Effects of Pre- and Postnatal Early-Life Stress on Internalizing, Adiposity and Their Comorbidity

EarlyCause consortium

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Objective: Depression and obesity are 2 highly prevalent and often comorbid conditions. Exposure to early-life stress (ELS) has been associated with both depression and obesity in adulthood, as well as their preclinical manifestations during development. However, it remains unclear whether (1) associations differ depending on the timing of stress exposure (prenatal vs postnatal), and whether (2) ELS is a shared risk factor underlying the comorbidity between the 2 conditions. Method: Leveraging data from 2 large population-based birth cohorts (ALSPAC: n = 8,428 [52% male participants]; Generation R: n = 4,268 [48% male participants]), we constructed comprehensive cumulative measures of prenatal (in utero) and postnatal (from birth to 10 years) ELS. At age 13.5 years, we assessed the following: internalizing symptoms (using maternal reports); fat mass percentage (using dual-energy X-ray absorptiometry); and their comorbidity, defined as the co-occurrence of high internalizing and high adiposity. Results: Both prenatal (total effect [95% CI] = 0.20 [0.16; 0.22]) and postnatal stress (β [95%CI] = 0.22 [0.17; 0.25]) were associated with higher internalizing symptoms, with evidence of a more prominent role of postnatal stress. A weaker association (driven primarily by prenatal stress) was observed between stress and adiposity (prenatal: 0.07 [0.05; 0.09]; postnatal: 0.04 [0.01; 0.07]). Both prenatal (odds ratio [95%CI] = 1.70 [1.47; 1.97]) and postnatal (1.87 [1.61; 2.17]) stress were associated with an increased risk of developing comorbidity. Conclusion: We found evidence of timing and shared causal effects of ELS on psycho-cardiometabolic health in adolescence; however, future research is warranted to clarify how these associations may unfold over time. Diversity & Inclusion Statement: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group.

Original languageEnglish
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Early online date12 Jul 2023
Publication statusE-pub ahead of print - 12 Jul 2023

Bibliographical note

Funding Information:
This project received funding from the European Union’s Horizon 2020 research and innovation programme (848158, EarlyCause; 733206, LifeCycle; 874739, LongITools). The general design of the Generation R Study is made possible by financial support from the Erasmus MC, Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development and the Ministry of Health, Welfare and Sport. The UK Medical Research Council and Wellcome (grant ref: 217065/Z/19/) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website ( http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf ). This research was specifically funded by the Wellcome Trust and MRC (core) (grant ref: 102215/2/13/2). The Generation R Study is conducted by Erasmus MC, University Medical Center Rotterdam in close collaboration with the School of Law and Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR-MDC), Rotterdam.

Funding Information:
Disclosure: Prof. Pariante was supported by: a Senior Investigator award from the National Institute for Health Research (NIHR); the NIHR Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King's College London; the Medical Research Council (grants MR/L014815/1, MR/J002739/1 and MR/N029488/1); the European Commission (the Innovative Medicine Initiative 2 Joint Undertaking EUPEARL grant 853966); the NARSAD; the Psychiatry Research Trust; and the Wellcome Trust (SHAPER, Scaling-up Health-Arts Programme to scale up arts interventions, grant 219425/Z/19/Z). Less than 10% of his support in the last 10 years derives from commercial collaborations, including: a strategic award from the Wellcome Trust (Neuroimmunology of Mood Disorders and Alzheimer's Disease (NIMA) Consortium, grant 104025), in partnership with Janssen, GlaxoSmithKline, Lundbeck and Pfizer; a research grant from Janssen; and consultation and speakers fees from Boehringer Ingelheim, Eli Lilly, Compass, Eleusis, GH Research, Lundbeck, and Värde Partners. Prof. Tiemeier was supported by the Netherlands Organization for Health Research and Development ZonMw Vici Grant (016.VICI.170.200). Dr. Walton was funded by UK Research and Innovation (UKRI) under the UK government’s Horizon Europe / ERC Frontier Research Guarantee [BrainHealth, grant EP/Y015037/1]. Drs. Lekadir, Jaddoe, Serdarevic, Felix, and Cecil, Ms. Defina, Mr. Woofenden, and Ms. Baltramonaityte have reported no biomedical financial interests or potential conflicts of interest.


  • Generation R
  • adiposity
  • early-life stress
  • internalizing symptoms

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Developmental and Educational Psychology


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