1. ¹Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany
2. ²Department of Psychiatry and Psychotherapy, Medical Faculty of the University of Technology Aachen (RWTH), Aachen, Germany
3. ³Institute of Pharmacy, University of Tübingen, Tübingen, Germany

Correspondence: Professor E Gouzoulis-Mayfrank, Department of Psychiatry and Psychotherapy, University of Cologne, Kerpener Strasse 62, D-50924 Cologne, Germany. Tel: +49 221 478 4825; Fax: +49 221 478 3738; E-mail: e.gouzoulis@uni-koeln.de

Received 15 March 2005; Revised 11 July 2005; Accepted 18 July 2005; Published online 24 August 2005.

Abstract

Patients with schizophrenia exhibit disturbances of orienting of attention. However, findings have been inconsistent. Pharmacologic challenges with hallucinogens have been used as models for psychosis. The NMDA antagonist state (PCP, ketamine) resembles undifferentiated psychoses with positive and negative symptoms, while the 5-HT_2A agonist state (LSD, dimethyltryptamine (DMT)) is thought to be an appropriate model for psychoses with prominent positive symptoms. The aim of this study was to investigate orienting of attention in the human NMDA antagonist and 5-HT_2A agonist models of psychosis. A total of 15 healthy volunteers participated in a randomized, double-blind, crossover study with a low and a high dose of DMT and S-ketamine, which elicited subtle 'prepsychotic' or full-blown psychotic symptoms (low and high dose, respectively). Nine subjects completed both experimental days with the two doses of both drugs. Overall, both hallucinogens slowed down reaction times dose dependently (DMT >S-ketamine) and DMT diminished the general response facilitating (alerting) effect of spatially neutral cues. Inhibition of Return (IOR), that is, the normal reaction time disadvantage for validly cued trials with exogenous cues and long cue target intervals, was blunted after both doses of DMT and the low dose of S-ketamine. IOR reflects an automatic, inhibitory mechanism of attention, which is thought to protect the organism from redundant, distracting sensory information. In conclusion, our data suggest a deficit of IOR in both hallucinogen models of psychosis, with the effect being clearer in the serotonin model. Blunted IOR may underlie or predispose to different psychotic manifestations, but particularly to those with prominent positive symptoms.