It is unclear yet whether cannabis use is a moderating or causal factor contributing to grey matter alterations in schizophrenia and the development of psychotic symptoms. We therefore systematically reviewed structural brain imaging and post mortem studies addressing the effects of cannabis use on brain structure in psychosis. Studies with schizophrenia (SCZ) and first episode psychosis (FEP) patients as well as individuals at genetic (GHR) or clinical high risk for psychosis (ARMS) were included. We identified 15 structural magnetic resonance imaging (MRI) (12 cross sectional / 3 longitudinal) and 4 post mortem studies. The total number of subjects encompassed 601 schizophrenia or first episode psychosis patients, 255 individuals at clinical or genetic high risk for psychosis and 397 healthy controls. We found evidence for consistent brain structural abnormalities in cannabinoid 1 (CB1) receptor enhanced brain areas as the cingulate and prefrontal cortices and the cerebellum. As these effects have not consistently been reported in studies examining non-psychotic and healthy samples, psychosis patients and subjects at risk for psychosis might be particularly vulnerable to brain volume loss due to cannabis exposure

As cannabis use is more frequent in patients with psychosis than in the general population and is known to be a risk factor for psychosis, the question arises whether cannabis contributes to recently detected brain volume reductions in schizophrenic psychoses. This study is the first to investigate how cannabis use is related to the cingulum volume, a brain region involved in the pathogenesis of schizophrenia, in a sample of both at-risk mental state (ARMS) and first episode psychosis (FEP) subjects. A cross-sectional magnetic resonance imaging (MRI) study of manually traced cingulum in 23 FEP and 37 ARMS subjects was performed. Cannabis use was assessed with the Basel Interview for Psychosis. By using repeated measures analyses of covariance, we investigated whether current cannabis use is associated with the cingulum volume, correcting for age, gender, alcohol consumption, whole brain volume and antipsychotic medication. There was a significant three-way interaction between region (anterior/posterior cingulum), hemisphere (left/right cingulum) and cannabis use (yes/no). Post-hoc analyses revealed that this was due to a significant negative effect of cannabis use on the volume of the posterior cingulum which was independent of the hemisphere and diagnostic group and all other covariates we controlled for. In the anterior cingulum, we found a significant negative effect only for the left hemisphere, which was again independent of the diagnostic group. Overall, we found negative associations of current cannabis use with grey matter volume of the cingulate cortex, a region rich in cannabinoid CB1 receptors. As this finding has not been consistently found in healthy controls, it might suggest that both ARMS and FEP subjects are particularly sensitive to exogenous activation of these receptors.

Introduction:Gender differences in psychopathological symptoms have frequently been found in chronic schizophrenia and first-episode psychosis (FEP) patients. However, many of the existing studies suffer from methodological problems. Furthermore, very few studies have investigated gender differences in at-risk mental state (ARMS) individuals.Aims:To investigate whether male and female ARMS and FEP patients differ in self- and observer-rated psychopathological symptoms when adjusted for potential confounders.Methods:Psychopathological symptoms were assessed in 117 ARMS and 87 FEP patients by two observer-rated scales:the Brief Psychiatric Rating Scale (BPRS) and the Scale for the Assessment of Negative Symptoms (SANS), and one self-report scale,the Frankfurt Complaint Questionnaire (FCQ). Gender differences were investigated by applying Analyses of Variance using the BPRS, SANS and FCQ subscales as dependent variables and, group and sex as between-subject factors. Furthermore, Analyses of Covariance were conducted by including age, antipsychotic, antidepressant and cannabis use as covariates.Results:No significant gender × patient group interactions were found, suggesting that gender effects did not differ between patient groups. Women showed higher scores in positive psychotic symptoms (BPRS Psychosis/Thought Disturbance) while men had higher scores in negative symptoms (BPRS negative symptoms, SANS total score, and subscales Affective Flattening, Avolition-Apathy and Asociality-Anhedonia). However, the differences did not withstand correction for multiple testing. Furthermore, these results did not change when corrected for potential confounders.Conclusions:Our findings suggest that male and female ARMS and FEP patients do neither differ in self-report nor in observer-rated psychopathological symptoms when corrected for multiple testing and potential confounders.

This study could not confirm an association between duration of untreated psychosis or duration of untreated illness and neurocognitive performance in the ARMS-T and FEP samples. This could be because schizophrenic psychoses are neurodevelopmental disorders in which most cognitive deficits exist long before the onset of psychiatric symptoms.