Repetitive and restrictive behaviors (RRB) include simple motor stereotypes, tics and complex ritualized and rigid behaviors that are core symptoms in neurodevelopmental disorders such as obsessive–compulsive disorder (OCD), Tourette syndrome (TS) or autism spectrum disorder (ASD). Sensory phenomena (SP) are uncomfortable feelings, including bodily sensations, sense of inner tension, “just-right” perceptions, feelings of incompleteness, or “urge-only” phenomena, which have been described to precede, trigger, or accompany RRB. In such clinical contexts RRB and SP may be considered common variables that affect multiple aspects of daily functioning and are treatment targets. This study aims to further understand RRB and SP phenomenology in children and adolescents diagnosed with OCD, TS or ASD and identify whether specific RRB or SP can distinguish these groups. We assessed RRB and SP in participants aged between 6 and 17 with a main diagnosis of OCD (n = 23), TS (n = 19), or ASD (n = 21) with the Repetitive Behavior Scale-Revised (RBS-R) and The University of Sao Paulo-Sensory Phenomena Scale (USP-SPS). The RBS-R mean was 17.3 ± 14.9 with no group differences for total RBS-R symptom severity, except for the routine subscale (OCD > ASD, p = 0.03). Ninety percent of participants showed at least one type of SP on the USP-SPS with a mean total severity of 5.3 ± 3.8, with no statistical differences between groups. The most frequent SP subtype was physical sensations (68.4

White matter pathways, typically studied with diffusion tensor imaging (DTI), have been implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, due to limited sample sizes and the predominance of single-site studies, the generalizability of OCD classification based on diffusion white matter estimates remains unclear. Here, we tested classification accuracy using the largest OCD DTI dataset to date, involving 1336 adult participants (690 OCD patients and 646 healthy controls) and 317 pediatric participants (175 OCD patients and 142 healthy controls) from 18 international sites within the ENIGMA OCD Working Group. We used an automatic machine learning pipeline (with feature engineering and selection, and model optimization) and examined the cross-site generalizability of the OCD classification models using leave-one-site-out cross-validation. Our models showed low-to-moderate accuracy in classifying (1) “OCD vs. healthy controls” (Adults, receiver operator characteristic-area under the curve = 57.19 ± 3.47 in the replication set; Children, 59.8 ± 7.39), (2) “unmedicated OCD vs. healthy controls” (Adults, 62.67 ± 3.84; Children, 48.51 ± 10.14), and (3) “medicated OCD vs. unmedicated OCD” (Adults, 76.72 ± 3.97; Children, 72.45 ± 8.87). There was significant site variability in model performance (cross-validated ROC AUC ranges 51.6–79.1 in adults; 35.9–63.2 in children). Machine learning interpretation showed that diffusivity measures of the corpus callosum, internal capsule, and posterior thalamic radiation contributed to the classification of OCD from HC. The classification performance appeared greater than the model trained on grey matter morphometry in the prior ENIGMA OCD study (our study includes subsamples from the morphometry study). Taken together, this study points to the meaningful multivariate patterns of white matter features relevant to the neurobiology of OCD, but with low-to-moderate classification accuracy. The OCD classification performance may be constrained by site variability and medication effects on the white matter integrity, indicating room for improvement for future research.

Only a small number of studies have assessed structural differences between the two hemispheres during childhood and adolescence. However, the existing findings lack consistency or are restricted to a particular brain region, a specific brain feature, or a relatively narrow age range. Here, we investigated associations between brain asymmetry and age as well as sex in one of the largest pediatric samples to date (n = 4265), aged 1-18 years, scanned at 69 sites participating in the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. Our study revealed that significant brain asymmetries already exist in childhood, but their magnitude and direction depend on the brain region examined and the morphometric measurement used (cortical volume or thickness, regional surface area, or subcortical volume). With respect to effects of age, some asymmetries became weaker over time while others became stronger; sometimes they even reversed direction. With respect to sex differences, the total number of regions exhibiting significant asymmetries was larger in females than in males, while the total number of measurements indicating significant asymmetries was larger in males (as we obtained more than one measurement per cortical region). The magnitude of the significant asymmetries was also greater in males. However, effect sizes for both age effects and sex differences were small. Taken together, these findings suggest that cerebral asymmetries are an inherent organizational pattern of the brain that manifests early in life. Overall, brain asymmetry appears to be relatively stable throughout childhood and adolescence, with some differential effects in males and females.

The Child Obsessive-Compulsive Impact Scale (COIS-R) is a parent- and self-report measure of the impairment related to Obsessive–Compulsive Disorder (OCD) symptoms. Previous research has demonstrated the reliability and validity of the original version of the COIS-R; to date, however, the scale has not been validated for use in Spanish samples of pediatric OCD. The present study aimed to assess the psychometric properties of this in a clinical sample of pediatric OCD (n = 91). Analyses of internal consistency, convergent and divergent validity were conducted. For both the COIS-R report scales estimates similar to those in the original instrument were obtained for internal consistency, test-retest reliability, and convergent validity. Thus, the Spanish version of the COIS-R seems to retain sound psychometric properties of its original version; it appears to be a reliable instrument for the assessment of obsessive–compulsive impairment and the effects of treatment, and can be used in other cultural contexts.

Delusional thinking is a key symptom of first-episode psychosis (FEP), but it has also been studied in obsessive-compulsive disorder (OCD) and anorexia nervosa (AN). This study aimed to analyze the psychometric properties of the Brown Assessment of Beliefs Scale (BABS) in a sample of adolescents diagnosed with a FEP, AN, or OCD, and to compare delusional thinking among the three samples. The sample comprised 60 patients in three groups of 20 diagnosed with OCD, AN, or FEP. Participants underwent assessment by diagnostic interview, the BABS scale, and a measure of depressive symptomatology. Specific instruments were also used to assess the main symptomatology of each disorder. The BABS had good internal consistency, and high validity and reliability. The OCD group scored significantly lower than the other two groups in all scale items except for items 4 (fixation of ideas), 6 (insight), and 7 (delusions of reference). A significant difference only existed between the AN and FEP groups for item 7 (delusions of reference). The BABS scale is a valid and reliable tool for assessing delusionality in adolescents diagnosed with OCD, AN, or FEP, with evidence of marked differences between the disorders. Assessing these symptoms could influence management, helping to improve treatment adherence and prognosis.

Introduction Prader-Willi syndrome (PWS) is a genetic disorder with an estimated prevalence of 1:25,000. PWS results from defective gene expression on the paternal copy of chromosome 15. In 70% of the cases it is a deletion that means that part of the paternal chromosome 15 is missing. Maternal uniparental disomy (mUPD) is present in 25% of cases. Typical clinical features of PWS are dysmorphism, hypotonia, hyperphagia, hypogonadism and developmental delay. In addition, the syndrome is accompanied by various psychiatric symptoms that are often insufficiently known within the psychiatric field. Regarding the relationship between PWS and schizophrenia spectrum disorders (SSDs), individuals with mUPD appear to have a 3 to 4 times higher risk of psychotic symptoms than those with the deletion subtype. Psychotic episodes have an atypical presentation with recurrent episodes of confusion and rapidly fluctuating psychotic and mood symptoms. Objectives To describe an unusual clinical case in order to determine the management regarding clinical approach, and provide an overview of psychotic episodes in patients with PWS for the general practitioner with the most up-to-date information on workup and management. Methods We report a case involving a 13-year-old woman with PWS (mUPD of chromosome 15) and mild intellectual disability (IQs 59), who presented psychotic symptomatology in the form of disorganized behavior, delusional ideation, auditory hallucinations, self-referentiality and suspicion. Parents reported that these symptoms started two days prior the day of consultation. No environmentals stressors were identified and no recent treatment changes were made. Patient’s medication consists in 150 mg sertraline per day due to anxiety control and aid in emotional and behavioral regulation. Results Given the diagnostic approach of a psychotic episode (PE) in a patient with PWS, it was decided to offer 0.5mg risperidone per day, in an increasing pattern until reaching a final dose of 1.25 mg per day, presenting a global remission of the psychotic symptomatology. Recommendations for patients with PWS presenting PE are based upon systematic reviews. Patients with PWS, especially mUPD subjects, are at risk for SSDs and mood disorders. Antipsychotics (APs) are the gold standard in the treatment of SSDs, and some authors have suggested that APs protect patients with previous psychotic symptoms from relapse. It is unknown whether there is a protective effect of APs in mUPD patients who have not previously exhibited psychotic signs. Conclusions PWS represents a good example of a genetic disease with behavioral and psychiatric symptoms that may be challenging to treat with psychotropic medications. For a better understanding of psychiatric problems in adults with PWS, longitudinal studies with careful and standardized follow-up of psychiatric symptoms in PWS are necessary. Disclosure of Interest None Declared

Pediatric obsessive-compulsive disorder (OCD) clusters around three major symptom dimensions: contamination/cleaning, symmetry/ordering, and disturbing thoughts/checking. The Obsessive-Compulsive Inventory-Child Version (OCI-CV) is a self-report questionnaire that provides scores along six theory-based OCD dimensions, but no study has evaluated how well OCI-CV identifies clinically significant symptoms within each of the three major symptom dimensions of OCD. We examined this question using data from 197 Swedish and Spanish youth with OCD. All youth completed the OCI-CV and clinically significant symptom severity within each major OCD dimension was established with a validated interview-based measure. Results showed that a score ≥ 3 on the OCI-CV washing scale excellently captured those with clinically significant contamination/cleaning symptoms (AUC = 0.85 [0.80–0.90], 79% accuracy). A score ≥ 4 on the obsessing scale adequately captured those with disturbing thoughts/checking symptoms (AUC = 0.71 [0.64–0.78], 67% accuracy) and a score ≥ 3 on the ordering scale adequately captured those with symmetry/ordering symptoms (AUC = 0.72 [0.65–0.79], 70% accuracy). Similar accuracy of the breakpoints was found in the Swedish and Spanish samples. OCI-CV works well to identify youth with pediatric OCD that have clinically significant contamination/cleaning symptoms. The measure can also with adequate precision identify those with clinically significant disturbing thoughts/checking and symmetry/ordering symptoms. The breakpoints provided in this study can be used to examine differences in clinical presentation and treatment outcome for youth with different types of OCD.

OBJECTIVE:Cognitive-behavioral therapy (CBT) is considered a first-line treatment for obsessive-compulsive disorder (OCD) in pediatric and adult populations. Nevertheless, some patients show partial or null response. The identification of predictors of CBT response may improve clinical management of patients with OCD. Here, we aimed to identify structural magnetic resonance imaging (MRI) predictors of CBT response in 2 large series of children and adults with OCD from the worldwide ENIGMA-OCD consortium. METHOD:Data from 16 datasets from 13 international sites were included in the study. We assessed which variations in baseline cortical thickness, cortical surface area, and subcortical volume predicted response to CBT (percentage of baseline to post-treatment symptom reduction) in 2 samples totaling 168 children and adolescents (age range 5-17.5 years) and 318 adult patients (age range 18-63 years) with OCD. Mixed linear models with random intercept were used to account for potential cross-site differences in imaging values. RESULTS:Significant results were observed exclusively in the pediatric sample. Right prefrontal cortex thickness was positively associated with the percentage of CBT response. In a post hoc analysis, we observed that the specific changes accounting for this relationship were a higher thickness of the frontal pole and the rostral middle frontal gyrus. We observed no significant effects of age, sex, or medication on our findings. CONCLUSION:Higher cortical thickness in specific right prefrontal cortex regions may be important for CBT response in children with OCD. Our findings suggest that the right prefrontal cortex plays a relevant role in the mechanisms of action of CBT in children.

Introduction Higher thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population (Boedhoe et al. 2017, Weeland et al. 2021a). Functionally distinct thalamic nuclei are an integral part of OCD-relevant brain circuitry. Objectives We aimed to study the thalamic nuclei volume in relation to subclinical and clinical OCD across different age ranges. Understanding the role of thalamic nuclei and their associated circuits in pediatric OCD could lead towards treatment strategies specifically targeting these circuits. Methods We studied the relationship between thalamic nuclei and obsessive-compulsive symptoms (OCS) in a large sample of school-aged children from the Generation R Study (N = 2500) (Weeland et al. 2021b). Using the data from the ENIGMA-OCD working group we conducted mega-analyses to study thalamic subregional volume in OCD across the lifespan in 2,649 OCD patients and 2,774 healthy controls across 29 sites (Weeland et al. 2021c). Thalamic nuclei were grouped into five subregions: anterior, ventral, intralaminar/medial, lateral and pulvinar (Figure 1). Results Both children with subclinical and clinical OCD compared with controls show increased volume across multiple thalamic subregions. Adult OCD patients have decreased volume across all subregions (Figure 2), which was mostly driven by medicated and adult-onset patients. Conclusions Our results suggests that OCD-related thalamic volume differences are global and not driven by particular subregions and that the direction of effects are driven by both age and medication status. Disclosure No significant relationships.

Obsessive-compulsive disorder (OCD) has a complex etiology that seems to include immune dysfunction and alterations in circulating monocytes. To investigate the immune basis and the functional dysregulation of monocytes in this disease, we analyzed gene expression in the peripheral monocytes of pediatric patients with OCD (N = 102) compared to controls (N = 47). We examined gene expression in primary cultures of peripheral monocytes from participants, under basal conditions and under exposure to lipopolysaccharide (LPS) to stimulate immune response. Whole-genome expression was assessed in 8 patients and 8 controls. Differentially expressed genes were identified followed by protein-protein interaction network construction and functional annotation analysis to identify the genes and biological processes that are altered in the monocytes of OCD patients. We also explored the expression levels of selected genes in monocytes from the other participants using qPCR. Several changes in gene expression were observed in the monocytes of OCD patients, with several immune processes involved under basal conditions (antigen processing and presentation, regulation of immune system and leukocyte cell adhesion) and after LPS stimulation (immune and inflammatory response, cytokine production and leukocyte activation). Despite the qPCR analysis provided no significant differences between patients and controls, high correlations were observed between the expression levels of some of the genes and inflammatory markers (i.e., T helper 17 and regulatory T cell levels, total monocyte and proinflammatory monocyte subset levels, and the cytokine production by resting and stimulated monocytes) of the study participants. Our findings provide more evidence of the involvement of monocyte dysregulation in early-onset OCD, indicating a proinflammatory predisposition and an enhanced immune response to environmental triggers.

1Department of Basic Clinical Practice, Pharmacology Unit, University of Barcelona, Barcelona, Spain; 2Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic de Barcelona, Barcelona, Spain; 3Clinical and Experimental Neuroscience Area, The August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; 4G04 Group, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Carlos III Health Institute, Madrid, Spain; 5Department of Medicine, University of Barcelona, Barcelona, Spain

Objective: Higher thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Method: Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2,649 OCD patients and 2,774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were preregistered (https://osf.io/73dvy) and adjusted for age, sex and intracranial volume. Results: Unmedicated pediatric OCD patients (< 12 years) had larger lateral (d = 0.46), pulvinar (d = 0.33), ventral (d = 0.35) and whole thalamus (d = 0.40) volumes at unadjusted p-values <0.05. Adolescent patients showed no volumetric differences. Adult OCD patients compared with controls had smaller volumes across all subregions (anterior, lateral, pulvinar, medial, and ventral) and smaller whole thalamic volume (d = -0.15 to -0.07) after multiple comparisons correction, mostly driven by medicated patients and associated with symptom severity. The anterior thalamus was also significantly smaller in patients after adjusting for thalamus size. Conclusion: Our results suggest that OCD-related thalamic volume differences are global and not driven by particular subregions and that the direction of effects are driven by both age and medication status.

Purpose Here, we propose an integrative analysis of genome-wide methylation and gene expression to provide new insight into the biological mechanisms of Cognitive behavioral therapy (CBT) in pediatric obsessive-compulsive disorder (OCD). Patients and Methods Twelve children and adolescents with OCD receiving CBT for the first time were classified as responders or non-responders after eight weeks of CBT. Differentially methylated positions (DMPs) and gene co-expression modules were identified using specific R software packages. Correlations between the DMPs and gene co-expression modules were investigated. Results Two genes were enriched with significant DMPs (Δβ > ± 0.2, FDR-adjusted p-value < 0.05): PIWIL1 and MIR886. The yellowgreen module of co-expressed genes was associated with CBT response (FDR-adjusted p-value = 0.0003). Significant correlations were observed between the yellowgreen module and the CpGs in PIWIL1 and MIR886 (p < 0.008). Patients showing hypermethylation in these CpGs presented an upregulation in the genes in the yellowgreen module. Conclusion Taken together, the preliminary results of this systems-level approach, despite the study limitations, provide evidence that the epigenetic regulation of ncRNAs could be a predictor of CBT response. Limitations The sample size limited the statistical power, and given that the study was hypothesis-driven, our results should be seen as preliminary.

OBJECTIVE Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder whose etiology includes important genetic contributions. In a previous transmission disequilibrium study in which 75 complete trios were included, single-nucleotide polymorphisms (SNPs) in serotoninergic and GABAergic genes were associated with early-onset OCD. Our aim was to assess those findings in an extended collection of early-onset OCD trios. METHODS A transmission disequilibrium test for SNPs in HTR1B (rs2000292), SLC18A1 (rs6586896), GAD1 (rs3791860), and GAD2 (rs8190748) was performed in a total of 101 early-onset OCD trios, from which 26 trios were newly recruited for the purpose of the present analysis. RESULTS All the SNPs were overtransmitted from parents to OCD probands (p < 0.012, significant after Bonferroni correction). CONCLUSIONS These results are consistent with the previous findings and constitute more evidence of the role of genetic factors related to serotoninergic and GABAergic pathways in the pathophysiology of early-onset OCD.

El Trastorno de Espectro Autista (TEA) y el Trastorno Obsesivo Compulsivo (TOC) de inicio en la infancia son trastornos del neurodesarrollo con una prevalencia aproximada de entre el 1 y el 3%. Ambos trastornos tienen como característica similar la existencia de comportamientos repetitivos. Objetivos: describir la prevalencia de comportamientos repetitivos de los niños con TEA con la adaptación española del Child Yale-Brown Obsessive-Compulsive Scale por Autism Spectrum Disorder (CY-BOCS-ASD) y comparar el tipo de síntomas y la gravedad con los evaluados en un grupo de comparación con TOC. Metodología: se evaluó mediante el CY-BOCS-ASD una muestra de 39 sujetos con diagnóstico de TEA (confirmado por la Autism Disorder Interview-Revised -ADI-R-) y mediante el Child Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) 36 sujetos con diagnóstico de TOC siguiendo criterios DSM-IV. Para poder ser incluidos, todos los participantes debían tenir un cociente intelectual >70. Resultados: se obtuvieron puntuaciones más altas en los síntomas obsesivo-compulsivos actuales en el grupo de TOC (12,95+3,45) que en el grupo con TEA (8.23+5.65), (t = -3.632, p = .001). Las compulsiones de limpieza (p=.003), comprobación (p=.001), contaje (p=.001), orden y simetría (p=.004), y miscelánea (p=.001) fueron significativamente más prevalentes en el grupo de TOC. La frecuencia, malestar e interferencia fue mayor en pacientes con TOC que en los pacientes con TEA. Conclusiones: la CY-BOCS-ASD podría ser un instrumento útil para detectar síntomas compulsivos en niños y adolescentes con TEA. Disponer de un instrumento adaptado hará que dicha sintomatología, que requiere un abordaje específico, esté mejor evaluada y considerada en el tratamiento global de los pacientes con TEA.

Introduction: In childhood, diagnoses made at the first admission to a psychiatric unit are frequently unstable and temporary. In this study, we examined the stability of DSM-IV-TR disorders and groups of disorders among adolescents followed-up for 5 years after hospitalization. Method: All inpatients admitted for the first time between 2007 and 2008 were included and contacted after 5 years for re-evaluation. The final sample comprised 72 patients. At admission, diagnoses were based on the DSM-IV-TR criteria, Fourth Edition. At five years, diagnoses were made using structured clinical interviews for DSM-IV axis I Disorders and for axis II (SCID-I and SCID-II) as well as the Personality Diagnostic Questionnaire, Fourth Edition (PDQ-4). We also evaluated and collected information on the global assessment of functioning using the World Health Organization Quality of Life-BREF (WHOQOL-BREF) instrument. Depending on the distribution of variables, we used the chi-squared and Fisher exact tests or the Student t and McNemar tests for statistical analyses. Results: The most stable diagnoses were schizophrenia spectrum disorders, bipolar disorder, generalized anxiety disorder, obsessive-compulsive disorder, attention deficit hyperactivity disorder, Tourette syndrome, and pervasive developmental disorder. The most unstable diagnoses were disruptive disorders. Participants were satisfied with their quality of life and the global outcomes of the sample were positive. Conclusion: Major psychiatric disorders, including mood and schizophrenia spectrum disorders, were significantly more stable than other diagnoses and tended to continue into adulthood. In the case of study participants, suffering a mental disorder during adolescence did not appear to affect global functioning outcomes. (C) 2018 Elsevier Inc.