http://repub.eur.nl/res/aut/31859/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/26757/ 2011-07-20T00:00:00Z Genetic variation in AKT1 may be associated with sensitivity to the psychotomimetic effects of cannabis as well as with increased risk for psychotic disorder following cannabis use. Investigation of the effect of this interaction on relevant intermediate phenotypes for psychosis, such as cognition, may help to clarify the underlying mechanism. Thus, verbal memory (visually presented Word Learning Task), sustained attention (Continuous Performance Test, CPT), AKT1 rs2494732 genotype, and cannabis use were examined in a large cohort of patients with psychotic disorder. No evidence was found for AKT1 × cannabis interaction on verbal memory. Cannabis use preceding onset of psychotic disorder did interact significantly with AKT1 rs2494732 genotype to affect CPT reaction time (β=8.0, SE 3.9, p=0.037) and CPT accuracy (β=-1.2, SE 0.4, p=0.003). Cannabis-using patients with the a priori vulnerability C/C genotype were slower and less accurate on the CPT, whereas cannabis-using patients with the T/T genotype had similar or better performance than non-using patients with psychotic disorder. The interaction was also apparent in patients with psychotic disorder who had not used cannabis in the 12 months preceding assessment, but was absent in the unaffected siblings of these patients and in healthy controls. In conclusion, cannabis use before onset of psychosis may have long-lasting effects on measures of sustained attention, even in the absence of current use, contingent on AKT1 rs2494732 genotype. The results suggest that long-term changes in cognition may mediate the risk-increasing effect of the AKT1 × cannabis interaction on psychotic disorder.Neuropsychopharmacology advance online publication, 20 July 2011; doi:10.1038/npp.2011.141. http://repub.eur.nl/res/pub/24621/ 2009-12-01T00:00:00Z Objective. Multiple complex developmental disorder (MCDD) is a well-defined and validated behavioural subtype of pervasive developmental disorder-not otherwise specified (PDD-NOS) and is thought to be associated with a higher risk of developing a schizophrenic spectrum disorder. The question was addressed whether patients with MCDD show the same psychophysiological abnormalities as seen in patients with schizophrenia. Method. Smooth pursuit eye movement (pursuit gain and saccadic parameters) was measured in children with either MCDD (n=18) or autism (n=18), and in age-and IQ-matched controls (n=36), as well as in a group of adult patients with schizophrenia (n=14) and a group of adult controls (n=17). Results. We found the expected effect of lower velocity gain and increased number of saccades in schizophrenic patients. Children with MCDD also showed a lower velocity gain compared to controls children. In contrast, velocity gain was similar in autistic subjects and controls. No differences for velocity gain were found in a direct comparison between MCDD and autism. Saccadic parameters were not significantly different from controls in either MCDD or autistic subjects. Conclusion. Children with MCDD, like schizophrenic adults, show a reduced velocity gain, which could indicate that schizophrenia spectrum disorders and MCDD share (at least to some degree) a common neurobiological background.