Periodic Reporting for period 3 - BRAINMINT (Brains and minds in transition: The dark side of neuroplasticity during sensitive life phases)
Période du rapport: 2022-08-01 au 2024-01-31
Despite several breakthroughs, the genetic revolution has not provided a coherent account of the development of the mind and its disorders, and the missing heritability is large across human traits. One explanation of this impasse is the complexity of the gene-environment interactions. Our current knowledge about the determinants of a healthy mind is largely based on studies that treat the environment as a static entity, neglecting to consider the crucial fact that environmental inputs and their genetic interactions vary dramatically between life phases. The objective of BRAINMINT is to deepen our understanding of this link by zeroing in on two major life transitions: adolescence and pregnancy. These phases are characterized by temporarily increased brain plasticity, offering windows for adaptation and growth, but also have a “dark side” in that they are also associated with the emergence of mental disorders. Thus, it appears that the mechanisms that boost neuroplasticity promote adaptation to a dynamic environment, do so at the cost of increased risk of psychopathology if exposed to a combination of genetic and environmental triggers.
BRAINMINT strives to elucidate this phenomenon with the application of cutting-edge longitudinal brain imaging, electrophysiology, rich cognitive and clinical data, immune markers, gene expression and genetics, leveraging massive imaging data and novel tools to increase power and generalizability and improve brain- and gene-based predictions of complex traits, with a special emphasis on traits that are particularly responsive during adolescence and pregnancy.
As such, BRAINMINT is a pioneering and high risk/high gain effort to find mechanisms of brain plasticity that support and harm the brain, aiming to yield insights into how both normal and abnormal development occurs, and, importantly, elucidate the pathophysiological mechanisms underlying common mental disorders. This will pave the way for the development of novel diagnostic and therapeutic approaches, as well as providing novel clues into the fundamental architecture of the brain, how it changes over time, and the perturbations underlying mental disorders.
mon mental disorders. This will pave the way for the development of novel diagnostic and therapeutic approaches, as well as providing novel clues into the fundamental architecture of the brain, how it changes over time, and the perturbations underlying mental disorders.
BRAINMINT strives to elucidate this phenomenon with the application of cutting-edge longitudinal brain imaging, electrophysiology, rich cognitive and clinical data, immune markers, gene expression and genetics, leveraging massive imaging data and novel tools to increase power and generalizability and improve brain- and gene-based predictions of complex traits, with a special emphasis on traits that are particularly responsive during adolescence and pregnancy.
As such, BRAINMINT is a pioneering and high risk/high gain effort to find mechanisms of brain plasticity that support and harm the brain, aiming to yield insights into how both normal and abnormal development occurs, and, importantly, elucidate the pathophysiological mechanisms underlying common mental disorders. This will pave the way for the development of novel diagnostic and therapeutic approaches, as well as providing novel clues into the fundamental architecture of the brain, how it changes over time, and the perturbations underlying mental disorders.
mon mental disorders. This will pave the way for the development of novel diagnostic and therapeutic approaches, as well as providing novel clues into the fundamental architecture of the brain, how it changes over time, and the perturbations underlying mental disorders.
The main achievement of the current period is the successful implementation of a robust pipeline for the longitudinal collection of brain imaging, genetic, biochemical and behavioural data. The beginning of data collection coincided with the onset of the COVID-19 pandemic, meaning that there were initial delays in data collection. This delay has now been overcome and we have so far successfully collected almost 1700 datasets in the two arms of the study. Continuously employed quality assurance measures indicate excellent data quality throughout. Thus, we have successfully generated one of the highest quality genetic imaging datasets in existence. We are proceeding to exploit the dataset with the first publications based on it already emerging, with more in preparation.
BRAINMINT is a cutting-edge imaging genetics project, utilizing both novel and highly advanced methodological approaches and big data to ensure that productive and robust insights can be gleaned into the mechanisms underlying the development of mental disorders. Critically, a central aim of BRAINMINT is to push the boundaries of our current understanding of mental disorders, establishing a novel approach to clinical nosology by identifying phenotypes that cut across current diagnostic boundaries. This is important because there is substantial clinical overlap and comorbidity between psychiatric disorders, suggesting that there is a common underlying dimensional organization to the mechanisms underlying the development of psychopathology. As such, BRAINMINT aims to push the boundary of evidence-based medicine forward, while simultaneously affording fundamental insights into the organization and development of the brain.