Negative symptoms and cannabis use in severe mental disorders. Weeding out important links and outcomes across diagnoses and time

“Negative symptoms” is an umbrella term divided into two main dimensions: diminished expression and apathy. Negative symptoms are considered intrinsic to psychotic disorders, yet are also evidently present across a wide range of disorders, including bipolar disorder. Negative symptoms may also manifest as a consequence of environmental factors such as substance use. Cannabis is the third most commonly used drug worldwide, and its use is more common in psychotic- and bipolar disorders, compared to the general population. It is associated with several detrimental outcomes, such as increased symptom severity, and reduced functioning. Clinical observations indicate an association between cannabis use and more severe negative symptoms, often referred to as the “amotivational syndrome”. However, results from naturalistic studies including participants with severe mental disorders are diverging. In the current thesis, which is based on three naturalistic studies including participants with severe mental disorders, we explored the specific link between the two dimensions of negative symptoms and cannabis use. Frequent cannabis use was associated with more severe levels of diminished expression in schizophrenia spectrum disorders, with a dose-response relationship. Both baseline- and persistent cannabis use predicted enduringly higher levels of diminished expression over a 10-year period after the first episode of psychosis, compared to non-use. There was no significant link between cannabis use and apathy, and no link to either dimensions of negative symptoms in bipolar disorders, suggesting that disorders on the more severe end of the psychosis spectrum are more vulnerable to the effects of cannabis. The differences in association between cannabis use and the two negative symptom dimensions show that they respond differently to cannabis exposure, which may indicate that the underlying pathophysiological mechanisms of diminished expression and apathy are divergent.