Investigating the link between early life stress and multiple long-term health conditions
| ISRCTN | ISRCTN44060592 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN44060592 |
| Secondary identifying numbers | Earlycause funding 848158 |
- Submission date
- 29/06/2020
- Registration date
- 15/07/2020
- Last edited
- 26/06/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Other
Plain English Summary
Background and study aims
Stress experienced in the early stages of life – from pregnancy to adolescence – is common and pervasive, affecting up to 75% of pregnant women (and the unborn baby) and nearly 50% of children, with long-term consequences for development and health. The aim of this study is to find out whether early life stress, a well-established risk factor for depressive, cardiovascular (heart) and metabolic disorders individually, is a cause of multiple long-term health conditions (multi-morbidity) in these disorders.
Who can participate?
Children and adults participating in the included population studies:
1. Population-based samples of children
2. Adults aged over 55 years
3. Adults aged over 18 years with depression or anxiety
What does the study involve?
Data from a set of human population studies are used to examine the relationship between early life stress and multi-morbidity across the lifespan, identify potential biological markers and quantify the role of modifiable lifestyle factors (e.g. exercise, diet, sleep, smoking, alcohol use).
What are the possible benefits and risks of participating?
In terms of benefits, this study will increase the health literacy of the participants by making them aware of the negative effects of early life stress on health and disease. This is an observational study with no interventions, so there are no risks for the participants.
Where is the study run from?
Rotterdam and Amsterdam (Netherlands), Oulu (Finland) and Bristol (UK)
When is the study starting and how long is it expected to run for?
September 2019 to June 2024
Who is funding the study?
European Commission
Who is the main contact?
1. Karim Lekadir
karim.lekadir@ub.edu
2. Cristian Izquierdo Morcillo
c.izquierdo@ub.edu
Contact information
Scientific
Gran Via de les Corts Catalanes 585
Barcelona
08007
Spain
 ORCID ID |
0000-0002-9456-1612 |
|---|---|
| Phone | +34 (0)934020852 |
| karim.lekadir@ub.edu |
Public
Gran Via de les Corts Catalanes 585
Barcelona
08007
Spain
| Phone | None provided |
|---|---|
| c.izquierdo@ub.edu |
Study information
| Study design | Observational study that will leverage existing data from a large set of population research studies (e.g. Generation R, ALSPAC, NFBC, Rotterdam, NESDA) |
|---|---|
| Primary study design | Observational |
| Secondary study design | Epidemiological study |
| Study setting(s) | Other |
| Study type | Other |
| Scientific title | EarlyCause - causative mechanisms & integrative models linking early life stress to psycho-cardio-metabolic multi-morbidity |
| Study acronym | EarlyCause |
| Study hypothesis | EarlyCause will investigate the hypothesis that early-life-stress (ELS), as a risk factor for depressive, cardiovascular and metabolic disorders individually, is linked to multi-morbidity between these conditions. From a biological point of view, the main hypothesis is that ELS activates a chain of events leading to cellular, molecular, epigenetic and microbial changes which result in dysregulations of processes across tissues. This causative chain would ultimately trigger specific cellular and tissue phenotypes and comorbid pathological traits in the mental, cardiovascular and metabolic domains. |
| Ethics approval(s) | Approved 30/11/2019, European Commission (Directorate-General for Research and Innovation, European Commission, Brussels; Tel: not provided; david.canovas-jorda@ec.europa.eu), no ref provided |
| Condition | Multi-morbidity between unipolar depression, type 2 diabetes, and coronary heart disease |
| Intervention | The EarlyCause study will leverage harmonised data from a set of human population studies to examine the relationship between ELS and multi-morbidity across the lifespan, identify potential molecular markers and quantify the protective vs. exacerbating role of modifiable lifestyle factors. These datasets together span from pregnancy to old age, including the well-known Avon Longitudinal Study of Parents and Children (ALSPAC), Generation R Study (GenR), Northern Finland Birth Cohorts (NFBC 1966 and NFBC 1986), Rotterdam Study, and the Netherlands Study of Depression and Anxiety (NESDA). The researchers will make use of correlational multivariate analyses as well as novel latent modelling techniques to model the shared versus unique contribution of ELS on multi-morbid outcomes. The researchers will apply Mendelian randomisation to infer causality using population-based human genetic data., and to establish the molecular mediation of biological markers (DNA methylation, cortisol, inflammation, microbiome) linking ELS exposure to later multi-morbidity. The researchers will also quantify the protective or exacerbating role of modifiable lifestyle factors (e.g. exercise, diet, sleep, smoking, alcohol use) in the relationships of ELS with biological markers and multi-morbidity. |
| Intervention type | Other |
| Primary outcome measure | Current primary outcome measures as of 28/12/2023: 1. Depression assessed using the DSM-IV scale at each round of data collection (every 2-5 years depending on the dataset) 2. Diabetes type 2 assessed using the glycated hemoglobin test at each round of data collection (every 2-5 years depending on the dataset) 3. Coronary heart disease assessed using standard cardiovascular exams (biomarkers, imaging, ECG) at each round of data collection (every 2-5 years depending on the dataset) 4. In NFBC, depressive symptoms were measured using Youth self report (YSR) scale at 16 years in NFBC1986 and using Hopkins Symptoms checklist (HSCL) at 31 and 46 years in NFBC1966 _____ Previous primary outcome measures: 1. Depression assessed using the DSM-IV scale at each round of data collection (every 2-5 years depending on the dataset) 2. Diabetes type 2 assessed using the glycated hemoglobin test at each round of data collection (every 2-5 years depending on the dataset) 3. Coronary heart disease assessed using standard cardiovascular exams (biomarkers, imaging, ECG) at each round of data collection (every 2-5 years depending on the dataset) |
| Secondary outcome measures | Current secondary outcome measures as of 28/12/2023: EarlyCause will re-use the outcomes already measured by the Generation R, ALSPAC, NFBC, Rotterdam and NESDA studies at each round of data collection (every 2-5 years depending on the study): 1. Depressive symptoms assessed using the Centre for Epidemiological Studies Depression Scale (CESD) at each round of data collection (every 2-5 years depending on the dataset) 2. Metabolic health-related measures such as obesity and glycemic traits 3. Hypertension assessed using blood pressure test (mmHg) at each round of data collection (every 2-5 years depending on the dataset) _____ Previous secondary outcome measures:EarlyCause will re-use the outcomes already measured by the Generation R, ALSPAC, NFBC, Rotterdam and NESDA studies at each round of data collection (every 2-5 years depending on the study): 1. Depressive symptoms assessed using the Centre for Epidemiological Studies Depression Scale (CESD) at each round of data collection (every 2-5 years depending on the dataset) 2. Glucose level assessed using glycated hemoglobin test at each round of data collection (every 2-5 years depending on the dataset) 3. Hypertension assessed using blood pressure test (mmHg) at each round of data collection (every 2-5 years depending on the dataset) |
| Overall study start date | 04/09/2019 |
| Overall study end date | 30/06/2024 |
Eligibility
| Participant type(s) | Mixed |
|---|---|
| Age group | Mixed |
| Sex | Both |
| Target number of participants | 70,000 |
| Participant inclusion criteria | Current inclusion criteria as of 28/12/2023: The inclusion criteria are the same as those of the population studies included in EarlyCause: 1. Generation R: Population-based sample of children 2. ALSPAC: Born of a mother resident in former Avon health authority, expected data of delivery between 1st April 1991 and 31st December 1992 3. NFBCs: Pregnant mothers living in the two northernmost province of Finland (Oulu and Lapland). NFBC-1966 included all mothers with expected date of delivery between 1st of January to 31st December 1966 and their offspring with data at birth, 31 and 46 years of age. NFBC-1986 included mothers with expected date of delivery between July 1985 to June 1986 and their offspring with data at birth and 16 years of age. 4. Rotterdam Study: Adults >55 years 5. NESDA: Adults >18 years with DSM-IV diagnosis of depression (minor or major depression, dysthymia) or anxiety _____ Previous inclusion criteria: The inclusion criteria are the same as those of the population studies included in EarlyCause: 1. Generation R, ALSPAC, NFBC: Healthy children at birth 2. Rotterdam: Adults > 55 3. NESDA: Adults > 18 with DSM-IV diagnosis of depression (minor or major depression, dysthymia) or anxiety |
| Participant exclusion criteria | For NESDA, severe mental health (e.g. psychosis, bipolar disorder, obsessive-compulsive disorder, or severe addiction) or disability |
| Recruitment start date | 01/01/1966 |
| Recruitment end date | 30/05/2020 |
Locations
Countries of recruitment
- England
- Finland
- Netherlands
- United Kingdom
Study participating centres
Rotterdam
3015 GD
Netherlands
Oulu
90570
Finland
Amsterdam
1081 HV
Netherlands
Bath
BA2 7AY
United Kingdom
Sponsor information
Government
Directorate-General for Research and Innovation
Brussels
1049
Belgium
| Phone | +32 (0)2 299 11 11 |
|---|---|
| David.CANOVAS-JORDA@ec.europa.eu | |
| Website | http://ec.europa.eu/index_en.htm |
"ROR" |
https://ror.org/00k4n6c32 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- EU Framework Programme for Research and Innovation H2020, Horizon 2020, Rahmenprogramm Horizont 2020, Programa Marco Horizonte 2020, Programme-cadre Horizon 2020, Programma quadro Orizzonte 2020, Program ramowy Horyzont 2020, Horizont 2020, Horizonte 2020, Orizzonte 2020, Horyzont 2020, Horizon 2020 Framework Programme (H2020), H2020
Results and Publications
| Intention to publish date | 30/06/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Peer-reviewed international journals such as: 1. Journal of Developmental Origins of Health and Disease 2. International Journal of Epidemiology |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available due to legal issues, consents and data policies of the included population studies. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | 07/08/2020 | No | No | ||
| Protocol file | 07/08/2020 | No | No | ||
| Protocol article | 21/01/2021 | 26/06/2024 | Yes | No | |
| Results article | Arterial Thickness, Stiffness, and Blood Pressure With Brain Morphology | 09/11/2023 | 26/06/2024 | Yes | No |
| Results article | Depression, cardiometabolic disease, and their co-occurrence after childhood maltreatment | 13/03/2023 | 26/06/2024 | Yes | No |
| Results article | Obesity | 21/08/2023 | 26/06/2024 | Yes | No |
| Results article | anorexia nervosa | 01/11/2022 | 26/06/2024 | Yes | No |
| Results article | depression prediction | 03/04/2024 | 26/06/2024 | Yes | No |
| Results article | early-life stress and adolescent psycho-physical health | 01/05/2024 | 26/06/2024 | Yes | No |
| Results article | maternal glycemic dysregulation during pregnancy and neonatal blood dna methylation | 04/03/2022 | 26/06/2024 | Yes | No |
| Results article | metabolic Syndrome | 20/11/2023 | 26/06/2024 | Yes | No |
| Results article | psycho-cardiometabolic multimorbidity | 30/06/2023 | 26/06/2024 | Yes | No |
Additional files
- ISRCTN44060592_PROTOCOL_text.pdf
- uploaded 07/08/2020
- ISRCTN44060592_PROTOCOL_figures.pdf
- uploaded 07/08/2020
Editorial Notes
26/06/2024: Publication references added.
24/06/2024: The study contacts were updated.
28/12/2023: The following changes have been made:
1. The overall study end date has been changed from 31/12/2023 to 30/06/2024.
2. The intention to publish date has been changed from 31/12/2023 to 30/06/2025.
3. The primary outcome measures have been changed.
4. The secondary outcome measures have been changed.
5. The participant inclusion criteria have been changed.
6. The plain English summary has been updated to reflect the above changes.
06/12/2023: The public contact was changed.
24/11/2020: The following changes were made to the trial record:
To reflect the fact that historical datasets are being used for this study:
1. The recruitment start date was changed from 01/01/2020 to 01/01/1966.
2. The recruitment end date was changed from 31/12/2023 to 30/05/2020.
07/08/2020: Uploaded protocol (not peer reviewed) Version n/a (2 files).
30/06/2020: Trial's existence confirmed by the European Commission.
