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Published Online: 21 September 2022

Genetic and Environmental Contribution to the Co-Occurrence of Endocrine-Metabolic Disorders and Depression: A Nationwide Swedish Study of Siblings

Publication: American Journal of Psychiatry

Abstract

Objective:

Depression is common in individuals with endocrine-metabolic disorders and vice versa, and a better understanding of the underlying factors contributing to the comorbidity of these disorders is needed. This study investigated the familial coaggregation of depression and endocrine-metabolic disorders and estimated the contribution of genetic and environmental factors to their co-occurrence.

Methods:

This population-based cohort study included 2.2 million individuals born in Sweden between 1973 and 1996, with follow-up through 2013. Participants were linked to their biological parents, allowing identification of full siblings, maternal half siblings, and paternal half siblings. Diagnoses of depression and endocrine-metabolic conditions were investigated, with the latter grouped into autoimmune disorders (autoimmune hypothyroidism, Graves’ disease, and type 1 diabetes) and non-autoimmune disorders (type 2 diabetes, obesity, and polycystic ovary syndrome). Logistic regression and Cox regression were used to estimate the associations between endocrine-metabolic disorders and depression within the same individual and across siblings. Quantitative genetic modeling was performed to investigate the relative contribution of genetic and environmental influences.

Results:

Individuals with endocrine-metabolic disorders had a significantly higher risk of depression, with odds ratios ranging from 1.43 (95% CI=1.30, 1.57) for Graves’ disease to 3.48 (95% CI=3.25, 3.72) for type 2 diabetes. Increased risks extended to full and half siblings. These correlations were mainly explained by shared genetic influences for non-autoimmune conditions, and by nonshared environmental factors for autoimmune disorders, especially for type 1 diabetes.

Conclusions:

These findings provide phenotypic and etiological insights into the co-occurrence of depression and various endocrine-metabolic conditions, which could guide future research aiming at identifying pathophysiological mechanisms and intervention targets.

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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 824 - 832
PubMed: 36128682

History

Received: 27 September 2021
Revision received: 9 May 2022
Accepted: 27 June 2022
Published online: 21 September 2022
Published in print: November 01, 2022

Keywords

  1. Depressive Disorders
  2. Metabolism

Authors

Details

Marica Leone, Ph.D.
Janssen Pharmaceutical Companies of Johnson & Johnson, Solna, Sweden (Leone, Leval); Department of Medical Epidemiology and Biostatistics (Leone, Kuja-Halkola, Leval, Butwicka, Zhang, Liu, Larsson, Bergen) and Department of Molecular Medicine and Surgery (Skov), Karolinska Institutet, Solna, Sweden; Child and Adolescent Psychiatry Stockholm, Stockholm Health Care Services, Region Stockholm, Sweden (Butwicka); Department of Child Psychiatry, Medical University of Warsaw, Warsaw (Butwicka); Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland (Butwicka); Department of Medicine, Karlstad Central Hospital, Karlstad, Sweden (Skov); School of Medical Sciences, Örebro University, Örebro, Sweden (Larsson).
Ralf Kuja-Halkola, Ph.D.
Janssen Pharmaceutical Companies of Johnson & Johnson, Solna, Sweden (Leone, Leval); Department of Medical Epidemiology and Biostatistics (Leone, Kuja-Halkola, Leval, Butwicka, Zhang, Liu, Larsson, Bergen) and Department of Molecular Medicine and Surgery (Skov), Karolinska Institutet, Solna, Sweden; Child and Adolescent Psychiatry Stockholm, Stockholm Health Care Services, Region Stockholm, Sweden (Butwicka); Department of Child Psychiatry, Medical University of Warsaw, Warsaw (Butwicka); Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland (Butwicka); Department of Medicine, Karlstad Central Hospital, Karlstad, Sweden (Skov); School of Medical Sciences, Örebro University, Örebro, Sweden (Larsson).
Amy Leval, Ph.D.
Janssen Pharmaceutical Companies of Johnson & Johnson, Solna, Sweden (Leone, Leval); Department of Medical Epidemiology and Biostatistics (Leone, Kuja-Halkola, Leval, Butwicka, Zhang, Liu, Larsson, Bergen) and Department of Molecular Medicine and Surgery (Skov), Karolinska Institutet, Solna, Sweden; Child and Adolescent Psychiatry Stockholm, Stockholm Health Care Services, Region Stockholm, Sweden (Butwicka); Department of Child Psychiatry, Medical University of Warsaw, Warsaw (Butwicka); Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland (Butwicka); Department of Medicine, Karlstad Central Hospital, Karlstad, Sweden (Skov); School of Medical Sciences, Örebro University, Örebro, Sweden (Larsson).
Agnieszka Butwicka, M.D., Ph.D.
Janssen Pharmaceutical Companies of Johnson & Johnson, Solna, Sweden (Leone, Leval); Department of Medical Epidemiology and Biostatistics (Leone, Kuja-Halkola, Leval, Butwicka, Zhang, Liu, Larsson, Bergen) and Department of Molecular Medicine and Surgery (Skov), Karolinska Institutet, Solna, Sweden; Child and Adolescent Psychiatry Stockholm, Stockholm Health Care Services, Region Stockholm, Sweden (Butwicka); Department of Child Psychiatry, Medical University of Warsaw, Warsaw (Butwicka); Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland (Butwicka); Department of Medicine, Karlstad Central Hospital, Karlstad, Sweden (Skov); School of Medical Sciences, Örebro University, Örebro, Sweden (Larsson).
Jakob Skov, M.D., Ph.D.
Janssen Pharmaceutical Companies of Johnson & Johnson, Solna, Sweden (Leone, Leval); Department of Medical Epidemiology and Biostatistics (Leone, Kuja-Halkola, Leval, Butwicka, Zhang, Liu, Larsson, Bergen) and Department of Molecular Medicine and Surgery (Skov), Karolinska Institutet, Solna, Sweden; Child and Adolescent Psychiatry Stockholm, Stockholm Health Care Services, Region Stockholm, Sweden (Butwicka); Department of Child Psychiatry, Medical University of Warsaw, Warsaw (Butwicka); Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland (Butwicka); Department of Medicine, Karlstad Central Hospital, Karlstad, Sweden (Skov); School of Medical Sciences, Örebro University, Örebro, Sweden (Larsson).
Ruyue Zhang, Ph.D.
Janssen Pharmaceutical Companies of Johnson & Johnson, Solna, Sweden (Leone, Leval); Department of Medical Epidemiology and Biostatistics (Leone, Kuja-Halkola, Leval, Butwicka, Zhang, Liu, Larsson, Bergen) and Department of Molecular Medicine and Surgery (Skov), Karolinska Institutet, Solna, Sweden; Child and Adolescent Psychiatry Stockholm, Stockholm Health Care Services, Region Stockholm, Sweden (Butwicka); Department of Child Psychiatry, Medical University of Warsaw, Warsaw (Butwicka); Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland (Butwicka); Department of Medicine, Karlstad Central Hospital, Karlstad, Sweden (Skov); School of Medical Sciences, Örebro University, Örebro, Sweden (Larsson).
Shengxin Liu, M.Sc.
Janssen Pharmaceutical Companies of Johnson & Johnson, Solna, Sweden (Leone, Leval); Department of Medical Epidemiology and Biostatistics (Leone, Kuja-Halkola, Leval, Butwicka, Zhang, Liu, Larsson, Bergen) and Department of Molecular Medicine and Surgery (Skov), Karolinska Institutet, Solna, Sweden; Child and Adolescent Psychiatry Stockholm, Stockholm Health Care Services, Region Stockholm, Sweden (Butwicka); Department of Child Psychiatry, Medical University of Warsaw, Warsaw (Butwicka); Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland (Butwicka); Department of Medicine, Karlstad Central Hospital, Karlstad, Sweden (Skov); School of Medical Sciences, Örebro University, Örebro, Sweden (Larsson).
Henrik Larsson, Ph.D.
Janssen Pharmaceutical Companies of Johnson & Johnson, Solna, Sweden (Leone, Leval); Department of Medical Epidemiology and Biostatistics (Leone, Kuja-Halkola, Leval, Butwicka, Zhang, Liu, Larsson, Bergen) and Department of Molecular Medicine and Surgery (Skov), Karolinska Institutet, Solna, Sweden; Child and Adolescent Psychiatry Stockholm, Stockholm Health Care Services, Region Stockholm, Sweden (Butwicka); Department of Child Psychiatry, Medical University of Warsaw, Warsaw (Butwicka); Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland (Butwicka); Department of Medicine, Karlstad Central Hospital, Karlstad, Sweden (Skov); School of Medical Sciences, Örebro University, Örebro, Sweden (Larsson).
Sarah E. Bergen, Ph.D. [email protected]
Janssen Pharmaceutical Companies of Johnson & Johnson, Solna, Sweden (Leone, Leval); Department of Medical Epidemiology and Biostatistics (Leone, Kuja-Halkola, Leval, Butwicka, Zhang, Liu, Larsson, Bergen) and Department of Molecular Medicine and Surgery (Skov), Karolinska Institutet, Solna, Sweden; Child and Adolescent Psychiatry Stockholm, Stockholm Health Care Services, Region Stockholm, Sweden (Butwicka); Department of Child Psychiatry, Medical University of Warsaw, Warsaw (Butwicka); Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland (Butwicka); Department of Medicine, Karlstad Central Hospital, Karlstad, Sweden (Skov); School of Medical Sciences, Örebro University, Örebro, Sweden (Larsson).

Notes

Send correspondence to Dr. Bergen ([email protected]).

Competing Interests

Dr. Leone is an employee of Johnson & Johnson. Dr. Leval is an employee of and owns stock in Johnson & Johnson. Dr. Larsson has received research grants from Shire/Takeda; he has served as a speaker for Evolan Pharma, Medice, and Shire/Takeda; he has received sponsorship from Evolan Pharma and Shire/Takeda for a conference; and he is editor-in-chief of JCPP Advances. The other authors report no financial relationships with commercial interests.

Funding Information

This study was funded by the European Union’s Horizon 2020 Research and Innovation Programme under Marie Sklodowska-Curie grant agreement no. 721567.

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