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Middle-ear disease and schizophrenia: case–control study

  • Peter Mason (a1), Michael Rimmer (a1), Anna Richman (a1), Gagan Garg (a1), Joe Johnson (a1) and Patricia G. Mottram (a2)...
Abstract
Background

One hundred years ago psychiatrists thought that ear disease could cause insanity by irritation of the brain. Current understanding of the role of the temporal lobes in schizophrenia and their proximity to the middle ear supports this hypothesis.

Aims

To establish the rate of middle-ear disease pre-dating the onset of schizophrenia.

Method

Eighty-four patients with schizophrenia were each matched to four non-psychiatric controls by age, gender and season of birth. History of ear disease was obtained from general practice records. Additional information on symptoms was collected for participants in the case group, who also had audiometry.

Results

The odds ratio of recorded middle-ear disease pre-dating schizophrenia was 3.68 (95% CI 1.86–7.28). This excess was particularly marked on the left (OR=4.15, 95% CI 2.08–8.29). Auditory hallucinations were associated with middle-ear disease but not with hearing loss.

Conclusions

There is an association between middle-ear disease and schizophrenia which may have aetiological significance.

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Copyright
Corresponding author
Correspondence: Dr Peter Mason, Cheshire & Wirral Partnership NHS Foundation Trust, The Stein Centre, St Catherine's Hospital, Derby Road, Birkenhead CH42 0LQ, UK. Email: peter.mason@cwp.nhs.uk
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Declaration of interest

None.

Footnotes
References
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Middle-ear disease and schizophrenia: case–control study

  • Peter Mason (a1), Michael Rimmer (a1), Anna Richman (a1), Gagan Garg (a1), Joe Johnson (a1) and Patricia G. Mottram (a2)...
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eLetters

Re: Middle-ear disease and Schizophrenia

Peter R Mason, Consultant Psychiatrist
27 November 2008

Ganapathy is correct in his assertion that this study could be improved by using incident cases of schizophrenia rather than the prevalent cases described by Mason et al (1) and it is hoped that with thedevelopment of Early Intervention in Psychosis Services in the UK that such a study may be possible.

It is likely that the study of Mason et al (1) is indeed over represented by poor prognosis cases as it is not possible to be sure how many good prognosis cases were living in the catchment area and dischargedor lost to follow-up. The possibility raised by Ganapathy that middle eardisease may be a risk factor for poor prognosis may be valid. The statistical power of the study was such that no meaningful comparisons could be made between good and poor prognosis cases, however left sided middle ear disease was over-represented in those with poor prognosis (oddsratio: 5.07, 95% CI: 2.27-11.31) and was over-represented in those cases with an insidious onset compared to those with an acute onset (odds ratio:5.67, 95% CI: 2.54-12.63).

I do not agree with Ganapathy’s suggestion about reverse causality since the study concerned itself with the rates of middle ear disease predating the onset of schizophrenia, and not the overall rates of middle ear disease.

References

1. Mason P, Rimmer M, Richman A, Garg G, Johnson J, Mottram PG. Middle ear disease and schizophrenia : case-control study. British Journalof Psychiatry 2008, 193,192-196.
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Conflict of interest: None Declared

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Middle Ear Disease (MED) and Schizophrenia...a differential association?

Naghma Malik, ST5
27 November 2008

Dear SirWe enjoyed reading this excellent article by Mason and et al. The methodology is indeed an improvement on a similar study carried out by Mason and Winton 13 years ago. The findings are interesting and if furtherresearched to provide significant evidence, may lead to another positive step in prevention of schizophrenia.

We can’t help but wonder if the association reported is in fact a differential one i.e it varies with the subtypes of schizophrenia. It is expected that absence of auditory hallucinations in simple schizophrenia, for instance, would have no association with MED.

It would be most interesting to know whether the authors have performed or may consider performing stratified analysis on their categorical data which may confirm or eliminate the assumption of a differential association.
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Conflict of interest: None Declared

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Re: Aetiological Significance of Middle ear disease in Schizophrenia

Peter R Mason, Consultant Psychiatrist
25 October 2008

Jainer & Shivanandaswamys' comments about the problems of bias incase control studies are well made. However this study (1) was designed toavoid such problems by recruiting all patients with a likely diagnosis of schizophrenia in contact with general practitioners in a defined catchmentarea. There was no possibility of influencing the selection of subjects since they were all the patients with a diagnosis of schizophrenia on a community mental health team's caseload.

The community mental health team concerned looked after an area of high socio-economic deprivation and the study included cases who had drifted down the social scale from more affluent rural areas where one would expect a lower prevalence of middle ear disease. If there is any bias in this study it is likely to favour the null hypothesis rather than that suggested by Jainer & Shivanandaswamy.

In addition, perhaps the most striking finding in this study was the excess of left sided middle ear disease. In this case the odds ratio of 4.15 meets the recommendation of Sackett (2) that an odds ratio of greaterthan 4 should be used to establish an association in case control studies.

References:

(1) Mason P, Rimmer M, Richman A, Garg G, Johnson J & Mottram P. Middle ear disease and schizophrenia: case-control study. Br J Psychiatry 2008;193: 192-196.

(2) Sackett d. Evidence Based Medicine. How to practice and teach FBM. Churchill Livingstone, 2000.
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Conflict of interest: None Declared

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Middle-ear disease and Schizophrenia

Ramanathan K Ganapathy, Specialist Registrar in General Psychiatry
25 October 2008

Mason et al’s study “Middle ear disease and Schizophrenia: case -control study ” concludes that there is an association between middle eardisease and schizophrenia which may have aetiological significance. It is reported that the study was a replicate of the case-control study of Mason& Winton using improved methodology. However going through the paper it appears that there are some issues which would not support the aetiological association.

Lewis & Pilon, 1990 in their article report that in studying aetiological association it is recommended that, when possible, new incident cases of disease are selected. If prevalent cases are studied there will be an over representation of subjects with a poor prognosis whohave had the condition for a long period. Therefore an observed association may indicate risk factors for a poor prognosis rather than forthe onset of disease.

Applying this to Mason et al’s study the cases included are prevalentcases of schizophrenia that may have had the condition for a long period. Therefore middle ear disease may be a risk factor for poor prognosis rather than the onset of schizophrenia.

It is also being reported that Schizophrenia is associated with poor physical health and co morbid medical diseases. Hence the association seenhere may be the fact that schizophrenia itself may have contributed to increased risk of middle ear infections possibly due to life style choices. This supports the view that the association seen here may be due to reverse causality and not true causality.

References:

1. Mason P, Rimmer M, Richman A, Garg G, Johnson J, Mottram PG. Middle ear disease and schizophrenia : case-control study. British Journalof Psychiatry 2008, 193,192-196.2. Mason PR, Winton FE. Ear disease and schizophrenia: a case control study. Acta Psychiatr Scand 1995; 91: 217 –21.3. Lewis G, Pelosi A J. The Case-Control Study in Psychiatry. British Journal of Psychiatry 1990, 57,197-207.4. Connolly M, Kelly C. Lifestyle and physical health in schizophrenia. Advances in Psychiatric Treatment 2005, 11, 125 -132.
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Conflict of interest: None Declared

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Aetiological Significance of Middle ear disease in Schizophrenia

Ashok K Jainer, Consultant Psychiatrist
20 October 2008

We read the study “Middle ear disease and Schizophrenia” [1] with great interest. The authors conclude that there is an association between middle ear disease and Schizophrenia which may have aetiological significance. As authors have concluded based on a case control study which is susceptible to biases and effects of confounding factors, we would like to raise concerns about author’s conclusions.

Firstly, we would like to highlight the strong possibility of selection bias as this study design is particularly prone to it. In this case, at the sample selection stage, no precautions were taken to ensure that the person selecting the patients was blind to the study hypothesis. This could lead to bias towards selecting patients with middle ear diseaseand schizophrenia.

Case control studies are more susceptible to bias and confounding factors as opposed to cohort studies. In order to establish the association, it is recommended that we should have an odds ratio>4 [2] because higher the odds ratio, stronger is the association. However, in this study authors have concluded about the association when the odds ratio is<4, which could be as a result of bias alone. This raised strong doubts about the validity of author’s conclusion

We would request the author to clarify these issues.References:[1]. Mason P, Rimmer M, Richman A, Garg G, Johnson J. Middle-ear disease and schizophrenia: case–control study. Br J Psychiatry 2008; 193: 192-196.[2]. Sackett D. Evidence Based Medicine. How to practice and Teach FBM. Churchill Livingstone, 2000.
... More

Conflict of interest: None Declared

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