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Pituitary volume in psychosis

  • Carmine M. Pariante (a1), Konstantina Vassilopoulou (a2), Dennis Velakoulis (a3), Lisa Phillips (a4), Bridget Soulsby (a5), Stephen J. Wood (a6), Warrick Brewer (a7), Deidrej. Smith (a1), Paola Dazzan (a8), Alison R. Yung (a2), Ioannis M. Zervas (a1), George N. Christodoulou (a9), Robin Murray (a10), Patrick D. McGorry (a10) and Christos Pantelis (a10)...

Abstract

Background

Patients with psychosis have activation of the hypothalamic-pituitary-adrenal (HPA) axis during the acute phase of the psychosis. Whether this has any morphological consequences for the pituitary gland is currently unknown.

Aims

To examine pituitary volume variation in people at different stages of psychotic disorder.

Method

Pituitary volume was measured using 1.5 mm, coronal magnetic resonance images in 24 people with first-episode psychosis, 51 with established schizophrenia and 59 healthy controls.

Results

Compared with the control group, the people with first-episode psychosis had pituitary volumes that were 10% larger, whereas those with established schizophrenia had pituitary volumes that were 17% smaller. In both of the groups with psychosis, there was no difference in pituitary volume between those receiving typical antipsychotic drugs and those receiving atypical antipsychotics.

Conclusions

The first episode of a psychosis is associated with a larger pituitary volume, which we suggest is due to activation of the HPA axis. The smaller pituitary volume in the group with established schizophrenia could be the consequence of repeated episodes of HPA axis hyperactivity.

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Copyright

Corresponding author

Dr Carmine M. Pariante, Division of Psychological Medicine, Box PO51, Institute of Psychiatry, King's College London, I Windsor Walk, Denmark Hill, London SE5 8AF, UK. Tel: +44(0)20 7848 0807; fax: +44(0)20 7848 0051; e-mail: spjucmp@iop.kcl.ac.uk

Footnotes

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Declaration of interest

None. Funding detailed in Acknowledgements.

Footnotes

References

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Pituitary volume in psychosis

  • Carmine M. Pariante (a1), Konstantina Vassilopoulou (a2), Dennis Velakoulis (a3), Lisa Phillips (a4), Bridget Soulsby (a5), Stephen J. Wood (a6), Warrick Brewer (a7), Deidrej. Smith (a1), Paola Dazzan (a8), Alison R. Yung (a2), Ioannis M. Zervas (a1), George N. Christodoulou (a9), Robin Murray (a10), Patrick D. McGorry (a10) and Christos Pantelis (a10)...

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Pituitary volume in psychosis

  • Carmine M. Pariante (a1), Konstantina Vassilopoulou (a2), Dennis Velakoulis (a3), Lisa Phillips (a4), Bridget Soulsby (a5), Stephen J. Wood (a6), Warrick Brewer (a7), Deidrej. Smith (a1), Paola Dazzan (a8), Alison R. Yung (a2), Ioannis M. Zervas (a1), George N. Christodoulou (a9), Robin Murray (a10), Patrick D. McGorry (a10) and Christos Pantelis (a10)...
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eLetters

Response to Dr. Sudhir Kumar's letter

Carmine M. Pariante, Senior Lecturer
10 August 2004

Sir,

We welcome Dr. Kumar’s comments, drawing attention to some of the limitations of our study (Pariante et al, 2004). Even if some of these points had already been discussed in the paper, we think it is helpful to reply to all comments.

We agree that there is a large degree of variation in the morphology of the pituitary. For example, in our sample approximately half of the subjects had a “concave” pituitary, and a third had a “flat” pituitary. However, we have minimised the influence of morphology on the volume measurement by tracing all coronal slices where the pituitary was visualized. Dr. Kumar also refers to the paper by Brooks et al (1989) showing intra-individual changes in the brightness of the posterior brightsignal, representing vasopressin released in the posterior lobe for fluidscontrol. We did not analyse the brightness of the posterior bright signal, as we were not interested in the regulation of fluids control in our sample.

In our study there were significant differences in age and gender among the groups. By definition, it was impossible to have one single control group that was comparable to the young first-episode subjects as well as to the older subjects with established schizophrenia, for both ageand gender distribution. However, we used two strategies to control for these confounders: first, gender and age (and whole-brain volume) were included as covariates in the analysis; second, the results obtained from this analysis were further corroborated by conducting separate tests comparing the clinical groups (first-episode and established) with selected control groups that had similar age and gender distribution. Both strategies led to the same results, thus demonstrating that the smaller pituitary volume in patients with established schizophrenia is notdue to differences in age and gender distribution.

We agree that the association between increased pituitary volume and HPA axis hyperactivity is speculative, and we have clearly stated this in the Limitations of the study. Nevertheless, already 30 years ago Sachar et al (1970) found that patients experiencing a first episode psychosis were more likely to present with HPA abnormalities, because of the distress associated with the “dramatic and ego-dystonic” nature of this experience. Several studies have confirmed that patients who are in the acute phase of a psychotic disorder, with florid symptoms, newly hospitalised or unmedicated, have an elevated HPA axis activity as shown by raised cortisol levels (Sachar et al, 1970), nonsuppression of cortisolsecretion by dexamethasone in the dexamethasone suppression test and in the dexamethasone/corticotropin releasing factor (CRF) test (Herz et al, 1985; Lammers et al, 1995), and elevated levels of CRF in the cerebrospinal fluid (Banki et al, 1987). Only patients who are clinically stable and receiving treatment tend to have a normal HPA axis (Ismail et al, 1998). Indeed, the study by Katona and Roth (1985), cited by Dr. Kumar, also reports, in the authors’ own words, “an increased frequency ofHPA axis abnormality” in schizo-affective depression.

We agree that the study would have been more complete if we had measured the adrenal gland size. Indeed, measuring hormonal levels would have been an important addition to the study. We will take this advice into consideration in our future studies.

Finally, we support Dr. Kumar’s view that the hyperactivity of the HPA axis occurs in a large number of conditions associated to stress. Indeed, in the Discussion we have suggested that glucocorticoid resistancecould be the molecular mechanisms by which stress induces HPA axis hyperactivity in patients with different mental disorders. We had never suggested that this biological abnormality could have any diagnostic values. However, we believe that measuring specific biological markers cangive us further insight into the pathological mechanisms affecting the brain (and the body) of our patients.

REFERENCES

Banki, C. M., Bissette, G., Arato, M., et al (1987) CSF corticotropin-releasing factor-like immunoreactivity in depression and schizophrenia. American Journal of Psychiatry, 144, 873-877.

Brooks, B. S., el Gammal, T., Allison, J. D., et al (1989) Frequency and variation of the posterior pituitary bright signal on MR images. AJNR Am.J.Neuroradiol., 10, 943-948.

Herz, M. I., Fava, G. A., Molnar, G., et al (1985) The dexamethasone suppression test in newly hospitalized schizophrenic patients. American Journal of Psychiatry, 142, 127-129.

Ismail, K., Murray, R. M., Wheeler, M. J., et al (1998) The dexamethasone suppression test in schizophrenia. Psychological Medicine, 28, 311-317.

Katona, C. L. and Roth, M. (1985) The dexamethasone suppression test in schizo-affective depression. Journal of Affective Disorders, 8, 107-112.

Lammers, C. H., Garcia-Borreguero, D., Schmider, J., et al (1995) Combined dexamethasone/corticotropin-releasing hormone test in patients with schizophrenia and in normal controls: II. Biological Psychiatry, 38, 803-807.

Pariante, C. M., Vassilopoulou, K., Velakoulis, D., et al (2004) Pituitary volume in psychosis. British Journal of Psychiatry, 185, 5-10.

Sachar, E. J., Kanter, S. S., Buie, D., et al (1970) Psychoendocrinology of ego disintegration. American Journal of Psychiatry,126, 1067-1078.
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Conflict of interest: None Declared

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Pituitary volume in patients with first-episode psychosis and chronic schizophrenia

Sudhir Kumar, Consultant Neurologist
16 July 2004

Sir,

Pariante et al (2004) conclude in their MRI-based study that patientswith first-episode psychosis have a larger pituitary volume and those withchronic schizophrenia a smaller pituitary volume in comparison to the controls. However, there are a number of factors that limit this conclusion:

1. Normal variation in pituitary volume: A large degree of variation is observed in the morphology of anterior and posterior pituitary in normal people (Fujisawa et al, 1987). Moreover, the variations may occur in the same individual if the measurements are repeated after an interval (Brooks et al, 1989). Therefore, the conclusions based on a single measurement may be unreliable and at least 2-3 measurements should have been performed for a better accuracy.

2. Effect of gender and age: Men tend to have smaller pituitaries, asmentioned by Pariante et al, and the pituitary size decreases with age (Brooks et al, 1989). In the present study, the schizophrenia group had a significantly larger number of men and significantly older people as compared to the controls; these differences could be partially responsiblefor the smaller pituitary size observed in them.

3. Failure to demonstrate the hyperactivity of HPA axis: The correlation between HPA axis and pituitary volume is purely speculative and Pariante el al have ignored the previous negative studies on the subject. Katona et al (1985) reported an abnormal dexamethasone suppression response in only 33% (10/30) of patients with schizo-affectivedepression.

4. Failure to measure the adrenal gland size: Adrenal gland hypertrophy has been shown to correlate with hyperactivity of HPA axis in depression (Nemeroff et al, 1992). Pariante et al have not measured the size of adrenal gland, probably as the study was not pre-planned and MRI performed for another study were utilized for this study. Measurement of adrenal gland size would have added more weight to the study findings.

Another comment worth a mention is that the hyperactivity of HPA axisdoes 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.

References

1. Brooks BS, el Gammal T, Allison JD, Hoffman WH (1989) Frequency and variation of the posterior pituitary bright signal on MR images. AJNR Am J Neuroradiol, 10, 943-948.

2. Fujisawa I, Asato R, Nishimura K, et al (1987) Anterior and posterior lobes of the pituitary gland: assessment by 1.5 T MR imaging. J Comput Assist Tomogr, 11, 214-220.

3. Katona CL, Roth M (1985). The dexamethasone suppression test in schizo-affective depression. J Affect Disord, 8, 107-112.

4. Nemeroff CB, Krishnan KR, Reed D, Leder R, Beam C, Dunnick NR (1992). Adrenal gland enlargement in major depression. A computed tomographic study. Arch Gen Psychiatry, 49, 384-387.

5. Pariante CM, Vassilopoulou K, Velakoulis D, et al (2004). Pituitary volume in psychosis. Br J Psychiatry, 185, 5-10
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Conflict of interest: None Declared

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