Charlotte Rapp

Effects of Cannabis Use on Human Brain Structure in Psychosis: A Systematic Review Combining In Vivo Structural Neuroimaging and Post Mortem Studies

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

Duration of untreated psychosis and cognitive functioning.

BACKGROUND Studies examining the influence of duration of untreated psychosis (DUP) or duration of untreated illness (DUI) on cognition vary with regard to results and methods. This study is the first in this field to include an at risk mental state with later transition to psychosis (ARMS-T) sample and to analyse how the DUI relates to their cognitive functioning. Because methodological operationalization of cognitive functioning in previous studies is highly heterogeneous, we aimed to compare different approaches. METHOD 60 first episode psychosis (FEP) patients and 24 ARMS-T patients were examined. Associations between DUP, DUI and neurocognitive performance were tested by three different operationalizations of cognition: as the raw outcome measure of different neuropsychological tests, as outcome scores which were normed on a sample of 75 healthy participants, and as the deterioration index (DI). RESULTS There were no significant correlations between DUP or DUI and outcome of neuropsychological tests in both normed and raw scores. When adjusted for covariates, DUP and DUI also did not significantly predict any cognitive performance. There was no significant relationship between DUP or DUI and the DI index. However, longer DUP and DUI were significantly associated with stronger negative symptoms. CONCLUSIONS 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.

Cannabis use and brain structural alterations of the cingulate cortex in early psychosis

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.

Cannabis use and cognitive functions in at-risk mental state and first episode psychosis

BackgroundMeta-analyses suggest that schizophrenia patients with a history of cannabis use have less impaired cognitive functioning compared to patients without cannabis use.AimsThe objective of this study was to assess the association between recency and frequency of cannabis use and cognitive functioning in at-risk mental state for psychosis (ARMS) and first episode psychosis (FEP) individuals.MethodsOne hundred thirty-six participants completed a cognitive test battery and were assessed for current and past cannabis use. Analyses of covariance models were applied to evaluate the main effects of cannabis use and patient group (ARMS vs. FEP) as well as their interactions on cognitive functioning.ResultsNo differences were observed in cognitive performance between current, former, and never users, and there were no significant interactions between cannabis use and patient group. Furthermore, within the group of current cannabis users, the frequency of cannabis use was not significantly associated with cognitive functioning.ConclusionThe results of the present study do not support the notion that FEP patients and ARMS individuals with a history of cannabis use have less impaired cognitive functioning compared to those without cannabis use.

Pituitary gland volume in at-risk mental state for psychosis: a longitudinal MRI analysis.

INTRODUCTION Pituitary enlargement has been reported in individuals with schizophrenic psychosis or an at-risk mental state for psychosis (ARMS). In a previous study, our group could show pituitary volume increase in first episode and ARMS patients with later transition to psychosis (ARMS-T). However, there are no longitudinal studies on this issue so far. We therefore examined longitudinally whether transition to psychosis would be accompanied by a further increase of pituitary volume in antipsychotic-naïve ARMS patients. METHODS Magnetic resonance imaging (MRI) data were acquired from 23 antipsychotic-naïve individuals with an ARMS. Ten subjects developed psychosis (ARMS-T) and 13 did not (ARMS-NT). ARMS-T were re-scanned after the onset of psychosis, and ARMS-NT were re-scanned at the end of the study period. RESULTS There was no significant difference of the pituitary volume between ARMS-T and ARMS-NT in our sample, and there were no significant pituitary volume changes over time. Discussion Longitudinally, we could not detect any further volumetric changes in the pituitary volume with transition to psychosis. CONCLUSIONS This, together with the result of our previous study, could indicate that the perceived level of stress in ARMS patients is constantly high from very early onward.

Hippocampal volume in subjects at clinical high-risk for psychosis: A systematic review and meta-analysis.

Several magnetic resonance imaging studies have reported reductions in hippocampal volume in patients with psychosis. It is unclear whether structural abnormalities predate illness onset. We conducted a detailed, systematic literature search for studies reporting hippocampal volume in subjects with clinical high-risk, compared to healthy controls. The overall sample size comprised 1429 subjects. Meta-analysis revealed no difference for left, but a small, albeit significant, difference for right hippocampal volume, such that clinical high-risk patients had slightly smaller hippocampal volume than healthy controls (g=0.24, p=0.0418). Meta-regression indicated a moderating effect of manual tracing approach, due to one outlying site. The small difference on the right side did not remain significant (g=0.14, 95%CI=[-0.03-0.32], p=0.11) after removal of this outlier. This meta-analysis suggests that there is no reduction in hippocampal volume before transition to psychosis and hippocampal volume cannot be used as a biomarker in clinical high-risk individuals.

Can cognitive deficits facilitate differential diagnosis between at-risk mental state for psychosis and depressive disorders?

Many studies have provided evidence of cognitive deficits in individuals in an ‘At Risk Mental State’ (ARMS) for psychosis, which makes neuropsychology potentially useful in the early detection of psychosis. As depression is an important differential diagnosis in prodromal states of psychosis, the specificity of neurocognitive deficits in ARMS individuals as compared with non‐psychotic depressive disorders is investigated.

Correlations between self-rating and observer-rating of psychopathology in at-risk mental state and first-episode psychosis patients: influence of disease stage and gender.

Research findings on the correlations between self‐rating and observer‐rating of schizophrenic psychopathology are inconsistent and have rarely considered first‐episode psychosis (FEP) and at‐risk mental state (ARMS) for psychosis patients. This study investigates these correlations in ARMS and FEP patients and how they are moderated by disease stage and gender.

2710 – Gender differences in the psychopathology of emerging psychosis

BACKGROUND Gender differences have often been found in psychopathological symptoms among chronic schizophrenia and first-episode psychosis (FEP) patients. However, many of these studies suffer from methodological problems and show inconsistent results. Furthermore, very few studies have investigated gender differences in individuals with an at-risk mental state (ARMS) for psychosis. METHODS Psychopathological symptoms were assessed in 117 ARMS and 87 FEP patients by two observer-rated scales, namely, the expanded version of the Brief Psychiatric Rating Scale (BPRS) and the Scale for the Assessment of Negative Symptoms (SANS), and by 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 - in a second step by including age, antipsychotic, antidepressant and cannabis use as covariates. RESULTS There were no significant gender × patient group interactions, suggesting that gender effects did not differ between patient groups. Women had higher scores in positive psychotic symptoms (BPRS Psychosis/ Thought Disturbance) while men had higher scores in negative symptoms (BPRS negative symptoms, SANS total score, as well as subscales Affective Flattening, Avolition-Apathy and Asociality-Anhedonia). However, the differences did not withstand correction for multiple testing. The results did not change when corrected for potential confounders. CONCLUSIONS There do not seem to be any gender differences in psychopathology, neither in ARMS nor in FEP patients, as regards self-reported or observerrated symptoms, when corrected for multiple testing and potential confounders.