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Early-life stress and psychological, cardiovascular, and metabolic disorders

Can early-life stress be the cause of the coexistent development of psychological, cardiovascular and metabolic disorders?

The EarlyCause project

The World Health Organization has identified mental disorders (including depression), cardiovascular diseases (particularly heart attacks and strokes), and diabetes among the six major non-communicable diseases (not transmissible directly from one person to another, like infectious diseases).

Alone, each of these groups of diseases represents a burden at the individual and population level. Depression alone is the single largest contributor to global disability, accounting for 12% of total years lived with disability with more than 300 million individuals affected per year. While cardiovascular diseases remain the prime cause of mortality worldwide, type 2 diabetes and related metabolic dysfunctions, including obesity, are a major public health challenge, with an average prevalence of over 8% in the general population.

In addition to their separate complexity, existing research has shown important multi-morbidity between these diseases, where multi-morbidity is defined as the simultaneous presence of two or more chronic conditions at the same time. This means that two or more illnesses or diseases occur in the same person at the same time. For example, patients experiencing depression are more likely to have multi-morbid cardiovascular diseases, type 2 diabetes, or both. However, the reasons or causes of this coexistence of psychological, cardiovascular and metabolic diseases is not well understood, which limits the development of effective preventive and treatments.

Interestingly, it has been suggested that many mental and physical conditions find their origins in exposure to early-life stress.

I am a researcher at the Stress, Psychiatry and Immunology Lab (the team who brings you the InSPire the Mind blog) trying to understand the role of stress and inflammation in depression. Currently, as part of the EarlyCause project, I investigate the role of early-life stress in the development of diseases in adulthood using cellular models of early-life stress. That means that I treat cells from the brain and from the heart with molecules related to stress in order to study their effects on the cellular models.

With this blog, I want to explain to you what early-life stress is and its importance for our mental and physical health, before introducing the EarlyCause project, showing how this ties in to improving our knowledge and possibly improve the ways to cure and prevent the development of early-life stress-related multi-morbidities.

What is early-life stress?

Early-life stress refers to the experience of stressful or adverse conditions during a child’s development, beginning anywhere from pregnancy to adolescence. When occurring prenatally (during pregnancy), early-life stress may be experienced because of maternal stress during pregnancy (job loss of caregiver, illnesses, death of a relative), whereas when occurring after birth, it can result from adverse events such as child abuse (sexual, physical, emotional) and neglect (emotional, physical), parental loss (death, separation), disease, accidents, prepubertal bullying, as well as victimisation or violence by peers.

Stress experienced in the early stages of life is common and pervasive, affecting up to 75% of pregnant women (and their unborn babies) and nearly 50% of children, with long term consequences for development and health.

Why is early-life stress important?

“It takes Wonder Woman courage and Superman strength to heal the wounds of our abuse… because it brings change… and we are inclined to hold on to the stability we created in the chaos of our past experiences.” — JEANNE MCELVANEY

Early-life stress can have a long-lasting impact on a child’s development, health and wellbeing. For example, early-life stress can affect a child’s neurodevelopment, hence increasing the risk of cognitive, emotional and behavioural problems. Neurodevelopment is the brain’s ability to develop the neurological pathways responsible for the normal functioning of the brain and the ability to learn, focus, develop memories and social skills, etc. In addition, early-life stress can dysregulate important physiological functions, affecting the way a child may respond to future stressors.

Importantly, early-life stress is a key determinant of health, not just early in life, but across the lifespan. It is known to dramatically increase the risk of developing a mental or physical illness and has been repeatedly associated with health problems such as depression, anxiety, and personality disorder, as well as cardiovascular diseases, obesity and type 2 diabetes, and possibly cancer. However, the biological mechanisms through which early-life stress affects health remain unclear and this limits the development of measures that can prevent or treat this.

What is the EarlyCause project?

The EarlyCause project is a Horizon 2020 project funded by the European Commission under grant number 848158 which investigates how early-life stress causes diseases in adulthood. You can find more details in our recently published paper. Its approach is original and novel because it examines which aspects of early-life stress are linked to the concomitant development of psychological, cardiovascular and metabolic diseases together, which is responsible for the increased mortality linked to early-life stress. Furthermore, the EarlyCause project assesses whether these risk pathways can be diminished or prevented by clinical and lifestyle interventions to avoid the development of diseases.

The project combines studies in large groups of people across Europe with validated animal models of early-life stress of prenatal and postnatal (just after birth) stress as well as cellular models of early-life stress in various tissues (including human brain and heart cells) to identify the chain of molecular and biological events that are activated in the brain and body by early-life stress and which result in clinical symptoms. In addition, the aim is to quantify the role of key factors such as sex, socioeconomics, and lifestyle in the association between early-life stress and the development of diseases to find potential intervention strategies that could reverse causative mechanisms and reduce the effect of early-life stress in individuals at high risk of developing multi-morbidity.

We will analyse the largest set of European cohorts, with longitudinal human data which include rich information on early-life stressors and biological data as well as depressive, cardiovascular and metabolic phenotype (characteristics that result from the interaction of the total genetic inheritance with the environment). Longitudinal data means that the data has been repetitively recorded over a long period of time. The generated data, tissue samples, experimental protocols and cell lines as well as best practices will be compiled into a new research platform accessible to everyone to support future researchers in the field.

Our ideal end-point will be to publish evidence to inform the future development of more efficient and optimised ways to cure and prevent the development of multi-morbidities, thus improving decision-making and clinical management of patients with early-life stress-related multi-morbidities.

If, while we are carrying out our research, you wish to stay up to date on our progress and publications, you can follow the EarlyCause project on Twitter and on its website.


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