Schizophrenia neurodevelopmental model

Among the animal models of schizophrenia a distinction can be made between pharmacological, lesion-induced and neurodevelopmental models. As is the case with models of depression and anxiety, it will be inappropriate to describe an animal with unusual behavior as suffering from schizophrenia however, it is possible in animals to mirror at least some of the symptoms or parameters known to be predominant and aberrant, respectively, in schizophrenic patients. 

Rapoport JL, Addington AM, Frangou S, Psych MRC. 2005. The neurodevelopmental model of schizophrenia Update 2005. Mol Psychiatry 10 434-449. 

Lipska BK, Weinberger DR. 2002. A neurodevelopmental model of schizophrenia Neonatal disconnection of the hippocampus. Neurotox Res 4 469-475. 

The concept of schizophrenia as a neurode- velopmental disorder has inspired attempts to create adverse and early postnatal events in, animals to model the psychopathological processes underlying the disorder (109, 110). These neurodevelopmental models include prenatal malnutrition, viral infection and hypoxia, disrupted neurogenesis by X-ray irradiation or neurotoxins in utero, adverse postnatal experiential factors such as maternal deprivation and social isolation, and postnatal brain damage created by hippocampal, neocor-tical, or thalamic lesions (109-111). With the possible exception of maternal deprivation and social isolation, these models have not been sufficiently characterized pharmacologically to be used for antipsychotic drug screening. 

A neurodevelopmental model has been evoked as one possible explanation for the etiology of schizophrenia." This model proposes that schizophrenia has its origins in some as yet unknown in utero disturbance, possibly occurring during the second trimester of pregnancy. Evidence for this is provided by the abnormal neuronal migration demonstrated in most studies of schizophrenic brains. This schizophrenic lesion may result in abnormalities in cell shape, position, symmetry, and connectivity, and functionally to the development... 

Neurodevelopmental models of schizophrenia have for the most part emphasized prenatal brain development, focusing on effects that may alter gene expression.15 For example, according to one idea, individuals with schizophrenia inherit genes that cause structural brain deviations that may be compounded by early environmental impact.16 Much of the focus of this hypothesis has been on postnatal impact, such as stress, that changes brain chemistry, but the idea can also accommodate a focus on prenatal impact. 

Lesion models are based on the idea that schizophrenia is, in part, a neurodegenerative or neurodevelopmental disorder. These lesions are generally neurotoxic, and have variable response to antipsychotic drugs (Marcotte et al., 2001). Recently, a novel model was studied in which pregnant mouse... 

Meyer U, Feldon J, Schedlowski M, Yee BK (2005) Towards an immuno-precipitated neurodevelopmental animal model of schizophrenia. Neurosci Biobehav Rev 29 913—947. 

Because of its genetic complexity and uncertain etiology, schizophrenia, like so many neu-ropsychiatricdisorders, has resisted the development of suitable animal models. Early progress in the field was hampered because of the prevailing belief that schizophrenia was a social or psychological disorder rather than a neurodevelopmental brain disorder. 

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