New research
Identifying Adolescents at Risk for Depression: A Prediction Score Performance in Cohorts Based in 3 Different Continents

https://doi.org/10.1016/j.jaac.2019.12.004Get rights and content
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Objective

Prediction models have become frequent in the medical literature, but most published studies are conducted in a single setting. Heterogeneity between development and validation samples has been posited as a major obstacle for the generalization of models. We aimed to develop a multivariable prognostic model using sociodemographic variables easily obtainable from adolescents at age 15 to predict a depressive disorder diagnosis at age 18 and to evaluate its generalizability in 2 samples from diverse socioeconomic and cultural settings.

Method

Data from the 1993 Pelotas Birth Cohort were used to develop the prediction model, and its generalizability was evaluated in 2 representative cohort studies: the Environmental Risk (E-Risk) Longitudinal Twin Study and the Dunedin Multidisciplinary Health and Development Study.

Results

At age 15, 2,192 adolescents with no evidence of current or previous depression were included (44.6% male). The apparent C-statistic of the models derived in Pelotas ranged from 0.76 to 0.79, and the model obtained from a penalized logistic regression was selected for subsequent external evaluation. Major discrepancies between the samples were identified, impacting the external prognostic performance of the model (Dunedin and E-Risk C-statistics of 0.63 and 0.59, respectively). The implementation of recommended strategies to account for this heterogeneity among samples improved the model’s calibration in both samples.

Conclusion

An adolescent depression risk score comprising easily obtainable predictors was developed with good prognostic performance in a Brazilian sample. Heterogeneity among settings was not trivial, but strategies to deal with sample diversity were identified as pivotal for providing better risk stratification across samples. Future efforts should focus on developing better methodological approaches for incorporating heterogeneity in prognostic research.

Key words

adolescent
cohort studies
depression
prognosis
risk assessment

Cited by (0)

This work is supported by research grants from Brazilian public funding agencies to Drs. Kieling and Rohde: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS). This article is based on data from the study “Pelotas Birth Cohort, 1993” conducted by Postgraduate Program in Epidemiology at Universidade Federal de Pelotas, currently supported by the Wellcome Trust through the program entitled Major Awards for Latin America on Health Consequences of Population Change. The E-Risk Study is funded by the UK Medical Research Council (G1002190). Additional support was provided by the National Institute of Child Health and Human Development (HD077482) and by the Jacobs Foundation. Dr. Arseneault is the Mental Health Leadership Fellow for the UK Economic and Social Research Council. The Dunedin Study is supported by the New Zealand Health Research Council, New Zealand Ministry of Business, Innovation, and Employment, National Institute on Aging Grant R01AG032282 and UK Medical Research Council Grant MR/P005918/1. The Identifying Depression Early in Adolescence (IDEA) project is funded by an MQ Brighter Futures grant (MQBF/1 IDEA). Additional support was provided by the UK Medical Research Council (MC_PC_MR/R019460/1) and the Academy of Medical Sciences (GCRFNG/100281) under the Global Challenges Research Fund. The views expressed are those of the authors. None of the funders played any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication.

Author Contributions

Conceptualization: Rohde, Kieling

Data curation: Rocha, Anselmi, Arseneault, Barros, Caspi, Danese, Gonçalves, Harrington, Menezes, Moffitt, Poulton, Wehrmeister, Kieling

Formal analysis: Rocha, Fisher, Caye, Harrington, Houts, Menezes, Moffitt, Mondelli, Rohde, Wehrmeister, Kieling

Funding acquisition: Fisher, Arseneault, Barros, Caspi, Mondelli, Kieling

Investigation: Fisher, Caye, Anselmi, Arseneault, Barros, Caspi, Danese, Gonçalves, Menezes, Moffitt, Poulton, Rohde, Kieling

Methodology: Rocha, Fisher, Caye, Arseneault, Barros, Caspi, Danese, Gonçalves, Harrington, Houts, Menezes, Moffitt, Mondelli, Poulton, Rohde, Wehrmeister, Kieling

Project administration: Arseneault, Mondelli, Kieling

Resources: Kieling

Supervision: Fisher, Kieling

Validation: Caye

Writing – original draft: Rocha, Kieling

Writing – review and editing: Rocha, Fisher, Caye, Anselmi, Arseneault, Barros, Caspi, Danese, Gonçalves, Harrington, Houts, Menezes, Moffitt, Mondelli, Poulton, Rohde, Wehrmeister, Kieling

ORCID

Thiago Botter-Maio Rocha, MD, PhD: https://orcid.org/0000-0002-3080-6078

Helen L. Fisher, PhD: https://orcid.org/0000-0003-4174-2126

Louise Arseneault, PhD: https://orcid.org/0000-0002-2938-2191

Fernando C. Barros, MD, PhD: https://orcid.org/0000-0001-5973-1746

Andrea Danese, MD, PhD: https://orcid.org/0000-0001-8718-5412

Helen Gonçalves, PhD: https://orcid.org/0000-0001-6470-3352

Hona Lee Harrington, BA: https://orcid.org/0000-0002-0225-0607

Valeria Mondelli, MD, PhD: https://orcid.org/0000-0001-8690-6839

Richie Poulton, PhD: https://orcid.org/0000-0002-1052-4583

Fernando Wehrmeister, PhD: https://orcid.org/0000-0001-7137-1747

Christian Kieling, MD, PhD: https://orcid.org/0000-0001-7691-4149

The authors are extremely grateful to the individuals who participated in the studies at each of the sites and to all members of the IDEA consortium and the study teams for their dedication, hard work, and insights. The authors thank all members of the ProDIA group for their assistance in the development of this work. The authors would like to especially thank João Ricardo Sato, PhD, of the Universidade Federal do ABC for his thoughtful insights into the initial version of this study and Rachel Latham, PhD, of King’s College London for assistance with checking the statistical analysis for the E-Risk study.

Disclosure: Dr. Mondelli has received research funding from Johnson and Johnson, a pharmaceutical company interested in the development of anti-inflammatory strategies for depression, but the research described in this article is unrelated to this funding. Dr. Rohde has been on the speakers’ bureau/advisory board and/or has acted as a consultant for Eli Lilly and Company, Janssen-Cilag, Novartis, and Shire (a Takeda company) in the last 3 years. He has received authorship royalties from Oxford University Press and ArtMed. He has received travel awards from Shire for taking part in the 2014 American Psychiatric Association 2014 Annual Meeting. The ADHD and Juvenile Bipolar Disorder Outpatient Programs chaired by him have received unrestricted educational and research support from the following pharmaceutical companies in the last 3 years: Eli Lilly and Company, Janssen-Cilag, Novartis, and Shire. Dr. Kieling is an Academy of Medical Sciences Newton Advanced Fellow and has received grant or research support from Brazilian governmental research funding agencies (Conselho Nacional de Desenvolvimento Científico e Tecnológico [CNPq], Coordenação de Aperfeiçoamento de Pessoal de Nível Superior [CAPES], and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul [Fapergs]) and United Kingdom funding agencies (MQ, Medical Research Council, and Academy of Medical Sciences). He has served on the editorial boards of Archives of Clinical Psychiatry, Global Mental Health, and Jornal Brasileiro de Psiquiatria. He has received authorship royalties from Brazilian publishers ArtMed and Editora Manole. Drs. Rocha, Fisher, Caye, Anselmi, Arseneault, Barros, Caspi, Danese, Gonçalves, Houts, Menezes, Moffitt, Poulton, and Wehrmeister and Ms. Harrington have reported no biomedical financial interests or potential conflicts of interest.