1. ¹Department of Psychiatry, University of Alabama at Birmingham, Birmingham, AL, USA
2. ²Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA
3. ³Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX, USA

Correspondence: Dr AC Lahti, Department of Psychiatry, University of Alabama at Birmingham, SC 501 1530 3rd AVE S, Birmingham, AL, 35294, USA, Tel: +205 996 6776, Fax: +205 975 4879, E-mail: alahti@uab.edu

Received 4 April 2009; Revised 20 June 2009; Accepted 1 July 2009; Published online 12 August 2009.

Abstract

The regional neuronal changes taking place in the early and late stages of antipsychotic treatment are still not well characterized in humans. In addition, it is not known whether these regional changes are predictive of or are correlated with treatment response. Using PET with ¹⁵O, we evaluated the time course of regional cerebral blood flow (rCBF) patterns generated by a first (haloperidol) and a second (olanzapine) generation antipsychotic drug in patients with schizophrenia during a 6-week treatment trial. Patients were initially scanned after withdrawal of all psychotropic medication (2 weeks), and then blindly randomized to treatment with haloperidol (n=12) or olanzapine (n=17) for a period of 6 weeks. Patients were scanned again after 1 and 6 weeks of treatment. All assessments, including scanning sessions, were obtained in a double-blind manner. As hypothesized, we observed rCBF changes that were common to both the drugs, implicating cortico-subcortical and limbic neuronal networks in antipsychotic action. In addition, in these regions, some patterns seen at weeks 1 and 6 were distinctive, indexing neuronal changes related to an early (ventral striatum, hippocampus) and consolidated (anterior cingulate/medial frontal cortex) stage of drug response. Finally, both after 1 and 6 weeks of treatment, we observed differential patterns of rCBF activation between good and poor responders. After 1 week of treatment, greater rCBF increase in the ventral striatum and greater decrease in the hippocampus were associated with good response.