Mental disorders in adolescents at familial high-risk of schizophrenia or bipolar disorder and population-based controls – an eight-year follow-up study, The Danish High Risk and Resilience Study, VIA 15

  1. Doris Helena Bjarnadóttir Streymá
  2. Maja Gregersen
  3. Nanna Weye
  4. Carsten Hjorthøj
  5. Mette Falkenberg Krantz
  6. Anne Søndergaard
  7. Marta Schiavon
  8. Sinnika Birkehøj Rohd
  9. Martin Wilms
  10. Ditte Ellersgaard
  11. Sofie Baltser Christensen
  12. Mette Enevoldsen
  13. Merete Birk
  14. Charlotte Sand Nielsen
  15. Andreas Færgemand Laursen
  16. Anette Faurskov Bundgaard
  17. Lotte Veddum
  18. Ole Mors
  19. Aja Neergaard Greve
  20. Nicoline Hemager
  21. Merete Nordentoft
  22. Anne AE Thorup
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Abstract

Background

Children of parents with schizophrenia (SZ) or bipolar disorder (BP) show elevated rates of mental disorders. Longitudinal studies comparing offspring at familial risk with the background population are lacking.

Method

This study is an eight-year follow-up of the Danish High Risk and Resilience study. We examined four-year prevalence from age 11 to age15 (n=416), cumulative incidence by age 15 (n=516), persistency of mental disorders from age 11to age 15 (n=396) and global functioning in 15-year-old adolescents with familial high risk of SZ (FHR-SZ) or BP (FHR-BP) compared to population-based controls (PBC). We assessed mental disorders and global functioning with the Kiddie Schedule for Affective Disorders and Schizophrenia – Present and Lifetime Version (K-SADS-PL) and the Children’s Global Assessment Scale (CGAS).

Results

Four-year prevalence of any mental disorder was higher in FHR-SZ (51.3%, OR=2.39, 95% CI 1.49-3.83) and FHR-BP (45.9%, OR=1.98, 95% CI 1.16-3.37) compared with PBC (30.5%). Cumulative incidence of mental disorders by age 15 was higher in FHR-SZ (67.2%, OR=3.19, 95% CI 2.11-4.82) and FHR-BP (64.4%, OR=2.82, 95% CI 1.75-4.54) than in PBC (39.1%). Adolescents with FHR-SZ showed the highest rate of persistent mental disorders (33.3%), followed by FHR-BP (24.5%), and PBC the lowest (12.9%). Global functioning at age 15 was lower in FHR-SZ than in both FHR-BP and PBC, and FHR-BP showed lower scores compared with PBC. Between-group differences in cumulative incidences of mental disorders and in global functioning scores remained stable across ages 7,11 and 15.

Conclusion

Adolescents at FHR-SZ or FHR-BP show elevated risks of a range of mental disorders, psychiatric comorbidity, and lower global functioning from childhood to mid-adolescence, not confined to the disorders for which they carry familial risk. This vulnerability underscores the need for early detection and support for FHR offspring and their families.

Key Point

What’s known?

  • Children of parents with schizophrenia or bipolar disorder (Familial High Risk (FHR) offspring) have an elevated risk of mental disorders. Adolescence is a recognized critical period for mental disorder onset and progression.

What’s new?

  • This eight-year prospective follow-up study brings novel insight into the transition from childhood to mid-adolescence, by comparing FHR offspring with population-based controls.

  • Our study showed higher four-year prevalence, cumulative incidence and persistency of mental disorders as well as lower global functioning in the FHR.

  • Adolescent psychopathology encompassed a broad range of diagnoses beyond parental disorders.

What’s relevant?

  • Group differences in mental disorders and global functioning remained stable from childhood to adolescence, indicating a persistent, early emerging vulnerability, which underscores the importance of early identification and family support.

Article activity feed

  1. Version published to 10.64898/2026.08.22.26360313 on medRxiv