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Idrizi R.,The Florey Institute of Neuroscience and Mental Health | Malcolm P.,The Florey Institute of Neuroscience and Mental Health | Weickert C.S.,Schizophrenia Research Institute | Weickert C.S.,University of New South Wales | And 6 more authors.
Psychiatry Research | Year: 2016

In utero maternal immune activation (MIA) and cannabinoid exposure during adolescence constitute environmental risk factors for schizophrenia. We investigated these risk factors alone and in combination ("two-hit") on epidermal growth factor receptor (EGFR) and neuregulin-1 receptor (ErbB4) levels in the rat brain. EGFR but not ErbB4 receptor protein levels were significantly increased in the nucleus accumbens and striatum of "two-hit" rats only, with no changes seen at the mRNA level. These findings support region specific EGF-system dysregulation as a plausible mechanism in this animal model of schizophrenia pathogenesis. © 2016 Elsevier Ireland Ltd.

Scarr E.,Mental Health Research Institute | Scarr E.,University of Melbourne | Sundram S.,University of Melbourne | Sundram S.,Mental Health Research Institute | And 14 more authors.
Schizophrenia Research | Year: 2012

It has been reported that people with schizophrenia who are homozygous at the c.267C>A single nucleotide polymorphism of the cholinergic muscarinic M1 receptor (CHRM1) perform less well on the Wisconsin Card Sorting Test than those who are heterozygous. We investigated whether CHRM1 sequence is associated with impaired executive function, a common problem in schizophrenia. We sequenced the CHRM1 using peripheral DNA from 97 people with schizophrenia who completed the Wisconsin Card Sorting Test, a verbal fluency test and the National Adult Reading Test. Clinical severity was assessed using the Positive and Negative Syndrome Scale. To determine whether CHRM1 sequence affected receptor expression, we used post-mortem data, from another cohort, to investigate associations between CHRM1 sequence and mRNA levels. On the Wisconsin Card Sorting Test, 267C/C participants with schizophrenia made more perseverative errors (p< 0.05) and perseverative responses (p< 0.05) than 267C/A participants. Genotype had no effect on verbal fluency (p= 0.8) or National Adult Reading test (p= 0.62). Cortical CHRM1 mRNA levels did not vary with gene sequence (p= 0.409).The clinical study supports the proposal that CHRM1 sequence is associated with alterations in some aspects of executive function. However, the post-mortem study indicates this is not simply due to altered expression at the level of mRNA, suggesting this sequence alteration may affect the functionality of the CHRM1. © 2012 Elsevier B.V.

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