LCB/BQ/PR22/11920017 - Paola Fuentes Claramonte

Predicción del riesgo de desarrollo de psicosis en jóvenes consumidores de cannabis

Cannabis is the world's most widely used illicit drug, and it is often regarded as ‘soft' or relatively harmless. However, in recent years, awareness has increased of harms associated with its use. The current literature links cannabis with two psychopathological outcomes: an increased risk of experiencing psychotic symptoms and the full syndrome of schizophrenia, and the so-called amotivational syndrome. Both outcomes are of especial relevance in adolescents and young adults, given that this is the common age range for the onset of psychotic disorders, and that lack of motivation appears to be a particular problem in young cannabis users. However, it is also clear that not all users develop such symptoms. This project aims to use functional brain imaging to detect and examine susceptibility to these harmful effects of cannabis.
The utility of three different brain functional imaging abnormalities in this respect will be examined. (i) Failure of deactivation of the medial prefrontal cortex during performance of attention-demanding tasks, which is well-documented in schizophrenia, including patients with a first-episode of illness and their unaffected relatives, suggesting that it may be a marker of vulnerability to psychosis. It is thought to reflect dysfunction of the default-mode network (DMN), a set of brain regions (including medial prefrontal cortex) that are active at rest but de-activate during performance of a wide range of attention-demanding tasks. (ii) Aberrant reward processing. Increased and aberrant brain dopamine signalling leading to salience being attributed to neutral stimuli has been proposed as the basis for positive schizophrenic symptoms such as referential delusions and abnormal perceptions. Reward processing can be examined using tasks measuring brain responses to reward and reward-associated stimuli, and has been found to be abnormal in schizophrenia. (iii) Goal neglect as an index of cannabisrelated amotivation. Brain functional correlates of goal-directed action can be examined using an fMRIadapted version of behavioral tasks sensitive to the so-called goal neglect, something that is believed to underlie the apathy seen in neurological patients with frontal lobe syndrome.
This project will use three functional imaging paradigms in a large sample of cannabis users (N=100) aged 18-25 years, and a group of non-drug consuming controls (N=50), to examine these three imaging markers. We will examine failure of DMN deactivation using an attention-demanding task (the n-back) and altered reward processing through a dynamic monetary reward learning task. We will also examine amotivation using the Computerised Multiple Elements Test (CMET), an fMRI-adapted test of goal neglect. Examination of associations between activations/de-activations during performance of these tasks and detailed clinical measures of psychosis-like experiences (for the n-back and reward tasks) and apathy (for the CMET) will be made.

Fundació La Caixa

115.500 €