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The relative and interactive impact of multiple risk factors in schizophrenia spectrum disorders: a combined register-based and clinical twin study

Published online by Cambridge University Press:  05 August 2021

C. Lemvigh Open the ORCID record for C. Lemvigh [Opens in a new window] ,
R. Brouwer Open the ORCID record for R. Brouwer [Opens in a new window] ,
R. Hilker ,
S. Anhøj Open the ORCID record for S. Anhøj [Opens in a new window] ,
L. Baandrup Open the ORCID record for L. Baandrup [Opens in a new window] ,
C. Pantelis Open the ORCID record for C. Pantelis [Opens in a new window] ,
B. Glenthøj Open the ORCID record for B. Glenthøj [Opens in a new window]  and
B. Fagerlund Open the ORCID record for B. Fagerlund [Opens in a new window]
C. Lemvigh*
Affiliation:
Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS) and Center for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Center Glostrup, Glostrup, Denmark Department of Psychology, Faculty of Social Sciences, University of Copenhagen, Copenhagen, Denmark
R. Brouwer
Affiliation:
Department of Psychiatry, UMC Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
R. Hilker
Affiliation:
Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS) and Center for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Center Glostrup, Glostrup, Denmark Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
S. Anhøj
Affiliation:
Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS) and Center for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Center Glostrup, Glostrup, Denmark
L. Baandrup
Affiliation:
Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS) and Center for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Center Glostrup, Glostrup, Denmark Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Mental Health Center Copenhagen, Copenhagen NV, Denmark
C. Pantelis
Affiliation:
Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS) and Center for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Center Glostrup, Glostrup, Denmark Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia
B. Glenthøj
Affiliation:
Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS) and Center for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Center Glostrup, Glostrup, Denmark Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
B. Fagerlund
Affiliation:
Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS) and Center for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Center Glostrup, Glostrup, Denmark Department of Psychology, Faculty of Social Sciences, University of Copenhagen, Copenhagen, Denmark
*
Author for correspondence: C. Lemvigh, E-mail: cecilie.koldbaek.lemvigh@regionh.dk
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Abstract

Background

Research has yielded evidence for genetic and environmental factors influencing the risk of schizophrenia. Numerous environmental factors have been identified; however, the individual effects are small. The additive and interactive effects of multiple risk factors are not well elucidated. Twin pairs discordant for schizophrenia offer a unique opportunity to identify factors that differ between patients and unaffected co-twins, who are perfectly matched for age, sex and genetic background.

Methods

Register data were combined with clinical data for 216 twins including monozygotic (MZ) and dizygotic (DZ) proband pairs (one or both twins having a schizophrenia spectrum diagnosis) and MZ/DZ healthy control (HC) pairs. Logistic regression models were applied to predict (1) illness vulnerability (being a proband v. HC pair) and (2) illness status (being the patient v. unaffected co-twin). Risk factors included: A polygenic risk score (PRS) for schizophrenia, birth complications, birth weight, Apgar scores, paternal age, maternal smoking, season of birth, parental socioeconomic status, urbanicity, childhood trauma, estimated premorbid intelligence and cannabis.

Results

The PRS [odds ratio (OR) 1.6 (1.1–2.3)], childhood trauma [OR 4.5 (2.3–8.8)], and regular cannabis use [OR 8.3 (2.1–32.7)] independently predicted illness vulnerability as did an interaction between childhood trauma and cannabis use [OR 0.17 (0.03–0.9)]. Only regular cannabis use predicted having a schizophrenia spectrum diagnosis between patients and unaffected co-twins [OR 3.3 (1.1–10.4)].

Conclusion

The findings suggest that several risk factors contribute to increasing schizophrenia spectrum vulnerability. Moreover, cannabis, a potentially completely avoidable environmental risk factor, seems to play a substantial role in schizophrenia pathology.

Keywords

Schizophreniatwinsrisk factorspolygenic risk scoreenvironmental influences
Type
Original Article
Information
Psychological Medicine , Volume 53 , Issue 4 , March 2023 , pp. 1266 - 1276
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Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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