The neurophysiological potential: Translatability and reproducibility of preclinical outcome measures in psychiatric research

Animal models are an important source of information for studying the biological mechanisms and complexity of mental disorders. In this thesis we studied which characteristics are most suitable to study psychiatric disorders in animal models. We sought for characteristics of which the findings in animals apply to patients and which are robust enough to give the same results when tested in different laboratories. Behavioural changes are important in psychiatric disorders, but turn out to be difficult to study in animal models. In a study where we combined all available data on the behaviour of an autism mouse mode, we found that the results were highly inconsistent, although mostly representing the symptoms of patients well. Physiological characteristics have the potential to generate more valuable results than behaviour, amongst other things because they can be measured in patients and animals in more similar ways. In the same mouse model, we studied brain activity in rest and in response to sensory stimulation. The responses to sensory stimuli also showed inconsistent results, however the characteristics of the brain activity in rest were consistent and in line with earlier findings. The brain activity of the mice was dominated by inhibitory activity. This was in contrast with the hypothesis of a hyperactive brain in autism, but in line with studies assessing the brain activity of autistic children using the same method. Our results suggest that studying physiological characteristics in psychiatric disorders can lead to more robust findings which translate better between the animal models and patients.