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The oxytocin system has been thought to contribute to obsessive-compulsive disorder (OCD). Few studies, only involving adults, have investigated this hypothesis and have found inconsistent results regarding oxytocin system activity and OCD. We investigated whether salivary oxytocin concentrations differed between children and adolescents with and without OCD and qualified our comparative analysis by investigating the possible covariates age, pubertal stage, and sex. Participants included 113 children and adolescents (8-17 years) with OCD and 88 children and adolescents without any previous or current psychiatric disorder and their parents (254 parents included). Salivary oxytocin concentrations were measured in children and parents with enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using frequentist and Bayesian approaches. We found no evidence of a difference in mean salivary oxytocin concentrations between children and adolescents with and without OCD. Bayesian analysis indicated anecdotal to moderate support for the null hypothesis. We found an association between oxytocin and age and between oxytocin and pubertal stage, which by visual inspection of plots and post-hoc tests indicated nonlinear relationships. We found no association between oxytocin concentration and sex. Our findings do not suggest elevated oxytocin concentrations in pediatric OCD. Nonlinear changes in oxytocin across development show the importance of accounting for hormonal and behavioral changes during puberty., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objectives: The traditional view on psychiatric disorders as categorical and distinct is being challenged by perspectives emphasizing the relevance of dimensional and transdiagnostic assessment. However, most diagnostic instruments are based on a categorical view with a threshold-approach to disease classification., Methods: We here describe algorithms for dimensionalizing the psychopathological ratings of the widely used diagnostic interview for children and adolescents, the Kiddie-Schedule for Affective Disorders and Schizophrenia - Present and Lifetime Version (K-SADS-PL). We further evaluate the criterion-related construct validity of the dimensionalized attention-deficit/hyperactivity disorder (ADHD) scales using Rasch models in a sample of 590 children (mean age 10.29 (.36), 49% girls)., Results: The algorithms generate scores of current symptom load, i.e., the sum of clinician-rated symptoms within each disorder assessed with the interview. We found support for counting symptoms of inattention and hyperactivity/impulsivity, respectively, but not for a single combined ADHD scale., Conclusions: The algorithms constitute an initial step in creating a framework for clinician-rated dimensional analyses of symptoms derived from the K-SADS-PL, but future studies are needed to further evaluate the construct validity of the remaining scales and the reliability and clinical utility of the method. We believe that our proposed algorithms offer a novel method of dimensional psychopathological assessment, which can be applied in multiple branches of child and adolescent psychiatry.

Introduction: Emotional dysregulation (ED) is a transdiagnostic phenomenon that has received increased attention, because of its potential ability to explain the development and maintenance of various psychiatric disorders. The identification of ED may serve as a potential target for both preventive and treatment interventions, however, the frequency of transdiagnostic ED among children and adolescents has not previously been evaluated. Our aim was to evaluate the frequency and types of ED in accepted and rejected referrals to the Child and Adolescent Mental Health Center (CAMHC), Mental Health Services, Copenhagen, Denmark, regardless of psychiatric status and across diagnoses. We aimed to evaluate how often ED would be a leading cause in seeking professional help, and whether children with ED not directly reflecting symptoms of known psychopathology would have higher rejection rates than children with more distinct symptoms of psychopathology. Finally, we assessed associations between sex and age with various types of ED., Methods: We examined ED in a retrospective chart review of referrals of children and adolescents aged 3-17 years to the CAMHC between August 1st, 2020, and August 1st, 2021. We ranked problems described in the referral as primary, secondary, and tertiary depending on severity. Further, we examined group differences in the frequency of ED in accepted versus rejected referrals, as well as group differences in types of ED in age and sex distributions, and diagnoses occurring with specific types of ED., Results: ED was present in 62.3% of the 999 referrals and was assessed as the primary issue in twice as many rejected referrals (11.4%) compared to accepted referrals (5.7%). Boys were significantly more often described with externalizing and internalizing behavior (55.5% vs. 31.6%; 35.1% vs. 26.5%) as well as incongruent affect (10.0% vs. 4.7%), whereas girls were more often described with depressed mood (47.5% vs. 38.0%) and self-harm (23.8% vs. 9.4%). The frequency of different types of ED varied with age., Conclusion: The present study is the first to evaluate the frequency of ED in children and adolescents referred to mental health services. The study offers insights into the high frequency of ED and the associations between ED and subsequent diagnoses, which may prove to be a method of early identification of risk of psychopathology. Our findings suggest that ED may rightly be considered a transdiagnostic factor, independent of specific psychiatric disorders, and that an ED-centered as opposed to diagnosis-specific approach to assessment, prevention, and treatment could target transversal symptoms of psychopathology in a more holistic manner., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The exact etiology of Tourette Syndrome (TS) remains unclear, making the search for impaired neuropsychological functions possibly connected to the underlying cause of TS as important as it is challenging. One neuropsychological domain of interest is fine motor skills., Method: This study compared fine motor skill performance on the Purdue Pegboard Task (PPT) in 18 children with TS, 24 unaffected first-degree siblings and 20 controls. A set of screening questionnaires was administered to determine comorbid psychiatric illness., Results: Children with TS, their siblings and controls did not differ significantly in fine motor skills as measured with the PPT. Performance on the PPT was not correlated with tic severity; however, we found an inverse correlation with severity of attention-deficit/hyperactivity disorder (ADHD) symptoms, as assessed by parent reported ADHD symptoms. Children with TS were found to have significantly higher parent reported ADHD symptoms compared to controls, yet only two out of the 18 participants had been diagnosed with ADHD., Conclusion: This study suggests that fine motor skill impairment in children with TS may be more strongly correlated with comorbid ADHD than to TS and tics., Competing Interests: Conflicts of Interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (© 2023 Marie Louise Boeg Tygesen et al., published by Sciendo.)

Background: Knowledge on adverse events in psychotherapy for youth with OCD is sparse. No official guidelines exist for defining or monitoring adverse events in psychotherapy. Recent recommendations call for more qualitative and quantitative assessment of adverse events in psychotherapy trials. This mixed methods study aims to expand knowledge on adverse events in psychotherapy for youth with OCD., Methods: This is an analysis plan for a convergent mixed methods study within a randomized clinical trial (the TECTO trial). We include at least 128 youth aged 8-17 years with obsessive-compulsive disorder (OCD). Participants are randomized to either family-based cognitive behavioral therapy (FCBT) or family-based psychoeducation and relaxation training (FPRT). Adverse events are monitored quantitatively with the Negative Effects Questionnaire. Furthermore, we assess psychiatric symptoms, global functioning, quality of life, and family factors to investigate predictors for adverse events. We conduct semi-structured qualitative interviews with all youths and their parents on their experience of adverse events in FCBT or FPRT. For the mixed methods analysis, we will merge 1) a qualitative content analysis with descriptive statistics comparing the types, frequencies, and severity of adverse events; 2) a qualitative content analysis of the perceived causes for adverse events with prediction models for adverse events; and 3) a thematic analysis of the participants' treatment evaluation with a correlational analysis of adverse events and OCD severity., Discussion: The in-depth mixed methods analysis can inform 1) safer and more effective psychotherapy for OCD; 2) instruments and guidelines for monitoring adverse events; and 3) patient information on potential adverse events. The main limitation is risk of missing data., Trial Registration: ClinicalTrials.gov identifier: NCT03595098. Registered on July 23, 2018., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objectives: Emotion regulation is a predictor of overall life outcome. Problems of emotion regulation are associated with multiple psychiatric disorders and could be a potential treatment target for improving well-being and functioning. Children at familial high risk of severe mental illness have a markedly increased risk of various psychopathology and constitute a group at significant risk of emotion regulation problems. Investigations of emotion regulation in children at familial high risk of severe mental illness are sparse., Methods: We applied an instrument for assessing emotion regulation, the Tangram Emotion Coding Manual (TEC-M), to a population-based cohort of 522 7-year-old children born to parents diagnosed with either schizophrenia or bipolar disorder and matched controls. The TEC-M is an ecologically valid, clinician-rated observational test measure of spontaneous emotion regulation. We aimed to compare emotion regulation between risk groups and to investigate associations between emotion regulation and psychopathology and daily life functioning, and between emotion regulation and an acknowledged questionnaire-based dysregulation profile., Results: In this early developmental phase, we found no between group differences in emotion regulation. We found a significant but weak negative association between emotion regulation and both child psychopathology and the presence of a dysregulation profile on the Child Behavior Checklist and a weak positive association between emotion regulation and current level of functioning., Conclusions: These findings contribute to the understanding of emotion regulation in familial high-risk children and further studies of emotion regulation in children at familial high risk of severe mental illness are warranted., (© 2022 British Psychological Society.)

Background: Artificial intelligence tools have the potential to objectively identify youth in need of mental health care. Speech signals have shown promise as a source for predicting various psychiatric conditions and transdiagnostic symptoms., Objective: We designed a study testing the association between obsessive-compulsive disorder (OCD) diagnosis and symptom severity on vocal features in children and adolescents. Here, we present an analysis plan and statistical report for the study to document our a priori hypotheses and increase the robustness of the findings of our planned study., Methods: Audio recordings of clinical interviews of 47 children and adolescents with OCD and 17 children and adolescents without a psychiatric diagnosis will be analyzed. Youths were between 8 and 17 years old. We will test the effect of OCD diagnosis on computationally derived scores of vocal activation using ANOVA. To test the effect of OCD severity classifications on the same computationally derived vocal scores, we will perform a logistic regression. Finally, we will attempt to create an improved indicator of OCD severity by refining the model with more relevant labels. Models will be adjusted for age and gender. Model validation strategies are outlined., Results: Simulated results are presented. The actual results using real data will be presented in future publications., Conclusions: A major strength of this study is that we will include age and gender in our models to increase classification accuracy. A major challenge is the suboptimal quality of the audio recordings, which are representative of in-the-wild data and a large body of recordings collected during other clinical trials. This preregistered analysis plan and statistical report will increase the validity of the interpretations of the upcoming results., International Registered Report Identifier (irrid): DERR1-10.2196/39613., (©Line Katrine Harder Clemmensen, Nicole Nadine Lønfeldt, Sneha Das, Nicklas Leander Lund, Valdemar Funch Uhre, Anna-Rosa Cecilie Mora-Jensen, Linea Pretzmann, Camilla Funch Uhre, Melanie Ritter, Nicoline Løcke Jepsen Korsbjerg, Julie Hagstrøm, Christine Lykke Thoustrup, Iben Thiemer Clemmesen, Kersten Jessica Plessen, Anne Katrine Pagsberg. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 28.10.2022.)

Background: Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder which affects up to 3% of children and adolescents. OCD in children and adolescents is generally treated with cognitive behavioural therapy (CBT), which, in more severely affected patients, can be combined with antidepressant medication. The TECTO trial aims to compare the benefits and harms of family-based CBT (FCBT) versus family-based psychoeducation/relaxation training (FPRT) in children and adolescents aged 8 to 17 years. This statistical analysis plan outlines the planned statistical analyses for the TECTO trial., Methods: The TECTO trial is an investigator-initiated, independently funded, single-centre, parallel-group, superiority randomised clinical trial. Both groups undergo 14 sessions of 75 min each during a period of 16 weeks with either FCBT or FPRT depending on the allocation. Participants are randomised stratified by age and baseline Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) score. The primary outcome is the CY-BOCS score. Secondary outcomes are health-related quality of life assessed using KIDSCREEN-10 and adverse events assessed by the Negative Effects Questionnaire (NEQ). Primary and secondary outcomes are assessed at the end of the intervention. Continuous outcomes will be analysed using linear regression adjusted for the stratification variables and baseline value of the continuous outcome. Dichotomous outcomes will be analysed using logistic regression adjusted for the stratification variables. The statistical analyses will be carried out by two independent blinded statisticians., Discussion: This statistical analysis plan includes a detailed predefined description of how data will be analysed and presented in the main publication before unblinding of study data. Statistical analysis plans limit selective reporting bias. This statistical analysis plan will increase the validity of the final trial results., Trial Registration: ClinicalTrials.gov NCT03595098. July 23, 2018., (© 2022. The Author(s).)

Background: Cognitive behavioural therapy (CBT) is the recommended first-line treatment for children and adolescents with obsessive-compulsive disorder (OCD), but evidence concerning treatment-specific benefits and harms compared with other interventions is limited. Furthermore, high risk-of-bias in most trials prevent firm conclusions regarding the efficacy of CBT. We investigate the benefits and harms of family-based CBT (FCBT) versus family-based psychoeducation and relaxation training (FPRT) in youth with OCD in a trial designed to reduce risk-of-bias., Methods: This is an investigator-initiated, independently funded, single-centre, parallel group superiority randomised clinical trial (RCT). Outcome assessors, data managers, statisticians, and conclusion drawers are blinded. From child and adolescent mental health services we include patients aged 8-17 years with a primary OCD diagnosis and an entry score of ≥16 on the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). We exclude patients with comorbid illness contraindicating trial participation; intelligence quotient < 70; or treatment with CBT, PRT, antidepressant or antipsychotic medication within the last 6 months prior to trial entry. Participants are randomised 1:1 to the experimental intervention (FCBT) versus the control intervention (FPRT) each consisting of 14 75-min sessions. All therapists deliver both interventions. Follow-up assessments occur in week 4, 8 and 16 (end-of-treatment). The primary outcome is OCD symptom severity assessed with CY-BOCS at end-of-trial. Secondary outcomes are quality-of-life and adverse events. Based on sample size estimation, a minimum of 128 participants (64 in each intervention group) are included., Discussion: In our trial design we aim to reduce risk-of-bias, enhance generalisability, and broaden the outcome measures by: 1) conducting an investigator-initiated, independently funded RCT; 2) blinding investigators; 3) investigating a representative sample of OCD patients; 3) using an active control intervention (FPRT) to tease apart general and specific therapy effects; 4) using equal dosing of interventions and therapist supervision in both intervention groups; 5) having therapists perform both interventions decided by randomisation; 6) rating fidelity of both interventions; 7) assessing a broad range of benefits and harms with repeated measures. The primary study limitations are the risk of missing data and the inability to blind participants and therapists to the intervention., Trial Registration: ClinicalTrials.gov : NCT03595098, registered July 23, 2018., (© 2022. The Author(s).)

Tourette Syndrome (TS) has previously been associated with deficits in inhibitory control (IC). However, studies on IC in individuals with TS have produced conflicting results. In the present study, we investigated IC, comparing the Stop Signal Reaction Time (SSRT) measure with parent and teacher ratings of daily life IC in 169 children aged 8-12 (60 with TS, 60 typically developing controls, 27 with attention-deficit/hyperactivity disorder (ADHD), and 22 with TS + ADHD). We further investigated associations of IC with TS and ADHD symptom severity. Children with TS showed intact SSRT performance, but impairments in daily life IC, as reported by parents and teachers. For the latter, we observed a staircase distribution of groups, with the healthy controls presenting with the best IC, followed by TS, TS + ADHD, and finally ADHD. Dimensional analyses indicated a strong association between ADHD severity and both measures of IC. Our results indicate that children with TS are not impaired in a laboratory-based measure of IC, although some difficulties were evident from measures of everyday behaviour, which may in part be due to parents and teachers interpreting tics as disinhibited behaviour. Comorbid ADHD or the severity of subthreshold ADHD symptomatology appeared to account for IC deficits.

Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene-environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene-environment studies., (© 2021. The Author(s).)

Tourette's Disorder (TD) is a neurodevelopmental disorder (NDD) that affects about 0.7% of the population and is one of the most heritable NDDs. Nevertheless, because of its polygenic nature and genetic heterogeneity, the genetic etiology of TD is not well understood. In this study, we combined the segregation information in 13 TD multiplex families with high-throughput sequencing and genotyping to identify genes associated with TD. Using whole-exome sequencing and genotyping array data, we identified both small and large genetic variants within the individuals. We then combined multiple types of evidence to prioritize candidate genes for TD, including variant segregation pattern, variant function prediction, candidate gene expression, protein-protein interaction network, candidate genes from previous studies, etc. From the 13 families, 71 strong candidate genes were identified, including both known genes for NDDs and novel genes, such as HtrA Serine Peptidase 3 (HTRA3), Cadherin-Related Family Member 1 (CDHR1), and Zinc Finger DHHC-Type Palmitoyltransferase 17 (ZDHHC17). The candidate genes are enriched in several Gene Ontology categories, such as dynein complex and synaptic membrane. Candidate genes and pathways identified in this study provide biological insight into TD etiology and potential targets for future studies., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Explosive outbursts occur in 25%-70% of children with Tourette syndrome (TS) and may cause more distress than the tics themselves. Previous studies have indicated that a comorbid diagnosis of attention-deficit/hyperactivity disorder (ADHD) is associated with emotional dysregulation in TS; however, this relationship has almost exclusively been studied using parent-reported questionnaires., Methods: We examined emotion regulation (ER) with an observational measure in 150 medication-naïve children aged 7-12 allocated to four groups: Forty-nine children with TS, 23 children with ADHD, 16 children with TS + ADHD, and 62 typically developing controls. We assessed participants' ER ability, as well as parent-child interactions in the context of a complex puzzle task, and coded the observed behavior with the Tangram Emotion Coding Manual (TEC-M). We examined group differences in ER, as well as associations between ER and severity of symptoms pertaining to TS and ADHD., Results: Children with TS did not differ from controls in their ER ability. However, children with ADHD and TS + ADHD had more problems with ER than those with TS only and controls. Finally, parents of children with ADHD displayed more tension during the experimental task. ER ability was not associated with tic severity nor premonitory urges; however, better ER ability was associated with less severe symptoms of ADHD., Conclusions: This study is the first to evaluate ER with an observational, clinician-rated measure in a controlled social setting in children with TS. Our findings support earlier questionnaire-based studies by showing impaired ER in children with TS + ADHD, but not in children with TS without comorbidity. These findings inform our understanding of the phenomenology of emotional dysregulation in TS and the role of comorbid disorders., (© 2020 Association for Child and Adolescent Mental Health.)

Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS.

Background and Objectives: Difficulties in emotion regulation (ER) have been associated with several psychiatric disorders, emphasizing a need for a greater understanding of the concept and its associations with disruptive behavior. We aimed to study the ER strategy of cognitive reappraisal with an experimental test to increase our knowledge of emotional processes in child psychopathology., Methods: In the present study, we examined emotional reactivity and cognitive reappraisal with a computer task in 160 medication-naïve children aged 8-12 comprising four groups: Fifty-eight children with Tourette syndrome (TS), 26 children with attention-deficit/hyperactivity disorder (ADHD), 19 children with TS and ADHD, and 57 typically developing controls., Results: The use of cognitive reappraisal reduced negative affect across all participants and the ability to reappraise was positively correlated with age, whereas reactivity was not. Overall, groups did not differ in reactivity or regulation success. Looking at specific differences within groups, however, only the ADHD group did not significantly decrease negative affect when reappraising. Finally, the use of strategies considered to be efficacious was correlated with regulation success, whereas the use of a less adaptive strategy related to suppression was associated with reactivity, but not regulation of emotions., Limitations: The study was limited by small, clinical contrast groups and a lack of blinding to diagnostic status in the coding of verbal strategies employed during the task., Conclusions: Cognitive reappraisal appears to be a beneficial ER strategy for children regardless of diagnostic status. Our findings indicate that children can learn and employ an adaptive ER strategy when instructed in the technique, even in the presence of attention problems, which is highly relevant to therapeutic approaches to dysregulated behavior., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The ability to regulate one's emotions is crucial to engaging successfully in social contexts. Difficulties in emotion regulation are seen in multiple psychiatric disorders, prompting an increased interest in the concept. Suitable methods for assessing emotion regulation, however, are lacking. In this study, we investigated the interrater and intrarater reliability, construct validity, and content validity of a new observational method for evaluating children's emotion regulation abilities (a complex puzzle task) in a sample of 62 children without psychiatric disorders and 23 children with attention-deficit/hyperactivity disorder (ADHD) aged 7-12, using intra-class correlation coefficients for the reliability analyses and Spearman's rank-order correlations for analyses of convergent and discriminant validity. A panel of experts examined the content validity of the test, and Mann-Whitney U -tests were used to investigate the ability of the test to differentiate the non-clinical group from the ADHD group. Results showed a high level of interrater and intrarater reliability of the test. There was mixed evidence for convergent and discriminant validity as expected due to the novelty and experimental nature of the test, making it difficult to compare with questionnaire-based measures. Content validity analysis was satisfactory, and the group comparison showed that the test differentiated the groups on the primary outcome measure. Overall, the measure demonstrated high feasibility and satisfactory psychometric properties. The generic nature of the test makes it suitable for use across psychiatric disorders and age groups with potential relevance in both research and clinical settings., (Copyright © 2019 Hagstrøm, Spang, Christiansen, Maigaard, Vangkilde, Esbjørn, Jepsen and Plessen.)

In children with Tourette syndrome (TS), tics are often attributed to deficient self-control by health-care professionals, parents, and peers. In this behavioural study, we examined response inhibition in TS using a modified Simon task which probes the ability to solve the response conflict between a new non-spatial rule and a highly-overlearned spatial stimulus-response mapping rule. We applied a distributional analysis to the behavioural data, which grouped the trials according to the individual distribution of reaction times in four time bins. Distributional analyses enabled us to probe the children's ability to control fast, impulsive, responses, which corresponded to the trials in the fastest time bin. Additionally, we tested whether the ability to suppress inappropriate action tendencies can be improved further by the prospect of a reward. Forty-one clinically well-characterized medication-naïve children with TS, 20 children with attention-deficit/hyperactivity disorder (ADHD), and 43 typically developing children performed a Simon task during alternating epochs with and without a prospect of reward. We applied repeated measures ANCOVAs to estimate how the prospect of reward modulated reaction times and response accuracy, while taking into account the distribution of the reaction times across trials. We found between-group differences in accuracy when subjects responded relatively fast. The TS group responded more accurately than typically developing control children when resolving the response conflict introduced by the Simon task. The opposite pattern was found in children with ADHD. Prospect of reward improved accuracy rates in all groups. Although the Tourette group performed with superior accuracy in the fast trials, it was still possible for them to benefit from prospect of reward in fast trials. The findings corroborate the notion that children with TS have an enhanced capacity to inhibit fast inappropriate response tendencies. This ability can be improved further by offering a prospect of reward which might be useful during non-pharmacological therapeutic interventions., (Copyright © 2019. Published by Elsevier Ltd.)

Pre- and perinatal complications have been implicated in the onset and clinical expression of Tourette syndrome albeit with considerable inconsistencies across studies. Also, little is known about their role in co-occurring obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) in individuals with a tic disorder. Therefore, we aimed to investigate the role of pre- and perinatal complications in relation to the presence and symptom severity of chronic tic disorder and co-occurring OCD and ADHD using data of 1113 participants from the Tourette International Collaborative Genetics study. This study included 586 participants with a chronic tic disorder and 527 unaffected family controls. We controlled for age and sex differences by creating propensity score matched subsamples for both case-control and within-case analyses. We found that premature birth (OR = 1.72) and morning sickness requiring medical attention (OR = 2.57) were associated with the presence of a chronic tic disorder. Also, the total number of pre- and perinatal complications was higher in those with a tic disorder (OR = 1.07). Furthermore, neonatal complications were related to the presence (OR = 1.46) and severity (b = 2.27) of co-occurring OCD and also to ADHD severity (b = 1.09). Delivery complications were only related to co-occurring OCD (OR = 1.49). We conclude that early exposure to adverse situations during pregnancy is related to the presence of chronic tic disorders. Exposure at a later stage, at birth or during the first weeks of life, appears to be associated with co-occurring OCD and ADHD., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Within one experiment and one T-maze, we examined the consequences of (i) bilateral lesions of the anteromedial prefrontal cortex (PFC), (ii) bilateral transections of the fimbria-fornix (FF), or (iii) combined lesions of both PFC and FF (COMB) on rats' ability to perform reversal or set-shifting. Postoperatively, the animals were trained to perform a spatial discrimination go-right task. This was followed by (1) a spatial reversal go-left task (reversal learning), or (2) a visual pattern discrimination task (set-shift). Neither single (PFC or FF) lesion nor combined (COMB) lesions affected the animals' ability to acquire the original spatial discrimination task. Regarding the reversal learning, the performance of the PFC and the FF groups was not significantly different from that of the sham operated control animals (Sham). In contrast, animals with combined lesion of both structures were impaired on both error rate and acquisition speed relative to all other groups. Regarding the set-shifting, all lesioned groups were impaired relative to the Sham group both regarding the error rate and the acquisition speed. There was, however, no difference in the degree of impairment between the lesioned groups. We conclude that both the PFC and the hippocampus contributed to the mediation of the reversal learning and set-shifting. During functional recovery of reversal learning, these two structures exhibited a mutual dependency, whilst the functional recovery of set-shifting was mediated by a substrate outside these two structures., (Copyright © 2015 Elsevier Inc. All rights reserved.)