PM505. Impaired glucose tolerance, symptoms and cognitive deficits in first-episode drug-naïve patients with schizophrenia

Psilocybin, a hallucinogen that models acute psychosis, alters brain connectivity in ways similar to psychotic disorders. In a double-blind placebo-controlled trial with 20 healthy subjects, standard coherence analysis showed decreased connectivity in theta, alpha, and beta bands, especially in frontotemporal and frontoparietal regions and between frontal hemispheres. Higher frequencies showed less significant changes, often in the opposite direction. Lagged coherence analysis revealed increased connectivity in high gamma (50-100 Hz) but no changes in lower frequencies. These preliminary findings suggest psilocybin induces brain connectivity changes characteristic of psychosis, supporting its use as a model for studying psychotic symptoms.

Study at a glance

Abstract

Psilocybin, a classical tryptamine hallucinogen, serves as a model of acute psychosis in humans.Intoxication with this compound induces significant alterations in perception, thought disturbance and emotional processing, effects that mimic psychotic symptoms.The neurochemical basis of its effects is related to the stimulation of serotonin 5-HT 1A a 5-HT 2A/C receptors.Disconnection is one of the core neurobiological features underlying psychosis with altered connectivity of resting state (default mode (DMN)) and executive (EN) and salient (SN) brain networks.Anterior posterior cingulum (ACC and PCC), cuneus and precuneus, orbitofrontal, dorsolateropreforntal (DLPFC), medial prefrontal cortex (mPFC) and insula are the key structures within these networks.Dysfunctional switching between these networks might underlie psychotic symptoms, e.g.hallucinations as misinterpretation of what are our own thoughts and what is perception of external stimuli.In our present study we have examined brain connectivity during the peak intoxication with psilocybin in a group of 20 healthy subjects in a double blind placebo controlled clinical trial.We have focused our attention on brain connectivity as measured by standard coherence (Neuroguide software) and lagged coherence (eLORETA software).Data pre-processing including artefact removal was performed in BrainVision Analyzer v. 2.1.Standard coherence analysis revealed a decrease of coherence in theta, alpha and beta bands with most significant changes represented by frontotemporal and frontoparietal homolateral and frontal interhemispheral disconnection.In higher frequencies were changes les significant and mostly with opposite direction.On the contrary eLORETA connectivity analysis did not detect any changes in lower frequencies but increased connectivity in high gamma (50-100Hz).Even though these data are preliminary, we have shown that psilocybin induces changes in the brain connectivity which is in line with those characteristic for psychotic patients.