Are auditory P300 and duration MMN heritable and putative endophenotypes of psychotic bipolar disorder? A Maudsley Bipolar Twin and Family Study
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.
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MMN deficits are heritable across the general population.
“Like P50 and PPI deficits, MMN deficits are heritable across the general population (66).”
From Sensory Processing Dysfunction in the Personal Experience and Neuronal Machinery of Schizophrenia (2015) · cites this paper as [66]
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- Authors
- Hall, M.-H., Schulze, K., Rijsdijk, F., Kalidindi, S., McDonald, C., Bramon, E., Murray, R. M., & Sham, P.
- Affiliations
- Harvard University (US)
- King's College London (GB)
- National University of Ireland (IE)
- University of Hong Kong (HK)
- Corresponding author
- Hall, M.-H.
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2009-03-02
- Volume
- 39
- Issue
- 8
- Pages
- 1277-1287
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- OpenAlex
- W2015772384
- Cited by
- 117
- References
- 42
- Citations by year
- 2025: 1 · 2024: 6 · 2023: 2 · 2022: 8 · 2021: 4 · 2020: 5 · 2019: 20 · 2018: 6 · 2017: 5 · 2016: 7 · 2015: 5 · 2014: 10 · 2013: 11 · 2012: 10
- FWCI
- 5.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Wellcome Trust
- National Institute for Health and Care Research (PDA/02/06/016)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- psychotic bipolar disorder, P300, mismatch negativity, endophenotypes, heritability, genetic overlap, P300 amplitude, P300 latency, twin studies
- MeSH terms
- Acoustic Stimulation, Adult, Bipolar Disorder, Cerebral Cortex, Contingent Negative Variation, Diseases in Twins, Dominance, Cerebral, Electrocardiography, England, Evoked Potentials, Auditory, Female, Humans, Male, Middle Aged, Models, Genetic, Phenotype, Psychiatric Status Rating Scales, Reaction Time, Signal Processing, Computer-Assisted, Social Environment, Statistics as Topic, Twins, Dizygotic, Twins, Monozygotic, Cohort Studies, Event-Related Potentials, P300
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