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Examining selection bias in a population-based cohort study of 522 children with familial high risk of schizophrenia or bipolar disorder, and controls: The Danish High Risk and Resilience Study VIA 7

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Abstract

Purpose

Knowledge about representativity of familial high-risk studies of schizophrenia and bipolar disorder is essential to generalize study conclusions. The Danish High Risk and Resilience Study (VIA 7), a population-based case–control familial high-risk study, creates a unique opportunity for combining assessment and register data to examine cohort representativity.

Methods

Through national registers, we identified the population of 11,959 children of parents with schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) and controls from which the 522 children participating in The VIA 7 Study (202 FHR-SZ, 120 FHR-BP and 200 controls) were selected. Socio-economic and health data were obtained to compare high-risk groups and controls, and participants versus non-participants. Selection bias impact on results was analyzed through inverse probability weights.

Results

In the total sample of 11,959 children, FHR-SZ and FHR-BP children had more socio-economic and health disadvantages than controls (p < 0.001 for most). VIA 7 non-participants had a poorer function, e.g. more paternal somatic and mental illness (p = 0.02 and p = 0.04 for FHR-SZ), notifications of concern (FHR-BP and PBC p < 0.001), placements out of home (p = 0.03 for FHR-SZ), and lower level of education (p ≤ 0.01 for maternal FHR-SZ and FHR-BP, p = 0.001 for paternal FHR-BP). Inverse probability weighted analyses of results generated from the VIA Study showed minor changes in study findings after adjustment for the found selection bias.

Conclusions

Familial high-risk families have multiple socio-economic and health disadvantages. In The VIA 7 Study, although comparable regarding mental illness severity after their child’s birth, socioeconomic and health disadvantages are more profound amongst non-participants than amongst participants.

Key summary points

Children with familial high risk of schizophrenia or bipolar disorder, and their parents, are more disadvantaged than controls regarding socio-economy, health, family level of function, and child school life.

Families participating in The VIA 7 Study have fewer preventive interventions, fewer notifications of concern and their children are less frequently placed outside of the home compared to non-participants, and thus the VIA 7 population may to some degree represent better functioning families than familial high-risk families in general.

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Acknowledgements

We thank the participating families for their great contribution to this study. We also thank Marianne Giørtz Pedersen and Carsten Bøcker Pedersen for their support in the extraction of data from registers.

Funding

The Danish High Risk and Resilience Study has received economic support from The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH, grant number R102-A9118 and R155-2014–1724), the Mental Health Services of the Capital Region of Denmark, University of Aarhus, University of Copenhagen, The Tryg Foundation, and The Beatrice Surovell Haskell Fund for Child Mental Health Research of Copenhagen. The funding sources have not had any influence on the study design or the reporting of data.

Author information

Authors and Affiliations

  1. CORE- Copenhagen Research Center for Mental Health, Mental Health Center Copenhagen, The Danish High Risk and Resilience Study VIA 7 and VIA 11, Capital Region of Denmark, Copenhagen University Hospital, Gentofte Hospitalsvej 15, opg. 15, 1. Sal., 2900, Hellerup, Denmark

    Mette Falkenberg Krantz, Carsten Hjorthøj, Ditte Ellersgaard, Nicoline Hemager, Camilla Christiani, Maja Gregersen, Anne Søndergaard, Jessica Ohland, Kerstin Jessica Plessen, Jens Richardt Møllegaard Jepsen, Anne A. E. Thorup & Merete Nordentoft

  2. Faculty of Health and Medical Sciences, Institute of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark

    Mette Falkenberg Krantz, Nicoline Hemager, Camilla Christiani, Maja Gregersen, Anne Søndergaard, Anne A. E. Thorup & Merete Nordentoft

  3. Research Unit at Child and Adolescent Mental Health Center Copenhagen, Gentofte Hospitalsvej 3A, opg. 3A, 1. sal, 2900, Hellerup, Denmark

    Katrine Søborg Spang, Birgitte Klee Burton, Jens Richardt Møllegaard Jepsen & Anne A. E. Thorup

  4. iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Fuglesangs Allé 26, Aarhus N, 8210, Arhus, Denmark

    Mette Falkenberg Krantz, Carsten Hjorthøj, Ditte Ellersgaard, Nicoline Hemager, Camilla Christiani, Katrine Søborg Spang, Maja Gregersen, Anne Søndergaard, Aja Greve, Jessica Ohland, Preben Bo Mortensen, Kerstin Jessica Plessen, Vibeke Bliksted, Jens Richardt Møllegaard Jepsen, Anne A. E. Thorup, Ole Mors & Merete Nordentoft

  5. The Psychosis Research Unit, Aarhus University Hospital, Psychiatry, Palle Juul-Jensens Boulevard 175, Aarhus N, 8200, Arhus, Denmark

    Aja Greve, Vibeke Bliksted & Ole Mors

  6. Mental Health Services, Capital Region of Denmark, Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Center Glostrup, Nordstjernevej 41, 2600, Glostrup, Denmark

    Jens Richardt Møllegaard Jepsen

  7. Department of Clinical Medicine, Faculty of Health and Medical Services, Aarhus University, Palle Juul-Jensens Boulevard 82, Aarhus N, 8200, Arhus, Denmark

    Aja Greve, Vibeke Bliksted & Ole Mors

  8. Division of Child and Adolescent Psychiatry, Department of Psychiatry, Lausanne University Hospital, Avenue d’Echallens 9, 1004, Lausanne, Switzerland

    Kerstin Jessica Plessen

  9. Department of Economics and Business Economics, National Centre for Register-Based Research, Aarhus University, Fuglesangs Allé 26, Bygning R2640-R2641, Aarhus V, 8210, Arhus, Denmark

    Preben Bo Mortensen

  10. Department of Public Health, Section of Epidemiology, University of Copenhagen, Copenhagen, Denmark

    Carsten Hjorthøj

Authors
  1. Mette Falkenberg Krantz
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  2. Carsten Hjorthøj
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  3. Ditte Ellersgaard
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  4. Nicoline Hemager
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  5. Camilla Christiani
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  6. Katrine Søborg Spang
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  7. Birgitte Klee Burton
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  8. Maja Gregersen
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  9. Anne Søndergaard
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  10. Aja Greve
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  11. Jessica Ohland
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  12. Preben Bo Mortensen
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  13. Kerstin Jessica Plessen
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  14. Vibeke Bliksted
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  15. Jens Richardt Møllegaard Jepsen
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  16. Anne A. E. Thorup
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  17. Ole Mors
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  18. Merete Nordentoft
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Contributions

Concept and design: MFK, MN, AAET, OM; Acquisition, analysis, or interpretation of data: MFK, CH, JO, MN; Manuscript draft: MFK, MN; Critical revision for intellectual content: All authors; Obtained funding: KJP, OM, JRMJ, AAET, MN; Administrative, technical, or material support: MFK, CH, JO, PBM, DE, AG, KSS, CC, MG, AS, BKB, NH, AAET, MN.

Corresponding author

Correspondence to Mette Falkenberg Krantz.

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Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethics approval

The Scientific Ethical Committee concluded upon approval of The VIA 7 Study that no approval of The Danish High Risk and Resilience Study was needed from their side according to Danish research legislation. The extraction of data concerning eligible participants was approved by The Danish Health Data Authority (approval number FSEID-00003828) and by Statistics Denmark (DST ID 707519). The Danish Data Protection Agency also approved the study (approval number 2007–58-0015), as did the Capital Region Authorities for Health Research (2012–58-0004). All human studies have been approved by the appropriate committees including the ethical committee which concluded that no approval was needed and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Consent to participate

All participants gave their informed consent prior to their inclusion in The VIA 7 Study. Parents consented on behalf of their children according to Danish legislation. For register-based anonymized data, no consent is needed according to Danish legislation upon the obtained approvals.

Consent for publication

All participants in The VIA 7 Study were informed that data would be published without disclosing the identity of the subjects and consented to participate upon this information. For register-based anonymized data, no consent is needed according to Danish legislation upon the obtained approvals.

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Krantz, M.F., Hjorthøj, C., Ellersgaard, D. et al. Examining selection bias in a population-based cohort study of 522 children with familial high risk of schizophrenia or bipolar disorder, and controls: The Danish High Risk and Resilience Study VIA 7. Soc Psychiatry Psychiatr Epidemiol 58, 113–140 (2023). https://doi.org/10.1007/s00127-022-02338-3

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