Prevalence of serum N-methyl-D-aspartate receptor autoantibodies in refractory psychosis.

N-methyl-d-aspartate receptor (NMDA-R) autoantibodies have been reported in people with acute psychosis. We hypothesised that their presence may be implicated in the aetiology of treatment-refractory psychosis. We sought to ascertain the point prevalence of NMDA-R antibody positivity in patients referred to services for treatment-refractory psychosis.

Functional outcome in people at high risk for psychosis predicted by thalamic glutamate levels and prefronto-striatal activation.

Little is known about the neurobiological factors that determine functional outcome in people at high risk for psychosis. We use multimodal neuroimaging to investigate whether cortical responses during a cognitive task and thalamic glutamate levels were associated with subsequent functional outcome. Sixty subjects participated: 27 healthy controls (CTRL) and 33 at ultrahigh risk (UHR) for psychosis.

Alterations in cortical and extrastriatal subcortical dopamine function in schizophrenia: systematic review and meta-analysis of imaging studies.

Background: The hypothesis that cortical dopaminergic alterations underlie aspects of schizophrenia has been highly influential.

Aims: To bring together and evaluate the imaging evidence for dopaminergic alterations in cortical and other extrastriatal regions in schizophrenia.

Method: Electronic databases were searched for in vivo molecular studies of extrastriatal dopaminergic function in schizophrenia.

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 thalamus and anterior cingulate cortex (ACC) using 3-Tesla proton magnetic resonance spectroscopy in 75 participants at ultra high risk (UHR) of psychosis and 56 healthy controls. The severity of attenuated positive symptoms and overall functioning were assessed.

Test-retest reproducibility of cannabinoid-receptor type 1 availability quantified with the PET ligand [¹¹C]MePPEP.

Background: Endocannabinoids are involved in normal cognition, and dysfunction in cannabinoid-receptor-mediated neurotransmission has been suggested in a variety of neurological and psychiatric pathologies. The type 1 cannabinoid receptor (CB1) is widely expressed in the human central nervous system. The objective of this study was to quantify the test-retest reproducibility of measures of the PET ligand [(11)C]MePPEP in order to assess the stability of CB1-receptor quantification in humans in vivo.

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 capacity in cigarette smokers.

The link between dopamine function and apathy in cannabis users: an [18F]-DOPA PET imaging study.

Rationale: Cannabis is the most widely used illicit drug in the world, and regular use has been associated with reduced motivation, i.e. apathy.

The predictive power of brain mRNA mappings for in vivo protein density: a positron emission tomography correlation study.

Substantial efforts are being spent on postmortem mRNA transcription mapping on the assumption that in vivo protein distribution can be predicted from such data. We tested this assumption by comparing mRNA transcription maps from the Allen Human Brain Atlas with reference protein concentration maps acquired with positron emission tomography (PET) in two representative systems of neurotransmission (opioid and serotoninergic). We found a tight correlation between mRNA expression and specific binding with 5-HT1A receptors measured with PET, but for opioid receptors, the correlation was weak.

The relationship between reward and punishment processing and the 5-HT1A receptor as shown by PET.

Rationale: The serotonin (5-HT) system has been reported to be involved in decision-making. A key component of this neurotransmitter system is the 5-HT1A receptor, and research is beginning to show how this receptor can influence decision-making. However, this relationship has rarely been studied in humans.

Dopaminergic basis of salience dysregulation in psychosis.

Disrupted salience processing is proposed as central in linking dysregulated dopamine function with psychotic symptoms. Several strands of evidence are now converging in support of this model. Animal studies show that midbrain dopamine neurons are activated by unexpected salient events.

Schizophrenia: an integrated sociodevelopmental-cognitive model.

Schizophrenia remains a major burden on patients and society. The dopamine hypothesis attempts to explain the pathogenic mechanisms of the disorder, and the neurodevelopmental hypothesis the origins. In the past 10 years an alternative, the cognitive model, has gained popularity.

Glutamate, N-acetyl aspartate and psychotic symptoms in chronic ketamine users.

Rationale: Ketamine, a non-competitive NMDA receptor antagonist, induces acute effects resembling the positive, negative and cognitive symptoms of schizophrenia. Chronic use has been suggested to lead to persistent schizophrenia-like neurobiological changes.

Objectives: This study aims to test the hypothesis that chronic ketamine users have changes in brain neurochemistry and increased subthreshold psychotic symptoms compared to matched poly-drug users.

Molecular imaging as a guide for the treatment of central nervous system disorders.

Molecular imaging techniques have a number of advantages for research into the pathophysiology and treatment of central nervous system (CNS) disorders. Firstly, they provide a noninvasive means of characterizing physiological processes in the living brain, enabling molecular alterations to be linked to clinical changes. Secondly, the pathophysiological target in a given CNS disorder can be measured in animal models and in experimental human models in the same way, which enables translational research.

Midbrain dopamine function in schizophrenia and depression: a post-mortem and positron emission tomographic imaging study.

Elevated in vivo markers of presynaptic striatal dopamine activity have been a consistent finding in schizophrenia, and include a large effect size elevation in dopamine synthesis capacity. However, it is not known if the dopaminergic dysfunction is limited to the striatal terminals of dopamine neurons, or is also evident in the dopamine neuron cell bodies, which mostly originate in the substantia nigra. The aim of our studies was therefore to determine whether dopamine synthesis capacity is altered in the substantia nigra of people with schizophrenia, and how this relates to symptoms.

Dopaminergic function in cannabis users and its relationship to cannabis-induced psychotic symptoms.

Background: Cannabis is the most widely used illicit drug globally, and users are at increased risk of mental illnesses including psychotic disorders such as schizophrenia. Substance dependence and schizophrenia are both associated with dopaminergic dysfunction. It has been proposed, although never directly tested, that the link between cannabis use and schizophrenia is mediated by altered dopaminergic function.

Partial volume correction using structural-functional synergistic resolution recovery: comparison with geometric transfer matrix method.

We validated the use of a novel image-based method for partial volume correction (PVC), structural-functional synergistic resolution recovery (SFS-RR) for the accurate quantification of dopamine synthesis capacity measured using [(18)F]DOPA positron emission tomography. The bias and reliability of SFS-RR were compared with the geometric transfer matrix (GTM) method. Both methodologies were applied to the parametric maps of [(18)F]DOPA utilization rates (ki(cer)).

Presynaptic striatal dopamine dysfunction in people at ultra-high risk for psychosis: findings in a second cohort.

Background: Using positron emission tomography (PET), we previously observed increases in 3,4-dihydroxy-6-[(18)F]fluoro-L-phenylalanine ((18)F-DOPA) uptake in the striatum of subjects at ultra-high risk (UHR) for psychosis, indicating elevated presynaptic dopamine synthesis capacity. The purpose of this study was to test if this finding would be replicated in a second UHR cohort.

Methods: (18)F-DOPA PET was used to estimate dopamine synthesis capacity in the striatum of an entirely new cohort of 26 individuals at UHR for psychosis (14 males, mean±SD age = 22.

The relationship between antipsychotic D2 occupancy and change in frontal metabolism and working memory : A dual [(11)C]raclopride and [(18) F]FDG imaging study with aripiprazole.

Rationale: The effects of aripiprazole on cognitive function are obscure, possibly due to the difficulty in disentangling the specific effects on cognitive function from effects secondary to the improvement of other schizophrenic symptoms. This prompts the necessity of using an intermediate biomarker relating the drug effect on the brain to change in cognitive function.

Objectives: To explore the effect of aripiprazole on cognitive function, we measured changes in frontal metabolism as an intermediate biomarker and sought to determine its relationship with D2 receptor occupancy and changes in working memory.

Neural and behavioral correlates of aberrant salience in individuals at risk for psychosis.

The "aberrant salience" model proposes that psychotic symptoms first emerge when chaotic brain dopamine transmission leads to the attribution of significance to stimuli that would normally be considered irrelevant. This is thought to occur during the prodromal phase of psychotic disorders, but this prediction has not been tested previously. In the present study, we tested this model in 18 healthy volunteers and 18 unmedicated individuals at ultra-high risk of psychosis.

Nature or nurture? Determining the heritability of human striatal dopamine function: an [18F]-DOPA PET study.

Striatal dopamine function is important for normal personality, cognitive processes and behavior, and abnormalities are linked to a number of neuropsychiatric disorders. However, no studies have examined the relative influence of genetic inheritance and environmental factors in determining striatal dopamine function. Using [18F]-DOPA positron emission tomography (PET), we sought to determine the heritability of presynaptic striatal dopamine function by comparing variability in uptake values in same sex monozygotic (MZ) twins to dizygotic (DZ) twins.