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Are auditory P300 and duration MMN heritable and putative endophenotypes of psychotic bipolar disorder? A Maudsley Bipolar Twin and Family Study

Published online by Cambridge University Press:  02 March 2009

M.-H. Hall ,
K. Schulze ,
F. Rijsdijk ,
S. Kalidindi ,
C. McDonald ,
E. Bramon ,
R. M. Murray  and
P. Sham
M.-H. Hall*
Affiliation:
Psychology Research Laboratory, Harvard Medical School, McLean Hospital, USA
K. Schulze
Affiliation:
Division of Psychological Medicine, Institute of Psychiatry, King's College London, UK
F. Rijsdijk
Affiliation:
Social, Genetic Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, UK
S. Kalidindi
Affiliation:
Division of Psychological Medicine, Institute of Psychiatry, King's College London, UK
C. McDonald
Affiliation:
Department of Psychiatry, Clinical Science Institute, National University of Ireland, Galway, Ireland
E. Bramon
Affiliation:
Division of Psychological Medicine, Institute of Psychiatry, King's College London, UK
R. M. Murray
Affiliation:
Division of Psychological Medicine, Institute of Psychiatry, King's College London, UK
P. Sham
Affiliation:
Department of Psychiatry, University of Hong Kong, China
*
*Address for correspondence: M.-H. Hall, Ph.D., Psychology Research Laboratory, Harvard Medical School, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA. (Email: mhall@mclean.harvard.edu)
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Abstract

Background

Impaired P300 auditory response has been reported in patients with psychotic bipolar disorder (BPD) and unaffected relatives of psychotic bipolar patients. Deficits in mismatch negativity (MMN), however, have not been observed in bipolar patients. To our knowledge, no family study of MMN in BPD has been reported. The current study combined the Maudsley twin and bipolar family samples using genetic model fitting analyses to: (1) assess the relationship between BPD and MMN, (2) substantiate the association between psychotic BPD and P300 variables, (3) verify the genetic overlap of BPD with P300 amplitude previously reported in the twin sample, and (4) examine the shared genetic influences between BPD and bilateral temporal scalp locations of P300 components.

Method

A total of 301 subjects were included in this study, including 94 twin pairs, 31 bipolar families, and 39 unrelated healthy controls. Statistical analyses were based on structural equation modelling.

Results

Both P300 and MMN are heritable, with heritability estimates of 0.58 for MMN, 0.68–0.80 for P300 amplitude, and 0.21–0.56 for P300 latency. The bipolar patients and their relatives showed normal MMN. No significant association, either genetic or environmental, was found with BPD. BPD was significantly associated with reduced P300 amplitude and prolonged latency on midline and bilateral temporal-posterior scalp areas. Shared genetic factors were the main source of these associations.

Conclusions

The results confirm that MMN is not an endophenotype for psychotic BPD whereas P300 amplitude and latency components are valid endophenotypes for psychotic BPD.

Keywords

P300MMNERPsendophenotypebipolar disordertwin modelling
Type
Original Articles
Information
Psychological Medicine , Volume 39 , Issue 8 , August 2009 , pp. 1277 - 1287
Copyright
Copyright © 2009 Cambridge University Press

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Footnotes

†

These authors contributed equally to this work.

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