Proteomic Biomarkers for the Prediction of Transition to Psychosis in Individuals at Clinical High Risk: A Multi-cohort Model Development Study,Schizophrenia Bulletin

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Proteomic Biomarkers for the Prediction of Transition to Psychosis in Individuals at Clinical High Risk: A Multi-cohort Model Development Study
Schizophrenia Bulletin ( IF 6.6 ) Pub Date : 2024-01-20 , DOI: 10.1093/schbul/sbad184
Jonah F Byrne _{1,

2} , Colm Healy _{1,

3} , Melanie Föcking ₁ , Subash Raj Susai ₁ , David Mongan _{1,

4} , Kieran Wynne ₅ , Eleftheria Kodosaki ₆ , Meike Heurich ₆ , Lieuwe de Haan ₇ , Ian B Hickie ₈ , Stefan Smesny ₉ , Andrew Thompson _{10,

11} , Connie Markulev _{10,

11} , Alison Ruth Young _{10,

12,

13} , Miriam R Schäfer _{10,

11} , Anita Riecher-Rössler ₁₄ , Nilufar Mossaheb ₁₅ , Gregor Berger ₁₆ , Monika Schlögelhofer ₁₇ , Merete Nordentoft _{18,

19} , Eric Y H Chen _{20,

21} , Swapna Verma _{22,

23} , Dorien H Nieman ₇ , Scott W Woods ₂₄ , Barbara A Cornblatt ₂₅ , William S Stone ₂₆ , Daniel H Mathalon _{27,

28} , Carrie E Bearden ₂₉ , Kristin S Cadenhead ₃₀ , Jean Addington ₃₁ , Elaine F Walker _{32,

33} , Tyrone D Cannon _{34,

35} , Mary Cannon _{1,

2,

36} , Pat McGorry _{10,

11} , Paul Amminger _{10,

11} , Gerard Cagney ₅ , Barnaby Nelson _{10,

11} , Clark Jeffries ₃₇ , Diana Perkins ₃₈ , David R Cotter _{1,

2,

36}

Affiliation

Department of Psychiatry, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences , Dublin , Ireland
SFI FutureNeuro Research Centre, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences , Dublin , Ireland
Department of Psychology, Royal College of Surgeons in Ireland , Dublin 2 , Ireland
Centre for Public Health, Queen’s University Belfast , Belfast , UK
School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin , Dublin , Ireland
School of Pharmacy and Pharmaceutical Sciences, Cardiff University , Wales , UK
Department of Psychiatry, Academic Medical Center , Amsterdam , The Netherlands
Brain and Mind Centre, The University of Sydney , Sydney, NSW , Australia
Department of Psychiatry, Jena University Hospital , Jena , Germany
Centre for Youth Mental Health, University of Melbourne , Parkville, VIC , Australia
Orygen, The National Centre of Excellence in Youth Mental Health , Melbourne, VIC , Australia
Institute for Mental and Physical Health and Clinical Translation (IMPACT), Deakin University , Geelong, VIC , Australia
School of Health Sciences, University of Manchester , Manchester , UK
Medical Faculty, University of Basel , Switzerland
Department of Psychiatry and Psychotherapy, Clinical Division of Social Psychiatry, Medical University of Vienna , Vienna , Austria
Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich , Zurich , Switzerland
BioPsyC—Biopsychosocial Corporation, Non-profit Association for Research Funding Ltd , Vienna , Austria
Mental Health Center Copenhagen, Research Unit (CORE) , Copenhagen , Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen , Denmark
Department of Psychiatry, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, 2/F New Clinical Building, Queen Mary Hospital , Pok Fu Lam , Hong Kong
The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong , Pok Fu Lam , Hong Kong
Office of Education, Duke-NUS Graduate Medical School , Singapore , Singapore
Department of Psychosis & East Region, Institute of Mental Health , Singapore , Singapore
Department of Psychiatry, Yale University School of Medicine , New Haven, CT , USA
Department of Psychiatry, Zucker Hillside Hospital , Long Island, NY , USA
Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center and Massachusetts General Hospital , Boston, MA , USA
Department of Psychiatry and Behavioral Sciences, University of California, San Francisco , San Francisco, CA , USA
Mental Health Service 116d, Veterans Affairs San Francisco Health Care System , San Francisco, CA , USA
Semel Institute for Neuroscience and Human Behavior, Departments of Psychiatry and Biobehavioral Sciences and Psychology, University of California , Los Angeles, CA , USA
Department of Psychiatry, University of California, San Diego , CA , USA
Department of Psychiatry, Hotchkiss Brain Institute, University of Calgary , Calgary , Canada
Department of Psychology, Emory University , Atlanta, GA , USA
Department of Psychiatry, Emory University , Atlanta, GA , USA
Department of Psychology, Yale University , New Haven, CT , USA
Department of Psychiatry, Yale University , New Haven, CT , USA
Department of Psychiatry, Beaumont Hospital , Dublin 9 , Ireland
Renaissance Computing Institute, University of North Carolina , Chapel Hill, NC , USA
Department of Psychiatry, University of North Carolina , Chapel Hill, NC , USA

Psychosis risk prediction is one of the leading challenges in psychiatry. Previous investigations have suggested that plasma proteomic data may be useful in accurately predicting transition to psychosis in individuals at clinical high risk (CHR). We hypothesized that an a priori-specified proteomic prediction model would have strong predictive accuracy for psychosis risk and aimed to replicate longitudinal associations between plasma proteins and transition to psychosis. This study used plasma samples from participants in 3 CHR cohorts: the North American Prodrome Longitudinal Studies 2 and 3, and the NEURAPRO randomized control trial (total n = 754). Plasma proteomic data were quantified using mass spectrometry. The primary outcome was transition to psychosis over the study follow-up period. Logistic regression models were internally validated, and optimism-corrected performance metrics derived with a bootstrap procedure. In the overall sample of CHR participants (age: 18.5, SD: 3.9; 51.9% male), 20.4% (n = 154) developed psychosis within 4.4 years. The a priori-specified model showed poor risk-prediction accuracy for the development of psychosis (C-statistic: 0.51 [95% CI: 0.50, 0.59], calibration slope: 0.45). At a group level, Complement C8B, C4B, C5, and leucine-rich α-2 glycoprotein 1 (LRG1) were associated with transition to psychosis but did not surpass correction for multiple comparisons. This study did not confirm the findings from a previous proteomic prediction model of transition from CHR to psychosis. Certain complement proteins may be weakly associated with transition at a group level. Previous findings, derived from small samples, should be interpreted with caution.

中文翻译：

用于预测临床高危个体向精神病转变的蛋白质组生物标志物：多队列模型开发研究

精神病风险预测是精神病学的主要挑战之一。先前的研究表明，血浆蛋白质组数据可能有助于准确预测临床高危（CHR）个体向精神病的转变。我们假设先验指定的蛋白质组预测模型对精神病风险具有很强的预测准确性，旨在复制血浆蛋白与精神病转变之间的纵向关联。本研究使用了 3 个 CHR 队列参与者的血浆样本：北美前驱症状纵向研究 2 和 3，以及 NEURAPRO 随机对照试验（总计 n = 754）。使用质谱法对血浆蛋白质组数据进行量化。主要结果是在研究随访期间转变为精神病。逻辑回归模型经过内部验证，并通过引导程序得出乐观校正的性能指标。在 CHR 参与者的总体样本中（年龄：18.5，标准差：3.9；51.9% 为男性），20.4% (n = 154) 在 4.4 年内出现精神病。先验指定模型显示精神病发展的风险预测准确性较差（C 统计量：0.51 [95% CI：0.50, 0.59]，校准斜率：0.45）。在群体水平上，补体 C8B、C4B、C5 和富含亮氨酸的 α-2 糖蛋白 1 (LRG1) 与向精神病的转变相关，但并未超过多重比较的校正。这项研究并没有证实之前从 CHR 到精神病转变的蛋白质组学预测模型的结果。某些补体蛋白可能与群体水平的转变有微弱的相关性。先前的研究结果来自小样本，应谨慎解释。

更新日期：2024-01-20

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