Journal of the International Neuropsychological Society (2013), 19, 646–655. Copyright E INS. Published by Cambridge University Press, 2013. doi:10.1017/S1355617713000167 Impaired Response Inhibition in Autism Spectrum Disorders, a Marker of Vulnerability to Schizophrenia Spectrum Disorders? Petra S. Barneveld, 1 Leo de Sonneville, 1,2 Sophie van Rijn, 1,2 Herman van Engeland, 3 AND Hanna Swaab 1,2 1 Department of Clinical Child and Adolescent Studies, Leiden University, Leiden, The Netherlands 2 Leiden Institute for Brain and Cognition, Leiden University, Leiden, The Netherlands 3 Department of Child and Adolescent Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, The Netherlands (RECEIVED January 24, 2012; FINAL REVISION January 18, 2013; ACCEPTED January 18, 2013; FIRST PUBLISHED ONLINE February 21, 2013) Abstract In this study, we addressed the relation between specific deficits in cognitive control and schizotypal symptomatology in adolescents with autism spectrum disorders (ASD) diagnosed in childhood. We aimed to identify cognitive control deficits as markers of vulnerability to the development of schizophrenia spectrum pathology in ASD. Symptoms of autism and the risk for schizotypal symptomatology were assessed in 29 high-functioning adolescents with ASD, and compared with 40 typically developing adolescents. Cognitive control (response inhibition, mental flexibility, visuo-motor control, interference control, and perseveration) was evaluated for specific association with schizotypal symptomatology. Impaired response inhibition appeared to be strongly and specifically associated with schizotypal symptomatology in adolescents with ASD, especially those with positive and disorganized symptoms. Response inhibition problems could indicate vulnerability to the development of schizotypal symptomatology in ASD. (JINS, 2013, 19, 646–655) Keywords: Autism spectrum, Schizophrenia spectrum, Schizotypy, Psychosis, Executive functions, Response inhibition INTRODUCTION Autism spectrum disorders (ASD) are lifelong conditions characterized by severe impairments in social interaction and dysfunctional communication, with serious impact on daily life [American Psychiatric Association (APA), 2000]. Although some individuals with ASD show successful adaptation to daily life, many others are at risk for severe deterioration of daily functioning during development (APA, 2000), and some are at risk for very serious psychopathology, such as psychosis, later in life (e.g., Mouridsen, Rich, & Isager, 2008; Stahlberg, Soderstrom, Rastam, & Gillberg, 2004). Results of studies focusing on this risk suggest that specific developmental abnormalities in childhood, such as dysregulation of affective state and primitive anxieties, occur before those children meet the criteria for psychotic disorder or schizophrenia later in life (e.g., Van der Gaag et al., 1995). In their review, Padgett, Miltsiou, and Tiffin (2010) argued that ASD could be a risk factor for psychosis. In a prevalence study on schizophrenia spectrum disorders (SSD) in 241 adults diagnosed with ASD in childhood, up to 7.8% were found to meet criteria for schizophrenia or another psychotic disorder in adulthood (Stahlberg et al., 2004). The authors conclude that the risk for psychosis in ASD is clearly higher than in the general population (approximately 1%) (McGrath et al., 2004), and in other developmental disorders (such as ADHD, approxi- mately 5%) (Stahlberg et al., 2004). Moreover, Raja and Azzoni (2010) reported that 84.6% of 26 adults with ASD showed psychotic symptoms, and 72.7% had a concurrent diagnosis of schizophrenia. In an earlier study, Volkmar and Cohen (1991) concluded on the basis of case records of 163 adolescents and adults with autism that the frequency of SSD in ASD is comparable to that in the general population. However, the comparability of their findings to those of more recent studies is restricted, since approximately 50% of their patients were mute. Other studies focussing on the presence of ASD in SSD found that in 25–50% of patients childhood- onset schizophrenia was preceded by and comorbid with ASD (Rapoport, Chavez, Greenstein, Addington, & Gogtay, 2009; Sporn et al., 2004). The link between ASD and SSD Correspondence and reprint requests to: Petra Barneveld, Leiden University, Faculty of Social Sciences, Department of Clinical Child and Adolescent Studies, P.O. Box 9555, 2300 RB Leiden, The Netherlands. E-mail: barneveldps@fsw.leidenuniv.nl 646