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Cognitive function in unaffected twins discordant for affective disorder
Abstract
Background. Patients may present with cognitive impairment in the euthymic phase of affective disorder, but it is unclear whether the impairment is prevalent before onset of the illness. The aim of the present study was to examine the hypothesis that genetic liability to affective disorder is associated with cognitive impairment. Method. In a cross-sectional high-risk case–control study, healthy monozygotic (MZ) and dizygotic (DZ) twins with (High-Risk twins) and without (the control group/Low-Risk twins) a co-twin history of affective disorder were identified through nationwide registers. Cognitive performance of 203 High-Risk and Low-Risk twins was compared. Results. Healthy twins discordant for unipolar disorder showed lower performance on almost all measures of cognitive function: selective and sustained attention, executive function, language processing and working and declarative memory, and also after adjustment for demographic variables, subclinical symptoms and minor psychopathology. Healthy twins discordant for bipolar disorder showed lower performance on tests measuring episodic and working memory, also after adjustment for the above-mentioned covariables. The discrete cognitive impairment found seemed to be related to genetic liability, as the MZ High-Risk twins showed significant impairment on selective and sustained attention, executive function, language processing and working and declarative memory, whereas the DZ High-Risk twins presented with significantly lower scores only on language processing and episodic memory. Conclusions. The hypothesis that discrete cognitive impairment is present before the onset of the affective disorder and is genetically transmitted was supported. Thus, cognitive function may be a candidate endophenotype for affective disorders.
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“In addition, there is evidence of cognitive control impairments in healthy, unaffected twins discordant for MDD (Christensen et al, 2006).”
From Neural Correlates of Three Promising Endophenotypes of Depression: Evidence from the EMBARC Study (2016) · cites this paper as Christensen et al, 2006
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Forester, B. P., Gildengers, A. G., & Young, R. C. (2016) · Cambridge University Press eBooks · doi:10.1017/cbo9781107477278.019
Neurocognitive Deficit in Bipolar Disorders
Dimellis, D., Gonda, X., & Fountoulakis, K. Ν. (2016) · Springer eBooks · doi:10.1007/978-81-322-2803-5_27
de Azevedo, E. B. (2018) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.5.2018.tde-04012018-083538
Roedding, A. S. (2013) · TSpace (University of Toronto)
Sareen, H., & Bhanot, N. (2020) · International Journal of Medical and Dental Sciences · doi:10.18311/ijmds/2020/24771
“Healthy twins discordant for bipolar disorder showed significant deficits in executive functioning[11].”
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Jabben, N. (2009) · Research Publications (Maastricht University) · doi:10.26481/dis.20090903nj
The Neurobiology and Treatment of Bipolar Disorder
Burdick, K. E., Ospina, L. H., Haggarty, S. J., & Perlis, R. H. (2017) · Oxford University Press eBooks · doi:10.1093/med/9780190681425.003.0020
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Çoban, C., & Bulut, S. D. (2025) · Psychiatry Research · doi:10.1016/j.psychres.2025.116778
Kjærstad, H. L., Nordseth, B. O. B., Vinberg, M., Kessing, L. V., & Miskowiak, K. W. (2026) · International Journal of Bipolar Disorders · doi:10.1186/s40345-026-00417-x
“…to be characterized by both poorer cognitive performance and fewer years of education compared to healthy controls, higher age and education may particularly benefit UR-HP as protective factors against the negative effect of illness on cognition (Christensen et al. 2006; Ponsoni et al. 2020).”
Self-citation
Metadata
- Authors
- CHRISTENSEN, M. V., KYVIK, K. O., & KESSING, L. V.
- Affiliations
- University of Southern Denmark (DK)
- Copenhagen University Hospital (DK)
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2006-05-31
- Volume
- 36
- Issue
- 8
- Pages
- 1119-1129
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- OpenAlex
- W2131328754
- Cited by
- 125
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 5 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 7 · 2017: 5 · 2016: 10 · 2015: 13 · 2014: 7 · 2013: 8 · 2012: 13
- FWCI
- 6.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- Funders
- Lundbeckfonden
- 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
- cognitive impairment, mood disorders, monozygotic twins, dizygotic twins, genetic susceptibility, endophenotypes, unipolar disorder, bipolar disorder, attention, executive function, memory, language processing
- MeSH terms
- Adult, Aged, Bipolar Disorder, Cognition Disorders, Denmark, Depressive Disorder, Diseases in Twins, Female, Humans, Individuality, Male, Middle Aged, Neuropsychological Tests, Phenotype, Psychometrics, Risk, Twins, Dizygotic, Twins, Monozygotic, Genetic Predisposition to Disease
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