Integrating information in stress research

Abstract

There are few experiences as engulfing as the subjective experience of stress. It affects multiple biological systems, with temporal and spatial specificity. It depends on genetic predisposition, early- and late- life events, and it leads to different responses depending on its type (e.g. psychological vs physiological) and frequency (e.g. acute vs chronic). This complex system has historically been studied by isolating each specific feature in an experiment. While this approach has been extremely successful, understanding stress as a system, rather than a collection of organs and hormones, can bring us closed to comprehend how it works in nature, in health and for the future improvement of disease. In this thesis, we examined stress as a biological system rather than isolating a specific feature in a single experiment. Specifically, we integrated information from multiple sources (i.e., literature, consortia, atlases, and newly generated data) to increase our understanding of the effects of acute stress and chronic stress experienced in early life on brain and behavior. Our approach was fully grounded in Open Science practices of collaboration, data and code sharing, as well as in software development. This thesis is subdivided into three sections. In Part A, we integrate information related to the healthy acute stress response, focusing on the rodent brain and salivary cortisol concentration in humans. While our studies have been conducted in two different species, they both investigate acute stress as a dynamic process that occurs in time. Independently of whether integration of information is applied to animal or human data, it is most efficacious when aimed at investigating the stability and reproducibility of effects. In Part B, we integrated information related to chronic stress experienced early in life by rodents. Adversities early in life can have long lasting consequences on brain development and are one of the main risk factors for several mental health disorders. The effects of early life adversity (ELA) on behavior and neurobiology depend on a complex interaction between early-, late- life events, as well as the acute state of the animal. By using systematic reviews and meta-analyses, we can integrate information of the literature to identify robust conclusions and provide quantitative descriptions. This led to the extraction of 7 principles of ELA, which give insight in what is currently known and can also guide future research. In Part C, we developed methodologies for information integration. Specifically, information of previous control animal groups can be used to improve the statistical power of animal experiments. Open Software was developed to aid scientists to integrate information, and as a knowledge utilization strategy for the smoother communication of scientific results. In conclusion, in this thesis we integrated information related to the acute and chronic (i.e. ELA) stress response. This was achieved 1) by performing new experiments in rodents, 2) by founding and expanding the collaboration within consortia, 3) by extensively and systematically reviewing the literature, and lastly 4) by providing data and scripts freely available online. It is a first step towards a comprehensive, systems-view of stress.