Modelling psychiatric disorders in animals – from altered neural development to psychopathology
Psychiatric disorders can arise due to mutations in any of a very large number of different genes. The mechanisms by which they give rise to psychopathology are highly diverse and likely involve cascading, indirect effects. Mice with mutations in neurodevelopmental genes may provide models to elucidate these pathogenic mechanisms. We have been studying several lines of mice with defects in genes controlling early processes of cell migration and axon guidance, or later processes of synapse formation and specification. These mutants end up, respectively, in states that may model aspects of psychosis, or ADHD and epilepsy. In one of these, a very early defect in cell migration ultimately leads to defects in hippocampal development and physiology that may underlie the emergence of a pathophysiological state, illustrating how indirect such effects may be. Neural development may also be affected by environmental factors. One prominent theory holds that risk of schizophrenia is increased due to maternal infection and that such effects can be modelled in animals. Our findings suggest that the maternal immune activation model in mice does not robustly induce any behavioural phenotypes of relevance to schizophrenia and draw the underlying neuroimmune hypothesis into question.