Abstract
The associative striatum, an established substrate in psychosis, receives widespread glutamatergic projections. We sought to see if glutamatergic indices are altered between early psychosis patients with and without a history of cannabis use and characterise the relationship to grey matter. 92 participants were scanned: Early Psychosis with a history of cannabis use (EPC = 29); Early Psychosis with minimal cannabis use (EPMC = 25); Controls with a history of cannabis use (HCC = 16) and Controls with minimal use (HCMC = 22). Whole brain T1 weighted MR images and localised proton MR spectra were acquired from head of caudate, anterior cingulate and hippocampus. We examined relationships in regions with known high cannabinoid 1 receptor (CB1R) expression (grey matter, cortex, hippocampus, amygdala) and low expression (white matter, ventricles, brainstem) to caudate Glutamine+Glutamate (Glx). Patients were well matched in symptoms, function and medication. There was no significant group difference in Glx in any region. In EPC grey matter volume explained 31.9% of the variance of caudate Glx (p = 0.003) and amygdala volume explained 36.9% (p = 0.001) of caudate Glx. There was no significant relationship in EPMC. The EPC vs EPMC interaction was significant (p = 0.042). There was no such relationship in control regions. These results are the first to demonstrate association of grey matter volume and striatal glutamate in the EPC group. This may suggest a history of cannabis use leads to a conformational change in distal CB1 rich grey matter regions to influence striatal glutamatergic levels or that such connectivity predisposes to heavy cannabis use.
Highlights
A third of patients presenting with First Episode Psychosis use cannabis regularly[1]
In further exploratory analysis we investigated if Glx levels in any region were correlated with clinical measures (PANSS, Global Assessment of Functioning (GAF), and Chlorpromazine equivalents) in both patient groups
In three brain regions not previously studied we measured glutamatergic indices using an established biomarker (Glx) in psychosis[21]. This is the largest study to date to examine glutamatergic indices in early psychosis patients with and without a history of cannabis use
Summary
A third of patients presenting with First Episode Psychosis use cannabis regularly[1]. This dual diagnosis cohort has a worse clinical outcome for days in hospital, relapses and long term health[2,3,4,5] not accounted for by potential confounders such as alcohol, other drug use, adherence to treatment and severity of illness at onset[6], differences in genetic make-up or premorbid environment[7]. Cessation of cannabis use in patients with psychosis improves outcome[3], but is difficult to achieve[8]. There are no current effective pharmacological or psychological interventions that can mitigate harm from cannabis use in people with psychosis[10,11]. There is a pressing need to understand the neurobiological alterations in the dual diagnosis group, which may inform the development of more effective treatments
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