Dysregulated Lipid Metabolism Precedes Onset of Psychosis

EU-GEI High Risk Study Group

doi:10.1016/j.biopsych.2020.07.012

Dysregulated Lipid Metabolism Precedes Onset of Psychosis

EU-GEI High Risk Study Group

Turku Bioscience Center, University of Turku and Åbo Akademi University, Turku, Finland.
Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, United Kingdom.
Departament de Psicologia Clínica I de la Salut (Universitat Autònoma de Barcelona), Fundació Sanitària Sant Pere Claver (Spain), Spanish Mental Health Research Network (CIBERSAM), Spain.
Mental Health Center Copenhagen and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Center Glostrup, Mental Health Services in the Capital Region of Copenhagen, University of Copenhagen, Glostrup, Denmark.
University of Basel
Department of Psychiatry and Psychotherapy, Ludwig Maximilian University of Munich, Munich, Germany; Department of Psychiatry and Psychotherapy, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
Medical University of Vienna
Lab Interdisciplinar Neurociências Clínicas, Departimento Psiquiatria, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
University of Paris, Groupe Hospitalier Universitaire Paris Sainte-Anne, Centre d'Évaluation Pour Jeunes Adultes et Adolescents, Institut National de la Santé et de la Recherche Médicale U1266, Institut de Psychiatrie, Centre National de la Recherche Scientifique 3557, Paris, France.
University of Melbourne
Department of Psychiatry, Amsterdam University Medical Center, Faculty of Behavioural and Movement Sciences, Vrije Universiteit, Amsterdam, The Netherlands.
Department of Clinical Psychology and EMGO+ Institute for Health and Care Research, Faculty of Behavioural and Movement Sciences, Vrije Universiteit, Amsterdam, The Netherlands; Department of Psychosis Research, Parnassia Psychiatric Institute, The Hague, The Netherlands.
Department of Chemistry, Örebro University, 70281, Örebro, Sweden.
Turku Bioscience Center, University of Turku and Åbo Akademi University, Turku, Finland; School of Medical Sciences, Örebro University, Örebro, Sweden. Electronic address: [email protected].
Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom. Electronic address: [email protected].

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

55 Citations (Scopus)

Abstract

BACKGROUND: A key clinical challenge in the management of individuals at clinical high risk for psychosis (CHR) is that it is difficult to predict their future clinical outcomes. Here, we investigated if the levels of circulating molecular lipids are related to adverse clinical outcomes in this group.

METHODS: Serum lipidomic analysis was performed in 263 CHR individuals and 51 healthy control subjects, who were then clinically monitored for up to 5 years. Machine learning was used to identify lipid profiles that discriminated between CHR and control subjects, and between subgroups of CHR subjects with distinct clinical outcomes.

RESULTS: At baseline, compared with control subjects, CHR subjects (independent of outcome) had higher levels of triacylglycerols with a low acyl carbon number and a double bond count, as well as higher levels of lipids in general. CHR subjects who subsequently developed psychosis (n = 50) were distinguished from those that did not (n = 213) on the basis of lipid profile at baseline using a model with an area under the receiver operating curve of 0.81 (95% confidence interval = 0.69-0.93). CHR subjects who became psychotic had lower levels of ether phospholipids than CHR individuals who did not (p < .01).

CONCLUSIONS: Collectively, these data suggest that lipidomic abnormalities predate the onset of psychosis and that blood lipidomic measures may be useful in predicting which CHR individuals are most likely to develop psychosis.

Original language	English
Journal	Biological psychiatry
DOIs	https://doi.org/10.1016/j.biopsych.2020.07.012
Publication status	E-pub ahead of print - 25 Jul 2020

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10.1016/j.biopsych.2020.07.012

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title = "Dysregulated Lipid Metabolism Precedes Onset of Psychosis",

abstract = "BACKGROUND: A key clinical challenge in the management of individuals at clinical high risk for psychosis (CHR) is that it is difficult to predict their future clinical outcomes. Here, we investigated if the levels of circulating molecular lipids are related to adverse clinical outcomes in this group.METHODS: Serum lipidomic analysis was performed in 263 CHR individuals and 51 healthy control subjects, who were then clinically monitored for up to 5 years. Machine learning was used to identify lipid profiles that discriminated between CHR and control subjects, and between subgroups of CHR subjects with distinct clinical outcomes.RESULTS: At baseline, compared with control subjects, CHR subjects (independent of outcome) had higher levels of triacylglycerols with a low acyl carbon number and a double bond count, as well as higher levels of lipids in general. CHR subjects who subsequently developed psychosis (n = 50) were distinguished from those that did not (n = 213) on the basis of lipid profile at baseline using a model with an area under the receiver operating curve of 0.81 (95% confidence interval = 0.69-0.93). CHR subjects who became psychotic had lower levels of ether phospholipids than CHR individuals who did not (p < .01).CONCLUSIONS: Collectively, these data suggest that lipidomic abnormalities predate the onset of psychosis and that blood lipidomic measures may be useful in predicting which CHR individuals are most likely to develop psychosis.",

author = "{EU-GEI High Risk Study Group} and Dickens, {Alex M} and Partho Sen and Kempton, {Matthew J} and Neus Barrantes-Vidal and Conrad Iyegbe and Merete Nordentoft and Thomas Pollak and Anita Riecher-R{\"o}ssler and Stephan Ruhrmann and Gabriele Sachs and Rodrigo Bressan and Marie-Odile Krebs and Amminger, {G Paul} and {de Haan}, Lieuwe and {van der Gaag}, Mark and Lucia Valmaggia and Tuulia Hy{\"o}tyl{\"a}inen and Matej Ore{\v s}i{\v c} and Philip McGuire",

year = "2020",

month = jul,

day = "25",

doi = "10.1016/j.biopsych.2020.07.012",

language = "English",

journal = "Biological psychiatry",

issn = "0006-3223",

publisher = "Elsevier",

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TY - JOUR

T1 - Dysregulated Lipid Metabolism Precedes Onset of Psychosis

AU - EU-GEI High Risk Study Group

AU - Dickens, Alex M

AU - Sen, Partho

AU - Kempton, Matthew J

AU - Barrantes-Vidal, Neus

AU - Iyegbe, Conrad

AU - Nordentoft, Merete

AU - Pollak, Thomas

AU - Riecher-Rössler, Anita

AU - Ruhrmann, Stephan

AU - Sachs, Gabriele

AU - Bressan, Rodrigo

AU - Krebs, Marie-Odile

AU - Amminger, G Paul

AU - de Haan, Lieuwe

AU - van der Gaag, Mark

AU - Valmaggia, Lucia

AU - Hyötyläinen, Tuulia

AU - Orešič, Matej

AU - McGuire, Philip

PY - 2020/7/25

Y1 - 2020/7/25

N2 - BACKGROUND: A key clinical challenge in the management of individuals at clinical high risk for psychosis (CHR) is that it is difficult to predict their future clinical outcomes. Here, we investigated if the levels of circulating molecular lipids are related to adverse clinical outcomes in this group.METHODS: Serum lipidomic analysis was performed in 263 CHR individuals and 51 healthy control subjects, who were then clinically monitored for up to 5 years. Machine learning was used to identify lipid profiles that discriminated between CHR and control subjects, and between subgroups of CHR subjects with distinct clinical outcomes.RESULTS: At baseline, compared with control subjects, CHR subjects (independent of outcome) had higher levels of triacylglycerols with a low acyl carbon number and a double bond count, as well as higher levels of lipids in general. CHR subjects who subsequently developed psychosis (n = 50) were distinguished from those that did not (n = 213) on the basis of lipid profile at baseline using a model with an area under the receiver operating curve of 0.81 (95% confidence interval = 0.69-0.93). CHR subjects who became psychotic had lower levels of ether phospholipids than CHR individuals who did not (p < .01).CONCLUSIONS: Collectively, these data suggest that lipidomic abnormalities predate the onset of psychosis and that blood lipidomic measures may be useful in predicting which CHR individuals are most likely to develop psychosis.

AB - BACKGROUND: A key clinical challenge in the management of individuals at clinical high risk for psychosis (CHR) is that it is difficult to predict their future clinical outcomes. Here, we investigated if the levels of circulating molecular lipids are related to adverse clinical outcomes in this group.METHODS: Serum lipidomic analysis was performed in 263 CHR individuals and 51 healthy control subjects, who were then clinically monitored for up to 5 years. Machine learning was used to identify lipid profiles that discriminated between CHR and control subjects, and between subgroups of CHR subjects with distinct clinical outcomes.RESULTS: At baseline, compared with control subjects, CHR subjects (independent of outcome) had higher levels of triacylglycerols with a low acyl carbon number and a double bond count, as well as higher levels of lipids in general. CHR subjects who subsequently developed psychosis (n = 50) were distinguished from those that did not (n = 213) on the basis of lipid profile at baseline using a model with an area under the receiver operating curve of 0.81 (95% confidence interval = 0.69-0.93). CHR subjects who became psychotic had lower levels of ether phospholipids than CHR individuals who did not (p < .01).CONCLUSIONS: Collectively, these data suggest that lipidomic abnormalities predate the onset of psychosis and that blood lipidomic measures may be useful in predicting which CHR individuals are most likely to develop psychosis.

U2 - 10.1016/j.biopsych.2020.07.012

DO - 10.1016/j.biopsych.2020.07.012

M3 - Article

C2 - 32928501

SN - 0006-3223

JO - Biological psychiatry

JF - Biological psychiatry

ER -

Dysregulated Lipid Metabolism Precedes Onset of Psychosis

Abstract

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