Original Research Childhood and Adolescent Mental Health February 23, 2021

Association Between Tetralogy of Fallot and Psychiatric Disorders: A Nationwide Cohort Study

Wan-Fu Hsu, MD; Wu-Chien Chien, PhD; Chi-Hsiang Chung, PhD; Pi-Chang Lee, MD; Der-Shiun Wang, MD; Shao-Wei Huang, MD; Hsin-An Chang, MD; Yu-Chen Kao, MD, MSc; Sung-Sen Yang, PhD; Nian-Sheng Tzeng, MD

J Clin Psychiatry 2021;82(2):19m13126

ABSTRACT

Objective: The tetralogy of Fallot (TOF) has been reported to be associated with some neurodevelopmental impairment and psychiatric disorders. Nevertheless, a nationwide study to clarify the risk between TOF and comorbid psychiatric disorders is lacking. Using a nationwide database in Taiwan, this study aimed to explore the role of TOF in various psychiatric disorders and analyze whether there are patient-related risk factors.

Methods: A total of 16,824 enrolled patients, including 4,206 study subjects who were diagnosed with TOF and 12,618 controls with TOF matched (1:3) for sex, age, hospital visits, and index year, were randomly selected from the Taiwanese National Health Insurance Research Database (NHIRD) between 2000 and 2015. Patients’ diagnoses in the NHIRD were encoded using International Classification of Diseases, 9th Revision, Clinical Modification codes.

Results: Of patients with TOF, 256 (6.09%) developed psychiatric disorders compared to 394 (3.12%) in the control group. After adjusting for covariates, the adjusted hazard ratio of psychiatric disorders for patients with TOF was 3.192 (95% CI, 2.683–3.798; P < .001). After exclusion of psychiatric diagnoses within the first 5 years, TOF was associated with an increased risk of anxiety (P < .001), depression (P < .001), bipolar disorder (P < .001), and sleep disorders (P = .005).

Conclusions: This study revealed that TOF patients have a nearly 3-fold higher risk of psychiatric disorders, including anxiety, depressive, bipolar, and sleep disorders, than the general population. Therefore, continued mental health screening and surveillance are warranted in TOF patients.

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  1. Apitz C, Webb GD, Redington AN. Tetralogy of Fallot. Lancet. 2009;374(9699):1462–1471. PubMed CrossRef NLM
  2. Wu M-H, Chen H-C, Lu C-W, et al. Prevalence of congenital heart disease at live birth in Taiwan. J Pediatr. 2010;156(5):782–785. PubMed CrossRef NLM
  3. Wu M-H, Lu C-W, Chen H-C, et al. Arrhythmic burdens in patients with tetralogy of Fallot: a national database study. Heart Rhythm. 2015;12(3):604–609. PubMed CrossRef NLM
  4. Bellinger DC, Rivkin MJ, DeMaso D, et al. Adolescents with tetralogy of Fallot: neuropsychological assessment and structural brain imaging. Cardiol Young. 2015;25(2):338–347. PubMed CrossRef NLM
  5. Kashiwagi H, Ikezawa S, Sumiyoshi T, et al. A case of schizophrenia comorbid for tetralogy of Fallot treated with clozapine: further considerations on a role for 22q.11.2 in the proneness for seizures. Neuropsychiatr Dis Treat. 2017;13:2271–2273. PubMed CrossRef NLM
  6. Hulvershorn LA, Madou MRZ, Weis JR, et al. First-episode psychosis in an adolescent with seizure disorder and Tetralogy of Fallot. J Child Adolesc Psychopharmacol. 2009;19(3):307–311. PubMed CrossRef NLM
  7. Tastuzawa Y, Sekikawa K, Suda T, et al. An interictal schizophrenia-like psychosis in an adult patient with 22q11.2 deletion syndrome. Epilepsy Behav Case Rep. 2015;3:36–38. PubMed CrossRef NLM
  8. Holland JE, Cassidy AR, Stopp C, et al. Psychiatric disorders and function in adolescents with tetralogy of Fallot. J Pediatr. 2017;187:165–173. PubMed CrossRef NLM
  9. Hsieh C-Y, Su C-C, Shao S-C, et al. Taiwan’s National Health Insurance Research Database: past and future. Clin Epidemiol. 2019;11:349–358. PubMed CrossRef NLM
  10. Yang C-W, Tzeng N-S, Yin Y-J, et al. Angiotensin receptor blockers decrease the risk of major adverse cardiovascular events in patients with end-stage renal disease on maintenance dialysis: a nationwide matched-cohort study. PLoS One. 2015;10(10):e0140633. PubMed CrossRef NLM
  11. Tzeng N-S, Chung C-H, Chang H-A, et al. Obstructive sleep apnea in children and adolescents and the risk of major adverse cardiovascular events: a nationwide cohort study in Taiwan. J Clin Sleep Med. 2019;15(2):275–283. PubMed CrossRef NLM
  12. Wang J-C, Chien W-C, Tzeng N-S, et al. Surgical repair of aortic aneurysms and reduced incidence of dementia. Int J Cardiol. 2019;278:46–50. PubMed CrossRef NLM
  13. Tzeng N-S, Chung C-H, Chang S-Y, et al. Risk of psychiatric disorders in pulmonary embolism: a nationwide cohort study. J Investig Med. 2019;67(6):977–986. PubMed CrossRef NLM
  14. Cheng T-M. Taiwan’s National Health Insurance System: High Value for the Dollar. Six Countries, Six Reform Models: The Healthcare Reform Experience of Israel, The Netherlands, New Zealand, Singapore, Switzerland and Taiwan. World Scientific; 2009:171–204.
  15. Cheng C-L, Kao Y-H, Lin S-J, et al. Validation of the national health insurance research database with ischemic stroke cases in Taiwan. Pharmacoepidemiol Drug Saf. 2011;20(3):236–242. PubMed CrossRef NLM
  16. Hsieh C-Y, Chen C-H, Li C-Y, et al. Validating the diagnosis of acute ischemic stroke in a National Health Insurance claims database. J Formos Med Assoc. 2015;114(3):254–259. PubMed CrossRef NLM
  17. Needham DM, Scales DC, Laupacis A, et al. A systematic review of the Charlson comorbidity index using Canadian administrative databases: a perspective on risk adjustment in critical care research. J Crit Care. 2005;20(1):12–19. PubMed CrossRef NLM
  18. Chang C-Y, Chen W-L, Liou Y-F, et al. Increased risk of major depression in the three years following a femoral neck fracture—a national population-based follow-up study. PLoS One. 2014;9(3):e89867. PubMed CrossRef NLM
  19. Blanche P, Proust-Lima C, Loubère L, et al. Quantifying and comparing dynamic predictive accuracy of joint models for longitudinal marker and time-to-event in presence of censoring and competing risks. Biometrics. 2015;71(1):102–113. PubMed CrossRef NLM
  20. Fu TST, Lee CS, Gunnell D, et al. Changing trends in the prevalence of common mental disorders in Taiwan: a 20-year repeated cross-sectional survey. Lancet. 2013;381(9862):235–241. PubMed CrossRef NLM
  21. Marino BS, Lipkin PH, Newburger JW, et al; American Heart Association Congenital Heart Defects Committee, Council on Cardiovascular Disease in the Young, Council on Cardiovascular Nursing, and Stroke Council. Neurodevelopmental outcomes in children with congenital heart disease: evaluation and management: a scientific statement from the American Heart Association. Circulation. 2012;126(9):1143–1172. PubMed CrossRef NLM
  22. Hövels-Gürich HH, Konrad K, Skorzenski D, et al. Long-term neurodevelopmental outcome and exercise capacity after corrective surgery for tetralogy of Fallot or ventricular septal defect in infancy. Ann Thorac Surg. 2006;81(3):958–966. PubMed CrossRef NLM
  23. Hövels-Gürich HH, Konrad K, Skorzenski D, et al. Attentional dysfunction in children after corrective cardiac surgery in infancy. Ann Thorac Surg. 2007;83(4):1425–1430. PubMed CrossRef NLM
  24. Davidson J, Gringras P, Fairhurst C, et al. Physical and neurodevelopmental outcomes in children with single-ventricle circulation. Arch Dis Child. 2015;100(5):449–453. PubMed CrossRef NLM
  25. Kaltman JR, Di H, Tian Z, et al. Impact of congenital heart disease on cerebrovascular blood flow dynamics in the fetus. Ultrasound Obstet Gynecol. 2005;25(1):32–36. PubMed CrossRef NLM
  26. Indredavik MS, Skranes JS, Vik T, et al. Low-birth-weight adolescents: psychiatric symptoms and cerebral MRI abnormalities. Pediatr Neurol. 2005;33(4):259–266. PubMed CrossRef NLM
  27. Loeber R, Burke JD, Lahey BB, et al. Oppositional defiant and conduct disorder: a review of the past 10 years, part I. J Am Acad Child Adolesc Psychiatry. 2000;39(12):1468–1484. PubMed CrossRef NLM
  28. Maughan B, Rowe R, Messer J, et al. Conduct disorder and oppositional defiant disorder in a national sample: developmental epidemiology. J Child Psychol Psychiatry. 2004;45(3):609–621. PubMed CrossRef NLM
  29. He P, Chen G, Wang Z, et al. Adults with intellectual disabilities in China: comorbid psychiatric disorder and its association with health service utilisation. J Intellect Disabil Res. 2018;62(2):106–114. PubMed CrossRef NLM
  30. Whitaker S, Read S. The prevalence of psychiatric disorders among people with intellectual disabilities: an analysis of the literature. J Appl Res Intellect Disabil. 2006;19(4):330–345. CrossRef
  31. Yi JJ, Tang SX, McDonald-McGinn DM, et al. Contribution of congenital heart disease to neuropsychiatric outcome in school-age children with 22q11.2 deletion syndrome. Am J Med Genet B Neuropsychiatr Genet. 2014;165B(2):137–147. PubMed CrossRef NLM
  32. Gothelf D, Presburger G, Levy D, et al. Genetic, developmental, and physical factors associated with attention deficit hyperactivity disorder in patients with velocardiofacial syndrome. Am J Med Genet B Neuropsychiatr Genet. 2004;126B(1):116–121. PubMed CrossRef NLM
  33. Gothelf D, Presburger G, Zohar AH, et al. Obsessive-compulsive disorder in patients with velocardiofacial (22q11 deletion) syndrome. Am J Med Genet B Neuropsychiatr Genet. 2004;126B(1):99–105. PubMed CrossRef NLM
  34. Pao M, Bosk A. Anxiety in medically ill children/adolescents. Depress Anxiety. 2011;28(1):40–49. PubMed CrossRef NLM
  35. Spijkerboer AW, De Koning WB, Duivenvoorden HJ, et al. Medical predictors for long-term behavioral and emotional outcomes in children and adolescents after invasive treatment of congenital heart disease. J Pediatr Surg. 2010;45(11):2146–2153. PubMed CrossRef NLM