Animal Models Relevant to Schizophrenia and Autism: Validity and Limitations

Abstract

Development of animal models is a crucial issue in biological psychiatry. Animal models provide the opportunity to decipher the relationships between the nervous system and behavior and they are an obligatory step for drug tests. Mouse models or rat models to a lesser extent could help to test for the implication of a gene using gene targeting or transfecting technologies. One of the main problem for the development of animal models is to define a marker of the psychiatric disorder. Several markers have been suggested for schizophrenia and autism, but for the moment no markers or etiopathogenic mechanisms have been identified for these disorders. We examined here animal models related to schizophrenia and autism and discussed their validity and limitations after first defining these two disorders and considering their similarities and differences. Animal models reviewed in this article test mainly behavioral dimensions or biological mechanisms related to autistic disorder or schizophrenia rather than providing specific categorical models of autism or schizophrenia. Furthermore, most of these studies focus on a behavioral dimension associated with an underlying biological mechanism, which does not correspond to the complexity of mental disorders. It could be useful to develop animal models relevant to schizophrenia or autism to test a behavioral profile associated with a biological profile. A multi-trait approach seems necessary to better understand multidimensional disorders such as schizophrenia and autism and their biological and clinical heterogeneity. Finally, animal models can help us to clarify complex mechanisms and to study relationships between biological and behavioral variables and their interactions with environmental factors. The main interest of animal models is to generate new pertinent hypotheses relevant to humans opening the path to innovative research.

Class I histone deacetylase inhibition ameliorates social cognition and cell adhesion molecule plasticity deficits in a rodent model of autism spectrum disorder

“…This may yet provide the unique construct validity necessary to discriminate between animal models of autism and schizophrenia (Tordjman et al, 2007).…”

Estudos traducionais de neuropsiquiatria e esquizofrenia: modelos animais genéticos e de neurodesenvolvimento

“…However, the use of behavioural readouts is limited in disease specificity and this has been regarded as one of the major drawbacks of these approaches 189 . In particular, the assessment of similarities of animal behaviour and patient characteristics can be subjective, leading to problems of bias and irreproducibility.…”

Abnormal Mechanisms of Plasticity and Metaplasticity in Autism Spectrum Disorders and Fragile X Syndrome

“…Evidence both from animal FXS models (Simonyi et al 2005) (Huber et al 2002) and from studies in patients with FXS conducted in our laboratory indicate that loss of Fragile X mental retardation protein FMRP (the physiological consequence of the genetic mutation that leads to FXS) leads to abnormalities in synaptic plasticity. Apart from FXS, other animal ASD models also suggest a causal role for abnormal plasticity mechanisms (reviewed in Tordjman et al [2007]). However, metaplasticity has not been evaluated in these animal models.…”