Schizophrenia Research

Royce Abbey Postdoctoral Fellow - Dr Elizabeth Scarr

The mandate of the Royce Abbey Postdoctoral Fellowship is to conduct research into the causes or alleviation of schizophrenia.

What is schizophrenia?

• Schizophrenia is a severe, disabling, brain disorder.
• Approximately 1 percent of the population, worldwide, develops schizophrenia.
• It affects men and women equally, although symptoms often appear earlier in men (late teens/early twenties), than in women (twenties to early thirties).
• Symptoms suffered by patients can include; hearing voices not heard by others, believing that other people can read their minds, control their thoughts, or are plotting to harm them. Additionally, speech and behaviour can be disorganised - the patients may be incomprehensible or appear frightening to others.
• Treatments currently available can relieve some symptoms, but most people with schizophrenia continue to suffer symptoms throughout their lives.

Research Interests :

• To understand the role of muscarinic receptors in the pathology of schizophrenia and
• To translate these findings, using peripheral DNA studies, to assessing the role of muscarinic receptors in generating the cognitive deficits of schizophrenia.

Research into schizophrenia has produced numerous theories regarding the biochemical systems involved in the disorder. One of the robust findings, in both post-mortem and neuroimaging studies, is a decrease in the apparent density of a family of receptors that the neurochemical acetylcholine binds to, the muscarinic receptors. There are five membrers in the muscarinic receptor family, all have slightly different distribution throughout the brain and can instigate different downstream responses.

This research program combines studies using post-mortem brain tissue from subjects with either schizophrenia or no history of psychiatric illness (controls) and analysis of single nucleotide polymorphisms (SNPs) in the gene for the muscarinic M1 receptor (M1R). This approach will determine whether a specific mutation in the M1R gene, thought to be associated with abnormal cognitive functioning in subjects with schizophrenia, is associated with alterations in the level of cortical M1R expression. Knowing whether a M1R genotype is associated with low cortical receptor levels will allow the genotype to be used as a peripheral marker, identifying patients likely to benefit from treatment targeting the receptor.

Techniques Used:

In situ radioligand binding with autoradiography (Image 1)

Western blotting (Image 2)

Image analysis

Real time PCR (Image 3)

DNA sequencing (Image 4)

Relevant Publications:

Dean, B . , Keriakous, D., Thomas, E. and Scarr, E . (2005) Understanding the Pathology of Schizophrenia: The Impact of High-Throughput Screening of the Genome and Proteome in Postmortem CNS. Current Psychiatry Reviews 1: 1-9.

Dean, B., Gray, L., Keriakous, D. & Scarr, E ., ( 2004 ) A comparision of M1 and M4 muscarinic receptors in the thalamus from control subjects and subjects with schizophrenia. Thalamus and Related Systems. 2: 287-295.

Dean, B., Bymasters, F. & Scarr, E . (2003) Muscarinic receptors in Schizophrenia. Current Molecular Medicine . 3: 419-426.

Dean, B., McLeod, M., Keriakous, D., McKenzie, J. & Scarr, E . (2002) Decreased muscarinic 1 receptors in the dorsolateral prefrontal cortex of subjects with schizophrenia. Molecular Psychiatry . 7(10):1083-91.

Image 1:

[ 3 H]Pirenzepine binding in the hippocampus

Image 2:

Western blot of proteins from human brain

Image 3:

Roche Lightcycler TM

Image 4:

Sequence ladder

Contact Us

Elizabeth Scarr
Royce Abbey Postdoctoral Fellow
Rebecca L. Cooper Research Laboratories
Mental Health Research Institute

elscarr@unimelb.edu.au