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Behavioral Models of Dysfunction in Schizophrenia & Critical Periods of Gene x Environment Interactions

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Both Burrows et al. 2015 and Ayhan et al. 2010 aim to implicate genetic factors underlying the symptoms of schizophrenia. Schizophrenia in itself is a highly complex disorder in which many of the positive symptoms are psychotic and hallucinogenic. Although there are some known biological signatures of schizophrenia translated to mouse models, the behavioral aspect remains a challenge in the field as these symptoms are especially hard to translate if at all. This being said, these papers interestingly use different methods to model schizophrenia.
            Ayhan et al. 2010 shows convincing evidence that mutant human DISC1 can cause structural, behavioral, and neurochemical abnormalities, all of which most likely interact with each other. Their behavioral data measured sociability, aggressiveness, stress response, and locomotion. Burrows et al. 2015 investigates the gene and environmental interactions that contribute to schizophrenia related phenotypes in the context of mGlu5r deficiency. This study relies on learning and locomotion as a behavioral phenotype. All of these behaviors, if abnormal, could fall under the symptomology of schizophrenia but are not necessarily discrete to the disorder. Of course, there are no methods to truly test the core symptoms of schizophrenia but, these correlates show clear dysfunction. Considering the breadth of schizophrenia research done, it is disappointing to see that studies rely on the simple and traditional behavioral assays to show dysfunction when the disorder itself is complex in nature. 
Latly, it is interesting that Ayhan et al. describes critical periods in which these genetic factors have a more profound effect on development. If these stages were to be better translated to human development, this leads to an interesting window of opportunity to intervene or simply understand what predispositions may even be interacting with the environment to create such neurobiological deficits. Maybe it is possible that the dependence on hDISC1 can be modulated by the environment. Therefore, environmental enrichment and postnatal expression might provide interesting insights. It also might be interesting to preform similar developmental tet-dependent experiments in mGlu5r deficient mice to see if this receptor is more critical at one point than another. Certainly, during PFC development, glutamatergic control is relied on to begin to correctly assess salience and limit over-excitation. Two processes in which are most likely awry in schizophrenia. 

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