CHAPTER 5: Modelling Schizophrenia: Strategies for Identifying Improved Platforms for Drug Discovery

Schizophrenia is a neurodevelopmental disorder characterised by a variety of perceptual, motivational, and cognitive deficits, and is caused by the complex interplay of both genetic and environmental factors. The boundaries of this diagnostic category are arbitrary and likely to reflect the intersection of several domains of psychopathology found in psychotic illness. The failure to consistently replicate associations between susceptibility gene candidates and schizophrenia, as well as the absence of a clear neuropathological signature, has limited the capacity to generate and validate preclinical models that reflect the underlying pathobiology of the disorder. However, studies indicate that mice with either constitutive or conditional single risk gene mutations have the potential to both identify gene–phenotype, gene × environment [G × E]–phenotype, and gene × gene–phenotype relationships, and inform on the molecular mechanisms that underlie these relationships.