Pariante et al (Reference Pariante, Vassilopoulou and Velakoulis2004) conclude that patients with first-episode psychosis have a larger pituitary volume and those with chronic schizophrenia a smaller pituitary volume in comparison with the controls. However, there are a number of factors that limit this conclusion.

First, normal variation in pituitary volume: a large degree of variation is observed in the morphology of anterior and posterior pituitary in healthy individuals (Reference Fujisawa, Asato and NishimuraFujisawa et al, 1987). Moreover, the variations may occur in the same individual if the measurements are repeated after an interval (Reference Brooks, el Gammal and AllisonBrooks et al, 1989). Therefore, conclusions based on a single measurement may be unreliable and at least two or three measurements should have been performed for better accuracy.

Second, effect of gender and age: men tend to have smaller pituitaries, as mentioned by Pariante et al, and the pituitary size decreases with age (Reference Brooks, el Gammal and AllisonBrooks et al, 1989). In the study by Pariante et al the schizophrenia group contained a significantly larger number of men and significantly older people compared with the control group. These differences could be partially responsible for the smaller pituitary size observed in chronic schizophrenia.

Third, failure to demonstrate the hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis: the correlation between HPA axis and pituitary volume is purely speculative and Pariante et al did not discuss the negative studies on the subject. Katona & Roth (Reference Katona and Roth1985) reported an abnormal dexamethasone suppression response in only 33% of patients (10 out of 30) with schizo-affective depression.

Fourth, failure to measure the adrenal gland size: adrenal gland hypertrophy has been shown to correlate with hyperactivity of the HPA axis in depression (Reference Nemeroff, Krishnan and ReedNemeroff et al, 1992). Pariante et al did not measure the adrenal gland size, probably as the study was not pre-planned and magnetic resonance imaging data obtained for another study were utilised. Measurement of adrenal gland size would have added more weight to the study findings.

Another comment worth mentioning is that hyperactivity of the HPA axis does not point to a specific diagnosis and occurs in a large number of conditions associated with stress. Therefore, this finding alone has a limited role in diagnosis of a particular condition.