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The BEGIN study

The Bipolar Exposome-Gene Interaction Naturalistic (BEGIN) study

01/03/2023 - 28/02/2026
Lea Maitre
Funded by
Fundació La Marató de TV3

Bipolar disorder (BD) is a chronic illness characterized by recurring acute episodes of low mood and energy (“depression”), alternating with episodes of euphoria and excessive energy (“mania-hypomania”). BD affects at least 2% of the general population.

While not everyone experiences this illness the same way, acute BD relapses equally affect those suffering from it. The likelihood of an acute BD relapse, even when following an adequate treatment, is at least 75%. In BD, a relapse is defined as the return of an acute depressive or (hypo)manic episode after a period of relative remission.

The total number of episodes and the time spent acutely ill are associated with the worst outcomes and with a reduced quality of life, impacting a patient’s life in every aspect. Not surprisingly, the possibility to identify early signs of an acute relapse has pivotal importance, as it may avoid a full-blown episode, greatly improving the clinical management of BD, and by so a patient’s overall working, economic, social functioning, and ultimately the quality of life.

Sometimes it is possible to predict relapse, as some stressful life events or unhealthy habits may precipitate it, but sometimes relapses are apparently unrelated to identifiable triggers, or they need a trained eye to be recognized. Nowadays, the early recognition of acute relapses is a pillar of the management of BD, yet uniquely relying on clinical symptoms recognition.

One of the central mechanisms contributing to BD onset and course is the dysregulation of circadian rhythms, which are any physical and behavioral process that follows a 24-hour cycle, such as the variability in one’s energy, the ability to focus during the day, the spontaneous tendency to be more active in the morning or in the evening, or the secretion and circulation of hormones during the day.

These natural processes are internally regulated (by specific genes) but are also influenced by external, environmental cues such as daylight and temperatures. Indeed, urbanization, green spaces, light exposure, and pollution all affect circadian rhythms, but also mood. Coherently, a poor environment seems to play a negative effect on these aspects. People with BD seem to suffer the negative effects of a poor environment increasing the risk of hospitalization or suicide and this might relate to the relationship between BD and circadian rhythms.

For these reasons, we believe that the course of BD and the likelihood of mood relapses is influenced by the interaction of environmental aspects with one’s genetic disposition to circadian dysregulation. Understanding this interaction is of uttermost importance because patients with BD might be especially vulnerable to these potentially modifiable environmental aspects.

With our study, we pretend to explore and clarify the influence of genetic factors related to circadian rhythms and environmental factors, such as air pollution, urbanization, green spaces, light and noise exposure, on the course of BD. Also, we aim to create a computerized statistical model with combined genetic, clinical, sleep-activity, and environmental data that will help us to predict acute relapses in BD.

Total funding 

299.366,76 €

Our Team


ISGlobal team

  • Ximena Goldberg
    Ximena Goldberg Assistant Research Professor
  • Mark J Nieuwenhuijsen
    Mark J Nieuwenhuijsen Research Professor, Director of the Urban Planning, Environment and Health Initiative, and Head of the Climate, Air Pollution, Nature and Urban Health Programme
  • Paula Petrone
    Paula Petrone Associate Research Professor

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