Hypoxic-ischaemic encephalopathy (HIE), a condition caused by oxygen deprivation around birth, accounts for the death of around one million newborns worldwide every year, and the number of neonates who suffer permanent neurological damage is much higher. Even with a mild course, HIE can lead to long-term neurodevelopmental, behavioural, cognitive and psychiatric disorders. The aim of our research is to identify potential new therapeutic targets and biomarkers that may predict increased risk for subsequent psychiatric disorders by translational preclinical investigation of the brain disease mechanisms underlying the long-term effects of HIE.
Disruptions in a child's social environment, such as instances of abuse or neglect, can significantly modify the development of the brain. This alteration serves as a potential risk factor for the emergence of later psychopathological disorders, particularly those related to social behavior within psychiatric conditions. Using different translational, clinically relevant models of early social stress (abuse, neglect), we aim to reveal alterations in maturation processes of regions implicated in emotional control and their long-term functional (behavioural) consequences, allowing the understanding of cellular mechanisms and identification of novel molecular targets.
Coping with different stressors is essential for survival and success, which is regulated by complex neural networks integrating cognitive and emotional processes. Under pathological conditions, excessive passive coping becomes detrimental, observed in anxiety and depressive disorders. Animal models can help to identify the neural substrates of individual vulnerability to develop such maladaptive conditions. We use rodent models (transgenic mice, early-life stress, cell type-specific manipulations) to explore the molecular, cellular, neuronal network level changes underlying anxious-depressive phenotypes.
Most people experience at least one traumatic event during their lifetime. While the majority of individuals recover without long-term consequences, 10-30% of trauma-exposed individuals develop posttraumatic stress disorder (PTSD), a complex, severe and lasting mental condition which fundamentally decreases life quality. Therapeutic interventions in PTSD are insufficiently resolved to this day. Identification of individuals vulnerable to trauma-induced development of PTSD and treatment strategies selectively targeting this subpopulation represents a major clinical challenge with high therapeutic potential. Employing a translational laboratory animal model of trauma-induced lasting adverse behavioral changes, our group aims to identify behavioral markers of vulnerability and their neural correlates.
The prevalence of anxiety disorders is significantly the highest among all mental illnesses, estimated at around 34%. Despite its high prevalence and serious individual and societal impacts, the neurobiological mechanisms underlying this group of disorders are not fully understood. Consequently, the currently available pharmacotherapeutic treatments are ineffective in 40% of cases. Furthermore, promising new drug targets identified in preclinical studies prove ineffective in human clinical trials at an alarming rate. Our hypothesis suggests that preclinical anxiety tests can only measure transient anxious states that are highly influenced by environmental impacts, rendering them unsuitable for modelling high trait anxiety, a core symptom of anxiety disorders.
