Duration of Untreated Psychosis in First-Episode Psychosis is not Associated with Common Genetic Variants for Major Psychiatric Conditions: Results from the Multi-Center EU-GEI Study

Olesya Ajnakina; Victoria Rodriguez; Diego Quattrone; Marta Di Forti; Evangelos Vassos; Celso Arango; Domenico Berardi; Miguel Bernardo; Julio Bobes; Lieuwe De Haan; Cristina Marta Del-Ben; Charlotte Gayer-Anderson; Hannah E. Jongsma; Antonio Lasalvia; Sarah Tosato; Pierre-Michel Llorca; Paulo Rossi Menezes; Bart P. F. Rutten; Jose Luis Santos; Julio Sanjuán; Jean Paul Selten; Andrei Szöke; Ilaria Tarricone; Giuseppe D'Andrea; Alexander Richards; Andrea Tortelli; Eva Velthorst; Peter B. Jones; Manuel Arrojo-Romero; Caterina La Cascia; James B Kirkbride; Jim Van Os; Mick C. O'Donovan; Robin M Murray

doi:10.1093/schbul/sbab055

Duration of Untreated Psychosis in First-Episode Psychosis is not Associated with Common Genetic Variants for Major Psychiatric Conditions: Results from the Multi-Center EU-GEI Study

Olesya Ajnakina
, Victoria Rodriguez
, Diego Quattrone
, Marta Di Forti
, Evangelos Vassos
, Celso Arango
, Domenico Berardi
, Miguel Bernardo
, Julio Bobes
, Lieuwe De Haan
, Cristina Marta Del-Ben
, Charlotte Gayer-Anderson
, Hannah E. Jongsma
, Antonio Lasalvia
, Sarah Tosato
, Pierre-Michel Llorca
, Paulo Rossi Menezes
, Bart P. F. Rutten
, Jose Luis Santos
, Julio Sanjuán

Jean Paul Selten, Andrei Szöke, Ilaria Tarricone, Giuseppe D'Andrea, Alexander Richards, Andrea Tortelli, Eva Velthorst, Peter B. Jones, Manuel Arrojo-Romero, Caterina La Cascia, James B Kirkbride, Jim Van Os, Mick C. O'Donovan, Robin M Murray

Cardiff University
Alma Mater Studiorum Universita di Bologna
Local Health Authority
University of Barcelona
IDIBAPS August Pi i Sunyer Biomedical Research Institute
University of Zaragoza; Instituto de Investigacion Sanitaria de Aragon (IIS) and Centro de Investigacion Biomedica en Red de Salud Mental (CIBERSAM), Zaragoza, Spain.
Hospital Clínic de Barcelona
University of Oviedo
Biomedical Research Networking Centre in Mental Health (CIBERSAM)
Instituto de Investigación Sanitaria del Principado de Asturias
Mental Health Services of Principado de Asturias
University of Amsterdam
Learning Disability Psychiatry Department
AMC Academic Medical Center
Arkin
Amsterdam UMC
University of Amstderdam
Mental Health Institute
Genetic Risk and Outcome of Psychosis (GROUP) Investigators
Arkin Psychiatric Institution
Arkin Institute for Mental Health
Universidade de Sao Paulo - USP
Cambridge University Hospitals NHS Foundation Trust
UCL University College London
University of Verona
Policlinico G.B. Rossi
Université d'Auvergne
Clermont Ferrand University Hospital
Université Clermont Auvergne
Maastricht University
University Hospital Maastricht
Hospital Virgen de la Luz Cuenca
Valencia University Medical School
Hospital Clínico Universitario de Valencia
Universitat de València
IDIBAPS, CIBERSAM, Instituto de Salud Carlos III
Rivierduinen Institute for Mental Health Care
U955
Hopitaux Universitaires Henri Mondor
Fondation FondaMental
Université Paris-Est
Etablissement Public de Santé Maison Blanche
Icahn School of Medicine at Mount Sinai
Gallegan Health System (Servicio Gallego de Salud)
University of Palermo
UNIVERSITY COLLEGE LONDON
MRC Biostatistics Unit
King's College London

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

38 Downloads (Pure)

Abstract

Duration of untreated psychosis (DUP) is associated with clinical outcomes in people with a diagnosis of first-episode psychosis (FEP), but factors associated with length of DUP are still poorly understood. Aiming to obtain insights into the possible biological impact on DUP, we report genetic analyses of a large multi-center phenotypically well-defined sample encompassing individuals with a diagnosis of FEP recruited from 6 countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. Genetic propensity was measured using polygenic scores for schizophrenia (SZ-PGS), bipolar disorder (BD-PGS), major depressive disorder (MDD-PGS), and intelligence (IQ-PGS), which were calculated based on the results from the most recent genome-wide association meta-analyses. Following imputation for missing data and log transformation of DUP to handle skewedness, the association between DUP and polygenic scores (PGS), adjusting for important confounders, was investigated with multivariable linear regression models. The sample comprised 619 individuals with a diagnosis of FEP disorders with a median age at first contact of 29.0 years (interquartile range [IQR] = 22.0-38.0). The median length of DUP in the sample was 10.1 weeks (IQR = 3.8-30.8). One SD increases in SZ-PGS, BD-PGS, MDD-PGS or IQ-PGS were not significantly associated with the length of DUP. Our results suggest that genetic variation does not contribute to the DUP in patients with a diagnosis of FEP disorders.

Original language	English
Pages (from-to)	1653-1662
Number of pages	10
Journal	Schizophrenia bulletin
Volume	47
Issue number	6
DOIs	https://doi.org/10.1093/schbul/sbab055
Publication status	Published - 1 Nov 2021

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10.1093/schbul/sbab055

Ajnakina et al. Main manuscript

Cite this

Ajnakina, O., Rodriguez, V., Quattrone, D., Di Forti, M., Vassos, E., Arango, C., Berardi, D., Bernardo, M., Bobes, J., De Haan, L., Del-Ben, C. M., Gayer-Anderson, C., Jongsma, H. E., Lasalvia, A., Tosato, S., Llorca, P.-M., Menezes, P. R., Rutten, B. P. F., Santos, J. L., ... Murray, R. M. (2021). Duration of Untreated Psychosis in First-Episode Psychosis is not Associated with Common Genetic Variants for Major Psychiatric Conditions: Results from the Multi-Center EU-GEI Study. Schizophrenia bulletin, 47(6), 1653-1662. https://doi.org/10.1093/schbul/sbab055

@article{31bcf8ee9f04430a9a1a7d8697d9ec99,

title = "Duration of Untreated Psychosis in First-Episode Psychosis is not Associated with Common Genetic Variants for Major Psychiatric Conditions: Results from the Multi-Center EU-GEI Study",

abstract = "Duration of untreated psychosis (DUP) is associated with clinical outcomes in people with a diagnosis of first-episode psychosis (FEP), but factors associated with length of DUP are still poorly understood. Aiming to obtain insights into the possible biological impact on DUP, we report genetic analyses of a large multi-center phenotypically well-defined sample encompassing individuals with a diagnosis of FEP recruited from 6 countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. Genetic propensity was measured using polygenic scores for schizophrenia (SZ-PGS), bipolar disorder (BD-PGS), major depressive disorder (MDD-PGS), and intelligence (IQ-PGS), which were calculated based on the results from the most recent genome-wide association meta-analyses. Following imputation for missing data and log transformation of DUP to handle skewedness, the association between DUP and polygenic scores (PGS), adjusting for important confounders, was investigated with multivariable linear regression models. The sample comprised 619 individuals with a diagnosis of FEP disorders with a median age at first contact of 29.0 years (interquartile range [IQR] = 22.0-38.0). The median length of DUP in the sample was 10.1 weeks (IQR = 3.8-30.8). One SD increases in SZ-PGS, BD-PGS, MDD-PGS or IQ-PGS were not significantly associated with the length of DUP. Our results suggest that genetic variation does not contribute to the DUP in patients with a diagnosis of FEP disorders.",

author = "Olesya Ajnakina and Victoria Rodriguez and Diego Quattrone and \{Di Forti\}, Marta and Evangelos Vassos and Celso Arango and Domenico Berardi and Miguel Bernardo and Julio Bobes and \{De Haan\}, Lieuwe and Del-Ben, \{Cristina Marta\} and Charlotte Gayer-Anderson and Jongsma, \{Hannah E.\} and Antonio Lasalvia and Sarah Tosato and Pierre-Michel Llorca and Menezes, \{Paulo Rossi\} and Rutten, \{Bart P. F.\} and Santos, \{Jose Luis\} and Julio Sanju{\'a}n and Selten, \{Jean Paul\} and Andrei Sz{\"o}ke and Ilaria Tarricone and Giuseppe D'Andrea and Alexander Richards and Andrea Tortelli and Eva Velthorst and Jones, \{Peter B.\} and Manuel Arrojo-Romero and \{La Cascia\}, Caterina and Kirkbride, \{James B\} and \{Van Os\}, Jim and O'Donovan, \{Mick C.\} and Murray, \{Robin M\}",

note = "Publisher Copyright: {\textcopyright} 2021 The Author(s). Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.",

year = "2021",

month = nov,

day = "1",

doi = "10.1093/schbul/sbab055",

language = "English",

volume = "47",

pages = "1653--1662",

journal = "Schizophrenia bulletin",

issn = "0586-7614",

publisher = "Oxford University Press",

number = "6",

}

Ajnakina, O , Rodriguez, V , Quattrone, D , Di Forti, M , Vassos, E, Arango, C, Berardi, D, Bernardo, M, Bobes, J, De Haan, L, Del-Ben, CM, Gayer-Anderson, C, Jongsma, HE, Lasalvia, A, Tosato, S, Llorca, P-M, Menezes, PR, Rutten, BPF, Santos, JL, Sanjuán, J, Selten, JP, Szöke, A, Tarricone, I, D'Andrea, G, Richards, A, Tortelli, A, Velthorst, E, Jones, PB, Arrojo-Romero, M, La Cascia, C, Kirkbride, JB, Van Os, J, O'Donovan, MC & Murray, RM 2021, 'Duration of Untreated Psychosis in First-Episode Psychosis is not Associated with Common Genetic Variants for Major Psychiatric Conditions: Results from the Multi-Center EU-GEI Study', Schizophrenia bulletin, vol. 47, no. 6, pp. 1653-1662. https://doi.org/10.1093/schbul/sbab055

Duration of Untreated Psychosis in First-Episode Psychosis is not Associated with Common Genetic Variants for Major Psychiatric Conditions: Results from the Multi-Center EU-GEI Study. / Ajnakina, Olesya ; Rodriguez, Victoria ; Quattrone, Diego et al.
In: Schizophrenia bulletin, Vol. 47, No. 6, 01.11.2021, p. 1653-1662.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Duration of Untreated Psychosis in First-Episode Psychosis is not Associated with Common Genetic Variants for Major Psychiatric Conditions

T2 - Results from the Multi-Center EU-GEI Study

AU - Ajnakina, Olesya

AU - Rodriguez, Victoria

AU - Quattrone, Diego

AU - Di Forti, Marta

AU - Vassos, Evangelos

AU - Arango, Celso

AU - Berardi, Domenico

AU - Bernardo, Miguel

AU - Bobes, Julio

AU - De Haan, Lieuwe

AU - Del-Ben, Cristina Marta

AU - Gayer-Anderson, Charlotte

AU - Jongsma, Hannah E.

AU - Lasalvia, Antonio

AU - Tosato, Sarah

AU - Llorca, Pierre-Michel

AU - Menezes, Paulo Rossi

AU - Rutten, Bart P. F.

AU - Santos, Jose Luis

AU - Sanjuán, Julio

AU - Selten, Jean Paul

AU - Szöke, Andrei

AU - Tarricone, Ilaria

AU - D'Andrea, Giuseppe

AU - Richards, Alexander

AU - Tortelli, Andrea

AU - Velthorst, Eva

AU - Jones, Peter B.

AU - Arrojo-Romero, Manuel

AU - La Cascia, Caterina

AU - Kirkbride, James B

AU - Van Os, Jim

AU - O'Donovan, Mick C.

AU - Murray, Robin M

PY - 2021/11/1

Y1 - 2021/11/1

N2 - Duration of untreated psychosis (DUP) is associated with clinical outcomes in people with a diagnosis of first-episode psychosis (FEP), but factors associated with length of DUP are still poorly understood. Aiming to obtain insights into the possible biological impact on DUP, we report genetic analyses of a large multi-center phenotypically well-defined sample encompassing individuals with a diagnosis of FEP recruited from 6 countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. Genetic propensity was measured using polygenic scores for schizophrenia (SZ-PGS), bipolar disorder (BD-PGS), major depressive disorder (MDD-PGS), and intelligence (IQ-PGS), which were calculated based on the results from the most recent genome-wide association meta-analyses. Following imputation for missing data and log transformation of DUP to handle skewedness, the association between DUP and polygenic scores (PGS), adjusting for important confounders, was investigated with multivariable linear regression models. The sample comprised 619 individuals with a diagnosis of FEP disorders with a median age at first contact of 29.0 years (interquartile range [IQR] = 22.0-38.0). The median length of DUP in the sample was 10.1 weeks (IQR = 3.8-30.8). One SD increases in SZ-PGS, BD-PGS, MDD-PGS or IQ-PGS were not significantly associated with the length of DUP. Our results suggest that genetic variation does not contribute to the DUP in patients with a diagnosis of FEP disorders.

AB - Duration of untreated psychosis (DUP) is associated with clinical outcomes in people with a diagnosis of first-episode psychosis (FEP), but factors associated with length of DUP are still poorly understood. Aiming to obtain insights into the possible biological impact on DUP, we report genetic analyses of a large multi-center phenotypically well-defined sample encompassing individuals with a diagnosis of FEP recruited from 6 countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. Genetic propensity was measured using polygenic scores for schizophrenia (SZ-PGS), bipolar disorder (BD-PGS), major depressive disorder (MDD-PGS), and intelligence (IQ-PGS), which were calculated based on the results from the most recent genome-wide association meta-analyses. Following imputation for missing data and log transformation of DUP to handle skewedness, the association between DUP and polygenic scores (PGS), adjusting for important confounders, was investigated with multivariable linear regression models. The sample comprised 619 individuals with a diagnosis of FEP disorders with a median age at first contact of 29.0 years (interquartile range [IQR] = 22.0-38.0). The median length of DUP in the sample was 10.1 weeks (IQR = 3.8-30.8). One SD increases in SZ-PGS, BD-PGS, MDD-PGS or IQ-PGS were not significantly associated with the length of DUP. Our results suggest that genetic variation does not contribute to the DUP in patients with a diagnosis of FEP disorders.

UR - https://www.scopus.com/pages/publications/85119609461

U2 - 10.1093/schbul/sbab055

DO - 10.1093/schbul/sbab055

M3 - Article

SN - 0586-7614

VL - 47

SP - 1653

EP - 1662

JO - Schizophrenia bulletin

JF - Schizophrenia bulletin

IS - 6

ER -

Duration of Untreated Psychosis in First-Episode Psychosis is not Associated with Common Genetic Variants for Major Psychiatric Conditions: Results from the Multi-Center EU-GEI Study

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