Polygenic liabilities and treatment trajectories in early-onset depression: a Danish register-based study

Jessica Mundy; Alisha S M Hall; Jette Steinbach; Clara Albinaña; Esben Agerbo; Thomas D Als; Anita Thapar; John J McGrath; Bjarni J Vilhjálmsson; Merete Nordentoft; Thomas Werge; Anders Børglum; Preben B Mortensen; Katherine L Musliner

doi:10.1017/S0033291724002186

Polygenic liabilities and treatment trajectories in early-onset depression: a Danish register-based study

Jessica Mundy, Alisha S M Hall, Jette Steinbach, Clara Albinaña, Esben Agerbo, Thomas D Als, Anita Thapar, John J McGrath, Bjarni J Vilhjálmsson, Merete Nordentoft, Thomas Werge, Anders Børglum, Preben B Mortensen, Katherine L Musliner

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

Abstract

BACKGROUND: The clinical course of major depressive disorder (MDD) is heterogeneous, and early-onset MDD often has a more severe and complex clinical course. Our goal was to determine whether polygenic scores (PGSs) for psychiatric disorders are associated with treatment trajectories in early-onset MDD treated in secondary care.

METHODS: Data were drawn from the iPSYCH2015 sample, which includes all individuals born in Denmark between 1981 and 2008 who were treated in secondary care for depression between 1995 and 2015. We selected unrelated individuals of European ancestry with an MDD diagnosis between ages 10-25 ( N = 10577). Seven-year trajectories of hospital contacts for depression were modeled using Latent Class Growth Analysis. Associations between PGS for MDD, bipolar disorder, schizophrenia, ADHD, and anorexia and trajectories of MDD contacts were modeled using multinomial logistic regressions.

RESULTS: We identified four trajectory patterns: brief contact (65%), prolonged initial contact (20%), later re-entry (8%), and persistent contact (7%). Relative to the brief contact trajectory, higher PGS for ADHD was associated with a decreased odds of membership in the prolonged initial contact (odds ratio = 1.06, 95% confidence interval = 1.01-1.11) and persistent contact (1.12, 1.03-1.21) trajectories, while PGS-AN was associated with increased odds of membership in the persistent contact trajectory (1.12, 1.03-1.21).

CONCLUSIONS: We found significant associations between polygenic liabilities for psychiatric disorders and treatment trajectories in patients with secondary-treated early-onset MDD. These findings help elucidate the relationship between a patient's genetics and their clinical course; however, the effect sizes are small and therefore unlikely to have predictive value in clinical settings.

Originalsprog	Engelsk
Tidsskrift	Psychological Medicine
Sider (fra-til)	1-10
Antal sider	10
ISSN	0033-2917
DOI	https://doi.org/10.1017/S0033291724002186
Status	E-pub ahead of print - 14 okt. 2024

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Mundy, J., Hall, A. S. M., Steinbach, J., Albinaña, C., Agerbo, E., Als, T. D., Thapar, A., McGrath, J. J., Vilhjálmsson, B. J., Nordentoft, M., Werge, T., Børglum, A., Mortensen, P. B., & Musliner, K. L. (2024). Polygenic liabilities and treatment trajectories in early-onset depression: a Danish register-based study. Psychological Medicine, 1-10. Advance online publication. https://doi.org/10.1017/S0033291724002186

@article{c6d52295ba264f7a9a09a888c0c1f6a3,

title = "Polygenic liabilities and treatment trajectories in early-onset depression: a Danish register-based study",

abstract = "BACKGROUND: The clinical course of major depressive disorder (MDD) is heterogeneous, and early-onset MDD often has a more severe and complex clinical course. Our goal was to determine whether polygenic scores (PGSs) for psychiatric disorders are associated with treatment trajectories in early-onset MDD treated in secondary care.METHODS: Data were drawn from the iPSYCH2015 sample, which includes all individuals born in Denmark between 1981 and 2008 who were treated in secondary care for depression between 1995 and 2015. We selected unrelated individuals of European ancestry with an MDD diagnosis between ages 10-25 ( N = 10577). Seven-year trajectories of hospital contacts for depression were modeled using Latent Class Growth Analysis. Associations between PGS for MDD, bipolar disorder, schizophrenia, ADHD, and anorexia and trajectories of MDD contacts were modeled using multinomial logistic regressions. RESULTS: We identified four trajectory patterns: brief contact (65%), prolonged initial contact (20%), later re-entry (8%), and persistent contact (7%). Relative to the brief contact trajectory, higher PGS for ADHD was associated with a decreased odds of membership in the prolonged initial contact (odds ratio = 1.06, 95% confidence interval = 1.01-1.11) and persistent contact (1.12, 1.03-1.21) trajectories, while PGS-AN was associated with increased odds of membership in the persistent contact trajectory (1.12, 1.03-1.21). CONCLUSIONS: We found significant associations between polygenic liabilities for psychiatric disorders and treatment trajectories in patients with secondary-treated early-onset MDD. These findings help elucidate the relationship between a patient's genetics and their clinical course; however, the effect sizes are small and therefore unlikely to have predictive value in clinical settings.",

keywords = "antidepressants, depression, genetics, major depressive disorder, polygenic score, secondary care, trajectory, treatment",

author = "Jessica Mundy and Hall, {Alisha S M} and Jette Steinbach and Clara Albina{\~n}a and Esben Agerbo and Als, {Thomas D} and Anita Thapar and McGrath, {John J} and Vilhj{\'a}lmsson, {Bjarni J} and Merete Nordentoft and Thomas Werge and Anders B{\o}rglum and Mortensen, {Preben B} and Musliner, {Katherine L}",

year = "2024",

month = oct,

day = "14",

doi = "10.1017/S0033291724002186",

language = "English",

pages = "1--10",

journal = "Psychological Medicine",

issn = "0033-2917",

publisher = "Cambridge University Press",

}

TY - JOUR

T1 - Polygenic liabilities and treatment trajectories in early-onset depression

T2 - a Danish register-based study

AU - Mundy, Jessica

AU - Hall, Alisha S M

AU - Steinbach, Jette

AU - Albinaña, Clara

AU - Agerbo, Esben

AU - Als, Thomas D

AU - Thapar, Anita

AU - McGrath, John J

AU - Vilhjálmsson, Bjarni J

AU - Nordentoft, Merete

AU - Werge, Thomas

AU - Børglum, Anders

AU - Mortensen, Preben B

AU - Musliner, Katherine L

PY - 2024/10/14

Y1 - 2024/10/14

N2 - BACKGROUND: The clinical course of major depressive disorder (MDD) is heterogeneous, and early-onset MDD often has a more severe and complex clinical course. Our goal was to determine whether polygenic scores (PGSs) for psychiatric disorders are associated with treatment trajectories in early-onset MDD treated in secondary care.METHODS: Data were drawn from the iPSYCH2015 sample, which includes all individuals born in Denmark between 1981 and 2008 who were treated in secondary care for depression between 1995 and 2015. We selected unrelated individuals of European ancestry with an MDD diagnosis between ages 10-25 ( N = 10577). Seven-year trajectories of hospital contacts for depression were modeled using Latent Class Growth Analysis. Associations between PGS for MDD, bipolar disorder, schizophrenia, ADHD, and anorexia and trajectories of MDD contacts were modeled using multinomial logistic regressions. RESULTS: We identified four trajectory patterns: brief contact (65%), prolonged initial contact (20%), later re-entry (8%), and persistent contact (7%). Relative to the brief contact trajectory, higher PGS for ADHD was associated with a decreased odds of membership in the prolonged initial contact (odds ratio = 1.06, 95% confidence interval = 1.01-1.11) and persistent contact (1.12, 1.03-1.21) trajectories, while PGS-AN was associated with increased odds of membership in the persistent contact trajectory (1.12, 1.03-1.21). CONCLUSIONS: We found significant associations between polygenic liabilities for psychiatric disorders and treatment trajectories in patients with secondary-treated early-onset MDD. These findings help elucidate the relationship between a patient's genetics and their clinical course; however, the effect sizes are small and therefore unlikely to have predictive value in clinical settings.

AB - BACKGROUND: The clinical course of major depressive disorder (MDD) is heterogeneous, and early-onset MDD often has a more severe and complex clinical course. Our goal was to determine whether polygenic scores (PGSs) for psychiatric disorders are associated with treatment trajectories in early-onset MDD treated in secondary care.METHODS: Data were drawn from the iPSYCH2015 sample, which includes all individuals born in Denmark between 1981 and 2008 who were treated in secondary care for depression between 1995 and 2015. We selected unrelated individuals of European ancestry with an MDD diagnosis between ages 10-25 ( N = 10577). Seven-year trajectories of hospital contacts for depression were modeled using Latent Class Growth Analysis. Associations between PGS for MDD, bipolar disorder, schizophrenia, ADHD, and anorexia and trajectories of MDD contacts were modeled using multinomial logistic regressions. RESULTS: We identified four trajectory patterns: brief contact (65%), prolonged initial contact (20%), later re-entry (8%), and persistent contact (7%). Relative to the brief contact trajectory, higher PGS for ADHD was associated with a decreased odds of membership in the prolonged initial contact (odds ratio = 1.06, 95% confidence interval = 1.01-1.11) and persistent contact (1.12, 1.03-1.21) trajectories, while PGS-AN was associated with increased odds of membership in the persistent contact trajectory (1.12, 1.03-1.21). CONCLUSIONS: We found significant associations between polygenic liabilities for psychiatric disorders and treatment trajectories in patients with secondary-treated early-onset MDD. These findings help elucidate the relationship between a patient's genetics and their clinical course; however, the effect sizes are small and therefore unlikely to have predictive value in clinical settings.

KW - antidepressants

KW - depression

KW - genetics

KW - major depressive disorder

KW - polygenic score

KW - secondary care

KW - trajectory

KW - treatment

UR - http://www.scopus.com/inward/record.url?scp=85207365813&partnerID=8YFLogxK

U2 - 10.1017/S0033291724002186

DO - 10.1017/S0033291724002186

M3 - Journal article

C2 - 39397681

SN - 0033-2917

SP - 1

EP - 10

JO - Psychological Medicine

JF - Psychological Medicine

ER -

Polygenic liabilities and treatment trajectories in early-onset depression: a Danish register-based study

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