PM504. Theory of Mind in Clinical high risk as trait marker of conversion to psychosis: review

Psilocybin, a hallucinogen that mimics psychotic symptoms, alters brain connectivity in ways similar to psychosis. In a double-blind placebo-controlled trial with 20 healthy subjects, standard coherence analysis showed decreased connectivity in theta, alpha, and beta brainwave bands, particularly in frontotemporal and frontoparietal regions, along with frontal interhemispheric disconnection. Changes in higher frequencies were less significant and often opposite. In contrast, eLORETA connectivity analysis found no changes in lower frequencies but increased connectivity in high gamma (50-100 Hz). These preliminary results suggest psilocybin-induced connectivity changes align with those seen in psychotic patients.

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.