Abstract Body

Major mental disorders have typically a complex aetiology where both genetic and environmental risk factors have been implicated. It has also been suggested that these risk factors could be interactive rather than just additional. In the last decade, large genetic studies have began to unravel the genetic architecture of several of these disorders. While the mechanisms of action of environmental risk factors are still unclear.

At the molecular level, gene expression can be regulated at the epigenetic level, e.g. chromatin modifications or DNA methylation. Epigenetic modifications can be affected by both genetic variations as well as environment variations.

In this presentation, we will review recent results either from literature or from own data on how several known environmental risks for mental disorders can be associated with modifications of epigenetic markers, especially in DNA methylation. We will for instance look at the modifications associated with smoking, alcohol, cannabis, childhood trauma or obstetric complications. We will discuss also the limits of these studies and how epigenetic modifications can be relevant for the onset of mental disorders and their treatment.

Abstract Body

Nonhuman primates (NHPs) are critical for translational research due to their close genetic, physiological, and behavioral similarity to humans. In particular, higher brain functions depend on brain regions and neural circuits that evolved differently between primates and rodents. Thus, NHPs are a strong translational model system to investigate the pathophysiology and relevant biological correlates of mental disorders. This talk will focus on translational approaches leveraging NHP models to advance our understanding of environmentally induced epigenetic changes in post-traumatic stress disorder (PTSD). Environmental factors including early life stress significantly contribute to risk and resilience for psychiatric disorders including PTSD. However, human studies are often confounded, and it remains challenging to identify robust epigenetic signals in clinical populations even in large studies. We investigate the natural spectrum of behavioral phenotypes in rhesus macaques to complement human studies with a focus on stress and fear. This talk will present data on epigenetic signatures of fear and the effects of early life stress in rhesus monkeys and their relationship to human studies.