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Background Low recruitment in clinical trials is a common and costly problem which undermines medical research. This study aimed to investigate the challenges faced in recruiting children and adolescents with obsessive-compulsive disorder and autism spectrum disorder for a randomized, double-blind, placebo-controlled clinical trial and to analyze reasons for non-participation. The trial was part of the EU FP7 project TACTICS (Translational Adolescent and Childhood Therapeutic Interventions in Compulsive Syndromes). Methods Demographic data on pre-screening patients were collected systematically, including documented reasons for non-participation. Findings were grouped according to content, and descriptive statistical analyses of the data were performed. Results In total, n = 173 patients were pre-screened for potential participation in the clinical trial. Of these, only five (2.9%) were eventually enrolled. The main reasons for non-inclusion were as follows: failure to meet all inclusion criteria/meeting one or more of the exclusion criteria (n = 73; 42.2%), no interest in the trial or trials in general (n = 40; 23.1%), and not wanting changes to current therapy/medication (n = 14; 8.1%). Conclusions The findings from this study add valuable information to the existing knowledge on reasons for low clinical trial recruitment rates in pediatric psychiatric populations. Low enrollment and high exclusion rates raise the question of whether such selective study populations are representative of clinical patient cohorts. Consequently, the generalizability of the results of such trials may be limited. The present findings will be useful in the development of improved recruitment strategies and may guide future research in establishing the measurement of representativeness to ensure enhanced external validity in psychopharmacological clinical trials in pediatric populations. Trial registration EudraCT 2014-003080-38. Registered on 14 July 2014.

Autism spectrum disorder (ASD) and obsessive compulsive disorder (OCD) show overlapping symptomatology and deficits in inhibitory control, which are associated with altered functioning and glutamatergic signaling in fronto-striatal circuitry. These parameters have never been examined together. The purpose of the current study was to investigate functioning during inhibitory control and its association with fronto-striatal glutamate concentrations across these disorders using a multi-center, longitudinal approach. Adolescents with ASD (n = 24), OCD (n = 15) and controls (n = 35) underwent two magnetic resonance imaging (MRI) sessions with a one-year interval. This included proton magnetic resonance spectroscopy (1H-MRS; n = 74) and functional MRI during an inhibitory control task (n = 53). We investigated 1H-MRS data and fMRI data separately as well as integrated in a multimodal analysis using linear models focusing on diagnosis and continuous measures of overlapping compulsivity symptoms. ACC glutamate was reduced over time in the ASD group compared with controls, while striatal glutamate decreased over time independent of diagnosis. Increased compulsive behavior seemed to be associated with increased striatal activity during failed inhibitory control. The integrated analyses showed differential involvement of increased striatal glutamate during failed but decreased striatal glutamate during successful inhibitory control in the OCD group compared to controls and ASD, suggesting different underlying mechanisms for OCD compared to ASD., NeuroImage: Clinical, 30, ISSN:2213-1582

BackgroundAutism spectrum disorder (ASD) and obsessive compulsive disorder (OCD) are neurodevelopmental disorders with overlapping symptomatology. Both show deficits in inhibitory control, which are associated with altered functioning and glutamate concentrations in the fronto-striatal circuitry. These parameters have never been examined together. Here we, for the first time, used a multi-center, longitudinal approach to investigate fronto-striatal functioning during an inhibitory control task and its association with fronto-striatal glutamate concentrations across these two disorders.Methods74 adolescents with ASD (24) or OCD (15) and controls (35) aged 8-17 were recruited across three sites of the European TACTICS consortium. They underwent two magnetic resonance imaging (MRI) sessions with a one-year interval. This included proton magnetic resonance spectroscopy (1H-MRS; n=74) and functional MRI during an inhibitory control task (n=57). We used linear mixed effects models to investigate, over time, the relationship between fronto-striatal functioning and glutamate concentrations across these groups and continuous measures of overlapping compulsivity symptoms.ResultsDuring failed inhibitory control, in OCD increased striatal glutamate was associated with increased neural activation of ACC, an effect that decreased over time. During successful inhibitory control, higher ACC glutamate was positively associated with striatal activation in OCD and compulsivity across time. ACC glutamate levels decreased over time in the ASD group compared to controls, while striatal glutamate decreased over time, independent of diagnosis.ConclusionsSignificant differences in fronto-striatal glutamate were observed in ASD and OCD, affecting functional activity during failed- and successful inhibitory control differently, especially in OCD, with effects changing over time.

Repetitive behavior is a core symptom of Autism Spectrum Disorder (ASD) and Obsessive-Compulsive Disorder (OCD), and has been associated with impairments in cognitive control. However, it is unclear how cognitive control and associated neural circuitry relate to the development of repetitive behavior in children with these disorders. In a multicenter, longitudinal study (TACTICS; Translational Adolescent and Childhood Therapeutic Interventions in Compulsive Syndromes), the development of cognitive control was assessed during late childhood using a longitudinal fMRI design with a modified stop-signal task in children with ASD or OCD, and typically developing (TD) children (baseline: N=122 (8-12y), follow-up: N=72 (10-14y), average interval: 1.2y). Stop-signal reaction time (SSRT) decreased over development, regardless of diagnosis. Repetitive behavior in children with ASD and OCD was not associated with performance on the stop-signal task. There were no whole-brain between-group differences in brain activity, but ROI-analyses showed increases in activity in right precentral gyrus over development for children with OCD. In sum, even though subtle differences were observed in the development of brain activity in children with OCD, the findings overall suggest that the development of cognitive control, as assessed by the stop signal task, is similar in children with and without ASD or OCD.