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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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Bora, E., Yücel, M., & Pantelis, C. (2008) · Journal of Affective Disorders · doi:10.1016/j.jad.2008.06.009 · Cited by 1,058
“, 2007) or unaffected BD relatives (Christensen et al., 2006) were reported.”
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Arts, B. M. G., Jabben, N., Krabbendam, L., & van Os, J. (2007) · Psychological Medicine · doi:10.1017/s0033291707001675 · Cited by 726
“12 Controls Stroop 0.00 HAMD 0.35 (0.86) Trail A x0.”
BackgroundMethodInfluentialChronic stress, cognitive functioning and mental health
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Cognitive impairment in the remitted state of unipolar depressive disorder: A systematic review
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“A Danish case-control study on twins discordant for unipolar depression demonstrated that healthy twins had lower scores across several cognitive domains, further supporting the hypothesis that discrete cognitive impairment before the onset of affective disorders may be a candidate endophenotype for MDD [39].”
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“…for SZ patients and their first-degree relatives for verbal declarative memory ranging from 0.21 to 0.49 have been reported (Cannon et al., 2000; Christensen et al., 2006; Delawalla et al., 2006; Egan et al., 2001a; Krabbendam et al., 2001; O’Driscoll et al., 2001; Schubert and McNeil, 2005;…”
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Self-citationA Quantitative and Qualitative Review of Neurocognitive Performance in Pediatric Bipolar Disorder
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“Finding deficits in first-degree relatives may lend credibility to neurocognitive abnormalities as an endophenotype for BD (Glahn et al. 2005; Christensen et al. 2006; Antila et al. 2007; Trivedi et al. 2008).”
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“One interesting study aimed to clarify the genetic contribution to cognitive differences in patients with mood disorders by recruiting samples of dizygotic and monozygotic twins discordant for MDD or BD (39).”
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“In addition, there is evidence of cognitive control impairments in healthy, unaffected twins discordant for MDD (Christensen et al, 2006).”
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BackgroundCognitive deficits in the remitted state of unipolar depressive disorder.
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BackgroundNeurocognitive functioning in patients recently diagnosed with bipolar disorder
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“Both the Stroop and the TMT B or B-A impairments in relatives have been reported in previous studies (Zalla et al., 2004; Antila et al., 2007; Christensen et al., 2006).”
BackgroundResultEvidence of Disrupted Prepulse Inhibition in Unaffected Siblings of Bipolar Disorder Patients
Giakoumaki, S. G., Roussos, P., Rogdaki, M., Karli, C., Bitsios, P., & Frangou, S. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.12.002 · Cited by 72
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“Studies on twins discordant for BD concluded that non-BD co-twins had poorer working memory capacity (eg, Brown Peterson test) and learning and episodic memory (eg, Wechsler Memory Scale and CVLT) when compared with control twins.(45,55,56) Cognitive Impairment in Bipolar Disorder 479”
MethodA New Role for Endophenotypes in the GWAS Era: Functional Characterization of Risk Variants
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“Performance on the SCWIT did not differ significantly between unaffected siblings and controls.”
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“Our results are also consistent with a co-twin control study that compared pairs of monozygotic twins where one twin had been diagnosed with major depression and the other was not; similar cognitive impairments (language, declarative memory, executive function) were found in both twins regardless of diagnosis (14).”
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“, 2007) and signs of discrete cognitive dysfunction (Christensen et al., 2006) in comparison to low-risk twins, but no changes in whole blood BDNF levels.”
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“Finally, it is possible that subclinical psychopathology might influence the results, or that cognitive impairments in these patients reflect a pre-morbid condition (Christensen et al., 2006).”
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Trivedi, J. K., Goel, D., Sharma, S., Singh, A. P., Sinha, P. K., & Tandon, R. (2007) · PubMed · Cited by 24
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Neurocognitive performance as an endophenotype for bipolar disorder
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“, (70) showed that unaffected DZ co-twins of BD probands had lower scores on only TMT part A (a measure of sustained attention) than HC twins; findings in other studies are inconsistent.”
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Dell’Acqua, C., Palomba, D., Patron, E., & Benvenuti, S. M. (2023) · Frontiers in Psychology · doi:10.3389/fpsyg.2023.1108275 · Cited by 23
“In addition, there is some evidence of cognitive control impairments in healthy, unaffected twins at risk for MDD (Christensen et al., 2006).”
BackgroundHaastrup, E. K., Knorr, U., Erikstrup, C., Kessing, L. V., & Ullum, H. (2012) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2011.12.006 · Cited by 19
“, 2007) and cognitive dysfunction (Christensen et al., 2006) have been described as more prevalent in these high-risk persons compared with healthy persons without a family history of affective disorders.”
BackgroundSelf-citationHsu, K. J., Young‐Wolff, K. C., Kendler, K. S., Halberstadt, L. J., & Prescott, C. A. (2013) · Psychiatry Research · doi:10.1016/j.psychres.2013.10.037 · Cited by 17
“Given evidence of attentional impairment from the limited literature on neuropsychological performance in families at risk for MD (Belleau et al., 2013; Christensen et al., 2006), these deficits may exist prior to MD onset.”
BackgroundMethodResultInfluentialPrats, C., Arias, B., Ortet, G., Ibáñez, M. I., Moya-Higueras, J., Pomarol‐Clotet, E., Fañanás, L., & Fatjó‐Vilas, M. (2016) · Journal of Affective Disorders · doi:10.1016/j.jad.2016.11.017 · Cited by 23
“From an intermediate phenotypes framework, it is of mention that these cognitive deficits have also been found in healthy first degree relatives of patients with either MDD or SZ (Christensen et al. 2006; Barrantes-Vidal N, 2007).”
BackgroundGeorgiades, A., Rijsdijk, F. V., Kane, F., Rebollo‐Mesa, I., Kalidindi, S., Schulze, K., Stahl, D. R., Walshe, M., Sahakian, B. J., McDonald, C., et al. (2016) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.115.167239 · Cited by 19
Kravariti, E., Reichenberg, A., Morgan, K. D., Dazzan, P., Morgan, C., Zanelli, J., Lappin, J., Doody, G. A., Harrison, G., Jones, P. B., et al. (2009) · Bipolar Disorders · doi:10.1111/j.1399-5618.2009.00673.x · Cited by 17
Executive function in parents of patients with familial versus sporadic bipolar disorder
Köşger, F., Eşsizoğlu, A., Baltacıoğlu, M., Ülkgün, N., & Yenilmez, Ç. (2015) · Comprehensive Psychiatry · doi:10.1016/j.comppsych.2015.05.013 · Cited by 18
“Impairments in verbal memory, learning, processing speed, set shifting, selective attention, and response inhibition have been widely reported in relatives of bipolar disorder patients [12,13,19,20,22,25,26].”
Miskowiak, K. W., Svendsen, A. M. B., Harmer, C. J., Elliott, R., Macoveanu, J., Siebner, H. R., Kessing, L. V., & Vinberg, M. (2017) · Psychological Medicine · doi:10.1017/s0033291717000861 · Cited by 14
“In brief, the original cohort was recruited through record linkage between the Danish Twin Registry, the Danish Psychiatric Central Research Register and the Danish Civil Registration System and took part in a cross-sectional baseline study in 2003–2005 (see Christensen et al. 2006, 2007).”
MethodSelf-citationScala, S., Pousada-Casal, A., Stone, W. S., Thermenos, H. W., Manschreck, T. C., Tsuang, M. T., Faraone, S. V., & Seidman, L. J. (2013) · Schizophrenia Research · doi:10.1016/j.schres.2012.11.027 · Cited by 14
“, 2005), and in affective psychosis (Ferrier et al., 1999, 2004; Christensen et al., 2006; Balanzá-Martínez et al., 2008).”
BackgroundKnorr, U. B., Vinberg, M., Klose, M., Feldt‐Rasmussen, U., Hilsted, L. M., Gade, A., Haastrup, E. K., Paulson, O. B., Wetterslev, J., Gluud, C. N., et al. (2009) · Trials · doi:10.1186/1745-6215-10-66 · Cited by 13
Self-citationKarakurt, M. N., Mz, K., Yüce, M., Baykal, S., & Şenses, A. (2013) · PubMed · Cited by 13
Uchino, T., Okubo, R., Takubo, Y., Aoki, A., Wada, I., Hashimoto, N., Ikezawa, S., & Nemoto, T. (2023) · Journal of Personalized Medicine · doi:10.3390/jpm13040683 · Cited by 12
“These cognitive impairments might be a core feature of major depressive disorder and an independent symptom, rather than a symptom that arises secondarily from mood symptoms [29,34,35].”
BackgroundWu, M., Mwangi, B., Passos, I. C., Bauer, I. E., Cao, B., Frazier, T. W., Zunta‐Soares, G. B., & Soares, J. C. (2017) · International Journal of Bipolar Disorders · doi:10.1186/s40345-017-0101-9 · Cited by 11
“verbal, declarative, and working memory deficits were shown in unaffected siblings (Gourovitch et al. 1999; Kéri et al. 2001; Kieseppä et al. 2005; Christensen et al. 2006).”
BackgroundDeep, R., Sagar, R., & Mehta, M. (2012) · SAGE Open · doi:10.1177/2158244011436351 · Cited by 10
“The finding is in consonance with some of the previous studies showing impairments of TMT-B in unaffected relatives (Arts, Jabben, Krabbendam, & van Os, 2008; Christensen et al., 2006; Szoke et al., 2006).”
ResultMacoveanu, J., Vinberg, M., Madsen, K. H., Kessing, L. V., Siebner, H. R., & Baaré, W. F. C. (2016) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12638 · Cited by 10
“We previously found that healthy co-twins of patients with affective disorders (high-risk) had impaired executive function and attention and higher subclinical psychopathological ratings compared to healthy twins with no familial risk for affective disorders (low-risk) (16, 17).”
BackgroundSelf-citation5-HTTLPR, victimization and ecological executive function of adolescents
Liu, J., Cao, F., Li, P., Lou, F., & Lavebratt, C. (2016) · Psychiatry Research · doi:10.1016/j.psychres.2016.01.059 · Cited by 9
“Executive dysfunction (ED) has been proposed to precede depression (Christensen et al., 2006). cognitive performance, especially EFs in healthy population (Homberg and Lesch, 2011).”
Course and prognosis of mood disorders
Angst, J. (2012) · doi:10.1093/med/9780199696758.003.0089 · Cited by 9
Knorr, U., Vinberg, M., Gade, A., Winkel, P., Gluud, C. N., Wetterslev, J., Gether, U., & Kessing, L. V. (2011) · Therapeutic Advances in Psychopharmacology · doi:10.1177/2045125311422591 · Cited by 8
“…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 affective symptoms and other minor psychopathology [Christensen et al. 2006].”
BackgroundResultInfluentialSelf-citationRodriguez, C. C., Ruggero, C. J., Callahan, J. L., Kilmer, J. N., Boals, A., & Banks, J. (2012) · Journal of Affective Disorders · doi:10.1016/j.jad.2012.06.029 · Cited by 7
Parent depressive symptoms and offspring executive functioning
Craun, E. A., Lachance, K., Williams, C. L., & Wong, M. M.-H. (2018) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/13803395.2018.1504893 · Cited by 7
Wilson, D. R., & Price, J. (2006) · Current Psychosis & Therapeutics Reports · doi:10.1007/bf02629393 · Cited by 7
“Such endophenotypes include impairments of cognitive function [ 5 ,6], cyclothymia [7], dysmodulation of motivation and reward, and eye movement abnormalities [8].”
BackgroundNeurocognitive Functioning in Bipolar Disorder: A Comprehensive Review of Recent Data
Fountoulakis, K. N. (2014) · Springer eBooks · doi:10.1007/978-3-642-37216-2_4 · Cited by 6
Kravariti, E., Kane, F., & Murray, R. M. (2009) · Springer eBooks · doi:10.1007/978-1-4020-9464-4_13 · Cited by 5
Bipolar disorder - from endophenotypes to treatment.
Hranov, L. G., Marinova, P., Stoyanova, M. B., Pandova, M. S., & Hranov, G. (2013) · PubMed · Cited by 5
Pathways Driving Neuroprogression in Depression: The Role of Immune Activation
Oriolo, G., Grande, I., Martín‐Santos, R., Vieta, E., & Carvalho, A. F. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811073-7.00010-6 · Cited by 6
A nomogram to predict the risk of cognitive impairment in patients with depressive disorder
Jian, Y., Jia, S., Shi, S., Shi, Z., & Zhao, Y. (2023) · Research in Nursing & Health · doi:10.1002/nur.22364 · Cited by 4
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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