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The presence of obsessive-compulsive disorder (OCD) has been linked to decreased quality of life (QoL) among adults, yet little is known about the impact of OCD on QoL in pediatric patients. Sixty-two youth with OCD and their parent(s) were administered the Children's Yale-Brown Obsessive Compulsive Scale following a clinical interview. Children completed the Pediatric Quality of Life Inventory and parents completed the Pediatric Quality of Life Parent Proxy Inventory and Child Behavior Checklist. QoL scores for OCD patients were significantly lower than for healthy controls, but similar to QoL in a general psychiatric sample on the majority of domains. Parent-child agreement on QoL was moderate to strong across age groups. Results indicate that, in youth with OCD, QoL is reduced relative to healthy controls, related to OCD symptom severity per parent-report, and are strongly predicted by the presence of comorbid externalizing and internalizing symptoms. [ABSTRACT FROM AUTHOR]

This report describes the development and psychometric properties of the Children's Florida Obsessive Compulsive Inventory (C-FOCI). Designed specifically as a brief measure for assessing obsessive-compulsive symptoms, the C-FOCI was created for use in both clinical and community settings. Study 1 included 82 children and adolescents diagnosed with primary Obsessive-Compulsive Disorder, and their parents. The Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) was administered to assess symptom severity. Thereafter, parents completed the Child Obsessive-Compulsive Impact Scale-Parent Version and Child Behavior Checklist, and youth completed the C-FOCI, Child Obsessive-Compulsive Impact Scale-Child Version, Multidimensional Anxiety Scale for Children, and Children's Depression Inventory-Short Form. A subgroup of 21 individuals was retested with the C-FOCI after completing 14 sessions of intensive cognitive-behavioral therapy. Construct validity of the C-FOCI was supported vis-à-vis evidence of treatment sensitivity, and moderate relations with clinician-rated symptom severity, the CY-BOCS Symptom Checklist, child- and parent-rated functional impairment, child-rated anxiety, and parent-rated internalizing symptoms. Discriminant validity was evidenced by weak relationships with parent-reports of externalizing symptoms. For Study 2, 191 non-clinical adolescents completed the C-FOCI to assess the feasibility of internet administration. Overall, internal consistency was acceptable for the C-FOCI Symptom Checklist and Severity Scale, and respondents were able to complete the measure with little difficulty. Taken together, the findings of Studies 1 and 2 provide initial support for the reliability and validity of the C-FOCI for the assessment of pediatric obsessive-compulsive symptoms. [ABSTRACT FROM AUTHOR]

Background and Objectives: Tourette syndrome (TS) is defined by multiple motor tics and one or more phonic tics with a symptom duration of >1 year. Coprophenomena are uncommon tics characterized by obscene sounds, words, or gestures. Youth with TS commonly have psychiatric co-occurring conditions such as attention-deficit hyperactivity disorder or obsessive-compulsive disorder and have reported lower scores on measures of individual and family functioning than youth without TS. This study aimed to determine associations among co-occurring condition symptoms, tic severity, and function in youth with TS and coprophenomena compared with those with TS without coprophenomena., Methods: Data were collected through a multicenter, cross-sectional study. Youth with TS were recruited from 2 referral centers, and data were collected from youth and their parents or caregivers. Tic severity was assessed using the Yale Global Tic Severity Scale, and individual function was measured with the Children's Global Assessment Scale. Family impact was measured using the Family Impact Module in domains of parent health-related quality of life (HRQOL), family functioning, and total family impact. We compared individual and family function in youth with TS with coprophenomena (TS+copro) and without coprophenomena (TS-copro). Wilcoxon rank-sum tests were used to compare scores on individual function and family function measures., Results: Of 169 participants, 17 (10.1%) reported coprophenomena. Participants with TS and coprophenomena had higher tic severity scores than those without coprophenomena (TS+copro mean = 36.9, TS-copro = 20.8). Youth with coprophenomena had lower scores for global function (TS+copro median = 51, TS-copro = 60), family functioning (TS+copro = 43.8, TS-copro = 59.4), parent HRQOL (TS+copro = 57, TS-copro = 72), and total family QOL (TS+copro = 50.7, TS-copro = 65.3)., Discussion: Youth with TS and coprophenomena had lower individual function, family function, and parent HRQOL than youth without coprophenomena. Coprophenomena presence may indicate that youth have a more severe phenotype of TS, and youth with copropheneomena may benefit from additional caregiver or family supports., Competing Interests: The authors report no relevant disclosures. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (© 2024 American Academy of Neurology.)

Communicating with a speaker with a different accent can affect one's own speech. Despite the strength of evidence for perception-production transfer in speech, the nature of transfer has remained elusive, with variable results regarding the acoustic properties that transfer between speakers and the characteristics of the speakers who exhibit transfer. The current study investigates perception-production transfer through the lens of statistical learning across passive exposure to speech. Participants experienced a short sequence of acoustically variable minimal pair (beer/pier) utterances conveying either an accent or typical American English acoustics, categorized a perceptually ambiguous test stimulus, and then repeated the test stimulus aloud. In the canonical condition, /b/-/p/ fundamental frequency (F0) and voice onset time (VOT) covaried according to typical English patterns. In the reverse condition, the F0xVOT relationship reversed to create an "accent" with speech input regularities atypical of American English. Replicating prior studies, F0 played less of a role in perceptual speech categorization in reverse compared with canonical statistical contexts. Critically, this down-weighting transferred to production, with systematic down-weighting of F0 in listeners' own speech productions in reverse compared with canonical contexts that was robust across male and female participants. Thus, the mapping of acoustics to speech categories is rapidly adjusted by short-term statistical learning across passive listening and these adjustments transfer to influence listeners' own speech productions., (© 2023. The Author(s).)

Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by sudden onset of obsessive-compulsive disorder and/or eating restriction with associated neuropsychiatric symptoms from at least two of seven categories. The PANS 31-Item Symptom Rating Scale (PANS Rating Scale) was developed to identify and measure the severity of PANS symptoms. The objective of this study was to define the psychometric properties of the PANS Rating Scale. Methods: Children with PANS ( N  = 135) and their parents participated. Parents completed the PANS Rating Scale and other scales on Research Electronic Data Capture. The PANS Rating Scale includes 31 items that are rated on a Likert scale from 0 = none to 4 = extreme. Pearson's correlations were run between the PANS Total score and scores on the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), Yale Global Tic Severity Scale (YGTSS), Modified Overt Aggression Scale (MOAS), Columbia Impairment Scale (CIS), PANS Global Impairment Score (GIS), and Children's Global Assessment Scale (CGAS). Results: Convergent validity was supported by significant correlations between the PANS Total and scores on the CY-BOCS, YGTSS, MOAS, CIS, GIS, and CGAS. The largest correlations were with measures of functional impairment: PANS Total and CIS ( r  = 0.81) and PANS Total and GIS ( r  = 0.74). Cronbach's alpha was 0.89 which demonstrates strong internal consistency of the 31 items. PANS Total score was significantly higher in children in a flare of their neuropsychiatric symptoms compared to children who were not in a flare. Conclusions: This study provides preliminary support for the PANS Rating Scale as a valid research instrument with good internal consistency. The PANS Rating Scale appears to be a useful measure for assessing children with PANS.

Background: Tourette syndrome (TS) is associated with learning disabilities and educational impairment. Teacher knowledge about TS may have a positive impact on students with TS, but factors associated with teacher knowledge of TS are not known., Methods: In this cross-sectional study, teachers of youth with TS and of a community control group completed a Teacher Understanding of Tourette Syndrome Survey (TUTS), a pilot questionnaire enquiring about self-perceived understanding, teacher knowledge, and sources of information. We compared TUTS scores between TS and control groups and between those who did and did not use specific sources of information about TS using Wilcoxon rank-sum tests. Bivariate correlation analyses were used to evaluate associations between teacher knowledge and potential contributing factors., Results: Data from 114 teachers of children with TS and 78 teachers of control subjects were included. Teachers of youth with TS had significantly more knowledge, had higher self-perceived understanding, and used more sources of information than teachers of the control group. Teachers who knew of the Tourette Association of America and who gathered information themselves had higher knowledge about TS than those who did not., Conclusion: Teachers of children with TS know more about TS and use more sources to learn about TS than teachers of children without TS., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Tics are unwanted, repetitive movements and sounds that frequently present during childhood. They are typically brief and purposeless, but can create significant distress for individuals, and often co-occur with other neuropsychiatric conditions. Thus, early identification of tics is warranted. Unfortunately, tics are often misdiagnosed, and because tics may wax and wane, identification can be difficult, especially in the context of routine clinical visits. There are limited tools that can be used to reliably identify tics in clinical practice, especially in non-specialty settings. The purpose of the current study was to evaluate the performance of the Motor tic, Obsession and compulsion, and Vocal tic Evaluation Survey (MOVES), a self-report scale with some support as a screening tool. In addition, the performance of a subset of questions (the MOVES-6) was evaluated for rapid screening. Participants were recruited across two study sites and included children and adolescents diagnosed with Tourette syndrome ( n = 151) or another persistent tic disorder ( n = 10) and community controls ( n = 74). Results suggest both the MOVES and the MOVES-6 have high sensitivity (90% and 88%, respectively) and at least acceptable specificity (77% and 86%, respectively) compared with expert assessment of tic disorders, suggesting that both versions can identify tic disorders without high proportions of false negatives. Both versions were highly sensitive with acceptable specificity regardless of sex, race/ethnicity, and age. The MOVES and MOVES-6 show promise as a screener for tics or tic disorders, but additional research is needed, particularly in a general population setting.

The cognitive model of obsessive-compulsive disorder (OCD) posits that dysfunctional cognitive beliefs are crucial to the onset and maintenance of OCD; however, the relationship between these cognitive beliefs and the heterogeneity of OCD symptoms in children and adolescents remains unknown. We examined how the major belief domains of the cognitive model (inflated responsibility/threat estimation, perfectionism/intolerance of uncertainty, importance/control of thoughts) and dysfunctional metacognitions were related to OCD symptoms across the following dimensions: doubting/checking, obsessing, hoarding, washing, ordering, and neutralization. Self-report ratings from 137 treatment-seeking youth with OCD were analyzed. When cognitive beliefs and symptom dimensions were analyzed in tandem, inflated responsibility/threat estimation and dysfunctional metacognitions were uniquely related to doubting/checking, obsessing, and hoarding and perfectionism/intolerance of uncertainty to ordering. Cognitive beliefs explained a large proportion of variation in doubting/checking (61%) and obsessing (46%), but much less so in ordering (15%), hoarding (14%), neutralization (8%), and washing (3%). Similar relations between cognitive beliefs and symptom dimensions were present in children and adolescents. Cognitive beliefs appear to be relevant for pediatric OCD related to harm, responsibility, and checking, but they do not map clearly onto contamination and symmetry-related symptoms. Implications for OCD etiology and treatment are discussed., (Copyright © 2021. Published by Elsevier Ltd.)

Individuals with Tourette's Disorder and Persistent Tic Disorders (TD) often experience premonitory urges-aversive sensations that precede tics and are relieved by tic expression. Given its role in the neurobehavioral model of TD, understanding factors that influence premonitory urges and associated relief can advance understanding of urge phenomenology and optimize treatments for individuals with TD. This study examined whether the novel construct of urge intolerance-difficulty tolerating premonitory urges-predicted tic severity and tic-related disability. Participants included 75 youth with TD and their caregivers. Assessments characterized tic severity, premonitory urge, distress tolerance, internalizing symptoms, and tic-related disability. Structural equation modeling revealed that higher levels of urge intolerance predicted greater levels of tic-related disability. Furthermore, the relationship between urge intolerance and tic-related disability was more robust for youth with clinically-elevated levels of internalizing symptoms. While further investigation is needed, urge intolerance represents a promising treatment target to improve tic-related disability in youth with TD., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Irritability is a common, impairing transdiagnostic symptom in childhood psychopathology, though it has not been comprehensively studied in pediatric obsessive-compulsive disorder (OCD). Further, the central cognitive behavioral treatment component for OCD, exposure and response prevention therapy (ERP), has been recently proposed as a treatment for irritability. This study aimed to evaluate whether certain clinical characteristics are associated with irritability in pediatric OCD and whether irritability reduces following ERP. Participants were 161 youth (ages 7-17) with OCD and a caregiver participating in a randomized controlled trial of D-cycloserine or pill placebo augmented ERP. Participants completed validated assessments during treatment. Irritability was significantly and positively associated with depressive symptoms, defiance, functional impairment, and family accommodation, but was not associated with pretreatment OCD severity, symptom dimensions, obsessive beliefs. Irritability significantly declined following treatment, with over half of youth with any pretreatment irritability experiencing clinically significant change, though this change was not related to OCD improvement. Results suggest that irritability may be a marker of psychiatric comorbidity, parental accommodation, and impairment in youth with OCD. Implications for the exposure-based treatment of irritability are discussed., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Cancer patients with chemotherapy-induced peripheral neuropathy (CIPN) are at increased risk of falls and developing fear of falling (FoF). Although FoF may continue to impair motor performance and increase the risk of falling even further, this association remains unexplored in CIPN., Research Question: Does high FoF in patients with CIPN further deteriorate motor performance beyond the impairment from CIPN-related sensory deficits?, Methods: In this secondary analysis of data collected from two clinical trials, gait parameters during habitual walking condition and postural sway parameters during 30-second quiet standing (eye-open and eyes-closed) were compared among older participants (≥ 65 years) with CIPN and high FoF (CIPN FoF+; n=16), older participants with CIPN and low FoF (CIPN FoF-; n=19) and normal older controls (i.e., non-cancer, non-diabetic, non-neurologic, and non-orthopedic; n=16). We measured gait and postural sway parameters using wearable sensors (BioSensics, Newton, MA, USA), and FoF severity using the Falls Efficacy Scale-International., Results: The largest between-group differences were found in gait speed. The CIPN FoF + group had significantly slower gait speed (0.78 ± 0.21 m/s) than the CIPN FoF- (0.93 ± 0.17 m/s) and normal control groups (1.17 ± 0.13 m/s) (all p < .05; effect sizes = 0.79 and 2.23, respectively). We found a significant association between gait speed and FoF severity (R2 = 0.356; p < .001) across all participants with CIPN. Among participants with CIPN, no significant differences in postural sway parameters were found between the CIPN FoF+and CIPN FoF- groups., Significance: Our results suggest that gait performance further deteriorates in patients with CIPN and high FoF beyond the impairment from CIPN-related sensory deficits. Our results also suggest further research is needed regarding FoF, and fall risk, as FoF is a simple tool that healthcare providers can use in clinical practice., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We compared anxiety symptoms in youth with and without tic disorders by comparing scores on the Multidimensional Anxiety Scale for Children (MASC) in youth with tic disorders to those in a concurrent community control group and in a group of treatment-seeking anxious youth from the Child/Adolescent Anxiety Multimodal Study (CAMS). Data from 176 youth with tic disorders, 93 control subjects, and 488 CAMS participants were included. Compared to youth with tic disorders, controls had lower total MASC scores (p < 0.0001) and CAMS participants had similar total MASC scores (p = 0.13). Separation Anxiety (p = 0.0003) and Physical Symptom (p < 0.0001) subscale scores were higher in youth with tic disorders than in CAMS participants. We conclude that the anxiety symptom profile differs in youth with and without tic disorders, which may have important implications for targeting treatment of anxiety in youth with tic disorders.

Introduction: Anxiety expression varies by age in youth, and evaluation of putative mechanisms in treatment must consider both conjointly. Accordingly, age would moderate the mediation effect of anxiety in a youth obsessive-compulsive disorder (OCD) treatment trial., Methods: Fifty-six children ages 7 - 17 participated in an RCT comparing three treatments: CBT with standard dosing of sertraline, CBT with slow dosing of sertraline, and CBT with placebo. To examine the moderated-mediation effects for OCD symptom improvement, we discretized the continuous anxiety and OCD measures into three symptom outcome categories, "improved", "unchanged", and "deteriorated". To evaluate the moderating effect of age, we further examined the association of age and anxiety with the "improved" OCD category. For analysis, the age groups used as rows were cross tabulated with discretized anxiety and OCD measures. To estimate category associations with correlations, we adopted correspondence analysis., Results: The correlational results indicate that for all treatment conditions, age was a moderator of the mediation effect of physical anxiety symptoms for the improved OCD measures (outcomes). Specifically, age suppressed correlations with OCD outcomes, with Physical Symptoms as a mediator for the outcome measures. This moderated mediation effect was most evident for ages 8-10 in the CBT with placebo group., Limitations: The moderated mediation effect manifest in this single RCT-based study should be validated in other studies., Discussion: Future research investigating a wider range of ages as a potential moderator of other symptom and emotion mediators of outcome is warranted, particularly in relation to individual symptom profiles of OCD., (Copyright © 2021. Published by Elsevier B.V.)

Objective: Treatment guidelines for Tourette's Disorder (TD) are based on patients' degree of tic severity and impairment. However, clear benchmarks for determining tic severity and impairment have not been established. This study examined benchmarks of tic severity and tic impairment using the Yale Global Tic Severity Scale (YGTSS) and the Clinical Global Impression of Severity (CGI-S)., Method: Individuals with TD or another Tic Disorder (N = 519) recruited across nine sites were administered a diagnostic interview, the YGTSS, and the CGI-S. Correlations and trend analyses contrasted YGTSS scores across CGI-S ratings. A logistic regression model examined predictive benchmarks for tic severity, tic impairment, and global severity. Model classifications were compared against CGI-S ratings, and agreement was examined using kappa., Results: Spearman correlations between the CGI-S and YGTSS scores ranged from 0.54 to 0.63 (p < 0.001). Greater CGI-S ratings were associated with a linear stepwise increase in YGTSS Total Tic scores, Impairment scores, and Global Severity scores. Despite moderate-to-strong associations (ρ = 0.45-0.56, p < 0.001) between the CGI-S and predictive logistical regression models, only fair agreement was achieved when applying classification benchmarks (κ = 0.21-0.32, p < 0.001)., Conclusions: CGI-S ratings are useful to characterize benchmarks for tic severity, tic impairment, and global severity on the YGTSS. Logistic regression model benchmarks had only fair agreement with the CGI-S and underscore the heterogeneity of TD symptoms. Collectively, findings offer guidance on the delineation of tic severity categorizations to apply evidence-based treatment recommendations., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background . The mismatch negativity (MMN) brainwave indexes novelty detection. MMN to infrequent pitch (pMMN) and duration (dMMN) deviants is reduced in long-term schizophrenia. Although not reduced at first psychosis, pMMN is inversely associated with left hemisphere Heschl's gyrus (HG) gray matter volume within 1 year of first hospitalization for schizophrenia-spectrum psychosis, consistent with pathology of left primary auditory cortex early in disease course. We examined whether the relationship was present earlier, at first psychiatric contact for psychosis, and whether the same structural-functional association was apparent for dMMN. Method . Twenty-seven first-episode schizophrenia-spectrum (FESz) and 27 matched healthy comparison (HC) individuals were compared. EEG-derived pMMN and dMMN were measured by subtracting the standard tone waveform (80%) from the pitch- and duration-deviant waveforms (10% each). HG volumes were calculated from T1-weighted structural magnetic resonance imaging using Freesurfer. Results . In FESz, pMMN amplitudes at Fz were inversely associated with left HG (but not right) gray matter volumes, and dMMN amplitudes were associated significantly with left HG volumes and at trend-level with right HG. There were no structural-functional associations in HC. Conclusions . pMMN and dMMN index gray matter reduction in left hemisphere auditory cortex early in psychosis, with dMMN also marginally indexing right HG volumes. This suggest conjoint functional and structural pathology that affects the automatic detection of novelty with varying degrees of penetrance prior to psychosis. These brainwaves are sensitive biomarkers of pathology early in the psychotic disease course, and may serve as biomarkers of disease progression and as therapeutic outcome measures.

Working memory dysfunction may be central to neurocognitive deficits in schizophrenia. Maintenance of visual information in working memory, or visual short-term memory (vSTM), is linked to general cognitive dysfunction and predicts functional outcome. Lateralized change-detection tasks afford investigation of the contralateral delay activity (CDA), a useful tool for investigating vSTM dysfunction. Previous work suggests "hyperfocusing" of attention in schizophrenia, such that CDA is increased when a single item is maintained in vSTM but reduced for multiple items. If observed early in the disease, vSTM dysfunction may be a key feature of schizophrenia or target for intervention. We investigated CDA during lateralized vSTM of one versus three items using sensor-level electroencephalography and source-level magnetoencephalography in 26 individuals at their first episode of schizophrenia-spectrum psychosis (FESz) and 26 matched healthy controls. FESz were unable to modulate CDA with increased memory load - high-load CDA was reduced and low-load CDA was increased compared to controls. Further, sources of CDA in posterior parietal cortex were reduced in FESz and indices of working memory were correlated with neurocognitive deficits and symptom severity. These results support working memory maintenance dysfunction as a central and early component to the disorder. Targeted intervention focusing on vSTM deficits may be warranted to alleviate downstream effects of this disability., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: This study examined the phenomenology and predictors of early response and remission among youth with obsessive-compulsive disorder (OCD) receiving cognitive-behavioral therapy (CBT)., Methods: One hundred and thirty-nine youth with a current primary diagnosis of OCD participated in this study. Participants received 10 sessions of CBT augmented by either placebo or d-cycloserine (DCS) as part of a randomized double-blind multi-site clinical trial. Early response and remission status were determined by clinician-rated global symptom improvement (CGI-I) and severity (CGI-S), respectively., Results: At the mid-treatment assessment, 45.3% of youth were early responders, and 28.1% were early remitters. At post-treatment assessment, 79.1% of youth were responders and 67.6% were remitters. Early response predicted a higher likelihood of post-treatment response and remission; early remission significantly predicted a higher likelihood of post-treatment remission. Bivariate logistic regressions showed that early response was predicted by lower baseline clinician-rated global severity (CGI-S) and lower depression severity; however, only depression severity remained a significant predictor in the multivariable logistic regression model. Furthermore, bivariate logistic regressions showed that early remission was predicted by lower baseline clinician-rated global severity (CGI-S), lower depression severity, and lower obsessive-compulsive symptom severity (CY-BOCS); however, only global severity remained a significant predictor in the multivariable logistic regression model., Conclusions: Lower OCD and depression symptom severity predicted a greater likelihood of early treatment response and remission to CBT. Findings suggest that low OCD and depression symptom severity could serve as baseline characteristics to identify potential candidates for lower-intensity initial interventions in a stepped care approach. The modest predictive value of the variables examined suggests that additional factors could add to prediction of treatment response and remission.

The current study examined the temporal precedence of change in obsessive-compulsive symptoms and change in depressive symptoms during the course of an Exposure and Response Prevention (ERP) for pediatric OCD. Participants included 142 children and adolescents (7-17 years; mean age = 12.39, SD = 2.92; 51.40% female; 60.40% Non-Hispanic White) with a primary or co-primary diagnosis of OCD who received ERP in a two-site randomized controlled trial on d-cycloserine augmentation of CBT for pediatric OCD. Participants completed clinician-administered assessments of OC symptoms (Children's Yale-Brown Obsessive Compulsive Scale) and depressive symptoms (Children's Depression Rating Scale-Revised) from baseline to post-treatment follow-up. Lagged mediational analyses did not yield evidence in support of a mediating role for the change in OC symptoms in the effect of ERP on the change in depressive symptoms. In contrast, change in depressive symptoms mediated the effect of ERP treatment on the subsequent change in OC symptoms (95% confidence interval for indirect effect = -0.04 to -0.001), though the effect size was small. Controlling for the prior levels of the depressive symptoms this indirect effect became non-significant. Theoretical and clinical implications of the findings for the youth with OCD and comorbid depression are discussed., Competing Interests: Declaration of competing interest No potential conflicts of interests., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: Obsessive-compulsive disorder (OCD) is a heterogeneous condition with well-established symptom dimensions across the lifespan. The objective of the present study was to use network analysis to investigate the internal structure of these dimensions in unselected schoolchildren and in children with OCD., Method: We estimated the network structure of OCD symptom dimensions in 6,991 schoolchildren and 704 children diagnosed with OCD from 18 sites across 6 countries. All participants completed the Obsessive-Compulsive Inventory-Child Version., Results: In both the school-based and clinic-based samples, the OCD dimensions formed an interconnected network with doubting/checking emerging as a highly central node, that is, having strong connections to other symptom dimensions in the network. The centrality of the doubting/checking dimension was consistent across countries, sexes, age groups, clinical status, and tic disorder comorbidity. Network differences were observed for age and sex in the school-based but not the clinic-based samples., Conclusion: The centrality of doubting/checking in the network structure of childhood OCD adds to classic and recent conceptualizations of the disorder in which the important role of doubt in disorder severity and maintenance is highlighted. The present results suggest that doubting/checking is a potentially important target for further research into the etiology and treatment of childhood OCD., (Copyright © 2019 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Mismatch negativity (MMN) is elicited by infrequent physical parameter sound changes. MMN to pitch-deviants (pMMN) and duration-deviants (dMMN) are severely reduced in long-term schizophrenia (Sz). Although symptom factors (positive, negative, cognitive) are inconsistently associated with MMN amplitude in Sz, several studies have shown smaller dMMN is associated with impaired social functioning in Sz. MMN is less reduced at the first psychotic episode in the schizophrenia spectrum (FESz). Meta-analyses demonstrate that pMMN is not reduced, while dMMN is moderately impaired. Correlations of pMMN and dMMN with symptom factors in FESz are also equivocal. Associations with social functioning have not been reported. FESz and matched controls (n = 40/group), and Sz and matched controls (n = 50/group) were assessed for baseline and current cognitive functioning, symptoms, and social functioning, and pMMN and dMMN were recorded. Sz showed reductions in pMMN (p = 0.001) and dMMN (p = 0.006) amplitude. By contrast, pMMN (p = 0.27) and dMMN (p = 0.84) were not reduced in FESz. However, FESz showed associations between both MMNs and negative symptoms and social functioning. More impaired MMNs in FESz were associated with increased negative symptoms and impaired social functioning, both current and in the year prior to the emergence of psychosis. These data suggest that the extent of pathological process occurring before first psychosis as reflected in compromised social behavior prior to first break and reduced interpersonal communication and increased alogia at first break is indexed by pMMN and dMMN, putative biomarkers of disease progression sensitive to functional impairment., (Copyright © 2020 Murphy, Haigh, Coffman and Salisbury.)

Objective: Chronic tic disorders occur in approximately 3% of children. Neuropsychiatric symptoms of attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, anxiety, and depression are common. We evaluated the impact of tic disorders and comorbid symptoms on individual and parent quality of life and family functioning., Method: In two cross-sectional studies children with tic disorders were enrolled at the University of Rochester or the University of South Florida; data were pooled for analyses. Control subjects were enrolled at the University of Rochester. We compared quality of life and function in youth and families with and without tic disorders. We evaluated the associations between comorbid symptoms and individual quality of life and family impact in youth with tic disorders using multiple regression analyses., Results: We enrolled 205 youths with tic disorders and 100 control subjects. Psychosocial (P < 0.0001) and physical (P < 0.0001) quality of life were lower in individuals with tic disorders compared with controls. Severity of attention-deficit/hyperactivity disorder (P < 0.0001) and depression (P = 0.046) symptoms were associated with lower psychosocial quality of life in youth with tic disorders. Families of youths with tic disorders had worse parent quality of life (P < 0.001) and family functioning (P < 0.001) than control families. Severity of attention-deficit/hyperactivity disorder (P < 0.0001), obsessive-compulsive disorder (P = 0.0004), and depression (P = 0.01) symptoms were associated with predicted worse family impact., Conclusion: Youths with tic disorders had lower individual and parent quality of life and worse family functioning than controls. The impact of tic disorders on the family may have significant implications for approaches to providing comprehensive care to these families., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The apparent efficacy of d-cycloserine (DCS) for enhancing exposure treatment for anxiety disorders appears to have declined over the past 14 years. We examined whether variations in how DCS has been administered can account for this "declining effect". We also investigated the association between DCS administration characteristics and treatment outcome to find optimal dosing parameters. We conducted a secondary analysis of individual participant data obtained from 1047 participants in 21 studies testing the efficacy of DCS-augmented exposure treatments. Different outcome measures in different studies were harmonized to a 0-100 scale. Intent-to-treat analyses showed that, in participants randomized to DCS augmentation (n = 523), fewer DCS doses, later timing of DCS dose, and lower baseline severity appear to account for this decline effect. More DCS doses were related to better outcomes, but this advantage leveled-off at nine doses. Administering DCS more than 60 minutes before exposures was also related to better outcomes. These predictors were not significant in the placebo arm (n = 521). Results suggested that optimal DCS administration could increase pre-to-follow-up DCS effect size by 50%. In conclusion, the apparent declining effectiveness of DCS over time may be accounted for by how it has been administered. Optimal DCS administration may substantially improve outcomes. Registration: The analysis plan for this manuscript was registered on Open Science Framework (https://osf.io/c39p8/)., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Nocebo effects encompass negative responses to inert interventions in the research setting and negative outcomes with active treatments in the clinical research or practice settings, including new or worsening symptoms and adverse events, stemming from patients' negative expectations and not the pharmacologic action of the treatment itself. Numerous personality, psychosocial, neurobiological, and contextual/environmental factors contribute to the development of nocebo effects, which can impair quality of life and reduce adherence to treatment. Biologics are effective agents widely used in autoimmune disease, but their high cost may limit access for patients. Biosimilar products have gained regulatory approval based on quality, safety, and efficacy comparable to that of originator biologics in rigorous study programs. In this review, we identified gaps in patients' and healthcare professionals' awareness, understanding, and perceptions of biosimilars that may result in negative expectations and nocebo effects, and may diminish their acceptance and clinical benefits. We also examined features of nocebo effects with biosimilar treatment that inform research and clinical practices. Namely, when biosimilars are introduced to patients as possible treatment options, we recommend adoption of nocebo-reducing strategies to avoid negative expectations, including delivery of balanced information on risk-benefit profiles, framing information to focus on positive attributes, and promoting shared decision-making processes along with patient empowerment. Healthcare professionals confident in their knowledge of biosimilars and aware of bias-inducing factors may help reduce the risk of nocebo effects and improve patients' adherence in proposing biosimilars as treatment for autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease., (Copyright © 2019 Colloca, Panaccione and Murphy.)

Family accommodation (FA) has been linked with myriad negative outcomes in pediatric obsessive-compulsive disorder (OCD), but extant literature has yielded differential relationships between FA and clinical variables of interest. Consequently, this study examined the phenomenology, clinical profile, and effects of comorbid psychopathology on FA to better understand these behaviors. A total of 150 youths and their caregivers completed clinician- and self-reported measures at a baseline visit for a larger randomized controlled trial. Sociodemographic variables were not associated with FA, but specific types of OCD symptom clusters were. Higher OC-symptom severity and functional impairment were associated with increased FA. Comorbid anxiety disorders moderated the relationship between OC-symptom severity and FA, but comorbid attention deficit hyperactivity, oppositional defiant, and mood disorders did not. Internalizing and externalizing problems both mediated the relationship between FA and functional impairment. These findings provide clinical implications for important treatment targets and factors that may impact FA.

Background and Objectives: This study examined the occurrence of sudden gains (or reversal of gains) among children with obsessive-compulsive disorder (OCD) during the course of cognitive-behavioral therapy (CBT), as well as the association of sudden gains with treatment response, treatment group, and pre-treatment clinical characteristics., Methods: The sample consisted of 136 youth (ages 7-17) with a primary diagnosis of OCD who were randomized in a double-blinded fashion to 10 sessions of CBT with augmentation of either d-cycloserine or placebo. Sudden gain status was determined based on clinician-rated obsessive-compulsive symptom severity, which was collected on 9 occasions across the study period., Results: 42.6% of youth experienced at least one sudden gain, which tended to occur either after starting exposure and response prevention or towards the end of treatment. After applying the Benjamini-Hochberg procedure for multiple comparisons, there were no significant pre-treatment predictors of sudden gains and only reduced insight predicted the reversal of gains. Individuals with at least one sudden gain had improved overall treatment outcomes, measured both by reduction in OCD symptom severity, and by global illness severity., Limitations: Several clinical constructs were not examined. Symptomatology was not assessed at every treatment session. Differences in those who achieved sudden gains and those who did not may be obscured. There is the possibility that a sudden gain reflected a scoring error generated by an optimistic or inaccurate report. Finally, a relatively homogenous sample may limit the generalizability of results., Conclusions: The course of CBT for pediatric OCD is variable with many children experiencing sudden gains, but a sizable percentage experience a reversal of gains which was related to reduced insight. Sudden gains tended to occur after starting exposure and response prevention and towards the end of treatment., Trialsregistration: ClinicaltrialsgovRegistry:NCT00864123. https://www.clinicaltrials.gov/ct2/show/NCT00864123., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Although obsessive-compulsive disorder (OCD) has often been characterized as an internalizing disorder, some children with OCD exhibit externalizing behaviors that are specific to their OCD. This study sought to demonstrate that parents perceive both internalizing and externalizing behaviors in childhood OCD by examining the factor structure of the Child Obsessive-Compulsive Externalizing/Internalizing Scale (COCEIS), a parent-report questionnaire intended to measure these constructs. This study also investigated clinical correlates of internalizing and externalizing factors in the COCEIS. A factor analysis of questionnaire responses from 122 parents of youth with OCD revealed both externalizing and internalizing factors in the COCEIS. Externalizing behaviors in childhood OCD were associated with other, co-occurring externalizing behavior problems, while both factors were positively correlated with OCD severity and co-occurring internalizing symptoms. They were positively associated with each other at a trend level, and neither showed a significant relationship with insight. Sixty-two percent of parents endorsed "often" or "always" to at least one externalizing item, though modal responses to items suggested that each individual feature captured by the COCEIS may be relatively uncommon. Mean responses were significantly greater for internalizing items. This study provides evidence for distinct but related externalizing and internalizing behaviors specific to childhood OCD. Treatment for children with OCD presenting with more externalizing behaviors may require a greater emphasis on behavioral parent training and motivational enhancement.

Schizophrenia is associated with deficits in language processing that are evident even at first-episode. However, there is debate as to how early in the processing stream the linguistic deficits appear. We measured categorical processing of artificial syllables that varied in voice-onset time (VOT), and how sensory biasing impacts categorical perception. VOT varied in 5 ms increments from 0 ms (strong /ba/) to 40 ms (strong /pa/). Participants chose whether a syllable sounded more like /ba/ or /pa/. Twenty-two individuals with long-term schizophrenia (Sz) were compared to 21 controls (HCSz), and 17 individuals at their first-episode of schizophrenia (FE) were compared to 19 controls (HCFE). There were three conditions: equiprobable - each syllable had an equal probability of being presented; /ba/-biased - 0 ms VOT (strong /ba/) presented 70% of the time; /pa/-biased - 40 ms VOT (strong /pa/) presented 70% of the time. All groups showed categorical perception and category shifts during biased conditions. Sz and FE were statistically indistinguishable from controls in the point of categorical shift, slope of their response function, and the VOT needed to reliably perceive /pa/. Together, this suggests intact ability to map acoustic stimuli to phonetic categories when based on timing differences in voiced information, both early and late in the disease., (Copyright © 2019. Published by Elsevier B.V.)

Background: While cognitive behavior therapy (CBT) is an effective treatment for many children and adolescents with Obsessive Compulsive Disorder (OCD), therapeutic response is variable. Fear conditioning and extinction are central constructs underlying exposure-based CBT. Fear extinction learning assessed prior to CBT may be a useful predictor of CBT response for guiding treatment decisions., Methods: Sixty-four youth who participated in a randomized placebo-controlled trial of CBT with and without d-cycloserine (DCS) completed a fear conditioning task. Skin conductance response (SCR) scores were used to measure fear acquisition and extinction to determine whether extinction learning could predict CBT response., Results: CBT responders and non-responders appeared to acquire conditioned fear SCRs in a similar manner. However, differences between treatment responders and non-responders emerged during the extinction phase. A responder (responder, non-responder) by conditioned stimulus type (CS+, CS-) interaction showed that CBT responders differentiated the stimulus paired with (CS+) and without (CS-) the unconditioned stimulus correctly during early and late extinction, whereas the CBT non-responders did not (p = .004)., Conclusions: While the small sample size makes conclusions tentative, this study supports an emerging literature that differential fear extinction may be an important factor underlying clinical correlates of pediatric OCD, including CBT response., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

This study examined benchmarks of treatment response and clinical remission on the Obsessive Compulsive Inventory-Child Version (OCI-CV) for youth with obsessive-compulsive disorder (OCD). Participants were 91 youth who enrolled in a randomized controlled trial that examined the benefit of augmenting cognitive behavior therapy (CBT) with either d-cycloserine or placebo. Youth completed the OCI-CV at baseline, Week 4 (prior to initiating exposure therapy), and posttreatment. Receiver operator curve (ROC) analyses examined optimal benchmarks for treatment response and clinical remission as identified by independent evaluators at the posttreatment assessment using the Clinical Global Impression (CGI) scales of Improvement (CGI-Improvement), Severity (CGI-Severity), and Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Optimal benchmarks for treatment response were a 20%-25% reduction in the OCI-CV total score. Meanwhile, optimal benchmarks for remission were a 55%-65% reduction in the OCI-CV total score and a posttreatment total score ≤6-8. OCI-CV benchmarks exhibited moderate agreement with the CY-BOCS for treatment response and clinical remission. Meanwhile, fair agreement was observed for response and remission with CGI scales. A lower pretreatment OCI-CV total score was associated with less agreement between classification approaches. Findings provide benchmarks for classifying treatment response and clinical remission in an efficient manner. Given the moderate agreement between the CY-BOCS and OCI-CV benchmarks, the OCI-CV may serve as a useful alternative when clinician-rated scales cannot be administered due to limited resources (e.g., time, training). Thus, evidence-based measurement can be incorporated to monitor therapeutic response and remission in clinical practice., (Copyright © 2018. Published by Elsevier Ltd.)

Complex rule-based auditory processing is abnormal in individuals with long-term schizophrenia (SZ), as demonstrated by reduced mismatch negativity (MMN) to deviants in rule-based patterns and reduced auditory sustained potential (ASP) that appears when grouping tones together. Together, this suggests deficits later in the auditory processing hierarchy in Sz. Here, MMN and ASP were elicited by deviations from a complex zig-zag pitch pattern that cannot be predicted by simple linear rules. Twenty-seven SZ and 26 matched healthy controls (HC) participated. Frequent groups of patterns contained eight tones that zig-zagged in a two-up one-down pitch-based paradigm. There were two deviant patterns: the final tone was either higher in pitch than expected (creating a jump in pitch) or was repeated. Simple MMN to pitch-deviants among repetitive tones was measured for comparison. Sz exhibited a smaller pitch MMN compared to HC as expected. HC produced a late MMN in response to the repeat and jump-deviant and a larger ASP to the standard group of tones, all of which were significantly blunted in SZ. In Sz, the amplitude of the late complex MMN was related to neuropsychological functioning, whereas ASP was not. ASP and late MMN did not significantly correlate in HC or in Sz, suggesting that they are not dependent on one another and may originate within distinct processing streams. Together, this suggests multiple deficits later in the auditory sensory-perceptual hierarchy in Sz, with impairments evident in both segmentation and deviance detection abilities., (© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: Dopamine D2 receptor antagonists used to treat Tourette syndrome may have inadequate responses or intolerable side effects. We present results of a 4-week randomized, double-blind, placebo-controlled crossover study evaluating the safety, tolerability, and efficacy of the D1 receptor antagonist ecopipam in children and adolescents with Tourette syndrome., Methods: Forty youth aged 7 to 17 years with Tourette syndrome and a Yale Global Tic Severity Scale - total tic score of ≥20 were enrolled and randomized to either ecopipam (50 mg/day for weight of <34 kg, 100 mg/day for weight of >34 kg) or placebo for 30 days, followed by a 2-week washout and then crossed to the alternative treatment for 30 days. Stimulants and tic-suppressing medications were excluded. The primary outcome measure was the total tic score. Secondary outcomes included obsessive compulsive and attention deficit/hyperactivity disorder scales., Results: Relative to changes in placebo, reduction in total tic score was greater for ecopipam at 16 days (mean difference, -3.7; 95% CI, -6.5 to -0.9; P = 0.011) and 30 days (mean difference, -3.2; 95% CI, -6.1 to -0.3; P = 0.033). There were no weight gain, drug-induced dyskinesias, or changes in laboratory tests, electrocardiograms, vital signs, or comorbid symptoms. Dropout rate was 5% (2 of 40). Adverse events reported for both treatments were rated predominantly mild to moderate, with only 5 rated severe (2 for ecopipam and 3 for placebo)., Conclusions: Ecopipam reduced tics and was well tolerated. This placebo-controlled study of ecopipam supports further clinical trials in children and adolescents with Tourette syndrome. © 2018 International Parkinson and Movement Disorder Society., (© 2018 International Parkinson and Movement Disorder Society.)

The purpose of this study was to examine differences in: (1) mental health emotional and behavioral problems between young children experiencing PTSD with and without MDD; (2) the incidence of caregiver PTSD and MDD between children with PTSD ± MDD; and (3) the number of traumatic events and interpersonal versus non-interpersonal nature of trauma events among children whose parents sought child trauma-focused treatment. Sixty-six caregivers of children aged 3-7 with PTSD completed semi-structured interviews regarding caregiver and child diagnoses, and caregivers completed self-report measures regarding child symptomatology. Results indicated that young children with PTSD + MDD had significantly higher internalizing symptoms, dissociative symptoms, and posttraumatic stress severity than those without comorbid MDD. There were no significant group differences in the incidence of caregiver PTSD or MDD, or the number or types of traumatic events. Future research to understand the unique contributors to the etiology of MDD in the context of PTSD among young children is needed.

Objective: To examine the internal consistency and distribution of the Yale Global Tic Severity Scale (YGTSS) scores to inform modification of the measure., Methods: This cross-sectional study included 617 participants with a tic disorder (516 children and 101 adults), who completed an age-appropriate diagnostic interview and the YGTSS to evaluate tic symptom severity. The distributions of scores on YGTSS dimensions were evaluated for normality and skewness. For dimensions that were skewed across motor and phonic tics, a modified Delphi consensus process was used to revise selected anchor points., Results: Children and adults had similar clinical characteristics, including tic symptom severity. All participants were examined together. Strong internal consistency was identified for the YGTSS Motor Tic score (α = 0.80), YGTSS Phonic Tic score (α = 0.87), and YGTSS Total Tic score (α = 0.82). The YGTSS Total Tic and Impairment scores exhibited relatively normal distributions. Several subscales and individual item scales departed from a normal distribution. Higher scores were more often used on the Motor Tic Number, Frequency, and Intensity dimensions and the Phonic Tic Frequency dimension. By contrast, lower scores were more often used on Motor Tic Complexity and Interference, and Phonic Tic Number, Intensity, Complexity, and Interference., Conclusions: The YGTSS exhibits good internal consistency across children and adults. The parallel findings across Motor and Phonic Frequency, Complexity, and Interference dimensions prompted minor revisions to the anchor point description to promote use of the full range of scores in each dimension. Specific minor revisions to the YGTSS Phonic Tic Symptom Checklist were also proposed., (© 2018 American Academy of Neurology.)

Auditory scene analysis (ASA) dysfunction is likely an important component of the symptomatology of schizophrenia. Auditory object segmentation, the grouping of sequential acoustic elements into temporally-distinct auditory objects, can be assessed with electroencephalography through measurement of the auditory segmentation potential (ASP). Further, N2 responses to the initial and final elements of auditory objects are enhanced relative to medial elements, which may indicate auditory object edge detection (initiation and termination). Both ASP and N2 modulation are impaired in long-term schizophrenia. To determine whether these deficits are present early in disease course, we compared ASP and N2 modulation between individuals at their first episode of psychosis within the schizophrenia spectrum (FE, N=20) and matched healthy controls (N=24). The ASP was reduced by >40% in FE; however, N2 modulation was not statistically different from HC. This suggests that auditory segmentation (ASP) deficits exist at this early stage of schizophrenia, but auditory edge detection (N2 modulation) is relatively intact. In a subset of subjects for whom structural MRIs were available (N=14 per group), ASP sources were localized to midcingulate cortex (MCC) and temporal auditory cortex. Neurophysiological activity in FE was reduced in MCC, an area linked to aberrant perceptual organization, negative symptoms, and cognitive dysfunction in schizophrenia, but not temporal auditory cortex. This study supports the validity of the ASP for measurement of auditory object segmentation and suggests that the ASP may be useful as an early index of schizophrenia-related MCC dysfunction. Further, ASP deficits may serve as a viable biomarker of disease presence., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: This study examined the phenomenology and clinical characteristics of obsessive compulsive symptoms (OCS) in adults diagnosed with Lyme disease., Method: Participants were 147 adults aged 18-82 years (M = 43.81, SD = 12.98) who reported having been diagnosed with Lyme disease. Participants were recruited from online support groups for individuals with Lyme disease, and completed an online questionnaire about their experience of OCS, Lyme disease characteristics, and the temporal relationship between these symptoms., Results: OCS were common, with 84% endorsing clinically significant symptoms, 26% of which endorsed symptoms onset during the six months following their Lyme disease diagnosis and another 51% believed their symptoms were temporally related. Despite the common occurrence of OCS, only 44% of these participants self-identified these symptoms as problematic. Greater frequency of Lyme disease symptoms and disease-related impairment was related to greater OCS. In the majority of cases, symptom onset was gradual, and responded well to psychological and pharmacological treatment. Around half of participants (51%) reported at least some improvement in OCS following antibiotic treatment., Conclusions: This study highlights the common co-occurrence of OCS in patients with Lyme disease. It is unclear whether OCS are due to the direct physiological effects of Lyme disease or associated immunologic response, a psychological response to illness, a functional somatic syndrome, or some combination of these., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The study examined clinical correlates of quality of life (QoL), impact of treatment on QoL, and predictors of QoL change among children with obsessive-compulsive disorder (OCD)., Methods: One hundred forty-two children with primary OCD who were enrolled as part of a larger clinical trial participated. Children were administered a structured diagnostic interview, as well as clinician-administered measures of OCD and depression symptom severity. Children and parents completed reports of QoL, as well as measures of impairment and internalizing and externalizing symptoms. Youth received 10 sessions of family-based cognitive-behavioral therapy (CBT)., Results: At baseline, QoL was inversely related to obsessive-compulsive symptom severity, impairment, externalizing and internalizing symptoms, and severity of depression symptoms according to children and parents. After CBT, QoL improved according to parent ratings, but not child ratings. None of the predictors examined were associated with changes in QoL scores over time. Impairment, and externalizing and internalizing symptoms predicted QoL after accounting for OCD symptom severity. After accounting for OCD symptoms, externalizing symptoms inversely predicted changes in QoL., Conclusion: These data suggest that QoL is related to more severe clinical presentation and improves with evidence-based treatment, but QoL improvements may be inversely related to externalizing symptomology.

Objective: The goal of this study was to investigate treatment histories and outcomes in a large community sample of youth with Pediatric Acute-onset Neuropsychiatric Syndrome (PANS), and, where appropriate, to examine the impact of immune deficiency on treatment outcomes., Methods: A comprehensive internet-based survey was completed by parents or guardians of youth who had received physician diagnoses of PANS, or by young adults (age 18+) who had themselves been diagnosed by a physician (N = 698). Data regarding the treatment histories of these patients, including the variety of medical and psychological treatments employed and the caregiver- or self-reported response to each, are presented., Results: The PANS patients in this study had commonly been treated with antibiotic (N = 675), anti-inflammatory (N = 437), and/or psychotropic therapy (N = 378). Response to antibiotic treatment was best when treatment was relatively aggressive, with broad-spectrum antibiotics and courses of >30 days generally producing the best results (i.e., up to 52% of patients achieving a "very effective" response). For immune-deficient patients (caregiver-reported laboratory studies below normal limits; N = 108), use of broad-spectrum antibiotics appeared to be particularly desirable. Anti-inflammatory therapies, including over-the-counter medications such as ibuprofen, were at least "somewhat effective" for most patients. Intravenous immunoglobulin (IVIG) had been used to treat PANS in 193 (28%) of the patients and was at least "somewhat effective" for 89%, although for 18% of these, the effect was not sustained. The highest rate of sustained response to IVIG treatment was seen in immune-deficient patients who received doses of at least 0.8 g/kg IVIG on a regular basis. Psychotropic medications, most commonly SSRIs (38% reported a trial), were commonly employed, but were often ineffective (e.g., 44% found SSRIs "somewhat" to "very effective"). Many patients (N = 473) had received some form of psychotherapy with some benefit, with cognitive behavioral therapy found to be at least somewhat effective in a majority of those treated with this modality., Conclusion: Among the PANS patients represented in this study, relatively aggressive treatment courses targeted at eradicating infection and modulating the inflammatory response appeared to provide the best caregiver-reported therapeutic results, and to be generally well tolerated. Given its relative efficacy and tolerability, treatment targeting the inflammatory response may represent an underutilized approach in this population. The results of this study should be considered in light of the limitations inherent in a self-selected and administered online survey.