High concordance of bipolar I disorder in a nationwide sample of twins. Am J Psychiatry

Department of Dental Public Health, University of Helsinki, Helsinki, Uusimaa, Finland
American Journal of Psychiatry (Impact Factor: 12.3). 11/2004; 161(10):1814-21. DOI: 10.1176/appi.ajp.161.10.1814
Source: PubMed


The few studies of bipolar I disorder in twins have consistently emphasized the genetic contribution to disease liability. The authors report what appears to be the first twin study of bipolar I disorder involving a population-based twin sample, in which the diagnoses were made by using structured, personal interviews.
All Finnish same-sex twins (N=19,124) born from 1940 to 1957 were screened for a diagnosis of bipolar I disorder as recorded in the National Hospital Discharge Register between 1969 and 1991 or self-reported in surveys of the Finnish Twin Cohort in 1975, 1981, and 1990. Thirty-eight pairs were thereby identified and invited to participate in the study; the participation rate was 68%. Lifetime diagnoses were made by using the Structured Clinical Interview for DSM-IV. The authors calculated probandwise and pairwise concordances and correlations in liability and applied biometrical model fitting.
The probandwise concordance rates were 0.43 (95% CI=0.10 to 0.82) for monozygotic twins and 0.06 (95% CI=0.00 to 0.27) for dizygotic twins. The correlations in liability were 0.85 and 0.41, respectively. The model with no familial transmission was rejected. The best-fitting model was the one in which genetic and specific environmental factors explained the variance in liability, with a heritability estimate of 0.93 (95% CI=0.69 to 1.00).
The high heritability of bipolar disorder was demonstrated in a nationwide population-based twin sample assessed with structured personal interviews.

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Available from: Tuula Kieseppä, Oct 05, 2015
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    • "Individuals with a strong family history of MDD have shown a interest in having a genetic test, if such a test were available (Wilde et al., 2010), especially when the perceived risk of developing the disorder is high (Wilde et al., 2011). Evidence for a genetic component for affective disorders arises primarily from heritability estimates for MDD (33–48%) (Kendler and Prescott, 1999; McGuffin et al., 1996) and BD (79–83%) (Kieseppa et al., 2004; McGuffin et al., 2003), derived from twin studies. However, heritability estimates provide an approximation of the proportion of phenotypic variance that can be attributed to Contents lists available at ScienceDirect journal homepage: "
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    ABSTRACT: Background To conduct a meta-analysis to estimate the incidence of major depressive disorder (MDD) and bipolar disorder (BD) in first-degree relatives (FDRs) of probands affected by MDD or BD. The risk for MDD in FDR of BD probands and vice versa is also investigated. Methods A systematic review of case-control and cohort studies, which were published between 1977 and 2012; reported relative risks (RR) or odd ratios (OR) or equivalent raw data; made an explicit distinction between MDD and BD; used operational diagnostic criteria; and reported systematic proband recruitment and ascertainment of relatives. Studies were obtained by electronic MEDLINE and EMBASE searches and hand-searching. Estimates were derived from pooled data using random effects methods. Results Of an initial sample of 241 articles, 22 were eligible for inclusion. For FDRs of one proband with MDD compared to healthy control probands, estimates for MDD were OR=2.14 (95% CI 1.72–2.67), increasing to OR=3.23 (95% CI 2.11–4.94) for two MDD probands. For FDRs of one BD proband compared to healthy control probands, estimates for BD were OR=7.92 (95% CI 2.45–25.61), and OR=6.58 (95% CI 2.64–16.43) for FDRs of two BD probands. Conclusions These findings support previously published data indicating strong familiality for both MDD and BD. Data will be useful in providing individuals with a family history of MDD or BPD with tailored risk estimates.
    Journal of Affective Disorders 04/2014; 58:37-47. DOI:10.1016/j.jad.2014.01.014 · 3.38 Impact Factor
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    • "The etiology of mood disorders has not yet been fully described but believed to be multifactorial, and genetic factor plays a role in the pathogenesis of these disorders. Heritability of bipolar disorder is estimated at 90%, whereas for unipolar disorder it is around 40% [4], [5]. "
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    ABSTRACT: To assess the association of P2RX7 gene rs2230912 polymorphism with mood disorders using a meta-analysis. DATA WERE COLLECTED FROM THE FOLLOWING ELECTRONIC DATABASES: PubMed, Excerpta Medica Database, Elsevier Science Direct, Cochrane Library, and Chinese Biomedical Literature Database, with the last report up to April 1, 2013. Odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the association. Dependent on the results of heterogeneity test among individual studies, the fixed effect model (Mantel-Haenszel) or random effect model (DerSimonian-Laird) was selected to summarize the pooled OR. We identified 13 separate studies using search (6,962 cases and 9,262 controls). We detected significant between-study heterogeneity. No significant association of this polymorphism with mood disorders was found (P>0.05). We also performed disease-specific meta-analysis in unipolar depression and bipolar disorder. No significant association of this polymorphism with unipolar depression or bipolar disorder was found (P>0.05). Additionally, we performed subgroup analysis by different types of cases. No significant association of this polymorphism with mood disorders in clinical cohorts or population-based cohorts (P>0.05). A significant association of this polymorphism with mood disorders was found for the allele contrast in family-based cohorts (OR = 1.26, 95%CI = 1.05-1.50, P = 0.01). Overall, our meta-analysis suggests that P2RX7 gene rs2230912 polymorphism may not contribute to the risk of developing mood disorders using a case-control design. Given the discordance in the subgroup analysis by different types of cases, further studies based on larger sample size are still needed.
    PLoS ONE 02/2014; 9(2):e88575. DOI:10.1371/journal.pone.0088575 · 3.23 Impact Factor
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    • "Various studies (family, twin, and adoption) have revealed that bipolar disorder (BD) is largely hereditary (85 – 93%) (McGuffi n et al. 2003; Kieseppa et al. 2004; Balanz á -Mart í nez et al. 2008). Th e complex genetic structure and multifactorial etiology of BD has led researchers to investigate possible vulnerability factors using a variety of genetic approaches. "
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    ABSTRACT: Objective: Cognitive dysfunction in bipolar disorder (BD) is well established in the literature. The neurocognitive deficits have been considered to be endophenotypic markers of BD, and studies have examined whether neurocognitive deficits exist in first-degree relatives of individuals with BD I. We hypothesized that performance in tests of neurocognitive function would be impaired in euthymic BD I patients and their unaffected first-degree relatives compared to that of healthy controls. Methods: We compared the performance of bipolar patients, their first-degree relatives, and healthy controls in a battery of neurocognitive tests to reveal possible endophenotypes of BD. A diagnostic interview and neuropsychological test battery were administered to 30 BD I patients, 55 of their unaffected first-degree relatives and 32 healthy controls. Results: The patients and their first-degree relatives were significantly impaired in executive function assessed using the Wisconsin Card Sorting Test (WCST) and Trail Making Test-B (TMT-B) relative to the controls (WCST; perseverative errors: p < 0.0005, categories completed: p = 0.002, TMT-B; p = 0.002). There were no significant differences between the groups in terms of attention, psychomotor speed, verbal memory, or learning. Conclusion: Our study suggests that the deficits in executive function may be endophenotypic markers of genetic vulnerability to BD I.
    International Journal of Psychiatry in Clinical Practice 10/2013; 18(3). DOI:10.3109/13651501.2013.859706 · 1.39 Impact Factor
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