1. ¹Division of Psychological Medicine, Institute of Psychiatry, King's College London, UK
2. ²Sir Charles Gairdner Hospital, Department of Psychiatry, Perth, Australia
3. ³Department of Psychiatry, University of West Indies, Trinidad, Trinidad and Tobago
4. ⁴Department of Neurology, Institute of Psychiatry, King's College London, UK
5. ⁵Addenbrooke's Hospital, Department of Psychiatry, University of Cambridge, Cambridge, UK
6. ⁶Institute of Psychiatry, Section of Social Psychiatry, King's College London, UK

Correspondence: P Dazzan, Division of Psychological Medicine, Institute of Psychiatry, Box 63, De Crespigny Park, London SE5 8AF, UK. Tel: +44 207 848 0590; Fax: +44 207 701 9044; E-mail: spcbpad@iop.kcl.ac.uk

Received 20 February 2004; Revised 23 September 2004; Accepted 28 September 2004; Published online 9 February 2005.

Abstract

Typical antipsychotic drugs act on the dopaminergic system, blocking the dopamine type 2 (D2) receptors. Atypical antipsychotics have lower affinity and occupancy for the dopaminergic receptors, and a high degree of occupancy of the serotoninergic receptors 5-HT2A. Whether these different pharmacological actions produce different effects on brain structure remains unclear. We explored the effects of different types of antipsychotic treatment on brain structure in an epidemiologically based, nonrandomized sample of patients at the first psychotic episode. Subjects were recruited as part of a large epidemiological study (ÆSOP: aetiology and ethnicity in schizophrenia and other psychoses). We evaluated 22 drug-free patients, 32 on treatment with typical antipsychotics and 30 with atypical antipsychotics. We used high-resolution MRI and voxel-based methods of image analysis. The MRI analysis suggested that both typical and atypical antipsychotics are associated with brain changes. However, typicals seem to affect more extensively the basal ganglia (enlargement of the putamen) and cortical areas (reductions of lobulus paracentralis, anterior cingulate gyrus, superior and medial frontal gyri, superior and middle temporal gyri, insula, and precuneus), while atypical antipsychotics seem particularly associated with enlargement of the thalami. These changes are likely to reflect the effect of antipsychotics on the brain, as there were no differences in duration of illness, total symptoms scores, and length of treatment among the groups. In conclusion, we would like to suggest that even after short-term treatment, typical and atypical antipsychotics may affect brain structure differently.