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Risk and coaggregation of major psychiatric disorders among first-degree relatives of patients with bipolar disorder: a nationwide population-based study

  • Mu-Hong Chen (a1) (a2), Ju-Wei Hsu (a1) (a2), Kei-Lin Huang (a1) (a2), Tung-Ping Su (a1) (a2) (a3), Cheng-Ta Li (a1) (a2), Wei-Chen Lin (a1) (a2), Shih-Jen Tsai (a1) (a2), Chih-Ming Cheng (a1) (a2), Wen-Han Chang (a1), Tai-Long Pan (a4) (a5) (a6), Tzeng-Ji Chen (a7) (a8) and Ya-Mei Bai (a1) (a2)...

Abstract

Background

Bipolar disorder is a highly heritable mental illness that transmits intergeneratively. Previous studies supported that first-degree relatives (FDRs), such as parents, offspring, and siblings, of patients with bipolar disorder, had a higher risk of bipolar disorder. However, whether FDRs of bipolar patients have an increased risk of schizophrenia, major depressive disorder (MDD), autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD) remains unclear.

Methods

Among the entire population in Taiwan, 87 639 patients with bipolar disorder and 188 290 FDRs of patients with bipolar disorder were identified in our study. The relative risks (RRs) of major psychiatric disorders were assessed among FDRs of patients with bipolar disorder.

Results

FDRs of patients with bipolar disorder were more likely to have a higher risk of major psychiatric disorders, including bipolar disorder (RR 6.12, 95% confidence interval (CI) 5.95–6.30), MDD (RR 2.89, 95% CI 2.82–2.96), schizophrenia (RR 2.64, 95% CI 2.55–2.73), ADHD (RR 2.21, 95% CI 2.13–2.30), and ASD (RR 2.10, 95% CI 1.92–2.29), than the total population did. These increased risks for major psychiatric disorders were consistent across different familial kinships, such as parents, offspring, siblings, and twins. A dose-dependent relationship was also found between risk of each major psychiatric disorder and numbers of bipolar patients.

Conclusions

Our study was the first study to support the familial coaggregation of bipolar disorder with other major psychiatric disorders, including schizophrenia, MDD, ADHD, and ASD, in a Taiwanese (non-Caucasian) population. Given the elevated risks of major psychiatric disorders, the public health government should pay more attention to the mental health of FDRs of patients with bipolar disorder.

Copyright

Corresponding author

Author for correspondence: Ya-Mei Bai, E-mail: ymbi@mail2000.com.tw and Tung-Ping Su, E-mail: tomsu0402@gmail.com

References

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Axelson, D, Goldstein, B, Goldstein, T, Monk, K, Yu, H, Hickey, MB, Sakolsky, D, Diler, R, Hafeman, D, Merranko, J, Iyengar, S, Brent, D, Kupfer, D and Birmaher, B (2015) Diagnostic precursors to bipolar disorder in offspring of parents with bipolar disorder: a longitudinal study. Amercian Journal of Psychiatry 172, 638646.
Birmaher, B, Axelson, D, Monk, K, Kalas, C, Goldstein, B, Hickey, MB, Obreja, M, Ehmann, M, Iyengar, S, Shamseddeen, W, Kupfer, D and Brent, D (2009) Lifetime psychiatric disorders in school-aged offspring of parents with bipolar disorder: the Pittsburgh Bipolar Offspring study. Archives of General Psychiatry 66, 287296.
Birmaher, B, Axelson, D, Goldstein, B, Monk, K, Kalas, C, Obreja, M, Hickey, MB, Iyengar, S, Brent, D, Shamseddeen, W, Diler, R and Kupfer, D (2010) Psychiatric disorders in preschool offspring of parents with bipolar disorder: the Pittsburgh Bipolar Offspring Study (BIOS). Amercian Journal of Psychiatry 167, 321330.
Blanco, C, Compton, WM, Saha, TD, Goldstein, BI, Ruan, WJ, Huang, B and Grant, BF (2017) Epidemiology of DSM-5 bipolar I disorder: results from the national epidemiologic survey on alcohol and related conditions - III. Journal of Psychiatric Research 84, 310317.
Chen, MH, Su, TP, Chen, YS, Hsu, JW, Huang, KL, Chang, WH and Bai, YM (2013) Attention deficit hyperactivity disorder, tic disorder, and allergy: is there a link? A nationwide population-based study. Journal of Child Psychology Psychiatry 54, 545551.
Chen, MH, Pan, TL, Hsu, JW, Huang, KL, Su, TP, Li, CT, Lin, WC, Tsai, SJ, Chang, WH, Chen, TJ and Bai, YM (2016) Attention-deficit hyperactivity disorder comorbidity and antidepressant resistance among patients with major depression: a nationwide longitudinal study. European Neuropsychopharmacology 26, 17601767.
Chen, MH, Hsu, JW, Huang, KL, Bai, YM, Ko, NY, Su, TP, Li, CT, Lin, WC, Tsai, SJ, Pan, TL, Chang, WH and Chen, TJ (2018) Sexually transmitted infection among adolescents and young adults with attention-deficit/hyperactivity disorder: a nationwide longitudinal study. Journal of the American Academy of Child and Adolescent Psychiatry 57, 4853.
Cheng, CM, Chang, WH, Chen, MH, Tsai, CF, Su, TP, Li, CT, Tsai, SJ, Hsu, JW, Huang, KL, Lin, WC, Chen, TJ and Bai, YM (2018) Co-aggregation of major psychiatric disorders in individuals with first-degree relatives with schizophrenia: a nationwide population-based study. Molecular Psychiatry 23, 17561763.
Cross-Disorder Group of the Psychiatric Genomics Consortium (2013 a) Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics 45, 984994.
Cross-Disorder Group of the Psychiatric Genomics Consortium (2013 b) Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 381, 13711379.
Grande, I, Berk, M, Birmaher, B and Vieta, E (2016) Bipolar disorder. Lancet 387, 15611572.
Kuo, CF, Grainge, MJ, Valdes, AM, See, LC, Luo, SF, Yu, KH, Zhang, W and Doherty, M (2015) Familial aggregation of systemic lupus erythematosus and coaggregation of autoimmune diseases in affected families. JAMA Internal Medicine 175, 15181526.
Lin, PI, McInnis, MG, Potash, JB, Willour, V, MacKinnon, DF, DePaulo, JR and Zandi, PP (2006) Clinical correlates and familial aggregation of age at onset in bipolar disorder. American Journal of Psychiatry 163, 240246.
Maier, W, Lichtermann, D, Minges, J, Hallmayer, J, Heun, R, Benkert, O and Levinson, DF (1993) Continuity and discontinuity of affective disorders and schizophrenia. Results of a controlled family study. Archives of General Psychiatry 50, 871883.
McGuffin, P, Rijsdijk, F, Andrew, M, Sham, P, Katz, R and Cardno, A (2003) The heritability of bipolar affective disorder and the genetic relationship to unipolar depression. Archives of General Psychiatry 60, 497502.
Merikangas, KR, Cui, L, Kattan, G, Carlson, GA, Youngstrom, EA and Angst, J (2012) Mania with and without depression in a community sample of US adolescents. Archives of General Psychiatry 69, 943951.
Merikangas, KR, Cui, L, Heaton, L, Nakamura, E, Roca, C, Ding, J, Qin, H, Guo, W, Shugart, YY, Zarate, C and Angst, J (2014) Independence of familial transmission of mania and depression: results of the NIMH family study of affective spectrum disorders. Molecular Psychiatry 19, 214219.
Mesman, E, Nolen, WA, Reichart, CG, Wals, M and Hillegers, MH (2013) The Dutch bipolar offspring study: 12-year follow-up. American Journal of Psychiatry 170, 542549.
Muller-Oerlinghausen, B, Berghofer, A and Bauer, M (2002) Bipolar disorder. Lancet 359, 241247.
Rasic, D, Hajek, T, Alda, M and Uher, R (2014) Risk of mental illness in offspring of parents with schizophrenia, bipolar disorder, and major depressive disorder: a meta-analysis of family high-risk studies. Schizophrenia Bulletin 40, 2838.
Song, J, Bergen, SE, Kuja-Halkola, R, Larsson, H, Landen, M and Lichtenstein, P (2015) Bipolar disorder and its relation to major psychiatric disorders: a family-based study in the Swedish population. Bipolar Disorders 17, 184193.
Sucksdorff, D, Chudal, R, Suominen, A, Jokiranta, E, Brown, AS and Sourander, A (2014) Bipolar disorder and parental psychopathology. Social Psychiatry and Psychiatric Epidemiology 49, 19731984.
Vandeleur, CL, Merikangas, KR, Strippoli, MP, Castelao, E and Preisig, M (2014) Specificity of psychosis, mania and major depression in a contemporary family study. Molecular Psychiatry 19, 209213.
Weissman, MM, Bland, RC, Canino, GJ, Faravelli, C, Greenwald, S, Hwu, HG, Joyce, PR, Karam, EG, Lee, CK, Lellouch, J, Lepine, JP, Newman, SC, Rubio-Stipec, M, Wells, JE, Wickramaratne, PJ, Wittchen, H and Yeh, EK (1996) Cross-national epidemiology of major depression and bipolar disorder. JAMA 276, 293299.
Yelland, LN, Salter, AB and Ryan, P (2011) Performance of the modified Poisson regression approach for estimating relative risks from clustered prospective data. American Journal of Epidemiology 174, 984992.
Zou, G (2004) A modified Poisson regression approach to prospective studies with binary data. American Journal of Epidemiology 159, 702706.

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