Evidence That Familial Liability for Psychosis Is Expressed as Differential Sensitivity to Cannabis An Analysis of Patient-Sibling and Sibling-Control Pairs

Context: Individual differences in cannabis sensitivity may be associated with genetic risk for psychotic disorder. Objectives: To demonstrate and replicate, using 2 conceptually different genetic epidemiological designs, that (familial) liability to psychosis is associated with sensitivity to cannabis. Design, Setting, and Participants: Sibling-control and cross-sibling comparisons using samples of patients with a psychotic disorder (n=1120), their siblings (n=1057), and community controls (n=590) in the Netherlands and Flanders. Main Outcome Measures: Positive and negative schizotypy using the Structured Interview for Schizotypy-Revised (for siblings and controls) and self-reported positive and negative psychotic experiences using the Community Assessment of Psychic Experiences (for siblings and patients). Cannabis use was assessed as current use (by urinalysis) and lifetime frequency of use (by Composite International Diagnostic Interview). Results: In the sibling-control comparison, siblings displayed more than 15 times greater sensitivity to positive schizotypy associated with particularly current cannabis use by urinalysis (adjusted B=0.197, P