title: AKT1 moderation of cannabis-induced cognitive alterations in psychotic disorder.
abstract: 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.
authors.affiliation: Department of Psychiatry and Psychology, School of Mental Health and Neuroscience, European Graduate School of Neuroscience (EURON), South Limburg Mental Health Research and Teaching Network (SEARCH), Maastricht University Medical Centre, Maastricht, The Netherlands. ruud.vanwinkel@maastrichtuniversity.nl
authors.forename: Ruud
authors.initials: R
authors.lastname: van Winkel
authors.forename: Nico J M
authors.initials: NJ
authors.lastname: van Beveren
authors.forename: Claudia
authors.initials: C
authors.lastname: Simons
mesh_terms: D000293:Adolescent; D000328:Adult; D002188:Cannabis; D003072:Cognition Disorders / Q000235:genetics* / Q000523:psychology; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000235:genetics* / Q000523:psychology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D011618:Psychotic Disorders / Q000235:genetics* / Q000523:psychology; D055815:Young Adult
chemical_list: C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt