Working memory processes and the histamine-3 receptor in schizophrenia: a [C]MK-8278 PET-fMRI study.

Rationale: Working memory impairment is a prominent feature of schizophrenia which predicts clinical and functional outcomes. Preclinical data suggest histamine-3 receptor (H3R) expression in cortical pyramidal neurons may have a role in working memory, and post-mortem data has found disruptions of H3R expression in schizophrenia.

Objectives: We examined the role of H3R in vivo to elucidate its role on working memory impairment in schizophrenia.

Mitochondrial complex I density is associated with IQ and cognition in cognitively healthy adults: an in vivo [F]BCPP-EF PET study.

Background: Mitochondrial function plays a key role in regulating neurotransmission and may contribute to general intelligence. Mitochondrial complex I (MC-I) is the largest enzyme of the respiratory chain. Recently, it has become possible to measure MC-I distribution in vivo, using a novel positron emission tomography tracer [F]BCPP-EF, thus, we set out to investigate the association between MC-I distribution and measures of cognitive function in the living healthy brain.

Histamine-3 Receptor Availability and Glutamate Levels in the Brain: A PET-1H-MRS Study of Patients With Schizophrenia and Healthy Controls.

Background: The histamine-3 receptor (H3R) may have a role in cognitive processes through its action as a presynaptic heteroreceptor inhibiting the release of glutamate in the brain. To explore this, we examined anterior cingulate cortex (ACC) and striatum H3R availability in patients with schizophrenia and characterized their relationships with glutamate levels in corresponding brain regions.

Methods: We employed a cross-sectional study, recruiting 12 patients with schizophrenia and 12 healthy volunteers.

Synaptic Terminal Density Early in the Course of Schizophrenia: An In Vivo UCB-J Positron Emission Tomographic Imaging Study of SV2A.

Background: The synaptic hypothesis is an influential theory of the pathoetiology of schizophrenia (SCZ), which is supported by the finding that there is lower uptake of the synaptic terminal density marker [C]UCB-J in patients with chronic SCZ than in control participants. However, it is unclear whether these differences are present early in the illness. To address this, we investigated [C]UCB-J volume of distribution (V) in antipsychotic-naïve/free patients with SCZ who were recruited from first-episode services compared with healthy volunteers.

The histamine system and cognitive function: An in vivo H3 receptor PET imaging study in healthy volunteers and patients with schizophrenia.

Background: The histamine-3 receptor (H3R) is an auto- and heteroreceptor that inhibits the release of histamine and other neurotransmitters. Post-mortem evidence has found altered H3R expression in patients with psychotic disorders, which may underlie cognitive impairment associated with schizophrenia (CIAS).

Aims: We used positron emission tomography (PET) imaging to compare brain uptake of an H3R selective tracer between patients with schizophrenia and matched controls (healthy individuals).

The synaptic hypothesis of schizophrenia version III: a master mechanism.

The synaptic hypothesis of schizophrenia has been highly influential. However, new approaches mean there has been a step-change in the evidence available, and some tenets of earlier versions are not supported by recent findings. Here, we review normal synaptic development and evidence from structural and functional imaging and post-mortem studies that this is abnormal in people at risk and with schizophrenia.

Neurofunctional correlates of glutamate and GABA imbalance in psychosis: A systematic review.

Glutamatergic and GABAergic dysfunction are implicated in the pathophysiology of schizophrenia. Previous work has shown relationships between glutamate, GABA, and brain activity in healthy volunteers. We conducted a systematic review to evaluate whether these relationships are disrupted in psychosis.

The relationship between synaptic density marker SV2A, glutamate and N-acetyl aspartate levels in healthy volunteers and schizophrenia: a multimodal PET and magnetic resonance spectroscopy brain imaging study.

Glutamatergic excitotoxicity is hypothesised to underlie synaptic loss in schizophrenia pathogenesis, but it is unknown whether synaptic markers are related to glutamatergic function in vivo. Additionally, it has been proposed that N-acetyl aspartate (NAA) levels reflect neuronal integrity. Here, we investigated whether synaptic vesicle glycoprotein 2 A (SV2A) levels are related to glutamatergic markers and NAA in healthy volunteers (HV) and schizophrenia patients (SCZ).

The Effects of Acute Δ-Tetrahydrocannabinol on Striatal Glutamatergic Function: A Proton Magnetic Resonance Spectroscopy Study.

Background: Cannabis and its main psychoactive component, Δ-tetrahydrocannabinol (THC), can elicit transient psychotic symptoms. A key candidate biological mechanism of how THC induces psychotic symptoms is the modulation of glutamate in the brain. We sought to investigate the effects of acute THC administration on striatal glutamate levels and its relationship to the induction of psychotic symptoms.

The clinical significance of duration of untreated psychosis: an umbrella review and random-effects meta-analysis.

The idea that a longer duration of untreated psychosis (DUP) leads to poorer outcomes has contributed to extensive changes in mental health ser-vices worldwide and has attracted considerable research interest over the past 30 years. However, the strength of the evidence underlying this notion is unclear. To address this issue, we conducted an umbrella review of available meta-analyses and performed a random-effects meta-analysis of primary studies.

Proton Magnetic Resonance Spectroscopy of N-acetyl Aspartate in Chronic Schizophrenia, First Episode of Psychosis and High-Risk of Psychosis: A Systematic Review and Meta-Analysis.

N-acetyl-aspartate (NAA) is a readily measured marker of neuronal metabolism. Previous analyses in schizophrenia have shown NAA levels are low in frontal, temporal and thalamic regions, but may be underpowered to detect effects in other regions, in high-risk states and in first episode psychosis. We searched for magnetic resonance spectroscopy studies comparing NAA in chronic schizophrenia, first episode psychosis and high risk of psychosis to controls.

Synaptic density marker SV2A is reduced in schizophrenia patients and unaffected by antipsychotics in rats.

Synaptic dysfunction is hypothesised to play a key role in schizophrenia pathogenesis, but this has not been tested directly in vivo.  Here, we investigated synaptic vesicle glycoprotein 2A (SV2A) levels and their relationship to symptoms and structural brain measures using [C]UCB-J positron emission tomography in 18 patients with schizophrenia and 18 controls. We found significant group and group-by-region interaction effects on volume of distribution (V).