1. ¹Division of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK
2. ²Department of Psychiatry, Sir Charles Gairdner Hospital, Perth, WA, Australia
3. ³Department of Psychiatry, University of West Indies, Trinidad, Trinidad and Tobago
4. ⁴Melbourne Neuropsychiatry Centre, Mental Health Program, Department of Psychiatry, Royal Melbourne & Sunshine Hospitals, Melbourne, VIC, Australia
5. ⁵Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK
6. ⁶Section of Social Psychiatry, Institute of Psychiatry, King's College London, London, UK

Correspondence: Dr CM Pariante, Stress, Psychiatry and Immunology Laboratory (SPI-Lab), Clinical Neuropharmacology, PO51, Institute of Psychiatry, King's College London, 1 Windsor Walk, Denmark Hill, London SE5 8AF, UK. Tel: +44 20 7848 0807; Fax: +44 20 7848 0051; E-mail: c.pariante@iop.kcl.ac.uk

Received 11 January 2005; Revised 29 March 2005; Accepted 4 April 2005; Published online 1 June 2005.

Abstract

Subjects at their first psychotic episode show an enlarged volume of the pituitary gland, but whether this is due to hypothalamic–pituitary–adrenal (HPA) axis hyperactivity, or to stimulation of the prolactin-secreting cells by antipsychotic treatment, is unclear. We measured pituitary volume, using 1.5-mm, coronal, 1.5 T, high-resolution MRI images, in 78 patients at the first psychotic episode and 78 age- and gender-matched healthy controls. In all, 18 patients were antipsychotic-free (12 of these were antipsychotic-naïve), 26 were receiving atypical antipsychotics, and 33 were receiving typical antipsychotics. As hypothesized, patients had a larger pituitary volume than controls (+22%, p<0.001). When divided by antipsychotic treatment, and compared to controls, the pituitary volume was 15% larger in antipsychotic-free patients (p=0.028), 17% larger in patients receiving atypicals (p=0.01), and 30% larger in patients receiving typicals (p<0.001). Patients receiving typicals not only had the largest pituitary volume compared to controls but also showed a trend for a larger pituitary volume compared to the other patients grouped together (+11%, p=0.08). When divided by diagnosis, and compared to controls, the pituitary volume was 24% larger in patients with schizophrenia/schizophreniform disorder (n=40, p<0.001), 19% larger in depressed patients (n=13, p=0.022), 16% larger in bipolar patients (n=16, p=0.037), and 12% larger in those with other psychoses (n=9, p=0.2). In conclusion, the first-episode of a psychotic disorder is associated with a larger pituitary independently of the presence of antipsychotic treatment, and this could be due to activation of the HPA axis. Typical antipsychotics exert an additional enlarging effect on pituitary volume, likely to be related to activation of prolactin-secreting cells. This activation of the hormonal stress response could participate to the important metabolic abnormalities observed in patients with psychosis.