Muscarinic Mechanisms in Psychosis: a Multimodal Imaging Study

BackgroundThe majority of people with psychosis suffer from cognitive problems. These cognitive problems are among the most disabling features of the illness and have a negative effect on clinical outcome. Research has demonstrated that acetylcholine including muscarinic receptors play an important role in cognitive function. A post-mortem study in chronic patients with schizophrenia demonstrated a decrease of 75% of muscarinic M1 receptors.AimThe aim of this study was to investigate the role of M1 receptors in-vivo in brain and cognitive function in psychosis.MethodsThirty medication free patients with psychosis and 30 healthy controls matched for age, gender and IQ were included for 1) 1x IDEX Spect scan to determine M1 binding potential; 2) 2x fMRI scan using a visual memory task; 3) 2x MRS to determine choline concentrations; 2x CANTAB cognitive battery. Except for SPECT all subjects were tested twice, once with placebo and once with biperiden M1 antagonist.ResultatenPatients demonstrated a significant negative correlation between M1 binding potential and cognitive impairments and negative symptom scores on PANSS. Following biperiden challenge, performance on verbal learning and memory was worse. Hippocampal activity was larger during a visual memory task in patients.ConclusieThese results support a role for the M1 receptor in cognitive function in psychosis.Disclosure of interestThe author has not supplied his/her declaration of competing interest.