Hippocampal hyperperfusion has been observed in people at Clinical High Risk for Psychosis (CHR), is associated with adverse longitudinal outcomes and represents a potential treatment target for novel pharmacotherapies. Whether cannabidiol (CBD) has ameliorative effects on hippocampal blood flow (rCBF) in CHR patients remains unknown.

Using a double-blind, parallel-group design, 33 CHR patients were randomized to a single oral 600 mg dose of CBD or placebo; 19 healthy controls did not receive any drug. Hippocampal rCBF was measured using Arterial Spin Labeling. We examined differences relating to CHR status (controls v. placebo), effects of CBD in CHR (placebo v. CBD) and linear between-group relationships, such that placebo > CBD > controls or controls > CBD > placebo, using a combination of hypothesis-driven and exploratory wholebrain analyses.

Placebo-treated patients had significantly higher hippocampal rCBF bilaterally (all pFWE<0.01) compared to healthy controls. There were no suprathreshold effects in the CBD v. placebo contrast. However, we found a significant linear relationship in the right hippocampus (pFWE = 0.035) such that rCBF was highest in the placebo group, lowest in controls and intermediate in the CBD group. Exploratory wholebrain results replicated previous findings of hyperperfusion in the hippocampus, striatum and midbrain in CHR patients, and provided novel evidence of increased rCBF in inferior-temporal and lateral-occipital regions in patients under CBD compared to placebo.

These findings suggest that hippocampal blood flow is elevated in the CHR state and may be partially normalized by a single dose of CBD. CBD therefore merits further investigation as a potential novel treatment for this population.

Offspring exposed to prenatal maternal depression (PMD) are vulnerable to depression across their lifespan. The underlying cause(s) for this elevated intergenerational risk is most likely complex. However, depression is underpinned by a dysfunctional frontal-limbic network, associated with core information processing biases (e.g. attending more to sad stimuli). Aberrations in this network might mediate transmission of this vulnerability in infants exposed to PMD. In this study, we aimed to explore the association between foetal exposure to PMD and frontal-limbic network function in infancy, hypothesising that, in response to emotional sounds, infants exposed to PMD would exhibit atypical activity in these regions, relative to those not exposed to PMD.

We employed a novel functional magnetic resonance imaging sequence to compare brain function, whilst listening to emotional sounds, in 78 full-term infants (3–6 months of age) born to mothers with and without a diagnosis of PMD.

After exclusion of 19 datasets due to infants waking up, or moving excessively, we report between-group brain activity differences, between 29 infants exposed to PMD and 29 infants not exposed to PMD, occurring in temporal, striatal, amygdala/parahippocampal and frontal regions (p < 0.005). The offspring exposed to PMD exhibited a relative increase in activation to sad sounds and reduced (or unchanged) activation to happy sounds in frontal-limbic clusters.

Findings of a differential response to positive and negative valanced sounds by 3–6 months of age may have significant implications for our understanding of neural mechanisms that underpin the increased risk for later-life depression in this population.

Cannabis and its main psychoactive ingredient δ-9-tetrahydrocannibidiol (THC) can induce transient psychotic symptoms in healthy individuals and exacerbate them in those with established psychosis. However, not everyone experience these effects, suggesting that certain individuals are particularly susceptible. The neural basis of this sensitivity to the psychotomimetic effects of THC is unclear.

We investigated whether individuals who are sensitive to the psychotomimetic effects of THC (TP) under experimental conditions would show differential hippocampal activation compared with those who are not (NP). We studied 36 healthy males under identical conditions under the influence of placebo or THC (10 mg) given orally, on two separate occasions, in a pseudo-randomized, double-blind, repeated measures, within-subject, cross-over design, using psychopathological assessments and functional MRI while they performed a verbal learning task. They were classified into those who experienced transient psychotic symptoms (TP; n = 14) following THC administration and those who did not (NP; n = 22).

Under placebo conditions, there was significantly greater engagement of the left hippocampus (p < 0.001) in the TP group compared with the NP group during verbal encoding, which survived leave-one-out analysis. The level of hippocampal activation was directly correlated (Spearman's ρ = 0.44, p = 0.008) with the severity of transient psychotic symptoms induced by THC. This difference was not present when we compared two subgroups from the same sample that were defined by sensitivity to anxiogenic effects of THC.

These results suggest that altered hippocampal activation during verbal encoding may serve as a marker of sensitivity to the acute psychotomimetic effects of THC.

The cerebral mechanisms of traits associated with depersonalization-derealization disorder (DPRD) remain poorly understood.

Happy and sad emotion expressions were presented to DPRD and non-referred control (NC) subjects in an implicit event-related functional magnetic resonance imaging (fMRI) design, and correlated with self report scales reflecting typical co-morbidities of DPRD: depression, dissociation, anxiety, somatization.

Significant differences between the slopes of the two groups were observed for somatization in the right temporal operculum (happy) and ventral striatum, bilaterally (sad). Discriminative regions for symptoms of depression were the right pulvinar (happy) and left amygdala (sad). For dissociation, discriminative regions were the left mesial inferior temporal gyrus (happy) and left supramarginal gyrus (sad). For state anxiety, discriminative regions were the left inferior frontal gyrus (happy) and parahippocampal gyrus (sad). For trait anxiety, discriminative regions were the right caudate head (happy) and left superior temporal gyrus (sad).

The ascertained brain regions are in line with previous findings for the respective traits. The findings suggest separate brain systems for each trait.

Our results do not justify any bias for a certain nosological category in DPRD.

Autism-spectrum disorder is increasingly recognised, with recent studies estimating that 1% of children in South London are affected. However, the biology of comorbid mental health problems in people with autism-spectrum disorder is poorly understood.

To investigate the brain anatomy of people with autism-spectrum disorder with and without psychosis.

We used in vivo magnetic resonance imaging and compared 30 adults with autism-spectrum disorder (14 with a history of psychosis) and 16 healthy controls.

Compared with controls both autism-spectrum disorder groups had significantly less grey matter bilaterally in the temporal lobes and the cerebellum. In contrast, they had increased grey matter in striatal regions. However, those with psychosis also had a significant reduction in grey matter content of frontal and occipital regions. Contrary to our expectation, within autism-spectrum disorder, comparisons revealed that psychosis was associated with a reduction in grey matter of the right insular cortex and bilaterally in the cerebellum extending into the fusiform gyrus and the lingual gyrus.

The presence of neurodevelopmental abnormalities normally associated with autism-spectrum disorder might represent an alternative ‘entry-point’ into a final common pathway of psychosis.

Diffusion tensor magnetic resonance imaging studies in schizophrenia to date have been largely inconsistent. This may reflect variation in methodology, and the use of small samples with differing illness duration and medication exposure.

To determine the extent and location of white matter microstructural changes in schizophrenia, using optimised diffusion tensor imaging in a large patient sample, and to consider the effects of illness duration and medication exposure.

Scans from 76 patients with schizophrenia and 76 matched controls were used to compare fractional anisotropy, a measure of white matter microstructural integrity, between the groups.

We found widespread clusters of reduced fractional anisotropy in patients, affecting most major white matter tracts. These reductions did not correlate with illness duration, and there was no difference between age-matched chronically and briefly medicated patients.

The finding of widespread fractional anisotropy reductions in our larger sample of patients with schizophrenia may explain some of the inconsistent findings of previous, smaller studies.

People with prodromal symptoms have a very high risk of developing psychosis.

To use functional magnetic resonance imaging to examine the neurocognitive basis of this vulnerability.

Cross-sectional comparison of regional activation in individuals with an ‘at-risk mental state’ (at-risk group: n=17), patients with first-episode schizophreniform psychosis (psychosis group: n=10) and healthy volunteers (controls: n=15) during an overt verbal fluency task and an N-back working memory task.

A similar pattern of between-group differences in activation was evident across both tasks. Activation in the at-risk group was intermediate relative to that in controls and the psychosis group in the inferior frontal and anterior cingulate cortex during the verbal fluency task and in the inferior frontal, dorsolateral prefrontal and parietal cortex during the N-back task.

The at-risk mental state is associated with abnormalities of regional brain function that are qualitatively similar to, but less severe than, those in patients who have recently presented with psychosis.

Depersonalisation disorder is characterised by emotion suppression, but the cerebral mechanisms of this symptom are not yet fully understood.

To compare brain activation and autonomic responses of individuals with the disorder and healthy controls.

Happy and sad emotion expressions in increasing intensities (neutral to intense) were presented in an implicit event-related functional magnetic resonance imaging (fMRI) design with simultaneous measurement of autonomic responses.

Participants with depersonalisation disorder showed fMRI signal decreases, whereas the control group showed signal increases in response to emotion intensity increases in both happy and sad expressions. The analysis of evoked haemodynamic responses from regions exhibiting functional connectivity between central and autonomic nervous systems indicated that in depersonalisation disorder initial modulations of haemodynamic response occurred significantly earlier (2s post-stimulus) than in the control group (4–6s post-stimulus).

The results suggest that fMRI signal decreases are possible correlates of emotion suppression in depersonalisation disorder.

The neurocognitive basis of auditory verbal hallucinations is unclear.

To investigate whether people with a history of such hallucinations would misattribute their own speech as external and show differential activation in brain areas implicated in hallucinations compared with people without such hallucinations.

Participants underwent functional magnetic resonance imaging (fMRI) while listening to pre-recorded words. The source (self/non-self) and acoustic quality (undistorted/distorted) were varied across trials. Participants indicated whether the speech they heard was their own or that of another person. Twenty people with schizophrenia (auditory verbal hallucinations n=10, no hallucinations n=10) and healthy controls (n=11) were tested.

The hallucinator group made more external misattributions and showed altered activation in the superior temporal gyrus and anterior cingulate compared with both other groups.

The misidentification of self-generated speech in patients with auditory verbal hallucinations is associated with functional abnormalities in the anterior cingulate and left temporal cortex. This may be related to impairment in the explicit evaluation of ambiguous auditory verbal stimuli.

It has been suggested that people with psychopathic disorders lack empathy because they have deficits in processing distress cues (e.g. fearful facial expressions).

To investigate brain function when individuals with psychopathy and a control group process facial emotion.

Using event-related functional magnetic resonance imaging we compared six people scoring ⩾25 on the Hare Psychopathy Checklist–Revised and nine non-psychopathic healthy volunteers during an implicit emotion processing task using fearful, happy and neutral faces.

The psychopathy group showed significantly less activation than the control group in fusiform and extrastriate cortices when processing both facial emotions. However, emotion type affected response pattern. Both groups increased fusiform and extrastriate cortex activation when processing happy faces compared with neutral faces, but this increase was significantly smaller in the psychopathy group. In contrast, when processing fearful faces compared with neutral faces, the control group showed increased activation but the psychopathy group decreased activation in the fusiform gyrus.

People with psychopathy have biological differences from controls when processing facial emotion, and the pattern of response differs according to emotion type.

The production of grammatically complex sentences is impaired in schizophrenia. It has been suggested that impaired syntax processing reflects a risk for the disorder.

To examine the neural correlates of syntax production in people with schizophrenia using functional magnetic resonance imaging (fMRI).

Six patients with schizophrenia and six healthy volunteers spoke about seven Rorschach inkblots for 3 min each while correlates of brain activation were measured with fMRI. Participants produced varying amounts of syntactically simple and complex sentences during each 3 min run. The number of simple and complex sentences was correlated separately with the BOLD contrast.

In the comparison between the control group and the patient group, the number of complex sentences produced was correlated with activation in the posterior portion of the right middle temporal (Brodmann area 21) and left superior frontal (BA 10) gyri in the control group but not in the patients.

The absence of activation in the right posterior temporal and left superior frontal cortex in patients with schizophrenia might contribute to the articulation of grammatically more simple speech in people with this disorder.

The neurocognitive basis of auditory hallucinations is unclear, but there is increasing evidence implicating abnormalities in processing inner speech. Previous studies have shown that people with schizophrenia who were prone to auditory hallucinations demonstrated attenuated activation of brain areas during the monitoring of inner speech.

To investigate whether the same pattern of functional abnormalities would be evident as the rate of inner speech production was varied.

Eight people with schizophrenia who had a history of prominent auditory hallucinations and eight control participants were studied using functional magnetic resonance imaging while the rate of inner speech generation was varied experimentally.

When the rate of inner speech generation was increased, the participants with schizophrenia showed a relatively attenuated response in the right temporal, parietal, parahippocampal and cerebellar cortex.

In people with schizophrenia who are prone to auditory hallucinations, increasing the demands on the processing of inner speech is associated with attenuated engagement of the brain areas implicated in verbal self-monitoring.

The results of one randomised control trial testing a psychological rehabilitation programme aimed at information processing strategies showed improvements in cognition post-treatment.

To determine whether there are concomitant brain activation changes as a result of engaging in cognitive remediation therapy (CRT).

Three groups (patients receiving control therapyor CRT and a healthy control group) were investigated in a repeated measures design using the two-back test. Functional magnetic resonance imaging (fMRI) data and a broad assessment of executive functioning were completed at baseline and post-treatment. Brain activation changes were identified after accounting for possible task-correlated motion artefact.

fMRI analyses indicate that the control group showed decreased activation butthetwo patient groups showed an increase in activation over time. The patient group that received successful CRT had significantly increased brain activation in regions associated with working memory particularly the frontocortical areas.

This isthefirsttimethat brain activation changes in a seriously disabled group of patients with schizophrenia can be associated clearly with psychological rather than pharmacological therapy.