scholarly journals A single dose of cannabidiol modulates medial temporal and striatal function during fear processing in people at clinical high risk for psychosis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Cathy Davies ◽  
Robin Wilson ◽  
Elizabeth Appiah-Kusi ◽  
Grace Blest-Hopley ◽  
Michael Brammer ◽  
...  
Keyword(s):  
High Risk ◽  
Medial Temporal Lobe ◽  
Region Of Interest ◽  
Emotional Dysregulation ◽  
Parahippocampal Gyrus ◽  
Clinical High Risk ◽  
Double Blind ◽  
Parallel Group Design ◽  
Fearful Face ◽  
Striatal Function

Abstract Emotional dysregulation and anxiety are common in people at clinical high risk for psychosis (CHR) and are associated with altered neural responses to emotional stimuli in the striatum and medial temporal lobe. Using a randomised, double-blind, parallel-group design, 33 CHR patients were randomised to a single oral dose of CBD (600 mg) or placebo. Healthy controls (n = 19) were studied under identical conditions but did not receive any drug. Participants were scanned with functional magnetic resonance imaging (fMRI) during a fearful face-processing paradigm. Activation related to the CHR state and to the effects of CBD was examined using a region-of-interest approach. During fear processing, CHR participants receiving placebo (n = 15) showed greater activation than controls (n = 19) in the parahippocampal gyrus but less activation in the striatum. Within these regions, activation in the CHR group that received CBD (n = 15) was intermediate between that of the CHR placebo and control groups. These findings suggest that in CHR patients, CBD modulates brain function in regions implicated in psychosis risk and emotion processing. These findings are similar to those previously evident using a memory paradigm, suggesting that the effects of CBD on medial temporal and striatal function may be task independent.

scholarly journals T145. EFFECTS OF CANNABIDIOL ON EMOTION PROCESSING IN PSYCHOSIS RISK: AN FMRI INVESTIGATION

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S286-S286
Author(s):  
Cathy Davies ◽  
Robin Wilson ◽  
Elizabeth Appiah-Kusi ◽  
Michael Brammer ◽  
Jesus Perez ◽  
...  
Keyword(s):  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Emotion Processing ◽  
Region Of Interest ◽  
Blood Oxygen Level Dependent ◽  
Brain Regions ◽  
Emotional Dysregulation ◽  
Blood Oxygen Level ◽  
Double Blind ◽  
Parallel Group Design

Abstract Background There is currently a lack of effective pharmacological treatment for people at Clinical High Risk of Psychosis (CHR), who present with emotional dysregulation and high levels of anxiety. These individuals also show altered neural responses to emotional stimuli in key brain regions implicated in psychosis onset, including the striatum and medial temporal lobe. Cannabidiol (CBD), a non-intoxicating constituent of the cannabis plant, is thought to have antipsychotic and anxiolytic properties. The effects of CBD on brain function in CHR individuals during emotion processing has not been tested before. Methods In a randomised, double-blind, placebo-controlled, parallel-group design, 33 CHR individuals received a single oral 600mg dose of CBD or matched placebo, while 19 healthy controls did not receive any drug. Participants were studied using an emotion processing functional magnetic resonance imaging (fMRI) paradigm. Using a region-of-interest approach, we examined the differences in brain activation related to the CHR state and the effects of CBD, indexed using the blood oxygen level-dependent haemodynamic response fMRI signal. Results Compared to controls (n=19), CHR participants receiving placebo (n=15) showed significantly greater activation in the medial temporal lobe and less activation in the striatum during emotion processing. Within these same regions, activation in the CBD group (n=15) was (significantly) intermediate between that of the placebo and control groups. That is, CBD attenuated medial temporal and enhanced striatal activation in CHR participants. Discussion These findings suggest that CBD modulates the function of brain regions strongly implicated in psychosis onset and altered emotion processing. Further research is required to examine whether these neurofunctional effects translate into clinical efficacy after a period of treatment.

scholarly journals Altered relationship between cortisol response to social stress and mediotemporal function during fear processing in people at clinical high risk for psychosis: a preliminary report

2021 ◽  
Author(s):  
Cathy Davies ◽  
Elizabeth Appiah-Kusi ◽  
Robin Wilson ◽  
Grace Blest-Hopley ◽  
Matthijs G. Bossong ◽  
...  
Keyword(s):  
High Risk ◽  
Social Stress ◽  
Stress Test ◽  
Negative Relationship ◽  
Trier Social Stress Test ◽  
Cortisol Response ◽  
Healthy Controls ◽  
Clinical High Risk ◽  
Fearful Face ◽  
The Relationship

AbstractEvidence suggests that people at Clinical High Risk for Psychosis (CHR) have a blunted cortisol response to stress and altered mediotemporal activation during fear processing, which may be neuroendocrine–neuronal signatures of maladaptive threat responses. However, whether these facets are associated with each other and how this relationship is affected by cannabidiol treatment is unknown. We examined the relationship between cortisol response to social stress and mediotemporal function during fear processing in healthy people and in CHR patients. In exploratory analyses, we investigated whether treatment with cannabidiol in CHR individuals could normalise any putative alterations in cortisol-mediotemporal coupling. 33 CHR patients were randomised to 600 mg cannabidiol or placebo treatment. Healthy controls (n = 19) did not receive any drug. Mediotemporal function was assessed using a fearful face-processing functional magnetic resonance imaging paradigm. Serum cortisol and anxiety were measured immediately following the Trier Social Stress Test. The relationship between cortisol and mediotemporal blood-oxygen-level-dependent haemodynamic response was investigated using linear regression. In healthy controls, there was a significant negative relationship between cortisol and parahippocampal activation (p = 0.023), such that the higher the cortisol levels induced by social stress, the lower the parahippocampal activation (greater deactivation) during fear processing. This relationship differed significantly between the control and placebo groups (p = 0.033), but not between the placebo and cannabidiol groups (p = 0.67). Our preliminary findings suggest that the parahippocampal response to fear processing may be associated with the neuroendocrine (cortisol) response to experimentally induced social stress, and that this relationship may be altered in patients at clinical high risk for psychosis.

scholarly journals M163. GLUTAMATE METABOLITES ARE ASSOCIATED WITH ALTERED HIPPOCAMPAL ACTIVATION BUT NOT HIPPOCAMPAL-STRIATAL CONNECTIVITY IN SUBJECTS WITH A CLINICAL HIGH RISK FOR PSYCHOSIS

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S198-S198
Author(s):  
Emily Hird ◽  
Paul Allen ◽  
Natasza Orlov ◽  
Gemma Modinos ◽  
Matthijs Bossong ◽  
...  
Keyword(s):  
High Risk ◽  
Magnetic Resonance ◽  
Negative Relationship ◽  
Region Of Interest ◽  
First Episode ◽  
Resonance Spectroscopy ◽  
Clinical High Risk ◽  
Hippocampal Activity ◽  
Potential Biomarker ◽  
Psychophysiological Interaction

Abstract Background We recently used Magnetic Resonance Spectroscopy (MRS) to show that transition to psychosis is associated with higher baseline hippocampal glutamate levels (1). We also used functional Magnetic Resonance Imaging (fMRI) in the same CHR subjects and showed that compared to healthy controls (HC), subjects at a clinical high-risk of psychosis (CHR) show decreased hippocampal activation to novel stimuli and increased novelty-modulated hippocampal-striatal connectivity (2). The aim of the present analysis was to explore the relationship between hippocampal glutamatergic metabolites, hippocampal activity, and hippocampal-striatal connectivity in these CHR subjects. Methods 75 CHR and 31 HC subjects participated in a novelty salience task whilst undergoing fMRI to measure hippocampal and striatal activation, and MRS to measure hippocampal glutamatergic metabolite levels. First, we tested for a three-way interaction between the hippocampal response to novel versus neutral stimuli, hippocampal glutamatergic metabolite levels, and group, using a Region of Interest approach in the bilateral hippocampus. Second, we carried out a Psychophysiological Interaction (PPI) analysis on the extracted hippocampal coordinates from the first analysis and tested for an interaction with hippocampal glutamatergic metabolite levels and group. Results The CHR group had higher clinical scores and lower GAF scores at baseline than HC. CHR subjects were younger, more were taking antipsychotic medication and they smoked more cigarettes than HC. At follow-up, 12 CHR subjects (16%) developed a first episode of psychosis (CHR-TR) and 63 (86%) did not (CHR-NTR). The CHR-TR subjects smoked fewer cigarettes than the CHR-NTR subjects. The first analysis revealed a significant interaction between group, fMRI activity and MRS Glx (a combined measure of glutamate and glutamine) in the right hippocampus (pFWE= 0.03; x y z = 28 -32 -4; t=3.61, z=3.49). This was driven by the CHR-TR group: contrast estimates indicated a positive relationship between fMRI activity and MRS Glx in the HC and CHR-NTR subjects, but a negative relationship between fMRI activity and glutamate in the CHR-TR subjects. The second analysis revealed that CHR-TR individuals exhibited greater connectivity between the hippocampus and the striatum (pFWE= 0.03; x y z = -6 6 -8; t=3.35, z=3.17), but that this was not associated with Glx. Discussion Whilst hippocampal glutamate metabolite levels are associated with altered hippocampal activity in CHR individuals - especially in those who later transition to psychosis - hippocampal glutamate metabolite levels do not modulate connectivity between the hippocampus and striatum. These findings are broadly consistent with previous work indicating a role for glutamate in hippocampal dysfunction and risk for psychosis, and indicate a potential biomarker for psychosis risk. References

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