eISSN: 2084-9885
ISSN: 1896-6764
Neuropsychiatria i Neuropsychologia/Neuropsychiatry and Neuropsychology
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vol. 2

Review article
Modeling the genetics of schizophrenia – the curse of plentitude?

Barbara K. Lipska

Neuropsychiatria i Neuropsychologia 2007; 2, 2: 51–53
Online publish date: 2007/11/26
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Rapidly growing knowledge about the neurobiology and genetics of schizophrenia has stimulated new interest in animal models, which are used to dissect the molecular mechanisms of pathophysiological abnormalities in schizophrenia and create more effective therapies. The concepts about how to approach animal modeling of this complex, multifactorial (i.e., involving multiple genes and a variety of epigenetic causes) neuropsychiatric disorder have been evolving over years and reflect the changing ideas about the etiology and the mechanism of the illness (Lipska and Weinberger 2000; Chen et al. 2006). These past approaches included pharmacological manipulations of dopamine and glutamate systems, thought to be in the center of the neurotransmitter imbalance in schizophrenia and the main culprits in the psychotic symptoms and cognitive impairments (Costall and Naylor 1995). Subsequent concepts focused on disruptions of early brain development to address the evidence that the disorder has a neurodevelopmental origin; the onset of schizophrenia is typically in adolescence or early adulthood and early childhood is not normal in many cases (Lipska and Weinberger 2000; Moore et al. 2006). Manipulations of the psychosocial environment and induction of stressful conditions have also been considered as model targets due to the evidence that stress is involved in precipitating the illness (Jones et al. 1992). Most recently, however, a new generation of models based on the breakthroughs in the discovery of human schizophrenia susceptibility genes have yielded the most fascinating results. Although they brought us a bit closer to understanding the functions of some “faulty” genes, they have also raised more questions about the functions of the putative susceptibility genes and their role in the human disorder.

modeling the genetics schizophrenia, DISC1

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