eating underscores the need for careful differential diagnosis in complex cases.

Authors’ Contributions

L.B.: Conceptualization, methodology, formal analysis, writing—original draft, visualization, supervision, and funding acquisition. C.J.: Data Curation, methodology, formal analysis, writing—original draft, and visualization. Z.Z. and F.P.: Data curation, formal analysis, and writing—review and editing. J.G.: Data curation, investigation, and project administration. C.S. and D.L.K.: Data curation and writing—review and editing. P.E.K., H.B.-M., K.R.B., M.M., K.T.E., N.M., and K.W.: Writing—review and editing. E.A.L. and J.J.T.: Conceptualization, supervision, funding acquisition, and writing—review and editing.

Footnotes

Disclosures

E.A.L. receives grant support and research study drugs from Tonix Pharmaceuticals and receives royalties from UpToDate. E.A.L. and/or immediate family member holds stock in Thermo Fisher Scientific, Zoetis, Danaher Corporation, Intuitive Surgical, and Merck. E.A.L. is an inventor on U.S. provisional patent application no. 63/467,980 (Oxytocin-based therapeutics to improve cognitive control in individuals with attention-deficit/hyperactivity disorder).

Supplemental Material

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