دانلود رایگان مقاله منفی بودن عدم تطابق در مدل های پیش بالینی اسکیزوفرنی

abstract

Schizophrenia is a mental disorder associated with profoundly disruptive positive and negative symptomology that result in difficulties building close relationships with others, performing daily tasks and sustaining independent living, resulting in poor social, vocational and occupational attainment (functional outcome). Mismatch Negativity (MMN) is a change in the sensory event-related potential that occurs in response to deviation from an established pattern of stimulation. Patients with schizophrenia show a reduction in MMN that is positively associated with impaired cognition and poor functional outcome. This has led to interest in MMN as a potential clinical and pre-clinical biomarker of fundamental neural processes responsible for reduced functional outcome. To date, relatively few studies have sought to assess MMN in non-human primates or rodents. The validity of these studies will be reviewed using criteria used to identify true deviance detection based MMN responses in human subjects. Although MMN has been difficult to establish in pre-clinical models the weight of evidence suggests that non-human animals show true deviance based MMN.

6. Conclusions

It is difficult to reproduce any aspect of human cognition in nonhuman animals. Much validation is required for researchers to be confi- dent they have done so. Additionally, many of the criteria used to differentiate MMN from other phenomenon in humans are difficult to apply to non-human subjects. As such, although superficially simple, MMN has been difficult to demonstrate in rodents. While many studies have demonstrated MMN in rodents that satisfy some of the criteria listed in Section 4, only one study could be considered to have satisfied all (Shiramatsu et al., 2013). However, it should be noted that many human studies of MMN have failed to satisfy these criteria as well. For example, many of the key studies linking MMN to schizophrenia have not used the cascade or many standards control procedures. As such, it is not clear that the link between MMN and schizophrenia is necessarily dependent upon deviance detection per se rather than SSA. Thus, we may be holding animal research to an unreasonably high standard. Nonetheless, taken as a whole evidence for MMN in non-human subjects is compelling.

While the use of elaborate control measures, such as the cascade and many standards control, is useful there are clear limitations for their use in translational research. Both control conditions are cumbersome and require either long test sessions or repeated testing across sessions to complete. This is problematic when testing pharmaceutical agents with limited duration half-lives and/or which produce tolerance or sensitization across repeated dosing. One of the most compelling aspects of MMN as a translational measure is the fact that it is responsive to ketamine in both humans and laboratory animals, allowing for direct translational assessment across species. However, ketamine has a very short half-life which limits use of these control conditions.