Anxiety and Obsessive-Compulsive Disorder (OCD) in Adults with CHARGE Syndrome

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Madhavan-Brown, Timothy S. Hartshorne, Sarah B. Schneider, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7278769/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 02 Mar, 2026 Read the published version in Journal of Neurodevelopmental Disorders → Version 1 posted 8 You are reading this latest preprint version Abstract Background CHARGE syndrome is a rare genetic disorder with multiple physical, cognitive, behavioral, and sensory impairments. Anxiety is a common finding. Difficulties with pain, sleep, sensory impairment, communication, daily stress, and unpredictable environments are potential contributing factors to this anxiety. Further research is needed to gain a better understanding of the presentation of anxiety in CHARGE syndrome to promote proper diagnosis and treatment of anxiety. Methods An on-line survey was distributed to adults and guardians of adults with CHARGE syndrome. Fifty-two participants provided responses to the Developmental Behavior Checklist-Parent Version , the Florida Obsessive-Compulsive Inventory , and the Generalized Anxiety Disorder 7-Item Scale . Participants also provided demographic data, diagnostic characteristics of CHARGE, their perception of their anxiety, diagnosed mental health disorders, and the frequency of other potential factors of anxiety (i.e. pain and sleep concerns). Descriptive statistics, independent samples t-tests, and Pearson’s correlations provided information on the presentation of anxiety and the relationships between potential factors and anxiety subscale scores. A hierarchical multiple linear regression analysis and mediation analysis was used to investigate if sleep mediates the relationship between pain and anxiety. Results Generalized anxiety disorder and obsessive-compulsive disorder were the first (39% of sample) and fourth (27% of sample) most common mental health diagnoses reported and 50% of the sample had been diagnosed with at least one anxiety disorder. The most commonly reported anxious behaviors included getting obsessed with an idea or activity, being impatient, getting upset or distressed over small changes in the routine or environment, and being tense, anxious, or worried. Sleep was found to mediate the relationship between pain and anxiety. Conclusions This study has implications for understanding the behavioral phenotype of CHARGE syndrome. Based on self-report or legal guardian report, anxiety is a common experience among individuals with CHARGE; generalized anxiety disorder and obsessive-compulsive disorder diagnoses/behavior are the most frequently reported. Further research into the management of pain and improvement of sleep as anxiety interventions for individuals with CHARGE may prove fruitful. CHARGE syndrome anxiety obsessive-compulsive disorder pain sleep behavioral phenotype Figures Figure 1 BACKGROUND CHARGE syndrome is a rare (approximately 1 in every 10,000 live births) congenital disorder with multiple physical, cognitive, behavioral, and sensory impairments. The majority of cases are caused by a CHD7 gene mutation (1). The presence of major and minor anomalies is frequently used as an accurate method of clinical diagnosis (2). The major criteria are described as the four "C's" of CHARGE (coloboma, choanal atresia, cranial nerve anomalies, characteristic CHARGE inner & outer ear) with many other minor criteria used in diagnosis (3, 4). Anxiety and Obsessive-Compulsive Disorder Within CHARGE Syndrome Previous research, while limited, indicates obsessive-compulsive disorder (OCD) and anxiety disorders are among the top three most common mental health diagnoses among individuals with CHARGE syndrome. Blake et al. (5) found that 43% of caregivers of individuals with CHARGE reported that their child had an OCD diagnosis and 37% indicated an anxiety disorder diagnosis. Wachtel et al. (6) found that 19.5% of participants endorsed an anxiety disorder diagnosis and 17.2% endorsed an OCD diagnosis. N. Hartshorne et al. (7) found that 47% of adolescents and adults with CHARGE endorsed obsessive-compulsive behaviors and 45% endorsed anxiety. In a survey of parents and guardians of children and adolescents with CHARGE syndrome, Madhavan-Brown (8) found that OCD (11%) and generalized anxiety disorder (GAD; 7.5%) were the third and fourth most common mental health diagnoses reported and 16% of the total sample had been diagnosed with at least one anxiety disorder. Taken together, this research suggests that anxiety and related diagnoses are prevalent concerns in those with CHARGE syndrome and, therefore, can have a significant impact on the behavior of these individuals (9). Many of the most common anxious behaviors (10–12) are also exhibited by individuals with CHARGE syndrome, particularly self-injurious behavior, sleep problems, and repetitive behaviors (5, 8, 9, 13, 14). Hartshorne and Cypher (14) found that 36% of their 100 participants engaged in repetitive or compulsive behavior characteristic of OCD, despite only three participants having an official, clinical diagnosis. In another study, parents of children with CHARGE reported “obsession with an idea or activity” as occurring the most often (8). Bernstein & Denno (13) found that their participants with CHARGE received an above average score on the Compulsive Behavior Checklist (15) and 72% of participants engaged in repetitive behavior for an hour or more each day. A majority of the participants reported that these behaviors negatively interfered with social activities, relationships, and daily routines. Repetitive behavior is recognized as part of the CHARGE syndrome behavioral phenotype (16). Repetitive behavior is hypothesized to be correlated with anxiety, as it has been observed to increase during times of stress (9). Adults with CHARGE show higher rates of OCD symptomatology and diagnosis (i.e., 11–43% prevalence; 5, 6) compared to the general population (i.e., 2.3% incidence; 17). Preliminary research has also found a similar pattern in children with CHARGE (8). Thus, obsessions and (particularly) compulsive behaviors are commonly reported among individuals with CHARGE and updated research on the prevalence of OCD diagnoses in individuals with CHARGE would be beneficial. Etiology of Anxiety Within CHARGE Syndrome It has been suggested that the common physical, cognitive, and behavioral characteristics associated with CHARGE syndrome can lead to higher levels of anxious behavior (9). Some of these characteristics include pain, sleep concerns, and sensory impairment. Difficulties with communication, stress, and lack of predictability in the environment could also be contributing factors. Individuals with developmental disabilities experience a higher number of health conditions (e.g., constipation, gastroesophageal reflux disease, sleep problems) compared to the overall population (14, 16, 18, 19). Furthermore, people with CHARGE often contend with a high number of hospitalizations and surgeries (14, 20). Stratton and Hartshorne (20) found parents of children with CHARGE reported that a large number experienced pain at high frequencies. Research suggests that increased prevalence of challenging behaviors and anxiety among individuals with developmental disabilities (and/or CHARGE) could be a result of their overall health, medical conditions, and level of pain (18, 19). Pain has been described as an important—if not the most important—influence on the behavior of individuals with CHARGE (9). Over half of the CHARGE population has reported sleep problems (i.e., 59% incidence; 7) including: obstructive sleep apnea, initiation or maintenance of sleep, and difficulties sleeping due to visual impairment (21). Research has shown that lack of sleep is linked to increases in challenging behaviors (18, 22). The relationship between anxiety and sleep has been seen as reciprocal; a pattern seen in survey research of adolescents and adults with CHARGE (7). Given the high incidence of sleep problems among individuals with CHARGE syndrome and the apparent association between sleep problems and anxiety, it is not surprising that there is a common concern of anxiety among those with CHARGE. Individuals with CHARGE syndrome can experience deficits in some or all of the seven sensory systems (23) which, in turn, have a significant impact on behavior (9). The environment is often unpredictable—and potentially anxiety-provoking—to individuals with CHARGE because they have a reduced ability to efficiently or effectively gather information about the environment from their sensory systems. Challenges with communication are also common in the CHARGE population (4). Difficulties with communication, coupled with multi-sensory impairment, make it difficult for these individuals to explore, obtain, comprehend, and use information from their environment (24). This lack of predictability and daily stress can result in higher levels of anxiety (9, 25–27). Thus, individuals with CHARGE experience many of the common causes of anxiety. Research Questions Research on anxiety and anxious behavior among individuals with CHARGE syndrome is limited. Studies have indicated that particular subtypes of anxiety can vary between genetic syndromes or developmental disorders (28–31) but CHARGE has yet to be included. Preliminary research suggests that CHARGE syndrome might have uniquely higher levels of OCD-related behavior than individuals with other genetic syndromes and typically developing children with an anxiety diagnosis (8). The etiology of anxiety may be more nuanced in low-incidence populations (29), therefore, further analysis of the types and frequency of anxious behavior exhibited by persons with CHARGE syndrome is needed to develop a better understanding of how anxiety manifests among adults with CHARGE. This analysis could help inform diagnosticians when making a mental health diagnosis for an individual with CHARGE. There were three research questions addressed in this study: What is the prevalence of anxiety and obsessive-compulsive diagnoses among adults with CHARGE Syndrome? What is the presentation of anxious and obsessive-compulsive disorders in individuals with CHARGE syndrome (including the types and frequency of anxious behavior)? How do pain and sleep contribute to anxiety in individuals with CHARGE? METHODS Participants Adults with CHARGE syndrome (ADULT group; n = 32) and legal guardians of adults with CHARGE syndrome (LG group; n = 20) were recruited and created a combined participant group (COMBINED group). Five participant responses were removed because they did not meet the inclusion criteria (e.g., no diagnosis of CHARGE syndrome, completed the incorrect survey, did not meet age criteria) leaving the final COMBINED participant group ( n = 52). All adults in the COMBINED group reported at least one major or minor characteristics of CHARGE (with many indicating several). The characteristics of CHARGE reported the most included: hearing impairment, visual impairment, developmental delay, and cranial nerve abnormalities or dysfunction. See Table 1 for demographic information. Table 1 Demographic Information ADULT group LG group COMBINED group n 32 20 52 Age (Years) Mean (Range) 29.03 27.50 28.47 (19–45) Gender % Female 68.75 55.00 63.46 Tested positive for CHd7 gene mutation n (%) 14 (44%) 9 (45%) 23 (44%) Tested positive for CHd7 gene mutation n (%) 3 (9.37%) 3 (15.00%) 6 (11.53%) Hearing impairment n (%) 29 (91%) 19 (95%) 48 (92%) Visual impairment n (%) 26 (81%) 18 (90%) 44 (85%) Coloboma of the eye n (%) 23 (72%) 17 (85%) 40 (77%) Heart defects or malformations n (%) 18 (56%) 16 (80%) 34 (65%) Choanal atresia or stenosis n (%) 17 (53%) 10 (50%) 27 (52%) Growth delay n (%) 24 (75%) 13 (65%) 37 (71%) Genital hypoplasia n (%) 19 (59%) 14 (70%) 33 (64%) Ear abnormalities n (%) 23 (72%) 18 (90%) 41 (79%) Measures Participant responses were collected during the beginning of the COVID-19 pandemic (Spring/Summer 2020). Two questions were asked to gather participant's perceptions on how this impacted their levels of anxiety. All participants (the COMBINED group) completed the CHARGE Syndrome Demographic/Anxiety Questionnaire and the Developmental Behavior Checklist-Parent Version (DBC-P; 32). The ADULT group also completed the Florida Obsessive-Compulsive Inventory (FOCI; 33) and the Generalized Anxiety Disorder 7-Item Scale (GAD-7; 34). Most of the CHARGE Syndrome Demographic/Anxiety Questionnaire items were adapted from previous research studies of individuals with CHARGE (35) and gathered basic demographic data and information about the diagnostic characteristics of CHARGE (2, 36) and frequency of pain and sleep concerns. Questions regarding anxiety were designed for this study. Additionally, information about whether the adult has been diagnosed with a mental health disorder and/or anxiety disorder was collected. These questions allowed us to gather an understanding of other anxious behaviors that adults with CHARGE may be exhibiting that are not captured in the anxiety scales used. The DBC-P (32) is a rating scale used to assess the frequency of behavioral and emotional concerns of individuals with developmental and cognitive disabilities aged 4–18 years. As the focus on this study was anxiety, only the items from the DBC-P Anxiety subscale (9 items; Cronbach’s alpha for current study: α = .66), DBC-P Anxious Behavior Rating Scale (ABRS; 7 items; Cronbach’s alpha for current study: α = .69) and additional items that mapped onto an anxiety diagnosis (28 items total, total possible raw score = 84; Cronbach’s alpha for current study: α = .86) were selected for the questionnaire. The DBC-P has also been used to research the behaviors of individuals with genetic syndromes (28). The FOCI (33) is a self-report questionnaire used to assess the presence and severity of symptoms related to obsessive-compulsive behavior (OCD). This is accomplished by two concurrent parts of the scale: a symptom checklist (The Checklist; K-R 20 = 0.83; Current study K-R 20 is: α = .86) and a Severity Scale (SS; α = .89; Cronbach’s alpha for current study: α = .88). This scale was selected as a behavior checklist for adults with CHARGE to provide information on their own OCD related behaviors. Prior research has indicated that the FOCI is highly correlated with the Yale-Brown Obsessive Compulsive Scale Self-Report (Y-BOCS-SR; 37) and has good internal consistency - with the overall scale and both components (33, 38, 39). The GAD-7 (34) is a self-report rating scale intended to assess symptomology of Generalized Anxiety Disorder. This scale was selected because it is a brief measure and would give an indication of the frequency of GAD symptoms in adults with CHARGE syndrome. The seven items of the GAD-7 (α = .92; Cronbach’s alpha for current study: α = .93) are rated on a 4-point Likert scale based on the frequency in the last two weeks. The GAD-7 has a sensitivity of 89% and 82% specificity for GAD (34). A meta-analysis of 11 studies (40) indicated that the scale was effective at identifying GAD using a cut score between 7–10 (with the optimal sensitivity and specificity at a cut score of 8). Additional studies have indicated that it has convergent validity with the Beck Anxiety Inventory and the anxiety subtest of the Symptom Checklist-90 (40–43). Procedure and Ethics An invitation to participate was distributed through Facebook pages specific to CHARGE syndrome and by the CHARGE Syndrome Foundation. Qualtrics® was used to develop, distribute, and collect the survey results. The responses of adults with CHARGE and parents/guardians were analyzed separately and there was no attempt to link parent and adult child responses. Indeed, measures were put in place to have the survey answered only once per family unit. The procedures, informed consent form, and all materials from this project were submitted and approved by the Institutional Review Board (IRB) of Central Michigan University in accordance with the Declaration of Helsinki. Informed consent to participate in the study was received from each participant. Clinical trial number: not applicable. Data Analysis To analyze the prevalence of anxiety and obsessive-compulsive disorders, descriptive statistics on the reported mental health diagnoses, GAD-7 results, and FOCI results were analyzed and compared to the prevalence rates among the general population provided by the National Institute of Mental Health. To determine the manifestation of these disorders the DBC-P responses were ranked from highest to lowest mean score as an indication of frequency and the frequency of responses on the GAD-7, FOCI, and perceived anxiety questions was also gathered. Lastly, in order to answer the third research question (impact of pain and sleep on anxiety), independent samples t-tests and Pearson’s correlations were calculated to determine the relationships between the potential factors, anxiety subscale scores, and the scores of both participant groups. A hierarchical multiple linear regression analysis and a mediation analysis were used to investigate if sleep mediates the relationship between pain and anxiety. The indirect effect was tested using a percentile bootstrap estimation approach implemented with the PROCESS macro Version 3 (44). This model estimated the direct effects of pain on anxiety and indirect change in anxiety once sleep was added to the model. The indirect effect of pain on anxiety after mediation by sleep was considered significant if the 95% confidence interval (CI) of the estimated effect does not include zero. RESULTS Prevalence of Anxiety Disorders The most common mental health disorders for the COMBINED group were generalized anxiety disorder (GAD), major depressive disorder (33%), attention-deficit hyperactivity disorder (ADHD), and obsessive-compulsive disorder (OCD). Autism spectrum disorder (ASD) was also a more common diagnosis in the LG group. From the COMBINED group, 26 participants (50%) noted at least one anxiety disorder and/or obsessive-compulsive disorder diagnosis; 13 participants (25%) noted more than one anxiety disorder diagnosis. Table 2 displays the results for the ADULT , LG , and COMBINED groups. Table 2 Mental Health Disorder Diagnoses Mental Health Disorder Diagnosis ADULT group n (%) LG group n (%) COMBINED group n (%) Generalized Anxiety Disorder 14 (44%) 6 (30%) 20 (39%) Major Depressive Disorder 14 (44%) 3 (15%) 17 (33%) Attention-Deficit Hyperactivity Disorder 7 (22%) 8 (40%) 15 (29%) Obsessive-Compulsive Disorder 7 (22%) 7 (35%) 14 (27%) Post-Traumatic Stress Disorder 4 (13%) 4 (20%) 8 (15%) Autism Spectrum Disorder 0 (0%) 7 (35%) 7 (14%) Social Anxiety Disorder 5 (16%) 0 (0%) 5 (10%) The ADULT group provided responses on assessment scales for GAD (GAD-7) and OCD (FOCI). Fifty percent of participants ( n = 16) indicated on the GAD-7 that their symptoms made it somewhat difficult for them to function in their home life, work settings, and/or relationships. A quarter of the respondents indicated no difficulty resulting from their symptoms ( n = 7, 25%). Another quarter indicated that their symptoms made it very or extremely difficult ( n = 7, 25%). Based on the responses from the ADULT group, 63% ( n = 20) of participants met the criteria for further evaluation of GAD. The FOCI symptom checklist provides a total score of obsession and compulsion traits (ranging from 0–20) with a score of eight or more indicating the potential for symptomology of OCD. Eleven participants (34%) indicating eight or more obsessions and/or compulsions. On the Severity Scale of the FOCI, 28% of participants ( n = 9) indicated that their symptoms had moderate to extreme impact on their level of distress, cognitions, and daily living activities. The prevalence of anxiety disorders (50% reporting at least one anxiety disorder or OCD diagnosis; 39% reporting a GAD diagnosis) was higher than the estimated national average for adults (31.1% and 2.3%, respectively; 17, 45). The results from the GAD-7 screener also indicated much higher potential levels of GAD (63%) than the general population (5.7%; 46). Moreover, the prevalence of diagnosed OCD among adults with CHARGE (27%) was much higher than the estimated national average for adults (2.3%; NIMH, 2017c) and 34% of the ADULT group reported 8 or more OCD traits (the cut-off on the FOCI screener) suggesting that the prevalence of OCD in CHARGE is higher than the general population. Anxious Behaviors Types and Frequencies After being given a definition of anxiety, respondents in the LG group were asked if they thought that their adult with CHARGE syndrome experiences anxiety while participants in the ADULT group were asked if they thought they had anxiety. Ninety percent of participants ( n = 47) in the COMBINED group answered yes. These participants rated how frequently this anxiety was expressed and 68% ( n = 32) indicated that this anxiety was experienced several times a week or more frequently (Table 3 ). The participants in the COMBINED group who indicated that they experience anxiety ( n = 47) were also asked to indicate how this level of anxiety was impacted by the COVID-19 pandemic. The respondents reported that the anxiety increased ( n = 28, 60%), stayed the same ( n = 16, 34%), or decreased ( n = 3, 6%), since the start of the pandemic. Table 3 Reported Frequency of Anxiety Frequency of Anxiety ADULT group n (%) LG group n (%) COMBINED group n (%) At least once per day 10 (31%) 6 (30%) 16 (30%) Several times a week 9 (28%) 7 (35%) 16 (30%) Once a week 3 (9%) 3 (15%) 6 (12%) A couple times a month /Every other week 5 (16%) 1 (5%) 6 (12%) Once a month 1 (3%) 1 (5%) 2 (4%) Once every few months 0 (0%) 1 (5%) 1 (2%) No anxiety 4 (13%) 1 (5%) 5 (10%) All 52 participants completed selected items from the DBC-P, which were chosen because they described behaviors related to anxiety and internalizing behavior and included a 7-item anxiety behavior rating scale [ABRS] from the DBC-P. The behaviors that the majority of participants indicated as the most frequently reported (i.e., very/often true) included getting obsessed with an idea or activity, being impatient, and getting upset or distressed over small changes in the routine or environment, and being tense, anxious, or worried. Three DBC-P items, that match criteria for OCD from the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th Edition) were rated by participants as behavior that their child with CHARGE syndrome exhibits sometimes or very often (i.e., gets obsessed with an idea or activity [92%], preoccupied with only one or two particular interests [77%], arranging objects or routine in a strict order [83%]) Indeed, obsession with particular ideas or activities was rated the most frequent out of all of the behaviors, with 54% of participants indicating that this behavior was very frequently shown. The ADULT group responses to the GAD-7 and FOCI also provided information on the types and frequency of anxious behavior reported by adults with CHARGE syndrome. The behavior indicated as the most frequently occurring (i.e., Nearly every day) on the GAD-7 was “worrying too much about different things”. On the first part of the FOCI (i.e., a checklist of common obsessions and compulsions), “worry about harm coming to a love one” and “worry about losing something valuable” were the most frequently reported obsessions while “feeling a need to ‘confess’” or “repeatedly asking for reassurance that you said or did something correctly” was the most frequently reported compulsion. Pain and Sleep Impacts on Anxiety of Adults with CHARGE Syndrome Respondents in the ADULT group were asked to report the frequency of their pain (e.g., migraines, abdominal migraine, surgery pain, constipation, ear infections, etc.) and difficulties with sleep (e.g., trouble falling asleep, trouble staying asleep, waking up multiple times in the night, etc.). The LG group was asked to provide the same information regarding their adult with CHARGE syndrome. There was a wide range of reported frequency of pain and sleep concerns (see Table 4 ) that ranged from once every few months to at least once a day. Participants were also surveyed on their perceived level of anxiety (see Table 3 ), the DBC-P Anxiety Behavior Rating Scale (ABRS) and an DBC-P anxiety subscale. Independent samples t -tests were conducted to analyze the differences in means between the two participant groups surveyed and results indicated no significant differences between the means. Therefore, the two participant groups were combined (into the COMBINED group) for further analysis of the relationship between these variables. Table 4 Reported Frequency of Pain and Sleep Concerns Frequency COMBINED group Pain Concerns n (%) COMBINED group Sleep Concerns n (%) At least once per day 8 (16%) 14 (28%) Several times a week 8 (16%) 12 (24%) Once a week 4 (8%) 5 (10%) A couple times a month /Every other week 9 (17%) 6 (12%) Once a month 8 (16%) 4 (8%) Once every few months 14 (27%) 9 (18%) Correlations were conducted to determine the relationships between the potential contributing factors of anxious behavior (i.e., pain, sleep, and anxiety; see Table 5 ). Higher scores for each scale indicated higher level (i.e., higher frequency) of concerns. The results indicated no significant relationship between a few of the scales (e.g., pain and the Anxiety Subscale score, and pain and the perception of anxiety frequency). In contrast, a significant correlation between pain and sleep was found, indicating that higher pain was associated with increased sleep difficulties ( r [48] = .45, p < .001). Positive correlations were found between the ABRS and the Anxiety Subscale ( r [50] = .91, p < .001), the ABRS and anxiety frequency perception ( r [50] = .54, p < .001), and the Anxiety Subscale and anxiety frequency perception ( r [50] = .45, p < .001). Participants who reported higher frequency of anxious behavior on one measure also reported higher levels of anxiety on the other measures in the survey. Table 5 Correlations Scale 1 2 3 4 5 1. Pain — 2. Sleep .45** — 3. ABRS .33* .39** — 4. Anxiety Subscale .22 .34* .91** — 5. Anxiety Perception .28 .30* .54** .45** — Note. Pain = reported pain, Sleep = reported sleep difficulties, ABRS = DBC-P Anxiety Behavior Rating Scale, Anxiety Subscale = DBC-P Anxiety Subscale, Anxiety Perception = reported perceived anxiety * indicates significance at the .05 level ** indicates significance at the .01 level A positive correlation between pain and the ABRS ( p = .01) suggested that higher levels of pain was associated with higher anxiety. Similarly, a significant correlation between sleep and each measure of anxiety was found (with the ABRS, p = .005; with the Anxiety Subscale, p = .013; and with participant perception of anxiety frequency, p = .03). This indicated that higher sleep difficulties were associated with higher anxiety on each measure of anxious behavior. These results suggest that higher levels of pain and sleep concerns are significantly related to higher levels of anxiety. To further analyze these relationships, a two-step hierarchical multiple linear regression analysis was conducted to assess predicting factors of anxiety (measured by the ABRS). Pain was entered into the regression equation as the variable for Step 1 of this analysis to control for the participants’ reported pain frequency (see Table 17 ). The results indicated that pain accounted for 11.9% of variance in the ABRS score and the regression model was significant, F (1,48) = 6.50, p = .014. At Step 2, we entered the sleep difficulty variable and it predicted an additional 7.1% of variance and also created a significant model, F (2,47) = 5.51, p = .007. Table 17 Hierarchical Multiple Linear Regression Analysis Predicting Anxiety (ABRS) Step and Predictor Variable b(β) SE ΔR 2 Step 1 .11* Pain .56 (.34)* .22 Step 2 .07* Pain .34 (.20) .24 Sleep .48 (.29)* .24 Note. Pain = reported pain, Sleep = reported sleep difficulties, ABRS = DBC-P Anxiety Behavior Rating Scale. Higher scores indicated higher levels of concern. * indicates significance at the .05 level A mediation analysis was used to investigate if sleep mediates the relationship between pain and anxiety (as measured by the ABRS). The indirect effect was tested using a percentile bootstrap estimation approach implemented with the PROCESS macro Version 3 (44). These results indicated the indirect coefficient for sleep was significant, β = .2234, SE = .1229, 95% CI = .0241, .5066. These results suggest that pain increases anxiety by causing increased difficulties with sleep (see Fig. 1 ). DISCUSSION Prevalence and Presentation of Anxiety and OCD This research project surveyed adults with CHARGE and legal guardians of adults with CHARGE to further analyze anxiety among the population. The results of this survey provided updated information on anxiety diagnoses and anxious behavior among adults with CHARGE. In addition, new results were found to indicate the relationship between anxiety and potential contributing factors of anxious behavior in CHARGE syndrome (i.e., pain and sleep issues). Previous literature regarding children with CHARGE found small percentages of diagnosed anxiety disorders despite high levels of obsessive-compulsive behavior (7, 13, 14). Based on the responses of the participants, half of adults with CHARGE in the current study were reported having at least one diagnosed anxiety disorder and a quarter reported having more than one anxiety diagnosis. High levels of diagnosed anxiety disorders overall (and specifically GAD) could indicate that the presence of (generalized) anxious behavior should be added to the behavioral phenotype. The results also present an interesting dichotomy between perceived anxiety of adults with CHARGE syndrome and the presence of anxiety diagnoses. Regardless of clinical anxiety diagnoses, participants report anxiety and anxious behavior as very prevalent among adults with CHARGE syndrome. In other studies, individuals with CHARGE and their families have reported varied percentages of OCD (5, 6) but the prevalence has always been reported as higher than the national prevalence among the general population. Participants’ answers on scales and checklists (DBC-P and FOCI) in this study indicated that, in particular, obsessive-compulsive behavior is very common among adults with CHARGE syndrome. Across these measures, common compulsions reported were consistent with the literature (7, 13, 14). The results of this study support the continued inclusion of repetitive and obsessive-compulsive behavior as a core component of the CHARGE behavioral phenotype, as it provides a useful description of the behavior among individuals with CHARGE (9). The Relationship Between Pain, Sleep, and Anxiety Among Adults With CHARGE Experts on the behavior of individuals with CHARGE syndrome have categorized the basis of the behavior into the self-regulation of three major factors: pain, sensory impairment, and anxiety (also known as the Behavior Triangle, 9). Pain and sleep concerns were high among adults with CHARGE in this study. This result is comparable to previous research on children with CHARGE (8, 20, 21). Based on the relationship between pain, sleep, and anxiety found in previous literature (7, 18) and the theorized factors behind anxious behavior in CHARGE syndrome it was expected that pain and sleep would have a significant impact on the anxiety of adults with CHARGE syndrome. The significant correlation between pain and anxiety lends evidence to the theory that pain is an important predictor of the anxious behavior of individuals with CHARGE (9). Additionally, the results also showed that sleep concerns among adults with CHARGE had a strong correlation to both pain and anxiety. A hierarchical regression analysis indicated that sleep mediates the relationship between pain and anxiety. This suggests that increased pain causes increased difficulties with sleep which then predicts an increase in anxiety. There are strategies to combat pain. However, sometimes in the case of medical pain with CHARGE, further medical procedures may be needed to reach the source of the pain (e.g., anesthesia for a dental procedure for a cavity). These additional procedures can lead to more anxiety and pain, particularly when individuals with CHARGE frequently have a surplus of surgeries or other invasive medical procedures in their lifetime (20). Additionally, pain and chronic pain can lead to anticipation or fear of pain among individuals with CHARGE syndrome. Indeed, preliminary research has shown that the increased number of medical procedures has led to Post Traumatic Stress Disorder symptoms in children with CHARGE (47). Taken together, this indicates that while pain intervention might be a useful way to lower anxiety among adults with CHARGE, use of additional medical procedures to reduce pain may have the unintended side effect of increasing anxiety and stress. In contrast, there are many evidence-based behavioral interventions (e.g., sleep hygiene routines) and non-invasive medical techniques (e.g., use of melatonin) to improve sleep and several that have been found effective for individuals with CHARGE syndrome. Kennert (48) found in a study of children with CHARGE that positive bedtime routines with scheduled awakening, melatonin treatment, and the combination of these two strategies were viable treatment options to improve sleep outcomes. Sleep and self-regulation of behavior may also be connected (49) which could provide further evidence for sleep being an important part of the behavior triangle for CHARGE syndrome (9). Therefore, because sleep mediates the relationship between pain and anxiety, it could be possible that sleep interventions would be a feasible strategy for adults with CHARGE and parents of children with CHARGE to decrease anxiety and related behaviors. Previous research indicates that sleep interventions can be effective when implemented by a parent and among children with CHARGE (46) and perhaps can break the cycle of pain and anxiety experienced by individuals with CHARGE while improving self-regulation and avoiding exacerbation of other potential contributing factors of anxiety. LIMIATAIONS AND CONCLUSIONS It should be noted that the current and previous studies relied on self-report or parent report of mental health diagnoses. There is a possibility that participants were unaware of their child’s mental health diagnoses, therefore, our current estimates on OCD diagnoses may be an underestimate or overestimate. While the results of this study provide a useful description of anxious behavior among adults with CHARGE, parents and legal guardians may not always understand the distinction between experiencing anxiety and having a diagnosed anxiety disorder. Additionally, while self-report is a useful assessment tool for the diagnosis of anxiety, further behavior observation and direct testing of anxiety would likely lead to a more accurate diagnosis than solely relying on the self-reflection of adults with CHARGE syndrome or their caregivers. As such, future studies should attempt to use alternative and more descriptive methods to gather information on anxiety (e.g., interviews, self-report, direct testing, clinical assessment, analysis of clinical documents, etc.). Accurate description of anxiety among the participants may also have been hindered by the lingering presence and impact of the COVID-19 pandemic. As participant responses were collected during the beginning of the COVID-19 pandemic (Spring/Summer 2020) it is likely that anxious behavior was affected. Indeed, over half of participants indicated that their anxiety had risen since the beginning of the pandemic. Future studies will need to be done to see if the increased levels of anxiety persist or are merely a result of the zeitgeist. Regardless, researching and developing effective anxiety interventions for individuals with CHARGE is important and will continue to be important (perhaps even more so if the pandemic has led to a permanent increase in anxious behavior). Sensory impairment and communication difficulties provide particular challenges to the current research. It may be difficult for adults with CHARGE and their caregivers (and professionals for that matter) to differentiate between what is true anxiety, rational fear, and which behaviors are filling sensory or communicative needs. For example, children with CHARGE syndrome may engage in repetitive checking behaviors more frequently as a functional way to compensate for their compromised vision and auditory systems and navigate their environment (9). If it is difficult for those with an expertise in CHARGE syndrome to make these distinctions, it is reasonable to assume that other legal guardians and professionals with limited exposure to CHARGE, genetic syndromes, and sensory impairment may have difficulties in truly understanding anxiety within CHARGE syndrome. Research geared towards analysis of the clinical process behind an anxiety diagnosis and other clinical diagnoses (e.g., MDD, ADHD, ASD, etc.) may provide a better indication of what clinicians consider during their assessment and in their conclusions regarding clinical diagnoses and the interventions that they recommend. Further exploration of alternative diagnostic models (e.g., RDoC) could offer a more defined or tailored approach to diagnosing anxiety among individuals with CHARGE. Research suggests that high rates of anxiety are prevalent among other developmental disorders and genetic syndromes (28, 29, 31). In addition, there is growing evidence to suggest that different genetic syndromes exhibit differential presentations of specific anxiety disorders (28). Although not yet empirically supported, it is possible that CHARGE syndrome might also have uniquely higher levels of a particular anxiety disorder (namely OCD) or higher levels of behavior characteristic of particular subtypes of anxiety. Indeed, preliminary results from previous research (8) indicated that children and adolescents with CHARGE syndrome received higher OCD subscale scores than individuals with other genetic syndromes and typically developing children with an anxiety diagnosis. There were no significant differences between the anxiety scores between children with CHARGE (8) and adults with CHARGE (current study) indicating that the increased levels of anxiety and behaviors characteristic of OCD are prevalent across the community regardless of age. Further research is necessary to measure, describe, and compare the anxiety of adults with CHARGE to children and adolescents with CHARGE syndrome and to individuals with other genetic syndromes. Anxiety is a significant concern within the CHARGE community. The current study was designed to gain a thorough description of the anxiety diagnoses and behaviors of adults with CHARGE syndrome and how it can be influenced by potential contributing factors of anxiety. Professionals working with clients with CHARGE should consider the multitude of unique factors influencing the expression of anxiety symptoms among these individuals, particularly pain and sleep. Future research should continue to study the clinical process in anxiety diagnosis among the CHARGE community and methods to increase access to anxiety interventions that are effective and adapted to the needs of individuals with CHARGE syndrome – such as sleep interventions. Abbreviations ABRS Anxiety Behavior Rating Scale from the DBC-P ADULT group Participants who were adults with CHARGE Syndrome CHARGE CHARGE Syndrome CHD7 Chromodomain helicase DNA binding protein 7 COMBINED group All participants, which included both the Adult and LG participants DBC-P Developmental Behavior Checklist-Parent Version DSM-5 Diagnostic and Statistical Manual of Mental Disorders, 5th Edition FOCI Florida Obsessive-Compulsive Inventory GAD Generalized anxiety disorder GAD- 7 Generalized Anxiety Disorder 7-Item Scale LG group Participants who were legal guardians of an adult with CHARGE Syndrome OCD Obsessive-compulsive disorder Declarations Human Ethics Approval and Consent to Participate The procedures, informed consent form, and all materials from this project were submitted and approved by the Institutional Review Board (IRB) of Central Michigan University in accordance with the Declaration of Helsinki. Informed consent to participate in the study was received from each participant. Clinical trial number: not applicable. Consent for Publication Not applicable. Availability of data and materials The data sets generated during the current study are not publicly available because the participants of this study did not give written consent for their data to be shared publicly and our Institutional Review Board advised the researchers that the data could contain information that could compromise the privacy of research participants. Competing Interests The authors declare that they have no competing interests. Funding There was no funding used for this research. Authors' contributions S.MB and T.H. and L.S. contributed to the conception and design of this study. S.MB completed the acquisition and analysis of the data while S.MB and T.H. interpreted the results. S.MB wrote the main manuscript text and prepared the figures and tables. All authors reviewed and substantively revised the manuscript. Acknowledgements Not applicable. References Janssen N, Bergman JEH, Swertz MA, Tranebjaerg L, Lodahl M, Schoots J, Hofstra RMW, Ravenswaaij-Arts CMA, Hoefsloot LH. Mutation update on the CHD7 gene involved in CHARGE syndrome. Hum Mutat. 2012;33(8):1149-60. doi:10.1002/humu.22086. Blake KD, Davenport SLH, Hall BD, Hefner MA, Pagon RA, Williams MS, Lin AE, Graham JM. CHARGE association: An update and review for the primary pediatrician. Clin Pediatr (Phila). 1998;37(3):159 − 73. doi:10.1177/000992289803700302. Pagon RA, Graham JM, Zonana J, Yong SL. Coloboma, congenital heart disease, and choanal atresia with multiple anomalies: CHARGE association. J Pediatr. 1981;99(2):223–7. doi:10.1016/s0022-3476(81)80454-4. Hefner MA. Introduction to CHARGE syndrome. In: Hartshorne TS, Hefner MA, Blake KD, editors. CHARGE syndrome. 2nd ed. San Diego (CA): Plural Publishing; 2021. p. xi-xvi. 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[Internet]. Maryland: ADAA [cited 2022 Apr]. Available from: https://adaa.org/understanding-anxiety Lebowitz ER, Omer H. Treating childhood and adolescent anxiety: A guide for caregivers. Hoboken (NJ): John Wiley & Sons, Inc.; 2013. National Institute of Mental Health. Anxiety Disorders [Internet]. Maryland: NIMH [cited 2024 Dec]. Available from: https://www.nimh.nih.gov/health/topics/anxiety-disorders/index.shtml Bernstein V, Denno LS. Repetitive behaviors in CHARGE syndrome: Differential diagnosis and treatment options. Am J Med Genet A. 2005;133(3):232-9. doi:10.1002/ajmg.a.30542. Hartshorne TS, Cypher AD. Challenging behavior in CHARGE syndrome. Mental Health Aspects of Developmental Disabilities, 2004;7(2):41–52. Gedye A. Recognizing obsessive-compulsive disorder in clients with developmental disabilities. The Habilitative Mental Healthcare Newsletter, 1992;11(1): 73 − 7. Hartshorne TS. Behavior. In: Hartshorne TS, Hefner MA, Blake KD, editors. CHARGE syndrome. 2nd ed. San Diego (CA): Plural Publishing; 2021. p. 413–424 National Institute of Mental Health. Statistics: Obsessive-compulsive disorder (OCD) [Internet]. Maryland; NIMH. [cited 2022 Apr]. Available from: https://www.nimh.nih.gov/health/statistics/obsessive-compulsive-disorder-ocd May ME, Kennedy CH. Health and problem behavior among people with intellectual disabilities. Behav Anal Pract. 2010;3(2):4–12. doi:10.1007/BF03391759 Stratton KK. Pain. In: Hartshorne TS, Hefner MA, Blake KD, editors. CHARGE syndrome. 2nd ed. San Diego (CA): Plural Publishing; 2021. p. 439–448 Stratton KK, Hartshorne T. Identifying pain in children with CHARGE syndrome. Scand J Pain . 2019;19(1):157–166. doi:10.1515/sjpain-2018-0080 Hartshorne TS, Heussler HS, Dailor AN, Williams GL, Papadopoulos D, Brandt KK. Sleep disturbances in CHARGE syndrome: Types and relationships with behavior and caregiver well-being. Dev Med Child Neurol. 2009;51(2):143 − 50. doi:10.1111/j.1469-8749.2008.03146.x. Gregory AM, Eley TC. Sleep problems, anxiety and cognitive style in school-aged children. Infant Child Dev. 2005;14(5):435 − 44. doi:10.1002/icd.409. Hefner MA, Davenport SLH. Overview and sensory issues. In: Hartshorne TS, Hefner MA, Blake KD, editors. CHARGE syndrome. 2nd ed. San Diego (CA): Plural Publishing; 2021. p. 3–13. Swanson LA. Communication: The speech and language perspective. In: Hartshorne TS, Hefner MA, Blake KD, editors. CHARGE syndrome. 2nd ed. San Diego (CA): Plural Publishing; 2021. p. 329–352 Pinquart M, Shen Y. Anxiety in children and adolescents with chronic physical illnesses: A meta-analysis. Acta Paediatr. 2011;100(8):1069–76. doi:10.1111/j.1651-2227.2011.02223.x. Hartshorne TS, Schmittel MC. Social-emotional development in children and youth who are deafblind. American Annals of the Deaf. 2016;161(4):444–53. doi:10.1353/aad.2016.0036 Stratton KK. Stress. In: Hartshorne TS, Hefner MA, Blake KD, editors. CHARGE syndrome. 2nd ed. San Diego (CA): Plural Publishing; 2021. p. 449 − 54. Crawford H, Waite J, Oliver C. Diverse profiles of anxiety related disorders in fragile X, Cornelia de Lange, and Rubinstein-Taybi syndromes. J Autism Dev Disord. 2017;47(12):3728-40. doi:10.1007/s10803-016-3015-y. Dankner N, Dykens EM. Anxiety in intellectual disabilities: Challenges and next steps. Int Rev Res Dev Disabil. 2012;42:57–83. doi:10.1016/b978-0-12-394284-5.00003-6. Groves L, Moss J, Oliver C, Royston R, Waite J, Crawford H. Divergent presentation of anxiety in high-risk groups within the intellectual disability population. Journal of Neurodevelopmental Disorders. 2022 Oct 5;14(1). Leyfer O, Woodruff-Borden J, Mervis CB. Anxiety disorders in children with Williams syndrome, their mothers, and their siblings: Implications for the etiology of anxiety disorders. J Neurodev Disord. 2009;1(1):4–14. doi:10.18297/etd/821. Einfeld SL, Tonge BJ. Manual for the developmental behaviour checklist: Primary carer version (DBC-P) and teacher version (DBC-T). 2nd ed. Monash University Centre for Developmental Psychiatry and Psychology; 2002. Storch EA, Kaufman DA, Bagner D, Merlo LJ, Shapira NA, Geffken GR, Murphy TK, Goodman WK. Florida Obsessive-Compulsive Inventory: Development, reliability, and validity. J Clin Psychol. 2007;63(9):851-9. doi: 10.1002/jclp.20382. Spitzer RL, Kroenke K, Williams JB, Lowe B. A brief measure for assessing generalized anxiety disorder: The GAD-7. Arch Intern Med. 2006;166(10):1092–7. doi:10.1001/archinte.166.10.1092. Salem-Hartshorne N, Jacob S. Characteristics and development of children with CHARGE association/syndrome. J Early Interv. 2004;26(4):292–301. doi:10.1177/105381510402600405. Verloes A. Updated diagnostic criteria for CHARGE syndrome: A proposal. Am J Med Genet A. 2005;133(3):306–8. doi:10.1002/ajmg.a.30559. Rosenfeld R, Dar R, Anderson D, Kobak KA, Greist JH. A computer-administered version of the Yale-Brown Obsessive-Compulsive Scale. Psychological Assessment. 1992 Sep;4(3):329–32. Aleda MA, Geffken GR, Jacob ML, Goodman WK, Storch EA. Further psychometric analysis of the Florida obsessive-compulsive inventory. J Anxiety Disord. 2009;23(1):124-9. doi:10.1016/j.janxdis.2008.05.001. Goodman WK, Price LH, Rasmussen SA, Mazure C, Fleischmann RL, Hill CL, Heninger GR, Charney DS. The Yale-Brown Obsessive Compulsive Scale: I. Development, use, and reliability. Arch Gen Psychiatry. 1989;46(11):1006-11. doi:10.1001/archpsyc.1989.01810110048007. Plummer F, Manea L, Trepel D, McMillan D. Screening for anxiety disorders with the GAD-7 and GAD-2: A systematic review and diagnostic meta-analysis. Gen Hosp Psychiatry. 2016;39:24–31. doi:10.1016/j.genhosppsych.2015.11.005. Beck AT, Epstein N, Brown G, Steer RA. An inventory for measuring clinical anxiety: Psychometric properties. J Consult Clin Psychol. 1988;56(6):893-7. doi:10.1037//0022-006x.56.6.893. Derogatis LR, Lipman RS, Rickels K, Uhlenhuth EH, Covi L. The Hopkins Symptom Checklist (HSCL): A self-report symptom inventory. Behav Sci. 1974;19(1):1–15. doi:10.1002/bs.3830190102. Spitzer RL, Williams JB, Kroenke K, Hornyak R, McMurray J. Validity and utility of the PRIME-MD patient health questionnaire in assessment of 3000 obstetric-gynecologic patients: The PRIME-MD patient health questionnaire obstetrics-gynecology study. Am J Obstet Gynecol. 2000;183(3):759–69. doi:10.1067/mob.2000.106580. Hayes AF. Introduction to mediation, moderation, and conditional process analysis: A regression-based approach. New York: The Guilford Press; 2018. National Institute of Mental Health. Statistics: Any anxiety disorders [Internet]. Maryland; NIMH. [cited 2022 Apr]. Available from: https://www.nimh.nih.gov/health/statistics/any-anxiety-disorder.shtml National Institute of Mental Health. Statistics: Generalized anxiety disorder (GAD) [Internet]. Maryland; NIMH. [cited 2022 Apr]. Available from: https://www.nimh.nih.gov/health/statistics/generalized-anxiety-disorder Sykes SM. Medical experiences and subsequent behaviors in children and adolescents with CHARGE syndrome. [master’s thesis]. Mount Pleasant (MI): Central Michigan University; 2021. Kennert BA. Investigation of two methods for treating sleep problems among children with CHARGE syndrome [dissertation]. Mount Pleasant (MI): Central Michigan University; 2018. Kroese FM, De Ridder DT, Evers C, Adriaanse MA. Bedtime procrastination: Introducing a new area of procrastination. Front Psychol. 2014;5:611. doi:10.3389/fpsyg.2014.00611. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 02 Mar, 2026 Read the published version in Journal of Neurodevelopmental Disorders → Version 1 posted Editorial decision: Revision requested 18 Nov, 2025 Reviews received at journal 24 Sep, 2025 Reviewers agreed at journal 14 Aug, 2025 Reviewers agreed at journal 12 Aug, 2025 Reviewers invited by journal 12 Aug, 2025 Editor assigned by journal 07 Aug, 2025 Submission checks completed at journal 07 Aug, 2025 First submitted to journal 02 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7278769","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":500706050,"identity":"3d39c168-cdb1-4ca4-b894-22c566648d7e","order_by":0,"name":"Shanti A. Madhavan-Brown","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwElEQVRIiWNgGAWjYFACHjApx8DOw3AAzDxApBZjBmZStSQ2MPNABQhpkW8/e+zDx7Y76f3NvAcPfNzBIMd3IwG/FoMzeckzZ7Y9y51xmC/h4MwzDMaSBLUw5Bgz8247nNtwmMfgMG8bQ+IGQlrk+9+AtaTLQ7XUE9TCcANiS4IBVEuCAUGH3XiXzDjz32HDjWC/tEkYzjzzgJDDcg8zfDhzWF7ueO9hYNDZyPMdJ+QwNCBBmvJRMApGwSgYBdgBAF1tSUARkSM1AAAAAElFTkSuQmCC","orcid":"","institution":"Albion College","correspondingAuthor":true,"prefix":"","firstName":"Shanti","middleName":"A.","lastName":"Madhavan-Brown","suffix":""},{"id":500706054,"identity":"c228a791-0c00-474b-9014-bb4ac4952483","order_by":1,"name":"Timothy S. Hartshorne","email":"","orcid":"","institution":"Central Michigan University","correspondingAuthor":false,"prefix":"","firstName":"Timothy","middleName":"S.","lastName":"Hartshorne","suffix":""},{"id":500706056,"identity":"dd99108d-a881-4490-abbc-8b184533eeed","order_by":2,"name":"Sarah B. Schneider","email":"","orcid":"","institution":"Cincinnati Children’s Hospital Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Sarah","middleName":"B.","lastName":"Schneider","suffix":""},{"id":500706060,"identity":"a1d955b3-223e-4d75-b420-a4192bdb2a46","order_by":3,"name":"Lillian J. Slavin","email":"","orcid":"","institution":"Nemours Children's Hospital, Delaware.","correspondingAuthor":false,"prefix":"","firstName":"Lillian","middleName":"J.","lastName":"Slavin","suffix":""}],"badges":[],"createdAt":"2025-08-02 14:08:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7278769/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7278769/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s11689-026-09673-5","type":"published","date":"2026-03-02T15:57:30+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":89544057,"identity":"2107fb5c-27e9-49bd-9130-759b203f60e6","added_by":"auto","created_at":"2025-08-21 06:55:48","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":22970,"visible":true,"origin":"","legend":"\u003cp\u003eSleep Mediated Relationship Between Pain and Anxiety in Adults with CHARGE Syndrome\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eNote.\u003c/em\u003eThe mediation analysis was conducted using PROCESS model 4 (44). Pain = reported pain, Sleep = reported sleep difficulties, ABRS = DBC-P Anxiety Behavior Rating Scale. Higher scores indicated higher levels of concern. Both \u003cem\u003eb \u003c/em\u003eare unstandardized regression coefficients\u003c/p\u003e\n\u003cp\u003e* = \u003cem\u003ep\u003c/em\u003e \u0026lt; .05; ** = \u003cem\u003ep\u003c/em\u003e \u0026lt; .005\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7278769/v1/ea88497e00283c2cae5ef7bd.png"},{"id":104250603,"identity":"8b6cb03d-3501-4d0d-9841-83e2003cf77f","added_by":"auto","created_at":"2026-03-09 16:01:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":991220,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7278769/v1/29b3292d-c81d-4193-a990-42cba99af278.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Anxiety and Obsessive-Compulsive Disorder (OCD) in Adults with CHARGE Syndrome","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eCHARGE syndrome is a rare (approximately 1 in every 10,000 live births) congenital disorder with multiple physical, cognitive, behavioral, and sensory impairments. The majority of cases are caused by a \u003cem\u003eCHD7\u003c/em\u003e gene mutation (1). The presence of major and minor anomalies is frequently used as an accurate method of clinical diagnosis (2). The major criteria are described as the four \"C's\" of CHARGE (coloboma, choanal atresia, cranial nerve anomalies, characteristic CHARGE inner \u0026amp; outer ear) with many other minor criteria used in diagnosis (3, 4).\u003c/p\u003e\n\u003ch3\u003eAnxiety and Obsessive-Compulsive Disorder Within CHARGE Syndrome\u003c/h3\u003e\n\u003cp\u003ePrevious research, while limited, indicates obsessive-compulsive disorder (OCD) and anxiety disorders are among the top three most common mental health diagnoses among individuals with CHARGE syndrome. Blake et al. (5) found that 43% of caregivers of individuals with CHARGE reported that their child had an OCD diagnosis and 37% indicated an anxiety disorder diagnosis. Wachtel et al. (6) found that 19.5% of participants endorsed an anxiety disorder diagnosis and 17.2% endorsed an OCD diagnosis. N. Hartshorne et al. (7) found that 47% of adolescents and adults with CHARGE endorsed obsessive-compulsive behaviors and 45% endorsed anxiety. In a survey of parents and guardians of children and adolescents with CHARGE syndrome, Madhavan-Brown (8) found that OCD (11%) and generalized anxiety disorder (GAD; 7.5%) were the third and fourth most common mental health diagnoses reported and 16% of the total sample had been diagnosed with at least one anxiety disorder. Taken together, this research suggests that anxiety and related diagnoses are prevalent concerns in those with CHARGE syndrome and, therefore, can have a significant impact on the behavior of these individuals (9).\u003c/p\u003e\u003cp\u003eMany of the most common anxious behaviors (10\u0026ndash;12) are also exhibited by individuals with CHARGE syndrome, particularly self-injurious behavior, sleep problems, and repetitive behaviors (5, 8, 9, 13, 14). Hartshorne and Cypher (14) found that 36% of their 100 participants engaged in repetitive or compulsive behavior characteristic of OCD, despite only three participants having an official, clinical diagnosis. In another study, parents of children with CHARGE reported \u0026ldquo;obsession with an idea or activity\u0026rdquo; as occurring the most often (8). Bernstein \u0026amp; Denno (13) found that their participants with CHARGE received an above average score on the \u003cem\u003eCompulsive Behavior Checklist\u003c/em\u003e (15) and 72% of participants engaged in repetitive behavior for an hour or more each day. A majority of the participants reported that these behaviors negatively interfered with social activities, relationships, and daily routines.\u003c/p\u003e\u003cp\u003eRepetitive behavior is recognized as part of the CHARGE syndrome behavioral phenotype (16). Repetitive behavior is hypothesized to be correlated with anxiety, as it has been observed to increase during times of stress (9). Adults with CHARGE show higher rates of OCD symptomatology and diagnosis (i.e., 11\u0026ndash;43% prevalence; 5, 6) compared to the general population (i.e., 2.3% incidence; 17). Preliminary research has also found a similar pattern in children with CHARGE (8). Thus, obsessions and (particularly) compulsive behaviors are commonly reported among individuals with CHARGE and updated research on the prevalence of OCD diagnoses in individuals with CHARGE would be beneficial.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eEtiology of Anxiety Within CHARGE Syndrome\u003c/h2\u003e\u003cp\u003eIt has been suggested that the common physical, cognitive, and behavioral characteristics associated with CHARGE syndrome can lead to higher levels of anxious behavior (9). Some of these characteristics include pain, sleep concerns, and sensory impairment. Difficulties with communication, stress, and lack of predictability in the environment could also be contributing factors.\u003c/p\u003e\u003cp\u003eIndividuals with developmental disabilities experience a higher number of health conditions (e.g., constipation, gastroesophageal reflux disease, sleep problems) compared to the overall population (14, 16, 18, 19). Furthermore, people with CHARGE often contend with a high number of hospitalizations and surgeries (14, 20). Stratton and Hartshorne (20) found parents of children with CHARGE reported that a large number experienced pain at high frequencies. Research suggests that increased prevalence of challenging behaviors and anxiety among individuals with developmental disabilities (and/or CHARGE) could be a result of their overall health, medical conditions, and level of pain (18, 19). Pain has been described as an important\u0026mdash;if not the most important\u0026mdash;influence on the behavior of individuals with CHARGE (9).\u003c/p\u003e\u003cp\u003eOver half of the CHARGE population has reported sleep problems (i.e., 59% incidence; 7) including: obstructive sleep apnea, initiation or maintenance of sleep, and difficulties sleeping due to visual impairment (21). Research has shown that lack of sleep is linked to increases in challenging behaviors (18, 22). The relationship between anxiety and sleep has been seen as reciprocal; a pattern seen in survey research of adolescents and adults with CHARGE (7). Given the high incidence of sleep problems among individuals with CHARGE syndrome and the apparent association between sleep problems and anxiety, it is not surprising that there is a common concern of anxiety among those with CHARGE.\u003c/p\u003e\u003cp\u003eIndividuals with CHARGE syndrome can experience deficits in some or all of the seven sensory systems (23) which, in turn, have a significant impact on behavior (9). The environment is often unpredictable\u0026mdash;and potentially anxiety-provoking\u0026mdash;to individuals with CHARGE because they have a reduced ability to efficiently or effectively gather information about the environment from their sensory systems. Challenges with communication are also common in the CHARGE population (4). Difficulties with communication, coupled with multi-sensory impairment, make it difficult for these individuals to explore, obtain, comprehend, and use information from their environment (24). This lack of predictability and daily stress can result in higher levels of anxiety (9, 25\u0026ndash;27). Thus, individuals with CHARGE experience many of the common causes of anxiety.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eResearch Questions\u003c/h3\u003e\n\u003cp\u003eResearch on anxiety and anxious behavior among individuals with CHARGE syndrome is limited. Studies have indicated that particular subtypes of anxiety can vary between genetic syndromes or developmental disorders (28\u0026ndash;31) but CHARGE has yet to be included. Preliminary research suggests that CHARGE syndrome might have uniquely higher levels of OCD-related behavior than individuals with other genetic syndromes and typically developing children with an anxiety diagnosis (8). The etiology of anxiety may be more nuanced in low-incidence populations (29), therefore, further analysis of the types and frequency of anxious behavior exhibited by persons with CHARGE syndrome is needed to develop a better understanding of how anxiety manifests among adults with CHARGE. This analysis could help inform diagnosticians when making a mental health diagnosis for an individual with CHARGE.\u003c/p\u003e\u003cp\u003eThere were three research questions addressed in this study:\u003c/p\u003e\u003cp\u003eWhat is the prevalence of anxiety and obsessive-compulsive diagnoses among adults with CHARGE Syndrome?\u003c/p\u003e\u003cp\u003eWhat is the presentation of anxious and obsessive-compulsive disorders in individuals with CHARGE syndrome (including the types and frequency of anxious behavior)?\u003c/p\u003e\u003cp\u003eHow do pain and sleep contribute to anxiety in individuals with CHARGE?\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eParticipants\u003c/h2\u003e\u003cp\u003eAdults with CHARGE syndrome (ADULT group; \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;32) and legal guardians of adults with CHARGE syndrome (LG group; \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;20) were recruited and created a combined participant group (COMBINED group). Five participant responses were removed because they did not meet the inclusion criteria (e.g., no diagnosis of CHARGE syndrome, completed the incorrect survey, did not meet age criteria) leaving the final COMBINED participant group (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;52). All adults in the COMBINED group reported at least one major or minor characteristics of CHARGE (with many indicating several). The characteristics of CHARGE reported the most included: hearing impairment, visual impairment, developmental delay, and cranial nerve abnormalities or dysfunction. See Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e for demographic information.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic Information\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eADULT group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLG group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCOMBINED group\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003en\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e52\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (Years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMean (Range)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e27.50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e28.47 (19\u0026ndash;45)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e% Female\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e68.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e55.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e63.46\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTested positive for CHd7 gene mutation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (44%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9 (45%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e23 (44%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTested positive for CHd7 gene mutation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (9.37%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (15.00%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6 (11.53%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHearing impairment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29 (91%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19 (95%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e48 (92%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVisual impairment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26 (81%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e18 (90%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e44 (85%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eColoboma of the eye\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23 (72%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17 (85%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e40 (77%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeart defects or malformations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18 (56%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16 (80%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e34 (65%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChoanal atresia or stenosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17 (53%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10 (50%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e27 (52%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrowth delay\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24 (75%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13 (65%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e37 (71%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGenital hypoplasia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19 (59%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14 (70%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e33 (64%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEar abnormalities\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23 (72%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e18 (90%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e41 (79%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eMeasures\u003c/h3\u003e\n\u003cp\u003eParticipant responses were collected during the beginning of the COVID-19 pandemic (Spring/Summer 2020). Two questions were asked to gather participant's perceptions on how this impacted their levels of anxiety. All participants (the COMBINED group) completed the CHARGE Syndrome Demographic/Anxiety Questionnaire and the Developmental Behavior Checklist-Parent Version (DBC-P; 32). The ADULT group also completed the Florida Obsessive-Compulsive Inventory (FOCI; 33) and the Generalized Anxiety Disorder 7-Item Scale (GAD-7; 34).\u003c/p\u003e\u003cp\u003eMost of the CHARGE Syndrome Demographic/Anxiety Questionnaire items were adapted from previous research studies of individuals with CHARGE (35) and gathered basic demographic data and information about the diagnostic characteristics of CHARGE (2, 36) and frequency of pain and sleep concerns. Questions regarding anxiety were designed for this study. Additionally, information about whether the adult has been diagnosed with a mental health disorder and/or anxiety disorder was collected. These questions allowed us to gather an understanding of other anxious behaviors that adults with CHARGE may be exhibiting that are not captured in the anxiety scales used.\u003c/p\u003e\u003cp\u003eThe DBC-P (32) is a rating scale used to assess the frequency of behavioral and emotional concerns of individuals with developmental and cognitive disabilities aged 4\u0026ndash;18 years. As the focus on this study was anxiety, only the items from the DBC-P Anxiety subscale (9 items; Cronbach\u0026rsquo;s alpha for current study: α\u0026thinsp;=\u0026thinsp;.66), DBC-P Anxious Behavior Rating Scale (ABRS; 7 items; Cronbach\u0026rsquo;s alpha for current study: α\u0026thinsp;=\u0026thinsp;.69) and additional items that mapped onto an anxiety diagnosis (28 items total, total possible raw score\u0026thinsp;=\u0026thinsp;84; Cronbach\u0026rsquo;s alpha for current study: α\u0026thinsp;=\u0026thinsp;.86) were selected for the questionnaire. The DBC-P has also been used to research the behaviors of individuals with genetic syndromes (28).\u003c/p\u003e\u003cp\u003eThe FOCI (33) is a self-report questionnaire used to assess the presence and severity of symptoms related to obsessive-compulsive behavior (OCD). This is accomplished by two concurrent parts of the scale: a symptom checklist (The Checklist; K-R 20\u0026thinsp;=\u0026thinsp;0.83; Current study K-R 20 is: α\u0026thinsp;=\u0026thinsp;.86) and a Severity Scale (SS; α\u0026thinsp;=\u0026thinsp;.89; Cronbach\u0026rsquo;s alpha for current study: α\u0026thinsp;=\u0026thinsp;.88). This scale was selected as a behavior checklist for adults with CHARGE to provide information on their own OCD related behaviors. Prior research has indicated that the FOCI is highly correlated with the Yale-Brown Obsessive Compulsive Scale Self-Report (Y-BOCS-SR; 37) and has good internal consistency - with the overall scale and both components (33, 38, 39).\u003c/p\u003e\u003cp\u003eThe GAD-7 (34) is a self-report rating scale intended to assess symptomology of Generalized Anxiety Disorder. This scale was selected because it is a brief measure and would give an indication of the frequency of GAD symptoms in adults with CHARGE syndrome. The seven items of the GAD-7 (α\u0026thinsp;=\u0026thinsp;.92; Cronbach\u0026rsquo;s alpha for current study: α\u0026thinsp;=\u0026thinsp;.93) are rated on a 4-point Likert scale based on the frequency in the last two weeks. The GAD-7 has a sensitivity of 89% and 82% specificity for GAD (34). A meta-analysis of 11 studies (40) indicated that the scale was effective at identifying GAD using a cut score between 7\u0026ndash;10 (with the optimal sensitivity and specificity at a cut score of 8). Additional studies have indicated that it has convergent validity with the Beck Anxiety Inventory and the anxiety subtest of the Symptom Checklist-90 (40\u0026ndash;43).\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eProcedure and Ethics\u003c/h2\u003e\u003cp\u003eAn invitation to participate was distributed through Facebook pages specific to CHARGE syndrome and by the CHARGE Syndrome Foundation. Qualtrics\u0026reg; was used to develop, distribute, and collect the survey results. The responses of adults with CHARGE and parents/guardians were analyzed separately and there was no attempt to link parent and adult child responses. Indeed, measures were put in place to have the survey answered only once per family unit. The procedures, informed consent form, and all materials from this project were submitted and approved by the Institutional Review Board (IRB) of Central Michigan University in accordance with the Declaration of Helsinki. Informed consent to participate in the study was received from each participant. Clinical trial number: not applicable.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003eData Analysis\u003c/h2\u003e\u003cp\u003eTo analyze the prevalence of anxiety and obsessive-compulsive disorders, descriptive statistics on the reported mental health diagnoses, GAD-7 results, and FOCI results were analyzed and compared to the prevalence rates among the general population provided by the National Institute of Mental Health. To determine the manifestation of these disorders the DBC-P responses were ranked from highest to lowest mean score as an indication of frequency and the frequency of responses on the GAD-7, FOCI, and perceived anxiety questions was also gathered. Lastly, in order to answer the third research question (impact of pain and sleep on anxiety), independent samples t-tests and Pearson\u0026rsquo;s correlations were calculated to determine the relationships between the potential factors, anxiety subscale scores, and the scores of both participant groups. A hierarchical multiple linear regression analysis and a mediation analysis were used to investigate if sleep mediates the relationship between pain and anxiety. The indirect effect was tested using a percentile bootstrap estimation approach implemented with the PROCESS macro Version 3 (44). This model estimated the direct effects of pain on anxiety and indirect change in anxiety once sleep was added to the model. The indirect effect of pain on anxiety after mediation by sleep was considered significant if the 95% confidence interval (CI) of the estimated effect does not include zero.\u003c/p\u003e\u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003ePrevalence of Anxiety Disorders\u003c/h2\u003e\u003cp\u003eThe most common mental health disorders for the \u003cem\u003eCOMBINED\u003c/em\u003e group were generalized anxiety disorder (GAD), major depressive disorder (33%), attention-deficit hyperactivity disorder (ADHD), and obsessive-compulsive disorder (OCD). Autism spectrum disorder (ASD) was also a more common diagnosis in the \u003cem\u003eLG\u003c/em\u003e group. From the \u003cem\u003eCOMBINED\u003c/em\u003e group, 26 participants (50%) noted at least one anxiety disorder and/or obsessive-compulsive disorder diagnosis; 13 participants (25%) noted more than one anxiety disorder diagnosis. Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e displays the results for the \u003cem\u003eADULT\u003c/em\u003e, \u003cem\u003eLG\u003c/em\u003e, and \u003cem\u003eCOMBINED\u003c/em\u003e groups.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMental Health Disorder Diagnoses\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMental Health Disorder Diagnosis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003eADULT\u003c/em\u003e group\u003c/p\u003e\u003cp\u003e\u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003eLG\u003c/em\u003e group\u003c/p\u003e\u003cp\u003e\u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eCOMBINED\u003c/em\u003e group\u003c/p\u003e\u003cp\u003e\u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGeneralized Anxiety Disorder\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (44%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (30%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e20 (39%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMajor Depressive Disorder\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (44%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (15%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17 (33%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAttention-Deficit Hyperactivity Disorder\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (22%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (40%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15 (29%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eObsessive-Compulsive Disorder\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (22%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (35%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14 (27%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePost-Traumatic Stress Disorder\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (13%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (20%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (15%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAutism Spectrum Disorder\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (35%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7 (14%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSocial Anxiety Disorder\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (16%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (10%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe \u003cem\u003eADULT\u003c/em\u003e group provided responses on assessment scales for GAD (GAD-7) and OCD (FOCI). Fifty percent of participants (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;16) indicated on the GAD-7 that their symptoms made it somewhat difficult for them to function in their home life, work settings, and/or relationships. A quarter of the respondents indicated no difficulty resulting from their symptoms (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7, 25%). Another quarter indicated that their symptoms made it very or extremely difficult (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7, 25%). Based on the responses from the \u003cem\u003eADULT\u003c/em\u003e group, 63% (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;20) of participants met the criteria for further evaluation of GAD. The FOCI symptom checklist provides a total score of obsession and compulsion traits (ranging from 0\u0026ndash;20) with a score of eight or more indicating the potential for symptomology of OCD. Eleven participants (34%) indicating eight or more obsessions and/or compulsions. On the Severity Scale of the FOCI, 28% of participants (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;9) indicated that their symptoms had moderate to extreme impact on their level of distress, cognitions, and daily living activities.\u003c/p\u003e\u003cp\u003eThe prevalence of anxiety disorders (50% reporting at least one anxiety disorder or OCD diagnosis; 39% reporting a GAD diagnosis) was higher than the estimated national average for adults (31.1% and 2.3%, respectively; 17, 45). The results from the GAD-7 screener also indicated much higher potential levels of GAD (63%) than the general population (5.7%; 46). Moreover, the prevalence of diagnosed OCD among adults with CHARGE (27%) was much higher than the estimated national average for adults (2.3%; NIMH, 2017c) and 34% of the \u003cem\u003eADULT\u003c/em\u003e group reported 8 or more OCD traits (the cut-off on the FOCI screener) suggesting that the prevalence of OCD in CHARGE is higher than the general population.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eAnxious Behaviors Types and Frequencies\u003c/h2\u003e\u003cp\u003eAfter being given a definition of anxiety, respondents in the \u003cem\u003eLG\u003c/em\u003e group were asked if they thought that their adult with CHARGE syndrome experiences anxiety while participants in the \u003cem\u003eADULT\u003c/em\u003e group were asked if they thought they had anxiety. Ninety percent of participants (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;47) in the \u003cem\u003eCOMBINED\u003c/em\u003e group answered yes. These participants rated how frequently this anxiety was expressed and 68% (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;32) indicated that this anxiety was experienced several times a week or more frequently (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The participants in the \u003cem\u003eCOMBINED\u003c/em\u003e group who indicated that they experience anxiety (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;47) were also asked to indicate how this level of anxiety was impacted by the COVID-19 pandemic. The respondents reported that the anxiety increased (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;28, 60%), stayed the same (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;16, 34%), or decreased (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;3, 6%), since the start of the pandemic.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eReported Frequency of Anxiety\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFrequency of Anxiety\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003eADULT\u003c/em\u003e group\u003c/p\u003e\u003cp\u003e\u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003eLG\u003c/em\u003e group\u003c/p\u003e\u003cp\u003e\u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eCOMBINED\u003c/em\u003e group\u003c/p\u003e\u003cp\u003e\u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAt least once per day\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (31%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (30%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16 (30%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSeveral times a week\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (28%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (35%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16 (30%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOnce a week\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (15%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (12%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eA couple times a month\u003c/p\u003e\u003cp\u003e/Every other week\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (16%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (12%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOnce a month\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOnce every few months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo anxiety\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (13%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (10%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAll 52 participants completed selected items from the DBC-P, which were chosen because they described behaviors related to anxiety and internalizing behavior and included a 7-item anxiety behavior rating scale [ABRS] from the DBC-P. The behaviors that the majority of participants indicated as the most \u003cem\u003efrequently\u003c/em\u003e reported (i.e., very/often true) included getting obsessed with an idea or activity, being impatient, and getting upset or distressed over small changes in the routine or environment, and being tense, anxious, or worried. Three DBC-P items, that match criteria for OCD from the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th Edition) were rated by participants as behavior that their child with CHARGE syndrome exhibits sometimes or very often (i.e., gets obsessed with an idea or activity [92%], preoccupied with only one or two particular interests [77%], arranging objects or routine in a strict order [83%]) Indeed, obsession with particular ideas or activities was rated the most frequent out of all of the behaviors, with 54% of participants indicating that this behavior was very frequently shown.\u003c/p\u003e\u003cp\u003eThe \u003cem\u003eADULT\u003c/em\u003e group responses to the GAD-7 and FOCI also provided information on the types and frequency of anxious behavior reported by adults with CHARGE syndrome. The behavior indicated as the most frequently occurring (i.e., Nearly every day) on the GAD-7 was \u0026ldquo;worrying too much about different things\u0026rdquo;. On the first part of the FOCI (i.e., a checklist of common obsessions and compulsions), \u0026ldquo;worry about harm coming to a love one\u0026rdquo; and \u0026ldquo;worry about losing something valuable\u0026rdquo; were the most \u003cem\u003efrequently\u003c/em\u003e reported obsessions while \u0026ldquo;feeling a need to \u0026lsquo;confess\u0026rsquo;\u0026rdquo; or \u0026ldquo;repeatedly asking for reassurance that you said or did something correctly\u0026rdquo; was the most \u003cem\u003efrequently\u003c/em\u003e reported compulsion.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003ePain and Sleep Impacts on Anxiety of Adults with CHARGE Syndrome\u003c/h2\u003e\u003cp\u003eRespondents in the \u003cem\u003eADULT\u003c/em\u003e group were asked to report the frequency of their pain (e.g., migraines, abdominal migraine, surgery pain, constipation, ear infections, etc.) and difficulties with sleep (e.g., trouble falling asleep, trouble staying asleep, waking up multiple times in the night, etc.). The \u003cem\u003eLG\u003c/em\u003e group was asked to provide the same information regarding their adult with CHARGE syndrome. There was a wide range of reported frequency of pain and sleep concerns (see Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) that ranged from once every few months to at least once a day. Participants were also surveyed on their perceived level of anxiety (see Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), the DBC-P Anxiety Behavior Rating Scale (ABRS) and an DBC-P anxiety subscale. Independent samples \u003cem\u003et\u003c/em\u003e-tests were conducted to analyze the differences in means between the two participant groups surveyed and results indicated no significant differences between the means. Therefore, the two participant groups were combined (into the \u003cem\u003eCOMBINED\u003c/em\u003e group) for further analysis of the relationship between these variables.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eReported Frequency of Pain and Sleep Concerns\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFrequency\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003eCOMBINED\u003c/em\u003e group\u003c/p\u003e\u003cp\u003ePain Concerns\u003c/p\u003e\u003cp\u003e\u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003eCOMBINED\u003c/em\u003e group\u003c/p\u003e\u003cp\u003eSleep Concerns\u003c/p\u003e\u003cp\u003e\u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAt least once per day\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (16%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (28%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSeveral times a week\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (16%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (24%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOnce a week\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (10%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eA couple times a month\u003c/p\u003e\u003cp\u003e/Every other week\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (17%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (12%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOnce a month\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (16%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOnce every few months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (27%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (18%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eCorrelations were conducted to determine the relationships between the potential contributing factors of anxious behavior (i.e., pain, sleep, and anxiety; see Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Higher scores for each scale indicated higher level (i.e., higher frequency) of concerns. The results indicated no significant relationship between a few of the scales (e.g., pain and the Anxiety Subscale score, and pain and the perception of anxiety frequency). In contrast, a significant correlation between pain and sleep was found, indicating that higher pain was associated with increased sleep difficulties (\u003cem\u003er\u003c/em\u003e[48]\u0026thinsp;=\u0026thinsp;.45, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.001). Positive correlations were found between the ABRS and the Anxiety Subscale (\u003cem\u003er\u003c/em\u003e[50]\u0026thinsp;=\u0026thinsp;.91, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.001), the ABRS and anxiety frequency perception (\u003cem\u003er\u003c/em\u003e[50]\u0026thinsp;=\u0026thinsp;.54, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.001), and the Anxiety Subscale and anxiety frequency perception (\u003cem\u003er\u003c/em\u003e[50]\u0026thinsp;=\u0026thinsp;.45, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.001). Participants who reported higher frequency of anxious behavior on one measure also reported higher levels of anxiety on the other measures in the survey.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCorrelations\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eScale\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1. Pain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2. Sleep\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e.45**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3. ABRS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e.33*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e.39**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4. Anxiety Subscale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e.34*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e.91**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5. Anxiety Perception\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e.28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e.30*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e.54**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e.45**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003cem\u003eNote.\u003c/em\u003e Pain\u0026thinsp;=\u0026thinsp;reported pain, Sleep\u0026thinsp;=\u0026thinsp;reported sleep difficulties, ABRS\u0026thinsp;=\u0026thinsp;DBC-P Anxiety Behavior Rating Scale, Anxiety Subscale\u0026thinsp;=\u0026thinsp;DBC-P Anxiety Subscale, Anxiety Perception\u0026thinsp;=\u0026thinsp;reported perceived anxiety\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003e* indicates significance at the .05 level\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003e** indicates significance at the .01 level\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eA positive correlation between pain and the ABRS (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.01) suggested that higher levels of pain was associated with higher anxiety. Similarly, a significant correlation between sleep and each measure of anxiety was found (with the ABRS, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.005; with the Anxiety Subscale, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.013; and with participant perception of anxiety frequency, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.03). This indicated that higher sleep difficulties were associated with higher anxiety on each measure of anxious behavior. These results suggest that higher levels of pain and sleep concerns are significantly related to higher levels of anxiety.\u003c/p\u003e\u003cp\u003eTo further analyze these relationships, a two-step hierarchical multiple linear regression analysis was conducted to assess predicting factors of anxiety (measured by the ABRS). Pain was entered into the regression equation as the variable for Step 1 of this analysis to control for the participants\u0026rsquo; reported pain frequency (see Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e17\u003c/span\u003e). The results indicated that pain accounted for 11.9% of variance in the ABRS score and the regression model was significant, \u003cem\u003eF\u003c/em\u003e(1,48)\u0026thinsp;=\u0026thinsp;6.50, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.014. At Step 2, we entered the sleep difficulty variable and it predicted an additional 7.1% of variance and also created a significant model, \u003cem\u003eF\u003c/em\u003e(2,47)\u0026thinsp;=\u0026thinsp;5.51, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.007.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 17\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eHierarchical Multiple Linear Regression Analysis Predicting Anxiety (ABRS)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStep and Predictor Variable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003eb(β)\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003eSE\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eΔR\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStep 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e.11*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e.56 (.34)*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStep 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e.07*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e.34 (.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e.24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSleep\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e.48 (.29)*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e.24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eNote.\u003c/em\u003e Pain\u0026thinsp;=\u0026thinsp;reported pain, Sleep\u0026thinsp;=\u0026thinsp;reported sleep difficulties, ABRS\u0026thinsp;=\u0026thinsp;DBC-P Anxiety Behavior Rating Scale. Higher scores indicated higher levels of concern.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e* indicates significance at the .05 level\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eA mediation analysis was used to investigate if sleep mediates the relationship between pain and anxiety (as measured by the ABRS). The indirect effect was tested using a percentile bootstrap estimation approach implemented with the PROCESS macro Version 3 (44). These results indicated the indirect coefficient for sleep was significant, β\u0026thinsp;=\u0026thinsp;.2234, \u003cem\u003eSE\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.1229, 95% CI\u0026thinsp;=\u0026thinsp;.0241, .5066. These results suggest that pain increases anxiety by causing increased difficulties with sleep (see Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003ePrevalence and Presentation of Anxiety and OCD\u003c/h2\u003e\u003cp\u003eThis research project surveyed adults with CHARGE and legal guardians of adults with CHARGE to further analyze anxiety among the population. The results of this survey provided updated information on anxiety diagnoses and anxious behavior among adults with CHARGE. In addition, new results were found to indicate the relationship between anxiety and potential contributing factors of anxious behavior in CHARGE syndrome (i.e., pain and sleep issues).\u003c/p\u003e\u003cp\u003ePrevious literature regarding children with CHARGE found small percentages of diagnosed anxiety disorders despite high levels of obsessive-compulsive behavior (7, 13, 14). Based on the responses of the participants, half of adults with CHARGE in the current study were reported having at least one diagnosed anxiety disorder and a quarter reported having more than one anxiety diagnosis. High levels of diagnosed anxiety disorders overall (and specifically GAD) could indicate that the presence of (generalized) anxious behavior should be added to the behavioral phenotype. The results also present an interesting dichotomy between perceived anxiety of adults with CHARGE syndrome and the presence of anxiety diagnoses. Regardless of clinical anxiety diagnoses, participants report anxiety and anxious behavior as very prevalent among adults with CHARGE syndrome.\u003c/p\u003e\u003cp\u003eIn other studies, individuals with CHARGE and their families have reported varied percentages of OCD (5, 6) but the prevalence has always been reported as higher than the national prevalence among the general population. Participants\u0026rsquo; answers on scales and checklists (DBC-P and FOCI) in this study indicated that, in particular, obsessive-compulsive behavior is very common among adults with CHARGE syndrome. Across these measures, common compulsions reported were consistent with the literature (7, 13, 14). The results of this study support the continued inclusion of repetitive and obsessive-compulsive behavior as a core component of the CHARGE behavioral phenotype, as it provides a useful description of the behavior among individuals with CHARGE (9).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003eThe Relationship Between Pain, Sleep, and Anxiety Among Adults With CHARGE\u003c/h2\u003e\u003cp\u003eExperts on the behavior of individuals with CHARGE syndrome have categorized the basis of the behavior into the self-regulation of three major factors: pain, sensory impairment, and anxiety (also known as the Behavior Triangle, 9). Pain and sleep concerns were high among adults with CHARGE in this study. This result is comparable to previous research on children with CHARGE (8, 20, 21). Based on the relationship between pain, sleep, and anxiety found in previous literature (7, 18) and the theorized factors behind anxious behavior in CHARGE syndrome it was expected that pain and sleep would have a significant impact on the anxiety of adults with CHARGE syndrome. The significant correlation between pain and anxiety lends evidence to the theory that pain is an important predictor of the anxious behavior of individuals with CHARGE (9). Additionally, the results also showed that sleep concerns among adults with CHARGE had a strong correlation to both pain and anxiety. A hierarchical regression analysis indicated that sleep mediates the relationship between pain and anxiety. This suggests that increased pain causes increased difficulties with sleep which then predicts an increase in anxiety.\u003c/p\u003e\u003cp\u003eThere are strategies to combat pain. However, sometimes in the case of medical pain with CHARGE, further medical procedures may be needed to reach the source of the pain (e.g., anesthesia for a dental procedure for a cavity). These additional procedures can lead to more anxiety and pain, particularly when individuals with CHARGE frequently have a surplus of surgeries or other invasive medical procedures in their lifetime (20). Additionally, pain and chronic pain can lead to anticipation or fear of pain among individuals with CHARGE syndrome. Indeed, preliminary research has shown that the increased number of medical procedures has led to Post Traumatic Stress Disorder symptoms in children with CHARGE (47). Taken together, this indicates that while pain intervention might be a useful way to lower anxiety among adults with CHARGE, use of additional medical procedures to reduce pain may have the unintended side effect of increasing anxiety and stress.\u003c/p\u003e\u003cp\u003eIn contrast, there are many evidence-based behavioral interventions (e.g., sleep hygiene routines) and non-invasive medical techniques (e.g., use of melatonin) to improve sleep and several that have been found effective for individuals with CHARGE syndrome. Kennert (48) found in a study of children with CHARGE that positive bedtime routines with scheduled awakening, melatonin treatment, and the combination of these two strategies were viable treatment options to improve sleep outcomes. Sleep and self-regulation of behavior may also be connected (49) which could provide further evidence for sleep being an important part of the behavior triangle for CHARGE syndrome (9). Therefore, because sleep mediates the relationship between pain and anxiety, it could be possible that sleep interventions would be a feasible strategy for adults with CHARGE and parents of children with CHARGE to decrease anxiety and related behaviors. Previous research indicates that sleep interventions can be effective when implemented by a parent and among children with CHARGE (46) and perhaps can break the cycle of pain and anxiety experienced by individuals with CHARGE while improving self-regulation and avoiding exacerbation of other potential contributing factors of anxiety.\u003c/p\u003e\u003c/div\u003e"},{"header":"LIMIATAIONS AND CONCLUSIONS","content":"\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\u003cp\u003eIt should be noted that the current and previous studies relied on self-report or parent report of mental health diagnoses. There is a possibility that participants were unaware of their child\u0026rsquo;s mental health diagnoses, therefore, our current estimates on OCD diagnoses may be an underestimate or overestimate. While the results of this study provide a useful description of anxious behavior among adults with CHARGE, parents and legal guardians may not always understand the distinction between experiencing anxiety and having a diagnosed anxiety disorder. Additionally, while self-report is a useful assessment tool for the diagnosis of anxiety, further behavior observation and direct testing of anxiety would likely lead to a more accurate diagnosis than solely relying on the self-reflection of adults with CHARGE syndrome or their caregivers. As such, future studies should attempt to use alternative and more descriptive methods to gather information on anxiety (e.g., interviews, self-report, direct testing, clinical assessment, analysis of clinical documents, etc.).\u003c/p\u003e\u003cp\u003eAccurate description of anxiety among the participants may also have been hindered by the lingering presence and impact of the COVID-19 pandemic. As participant responses were collected during the beginning of the COVID-19 pandemic (Spring/Summer 2020) it is likely that anxious behavior was affected. Indeed, over half of participants indicated that their anxiety had risen since the beginning of the pandemic. Future studies will need to be done to see if the increased levels of anxiety persist or are merely a result of the zeitgeist. Regardless, researching and developing effective anxiety interventions for individuals with CHARGE is important and will continue to be important (perhaps even more so if the pandemic has led to a permanent increase in anxious behavior).\u003c/p\u003e\u003cp\u003eSensory impairment and communication difficulties provide particular challenges to the current research. It may be difficult for adults with CHARGE and their caregivers (and professionals for that matter) to differentiate between what is true anxiety, rational fear, and which behaviors are filling sensory or communicative needs. For example, children with CHARGE syndrome may engage in repetitive checking behaviors more frequently as a functional way to compensate for their compromised vision and auditory systems and navigate their environment (9). If it is difficult for those with an expertise in CHARGE syndrome to make these distinctions, it is reasonable to assume that other legal guardians and professionals with limited exposure to CHARGE, genetic syndromes, and sensory impairment may have difficulties in truly understanding anxiety within CHARGE syndrome. Research geared towards analysis of the clinical process behind an anxiety diagnosis and other clinical diagnoses (e.g., MDD, ADHD, ASD, etc.) may provide a better indication of what clinicians consider during their assessment and in their conclusions regarding clinical diagnoses and the interventions that they recommend. Further exploration of alternative diagnostic models (e.g., RDoC) could offer a more defined or tailored approach to diagnosing anxiety among individuals with CHARGE.\u003c/p\u003e\u003cp\u003eResearch suggests that high rates of anxiety are prevalent among other developmental disorders and genetic syndromes (28, 29, 31). In addition, there is growing evidence to suggest that different genetic syndromes exhibit differential presentations of specific anxiety disorders (28). Although not yet empirically supported, it is possible that CHARGE syndrome might also have uniquely higher levels of a particular anxiety disorder (namely OCD) or higher levels of behavior characteristic of particular subtypes of anxiety. Indeed, preliminary results from previous research (8) indicated that children and adolescents with CHARGE syndrome received higher OCD subscale scores than individuals with other genetic syndromes and typically developing children with an anxiety diagnosis. There were no significant differences between the anxiety scores between children with CHARGE (8) and adults with CHARGE (current study) indicating that the increased levels of anxiety and behaviors characteristic of OCD are prevalent across the community regardless of age. Further research is necessary to measure, describe, and compare the anxiety of adults with CHARGE to children and adolescents with CHARGE syndrome and to individuals with other genetic syndromes.\u003c/p\u003e\u003cp\u003eAnxiety is a significant concern within the CHARGE community. The current study was designed to gain a thorough description of the anxiety diagnoses and behaviors of adults with CHARGE syndrome and how it can be influenced by potential contributing factors of anxiety. Professionals working with clients with CHARGE should consider the multitude of unique factors influencing the expression of anxiety symptoms among these individuals, particularly pain and sleep. Future research should continue to study the clinical process in anxiety diagnosis among the CHARGE community and methods to increase access to anxiety interventions that are effective and adapted to the needs of individuals with CHARGE syndrome \u0026ndash; such as sleep interventions.\u003c/p\u003e\u003c/div\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cem\u003eABRS\u003c/em\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAnxiety Behavior Rating Scale from the DBC-P\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cem\u003eADULT group\u003c/em\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eParticipants who were adults with CHARGE Syndrome\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cem\u003eCHARGE\u003c/em\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eCHARGE Syndrome\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cem\u003eCHD7\u003c/em\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eChromodomain helicase DNA binding protein 7\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cem\u003eCOMBINED group\u003c/em\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAll participants, which included both the \u003cem\u003eAdult\u003c/em\u003e and \u003cem\u003eLG\u003c/em\u003e participants\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cem\u003eDBC-P\u003c/em\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eDevelopmental Behavior Checklist-Parent Version\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cem\u003eDSM-5\u003c/em\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eDiagnostic and Statistical Manual of Mental Disorders, 5th Edition\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cem\u003eFOCI\u003c/em\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eFlorida Obsessive-Compulsive Inventory\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cem\u003eGAD\u003c/em\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eGeneralized anxiety disorder\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cem\u003eGAD-\u003c/em\u003e7\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eGeneralized Anxiety Disorder 7-Item Scale\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cem\u003eLG group\u003c/em\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eParticipants who were legal guardians of an adult with CHARGE Syndrome\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cem\u003eOCD\u003c/em\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eObsessive-compulsive disorder\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eHuman Ethics Approval and Consent to Participate\u003cbr\u003e\u003c/strong\u003eThe procedures, informed consent form, and all materials from this project were submitted and approved by the Institutional Review Board (IRB) of Central Michigan University in accordance with the Declaration of Helsinki. Informed consent to participate in the study was received from each participant. Clinical trial number: not applicable.\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;Consent for Publication\u003cbr\u003e\u0026nbsp;\u003c/strong\u003eNot applicable.\u003cbr\u003e\u003cstrong\u003eAvailability of data and materials\u003cbr\u003e\u0026nbsp;\u003c/strong\u003eThe data sets generated during the current study are not publicly available because the participants of this study did not give written consent for their data to be shared publicly and our Institutional Review Board advised the researchers that the data could contain information that could compromise the privacy of research participants.\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;Competing Interests\u003cbr\u003e\u003c/strong\u003eThe authors declare that they have no competing interests.\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;Funding\u003cbr\u003e\u0026nbsp;\u003c/strong\u003eThere was no funding used for this research.\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;Authors' contributions\u003cbr\u003e\u0026nbsp;\u003c/strong\u003eS.MB\u0026nbsp;and T.H. and L.S. contributed to the conception and design of this study.\u0026nbsp;S.MB\u0026nbsp;completed the acquisition and analysis of the data while\u0026nbsp;S.MB\u0026nbsp;and T.H. interpreted the results.\u0026nbsp;S.MB\u0026nbsp;wrote the main manuscript text and prepared the figures and tables. All authors reviewed and substantively revised the manuscript.\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;Acknowledgements\u003cbr\u003e\u003c/strong\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\n\u003col\u003e\n\u003cli\u003eJanssen N, Bergman JEH, Swertz MA, Tranebjaerg L, Lodahl M, Schoots J, Hofstra RMW, Ravenswaaij-Arts CMA, Hoefsloot LH. Mutation update on the CHD7 gene involved in CHARGE syndrome. Hum Mutat. 2012;33(8):1149-60. doi:10.1002/humu.22086.\u003c/li\u003e\n\u003cli\u003eBlake KD, Davenport SLH, Hall BD, Hefner MA, Pagon RA, Williams MS, Lin AE, Graham JM. CHARGE association: An update and review for the primary pediatrician. Clin Pediatr (Phila). 1998;37(3):159 − 73. doi:10.1177/000992289803700302.\u003c/li\u003e\n\u003cli\u003ePagon RA, Graham JM, Zonana J, Yong SL. Coloboma, congenital heart disease, and choanal atresia with multiple anomalies: CHARGE association. J Pediatr. 1981;99(2):223–7. doi:10.1016/s0022-3476(81)80454-4.\u003c/li\u003e\n\u003cli\u003eHefner MA. Introduction to CHARGE syndrome. In: Hartshorne TS, Hefner MA, Blake KD, editors. CHARGE syndrome. 2nd ed. San Diego (CA): Plural Publishing; 2021. p. xi-xvi.\u003c/li\u003e\n\u003cli\u003eBlake KD, Salem-Hartshorne N, Daoud MA, Gradstein J. Adolescent and adult issues in CHARGE syndrome. Clin Pediatr (Phila). 2005;44(2):151-9. doi:10.1177/000992280504400207.\u003c/li\u003e\n\u003cli\u003eWachtel LE, Hartshorne TS, Dailor AN. Psychiatric diagnoses and psychotropic medications in CHARGE syndrome: A pediatric survey. J Dev Phys Disabil. 2007;19(5):471–83. doi:10.1007/s10882-007-9064-6.\u003c/li\u003e\n\u003cli\u003eHartshorne N, Hudson A, MacCuspie J, Kennert B, Nacarato T, Hartshorne T, Blake K. Quality of life in adolescents and adults with CHARGE syndrome. Am J Med Genet A. 2016;170(8):2012-21. doi:10.1002/ajmg.a.37769.\u003c/li\u003e\n\u003cli\u003eMadhavan-Brown SA. 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In: Hartshorne TS, Hefner MA, Blake KD, editors. CHARGE syndrome. 2nd ed. San Diego (CA): Plural Publishing; 2021. p. 449 − 54.\u003c/li\u003e\n\u003cli\u003eCrawford H, Waite J, Oliver C. Diverse profiles of anxiety related disorders in fragile X, Cornelia de Lange, and Rubinstein-Taybi syndromes. J Autism Dev Disord. 2017;47(12):3728-40. doi:10.1007/s10803-016-3015-y.\u003c/li\u003e\n\u003cli\u003eDankner N, Dykens EM. Anxiety in intellectual disabilities: Challenges and next steps. Int Rev Res Dev Disabil. 2012;42:57–83. doi:10.1016/b978-0-12-394284-5.00003-6.\u003c/li\u003e\n\u003cli\u003eGroves L, Moss J, Oliver C, Royston R, Waite J, Crawford H. Divergent presentation of anxiety in high-risk groups within the intellectual disability population. Journal of Neurodevelopmental Disorders. 2022 Oct 5;14(1).\u003c/li\u003e\n\u003cli\u003eLeyfer O, Woodruff-Borden J, Mervis CB. 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Characteristics and development of children with CHARGE association/syndrome. J Early Interv. 2004;26(4):292–301. doi:10.1177/105381510402600405.\u003c/li\u003e\n\u003cli\u003eVerloes A. Updated diagnostic criteria for CHARGE syndrome: A proposal. Am J Med Genet A. 2005;133(3):306–8. doi:10.1002/ajmg.a.30559.\u003c/li\u003e\n\u003cli\u003eRosenfeld R, Dar R, Anderson D, Kobak KA, Greist JH. A computer-administered version of the Yale-Brown Obsessive-Compulsive Scale. Psychological Assessment. 1992 Sep;4(3):329–32.\u003c/li\u003e\n\u003cli\u003eAleda MA, Geffken GR, Jacob ML, Goodman WK, Storch EA. Further psychometric analysis of the Florida obsessive-compulsive inventory. J Anxiety Disord. 2009;23(1):124-9. doi:10.1016/j.janxdis.2008.05.001.\u003c/li\u003e\n\u003cli\u003eGoodman WK, Price LH, Rasmussen SA, Mazure C, Fleischmann RL, Hill CL, Heninger GR, Charney DS. The Yale-Brown Obsessive Compulsive Scale: I. Development, use, and reliability. Arch Gen Psychiatry. 1989;46(11):1006-11. doi:10.1001/archpsyc.1989.01810110048007.\u003c/li\u003e\n\u003cli\u003ePlummer F, Manea L, Trepel D, McMillan D. Screening for anxiety disorders with the GAD-7 and GAD-2: A systematic review and diagnostic meta-analysis. Gen Hosp Psychiatry. 2016;39:24–31. doi:10.1016/j.genhosppsych.2015.11.005.\u003c/li\u003e\n\u003cli\u003eBeck AT, Epstein N, Brown G, Steer RA. An inventory for measuring clinical anxiety: Psychometric properties. J Consult Clin Psychol. 1988;56(6):893-7. doi:10.1037//0022-006x.56.6.893.\u003c/li\u003e\n\u003cli\u003eDerogatis LR, Lipman RS, Rickels K, Uhlenhuth EH, Covi L. The Hopkins Symptom Checklist (HSCL): A self-report symptom inventory. Behav Sci. 1974;19(1):1–15. doi:10.1002/bs.3830190102.\u003c/li\u003e\n\u003cli\u003eSpitzer RL, Williams JB, Kroenke K, Hornyak R, McMurray J. 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Medical experiences and subsequent behaviors in children and adolescents with CHARGE syndrome. [master’s thesis]. Mount Pleasant (MI): Central Michigan University; 2021.\u003c/li\u003e\n\u003cli\u003eKennert BA. Investigation of two methods for treating sleep problems among children with CHARGE syndrome [dissertation]. Mount Pleasant (MI): Central Michigan University; 2018.\u003c/li\u003e\n\u003cli\u003eKroese FM, De Ridder DT, Evers C, Adriaanse MA. Bedtime procrastination: Introducing a new area of procrastination. Front Psychol. 2014;5:611. doi:10.3389/fpsyg.2014.00611.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-neurodevelopmental-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jndd","sideBox":"Learn more about [Journal of Neurodevelopmental Disorders](http://jneurodevdisorders.biomedcentral.com/)","snPcode":"11689","submissionUrl":"https://submission.nature.com/new-submission/11689/3","title":"Journal of Neurodevelopmental Disorders","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"CHARGE syndrome, anxiety, obsessive-compulsive disorder, pain, sleep, behavioral phenotype","lastPublishedDoi":"10.21203/rs.3.rs-7278769/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7278769/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eCHARGE syndrome is a rare genetic disorder with multiple physical, cognitive, behavioral, and sensory impairments. Anxiety is a common finding. Difficulties with pain, sleep, sensory impairment, communication, daily stress, and unpredictable environments are potential contributing factors to this anxiety. Further research is needed to gain a better understanding of the presentation of anxiety in CHARGE syndrome to promote proper diagnosis and treatment of anxiety.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eAn on-line survey was distributed to adults and guardians of adults with CHARGE syndrome. Fifty-two participants provided responses to the \u003cem\u003eDevelopmental Behavior Checklist-Parent Version\u003c/em\u003e, the \u003cem\u003eFlorida Obsessive-Compulsive Inventory\u003c/em\u003e, and the \u003cem\u003eGeneralized Anxiety Disorder 7-Item Scale\u003c/em\u003e. Participants also provided demographic data, diagnostic characteristics of CHARGE, their perception of their anxiety, diagnosed mental health disorders, and the frequency of other potential factors of anxiety (i.e. pain and sleep concerns). Descriptive statistics, independent samples t-tests, and Pearson\u0026rsquo;s correlations provided information on the presentation of anxiety and the relationships between potential factors and anxiety subscale scores. A hierarchical multiple linear regression analysis and mediation analysis was used to investigate if sleep mediates the relationship between pain and anxiety.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eGeneralized anxiety disorder and obsessive-compulsive disorder were the first (39% of sample) and fourth (27% of sample) most common mental health diagnoses reported and 50% of the sample had been diagnosed with at least one anxiety disorder. The most commonly reported anxious behaviors included getting obsessed with an idea or activity, being impatient, getting upset or distressed over small changes in the routine or environment, and being tense, anxious, or worried. Sleep was found to mediate the relationship between pain and anxiety.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThis study has implications for understanding the behavioral phenotype of CHARGE syndrome. Based on self-report or legal guardian report, anxiety is a common experience among individuals with CHARGE; generalized anxiety disorder and obsessive-compulsive disorder diagnoses/behavior are the most frequently reported. Further research into the management of pain and improvement of sleep as anxiety interventions for individuals with CHARGE may prove fruitful.\u003c/p\u003e","manuscriptTitle":"Anxiety and Obsessive-Compulsive Disorder (OCD) in Adults with CHARGE Syndrome","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-21 06:47:43","doi":"10.21203/rs.3.rs-7278769/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-11-18T17:22:02+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-24T15:27:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"78663850169027825120796110392898857752","date":"2025-08-14T19:24:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"98450323909041570375495904797385888731","date":"2025-08-12T14:29:34+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-12T07:17:41+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-07T06:57:57+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-07T06:55:15+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Neurodevelopmental Disorders","date":"2025-08-02T14:07:02+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-neurodevelopmental-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jndd","sideBox":"Learn more about [Journal of Neurodevelopmental Disorders](http://jneurodevdisorders.biomedcentral.com/)","snPcode":"11689","submissionUrl":"https://submission.nature.com/new-submission/11689/3","title":"Journal of Neurodevelopmental Disorders","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"15bfafd2-874c-4e8a-a00a-ef7a0d72daee","owner":[],"postedDate":"August 21st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-09T16:00:47+00:00","versionOfRecord":{"articleIdentity":"rs-7278769","link":"https://doi.org/10.1186/s11689-026-09673-5","journal":{"identity":"journal-of-neurodevelopmental-disorders","isVorOnly":false,"title":"Journal of Neurodevelopmental Disorders"},"publishedOn":"2026-03-02 15:57:30","publishedOnDateReadable":"March 2nd, 2026"},"versionCreatedAt":"2025-08-21 06:47:43","video":"","vorDoi":"10.1186/s11689-026-09673-5","vorDoiUrl":"https://doi.org/10.1186/s11689-026-09673-5","workflowStages":[]},"version":"v1","identity":"rs-7278769","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7278769","identity":"rs-7278769","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}