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RESEARCH PRODUCT

PREMORBID ADJUSTMENT AND CANNABIS USE IN FIRST-EPISODE-PSYCHOSIS PATIENTS. A CROSS-EUROPEAN CASE-CONTROL STUDY

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The harmful effects of cannabis use and possible neuropsychological impairment associated with its use are a contentious topic of debate in both research and public health,as is thefact that cannabis use has been repeatedly shown to be a risk factor for the development of psychosis. Surprisingly, three different meta-analyses on cognition and cannabis, among schizophrenic patients, found better cognitive performance in patients with a lifetime use of cannabis (Potvin, Joyal, Pelletier, & Stip, 2008; Rabin, Zakzanis, & George, 2011; Yücel et al., 2012). This counterintuitive finding, coupled with the fact that most psychotic patients suffer from cognitive impairment (Reichenberg et al., 2009) make it more difficult to understand the relationship between these two risk factors. Two different explanations have been advanced for this counterintuitive finding: a) a “premorbid-driven hypothesis” and b) a “neuroprotective-derived hypothesis”. The latter explanation has gained greater support from the evidence that the CBD component has been useful as part of the treatment in several neurological disorders. Cognition has been established as a predictor of real world community functioning in schizophrenia. However, studies on the relationship between cannabis use and neurocognitive functioning in psychosis, which have controlled for the potential bias of premorbid functioning, are rarely represented in this context and often inconclusive. The main objective of the work presented in this Thesis was to explore this association in an epidemiologically-derived case-control study in a sample derivedfrom TheEuropean Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) in order to test the first of these two hypotheses, with the aim of exploring IQ and premorbid conditions and how they are related to cannabis use in patients at their first episode of psychosis (FEP), by comparing those cannabis using patients to non-users and to their respective healthy controls. The final aim of this work was to identify the relationship between IQ, premorbid social and academic adjustment with cannabis use in psychotic patients, compared to healthy controls, in order to be able to explain in which cases you can expect a better IQ and a better premorbid adjustment and why, by clustering the sample, first according to cannabis use and, secondly, to frequency of cannabis use. I hypothesize the existence of a subgroup of patients with a recreational use of cannabis, who are less cognitively impaired at the onset and less socially withdrawn in the premorbid period than other patients. The final sample of the present study included 1,895 subjects (834 cases and 1,061 controls), with complete information about cannabis use (CEQ) and premorbid adjustment (PAS) at least. 1,739 subjects in total had also complete information on their IQ (derived from WAIS-short version). The study confirmed that patients who used cannabis in their lifetime with a recreational pattern of cannabis use have higher IQ scores and a better and more stable premorbid adjustment than other patients. The study also suggested that the better premorbid social adjustment of patients with cannabis-use might be responsible for the contact with the substance and that cannabis use increased the risk of psychosis in a subgroup of patients with less neurodevelopmental vulnerability. Taken together, these results are able to rule out the alternative explanation of a neuroprotective role of cannabis use on cognition, in favour of the hypothesis of a complex relationship between premorbid predisposition and different pattern of cannabis use in determining this paradoxical result.