Heavy cannabis use prior psychosis in schizophrenia: clinical, cognitive and neurological evidences for a new endophenotype?

Cannabis use is associated with an increased risk of schizophrenia, and is considered to impact late neurodevelopment. Neurological soft signs (NSS) associated with schizophrenia are considered as markers of early neurodevelopmental impairment. Our study examines the association between heavy cannabis use before the onset of psychosis and clinical, neuropsychological and neurological symptoms, including NSS. In a cross-sectional study, we consecutively included 61 patients with schizophrenia (34 reporting heavy cannabis use before the onset of psychosis and 27 not reporting such use), in the setting of a University Hospital and a Medical Center. Symptoms assessment and substance use disorder were evaluated with the Diagnostic Interview for Genetic Studies. NSS were assessed with the Neurological Evaluation Scale. Psychopathology was assessed with the Positive and Negative Symptom Scale. All patients underwent a battery of neurocognitive tests evaluating attention, memory and executive functions domains. Patients with heavy cannabis use before the onset of psychosis showed significantly less NSS (p < 0.05), less negative symptoms (p < 10-3) and a better cognitive functioning in different domains [median reaction time (p = 0.03), episodic memory (p = 0.04), visuoconstructive praxs (p = 0.03) than their non-heavy user counterparts]. Confounding effects of alcohol and tobacco were taken into account. Age and gender were not statistically different between the two groups (p = 0.70 and p = 0.16, respectively). Our study supports the clinical, neuropsychological and neurological specificity associated with the heavy use of cannabis before the onset of schizophrenia. Patients with heavy cannabis use before the onset of schizophrenia may exhibit later neurodevelopmental impairment than those who do not report such use. Schizophrenia associated with heavy cannabis use could represent a specific phenotype.