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Structure and function in the human brain are closely related. At the onset of psychosis, brain imaging studies have identified robust changes in brain function and structure, but no data are available relating these two domains. After systematic literature searches, we included all available studies reporting whole-brain structural or cognitive functional imaging findings in first-episode (FEP) subjects in multimodal Signed Differential Mapping (SDM). Forty-three studies met the inclusion criteria. The structural database comprised 965 FEP subjects matched with 1040 controls whilst the functional cohort included 362 FEP subjects matched with 403 controls. The analysis identified conjoint structural and functional differences in the insula/superior temporal gyrus and the medial frontal/anterior cingulate cortex bilaterally. In these regions, large and robust decreases in grey matter volume were found with either reduced or enhanced activation. Meta-regression analyses indicated that grey matter volume in the anterior cingulate and left insular clusters was influenced by exposure to antipsychotics: patients receiving medication were more likely to show structural abnormalities in these regions.

A number of structural brain imaging studies and meta-analytic reviews have shown that multiple subtle brain abnormalities are consistently found in schizophrenia and bipolar disorder. Several studies suggest that schizophrenia and affective psychoses share a largely common pattern of brain abnormalities. Aim of the present study was to compare, by means of a meta-analytic approach, brain structural abnormalities, as detected by Magnetic Resonance Imaging (MRI), found at the onset of schizophrenia and bipolar disorder in order to address the question of the specificity of brain abnormalities across diagnostic groups. Forty-five studies were identified as suitable for analysis. In both schizophrenic and bipolar patients significant overall effect sizes were demonstrated for intracranial, whole brain, total grey and white matter volume reduction as well as for an increase of lateral ventricular volume at disease onset. Thus, the available literature data strongly indicate that some brain abnormalities are already present in first-episode schizophrenia or bipolar disorder and that there is a significant overlap of brain abnormalities in affective and non-affective psychotic disorders at the onset of the disease. However, whole grey matter volume deficits and lateral ventricular enlargement appear to be more prominent in first-episode schizophrenia whereas white matter volume reduction seems more prominent in bipolar disorder. The common vs specific trajectories of brain pathomorphology in schizophrenia and bipolar disorder are discussed.

Aims: Despite growing research in the field of cannabis imaging, mostly in those with a psychotic illness, the possible neurotoxic effects of smoked cannabis on the healthy brain have yet to be fully understood. There appears to be a need to evaluate the existing imaging data on the neuroanatomical effects of cannabis use on non-psychotic populations. Methods:We conducted a meta-analytical review to estimate the putative neurotoxic effect of cannabis in non-psychotic subjects who were using or not using cannabis. We specifically tested the hypothesis that cannabis use can alter grey and white matter in nonpsychotic subjects.Results: Our systematic literature search uncovered 14 studies meeting the inclusion criteria for the metaanalysis. The overall database comprised 362 users and 365 non-users. At the level of the individual studies there is limited and contrasting evidence supporting a cannabis-related alteration on the white and grey matter structures of non-psychotic cannabis users. However, our meta-analysis showed a consistent smaller hippocampus in users as compared to nonusers. Heterogeneity across study designs, image acquisition, small sample sizes and limited availability of regions of interest to be included in the meta-analysis may undermine the core findings of this study. Conclusions:Our results suggest that in the healthy brain, chronic and long-term cannabis exposure may exert significant effects in brain areas enriched with cannabinoid receptors, such as the hippocampus, which could be related to a neurotoxic action.Key words: amygdala, cannabis, hippocampus, neuroimaging, psychosis. O VER THE PAST 2 decades, available imaging techniques have allowed researchers to carefully address the neurobiology of cannabinoids by employing functional or structural methods. One of the first functional magnetic resonance imaging (fMRI) studies carried out on healthy volunteers with less than 25 times cannabis life-time use directly compared delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), 1,2 two major compounds of the plant, and found distinct modulatory effects on regional neural responses to fearful faces.3 Specifically, the authors observed a CBD-induced attenuation of neural responses to intensely fearful faces in the amygdala and cingulate cortex, which was correlated with an electrophysiological response and behavioral evidence for an anxiolytic effect. There

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