A systems model of altered consciousness: integrating natural and drug-induced psychoses

Increasing evidence from neuroimaging and behavioral studies suggests that functional disturbances within cortico-striato-thalamic pathways are critical to psychotic symptom formation in drug-induced and possibly also naturally occurring psychoses. Recent basic and clinical research with psychotomimetic drugs, such as the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, ketamine, and the serotonin-2A (5-HT(2A)) receptor agonist, psilocybin, suggest that the hallucinogenic effects of these drugs arise, at least in part, from their common capacity to disrupt thalamo-cortical gating of external and internal information to the cortex. Deficient gating of sensory and cognitive information is thought to result in an overloading inundation of information and subsequent cognitive fragmentation and psychosis. Cross-species studies of homologues gating functions, such as prepulse inhibition of the startle reflex, in animal and human models of psychosis corroborate this view and provide a translational testing mechanism for the exploration of novel pathophysiologic and therapeutic hypotheses relevant to psychotic disorders, such as the group of schizophrenias.