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Open AccessEffects of diazepam on hippocampal blood flow in people at clinical high risk for psychosis
Elevated hippocampal perfusion has been observed in people at clinical high risk for psychosis (CHR-P). Preclinical evidence suggests that hippocampal hyperactivity is central to the pathophysiology of psychos...
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Open AccessThe relationship between striatal dopamine and anterior cingulate glutamate in first episode psychosis changes with antipsychotic treatment
The neuromodulator dopamine and excitatory neurotransmitter glutamate have both been implicated in the pathogenesis of psychosis, and dopamine antagonists remain the predominant treatment for psychotic disorde...
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Open AccessVariability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis
Glutamatergic dysfunction is implicated in schizophrenia pathoaetiology, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophreni...
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Open AccessAnterior cingulate glutamate metabolites as a predictor of antipsychotic response in first episode psychosis: data from the STRATA collaboration
Elevated brain glutamate has been implicated in non-response to antipsychotic medication in schizophrenia. Biomarkers that can accurately predict antipsychotic non-response from the first episode of psychosis ...
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Open AccessImpaired verbal memory function is related to anterior cingulate glutamate levels in schizophrenia: findings from the STRATA study
Impaired cognition is associated with lower quality of life and poor outcomes in schizophrenia. Brain glutamate may contribute to both clinical outcomes and cognition, but these relationships are not well-unde...
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Open AccessSubcortical volume reduction and cortical thinning 3 months after switching to clozapine in treatment resistant schizophrenia
The neurobiological effects of clozapine are under characterised. We examined the effects clozapine treatment on subcortical volume and cortical thickness and investigated whether macrostructural changes were ...
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Open AccessInteractions between hippocampal activity and striatal dopamine in people at clinical high risk for psychosis: relationship to adverse outcomes
Preclinical models propose that increased hippocampal activity drives subcortical dopaminergic dysfunction and leads to psychosis-like symptoms and behaviors. Here, we used multimodal neuroimaging to examine t...
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Open AccessThe potential of 1H-MRS in CNS drug development
Proton magnetic resonance spectroscopy (1H-MRS) is a cross-species neuroimaging technique that can measure concentrations of several brain metabolites, including glutamate and GABA. This non-invasive method has p...
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Article
Open AccessEvaluation of [ 13 N]ammonia positron emission tomography as a potential method for quantifying glutamine synthetase activity in the human brain
The conversion of synaptic glutamate to glutamine in astrocytes by glutamine synthetase (GS) is critical to maintaining healthy brain activity and may be disrupted in several brain disorders. As the GS catalys...
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Open AccessEffect of single dose N-acetylcysteine administration on resting state functional connectivity in schizophrenia
There is interest in employing N-acetylcysteine (NAC) in the treatment of schizophrenia, but investigations of the functional signatures of its pharmacological action are scarce.
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Open AccessDeterminants of treatment response in first-episode psychosis: an 18F-DOPA PET study
Psychotic illnesses show variable responses to treatment. Determining the neurobiology underlying this is important for precision medicine and the development of better treatments. It has been proposed that do...
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Article
Open AccessRemission from antipsychotic treatment in first episode psychosis related to longitudinal changes in brain glutamate
Neuroimaging studies in schizophrenia have linked elevated glutamate metabolite levels to non-remission following antipsychotic treatment, and also indicate that antipsychotics can reduce glutamate metabolite ...
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Open AccessAltered glutamatergic response and functional connectivity in treatment resistant schizophrenia: the effect of riluzole and therapeutic implications
Anterior cingulate cortex (ACC) glutamatergic abnormalities are reported in treatment-resistant schizophrenia (TRS) and implicated in functional dysconnectivity and psychopathology. Preclinical evidence indica...
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Open AccessEffects of N-acetylcysteine on brain glutamate levels and resting perfusion in schizophrenia
N-Acetylcysteine (NAC) is currently under investigation as an adjunctive treatment for schizophrenia. The therapeutic potential of NAC may involve modulation of brain glutamate function, but its effects on brai.....
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Article
Open AccessAcute induction of anxiety in humans by delta-9-tetrahydrocannabinol related to amygdalar cannabinoid-1 (CB1) receptors
Use of Cannabis, the most widely used illicit drug worldwide, is associated with acute anxiety, and anxiety disorders following regular use. The precise neural and receptor basis of these effects have not been...
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Open AccessIs treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? a systematic review
Schizophrenia is a highly heterogeneous disorder, and around a third of patients are treatment-resistant. The only evidence-based treatment for these patients is clozapine, an atypical antipsychotic with relat...
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Relationship Between Brain Glutamate Levels and Clinical Outcome in Individuals at Ultra High Risk of Psychosis
Alterations in brain glutamate levels may be associated with psychosis risk, but the relationship to clinical outcome in at-risk individuals is unknown. Glutamate concentration was measured in the left thalamu...
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Article
Dopamine Function in Cigarette Smokers: An [18F]-DOPA PET Study
Tobacco addiction is a global public health problem. Addiction to tobacco is thought to involve the effects of nicotine on the dopaminergic system. Only one study has previously investigated dopamine synthesis...
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Anterior Cingulate Glutamate Levels Related to Clinical Status Following Treatment in First-Episode Schizophrenia
Many patients with schizophrenia show a limited symptomatic response to treatment with dopaminergic antipsychotics. This may reflect the additional involvement of non-dopaminergic neurochemical dysfunction in ...
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Modulation of striatal dopamine release by 5-HT2A and 5-HT2C receptor antagonists: [11C]raclopride PET studies in the rat
Antagonism at serotonin 5-HT2A and 5-HT2C receptors modulates cortical and striatal dopamine (DA) release and may underlie some aspects of the clinical efficacy of ‘atypical’ antipsychotic compounds. However, it ...