AbstractsPsychology

1) Introduction Cannabis use has been associated to mental health problems and worsened outcome of established psychiatric disorders. Disturbances of the endocannabinoid system may be responsible for long-lasting effects, such as neuropsychological deficits and morphological brain alterations. As not all the exposed individuals are equally affected, proneness to cannabis induced impairment may rely on key factors such as age of onset, cannabis use parameters and genetic background. The aim of the present thesis is to expand current knowledge of the effects of cannabinoids, while assessing gene-environment interactions that are relevant for psychiatric disorders, based on the following hypothesis: - Cannabis use in first-episode psychosis would be associated with worse outcome regarding readmission rates (Chapter 3). - Acute and chronic cannabis use would be associated with alterations on brain function and structure in key areas relevant for psychiatric disorders (Chapters 4-5). - Early-onset chronic cannabis users would show morphological brain alterations compared to non-using controls, and variation in the dopamine-regulating genes would result in diverse liability to experience cannabis-related brain impairment (Chapters 6-7). 2) Methods We assessed a cohort of 58 first-episode psychosis patients. The main outcome was the time until first readmission. All subjects were interviewed using the Structured Clinical Interview SCIO-I, the Positive and Negative Syndrome Scale (PANSS) and the Dartmouth Assessment of Lifestyle Inventory (DALI) scale. The subjects also underwent blood and urine sampling for drug use (Chapter 3). In addition, we conducted two systematic literature reviews in accordance with PRISMA guidelines. Chapter 4 included 43 neuroimaging studies of experimental administration of cannabinoids involving animals naive to cannabinoids and naive/occasional cannabis users. Chapter 5 considered 4S neuroimaging studies involving chronic cannabis users with a matched control group. Finally, we performed a case-control study in male Caucasians, 30 early-onset chronic cannabis users and 29 age-, education- and intelligence-matched non-using controls. All subjects were assessed by a structured interview (PRISM). Catechol-a-methyltransferase (COMT Val(158)Met] and dopamine transporter (DATI-VNTR) genotyping were performed. MRI data was analysed by VBM (Chapter 6) and manual tracing of the hippocampus via well-validated methods (Chapter 7). 3) Results Cannabis was the most common drug found in the first-episode psychosis cohort, either in urinalysis (38%) or self-reported (50%). Both the DALI cannabis/cocaine subscale (p=0.002) and urinalysis for cannabis (p=0.02) were associated with increased readmission risk in survival curves. The DALI cannabis/cocaine subscale at baseline was a significant predictor of readmission over the study period (HR = 4.5: 95% CI = 1.1 to 18.7; p=0.036) after controlling for potential confounders (Chapter 3). Studies included in Chapter 4 showed that acute administration of…