The negative and cognitive symptoms of schizophrenia are predictive of quality of life and functional recovery, but there are no approved drug options that target these symptoms directly. TAK-041 (also known as NBI-1065846) is a selective and potent small-molecule agonist of GPR139, an orphan G-protein-coupled receptor, which has been shown to reverse deficits related to negative and cognitive symptoms in animal models. In thi...

Rationale It is hypothesised that modulation of striatal dopaminergic signalling plays a key role in the rewarding effects of opioids. The monetary incentive delay (MID) task is a functional magnetic resonance imaging (fMRI) paradigm used to investigate striatal responses, which may reflect striatal dopamine release, during the anticipation of a financial reward. Objectives We hypothesised that fentanyl would modulate striatal...

Background Major depressive disorder (MDD) is a common and serious psychiatric disorder associated with significant morbidity. There is mounting evidence for the role of oxidative stress in the pathophysiology of depression. Objective To investigate alterations in the brain antioxidant glutathione in depression by undertaking a meta-analysis of proton magnetic resonance spectroscopy (1H-MRS). Methods MEDLINE, EMBASE and Psych...

Rationale Working memory deficits and associated neurofunctional abnormalities are frequently reported in attention-deficit/hyperactivity disorder (ADHD). Methylphenidate and atomoxetine improve working memory performance and increase activation of regions under-functioning in ADHD. Additionally, methylphenidate has been observed to modulate functional networks involved in working memory. No research, however, has examined the...

Rationale LSD is the prototypical psychedelic. Despite a clear central role of the 5HT 2a receptor in its mechanism of action, the contributions of additional receptors for which it shows affinity and agonist activity remain unclear. Objectives We employed receptor-enriched analysis of functional connectivity by targets (REACT) to explore differences in functional connectivity (FC) associated with the distributions of the prim...

Rationale Schizophrenia is associated with impairments in cognitive functioning yet there are no approved drugs to treat these deficits. Objectives Based on animal models, we investigated the potential for roflumilast, a selective inhibitor of phosphodiesterase type 4 (PDE4), to improve cognition, which may act by increasing intracellular cyclic adenosine monophosphate in brain regions underlying cognitive deficits in schizoph...