From Humans to Animals: Animal Models in Schizophrenia

Schizophrenia is one of the most devastating psychiatric disorders. Schizophrenia affects 1.1% of the population or 51 million people (NIMH). Schizophrenia is a disorder that affects multiple brain regions and systems. Symptoms include positive symptoms, negative symptoms and cognitive deficits. Much research has focused on two neurotransmitter systems, dopamine and glutamate. Postmortem studies examining morphology have found alterations in dendrites and spines in the prefrontal cortex and the hippocampus, changes in cell number in volume in the thalamus and alterations in protein expression in the prefrontal cortex. Genetic studies have found a number of genes associated with schizophrenia including but not limited to DISC1, neuregulin1, and Dysibindin 1. The current hypothesis based on the postmortem work and genetic studies suggests the etiology of schizophrenia has its origins in development. The changes in dendrites and spines observed in the prefrontal cortex and hippocampus without a change in cell number could occur as a result of alterations in calcium signaling levels in development due to alterations in synaptic input into the prefrontal cortex and hippocampus. The various genes that have been shown to be altered in schizophrenia are also involved in neurodevelopment. DISC1, neuroregulin 1 and Dysbindin 1 have all been shown to be involved in neurite outgrowth and differentiation (Ghiani et al, 2010; Kamiya et al, 2005; Pitcher et al, 2011; Sebat et al., 2009; Wiliams et al., 2010). These data support the above hypothesis that schizophrenia is a neurodevelopmental disorder that may or may not have a genetic predisposition. In order to better understand the etiology of the disease, research needs good models with which to test theory. Genetic models, chemical lesions, and physical lesions have been used to produce animal models to mimic human disorders and are becoming the hallmark of translational research. Animal models in the past have been used to understand how the nervous system develops by using lesions to examine pathways or genetic knockouts to examine the role of genes in development and function of the nervous system. The use of animal models is not limited to basic research but is also used by pharmaceutical companies to test drugs to treat diseases to determine their viability. Whatever their use, animals provide us with a unique way in which to view how the nervous system develops, functions and what happens when development goes wrong. This chapter will focus on the use of animal models as a potential method to study neuropsychiatric disorders.