Psychological Medicine

Original Articles

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

M.-H. Halla1 c1, K. Schulzea2, F. Rijsdijka3, S. Kalidindia2, C. McDonalda4, E. Bramona2, R. M. Murraya2 and P. Shama5

a1 Psychology Research Laboratory, Harvard Medical School, McLean Hospital, USA

a2 Division of Psychological Medicine, Institute of Psychiatry, King's College London, UK

a3 Social, Genetic Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, UK

a4 Department of Psychiatry, Clinical Science Institute, National University of Ireland, Galway, Ireland

a5 Department of Psychiatry, University of Hong Kong, China


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.

(Received August 14 2008)

(Revised December 15 2008)

(Accepted January 07 2009)

(Online publication March 02 2009)


c1 Address for correspondence: M.-H. Hall, Ph.D., Psychology Research Laboratory, Harvard Medical School, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA. (Email:


† These authors contributed equally to this work.