Australian Rotary Health

Dr Elizabeth Scarr is a Research Fellow at the Centre for Neuroscience, University of Melbourne. She is based in the Rebecca L Cooper Research Laboratories at the Mental Health Research Institute.
 

Dr Scarr was awarded a BSc (Honours) in pharmacology by the University of Sunderland, England and completed her PhD studies at the University of Saskatchewan, Canada. Following a post-doctoral position in Dunedin, New Zealand, where she investigated Immediate Early Genes in hypoxic/ischemic rats, Dr Scarr began working at the Mental Health Research Institute in Melbourne. 
 

Dr Scarr has been investigating neurochemical changes associated with schizophrenia and bipolar disorder. She is focusing on the role played by muscarinic receptors in schizophrenia, with particular reference to variations in the gene for the muscarinic MI receptor and how they may affect its expression and function in human brain tissue.
 

Biochemical basis of cognitive deficits in schizophrenia
 

To identify potential targets for therapies designed to improve the cognitive deficits seen in people with schizophrenia.
 

The reduced expression of cortical muscarinic MI receptors in schizophrenia is associated with a decrease in expression of kainate receptors.
 

Schizophrenia is a debilitating psychiatric disorder that imposes a profound burden, not only on sufferers and their families, but on society as a whole.  Schizophrenia was originally described as a cognitive disorder, sometimes accompanied by delusions, hallucinations and excitement. The successful treatment of delusions, hallucinations and excitement meant that research focussed on this aspect of the disorder. However, it is now recognised that most people with schizophrenia have cognitive impairment symptoms when they first become ill. These impairments are recognised as the greatest obstacle to regaining a functional role in society.
 

The neurotransmitter acetylcholine is known to play a role in learning and memory, the foundations of cognition. More recent information suggests that the muscarinic M1 receptor, which is activated by acetylcholine, plays a major role in cognition. A “proof of principle” trial showed drugs that activate this receptor improved cognition in patients with schizophrenia. However it is difficult to design drugs that act only at the M1 receptor.
 

Dr Scarr’s previous research reveals that levels of the M1 receptor are decreased in the cortex of people with schizophrenia. Her research team studied a post-mortem brain collection and produced a cohort consisting of tissue from:
 

      1. 20 subjects who have no history of psychiatric illness (controls)
      2. 20 subjects with schizophrenia with levels of [3H]pirenzipine binding comparable to
          that of controls in Brodmann’s area 9* and
      3. 20 subjects with schizophrenia with low levels of [3H]pirenzipine binding in     

          Brodmann’s area 9*

Using this cohort it was found that patients with low levels of M1 receptors also had low levels of one of the glutamate receptors – the kainate receptor. If this association can be substantiated, the kainate receptor could prove to be a better target for drugs designed to improve cognitive deficits.
 

Dr Scarr’s research plan is to:
 

      I. Determine whether or not levels of kainate receptors are also low in other brain

         regions where levels of [3H]pirenzipine binding have previously been reported as low
     II. Ascertain which of the five subunits comprising the kainate receptor contributes to

         the lower levels of kainate receptors. Knowing the subunit involved will provide a

         highly specific target for drug development
    III. Investigate whether low M1 or low kainate receptors are contributory
 

This data will assist drug development and research strategies.
 

OUTCOMES/SIGNIFICANCE:
In 2003 the rate of suicide in people with schizophrenia was 10% compared with 1.7% in the general population. While reasons for the suicide of people with schizophrenia are unknown, improving their overall psychological wellbeing could prove to be a factor in reducing the suicide rate. Cognitive deficits suffered by people with schizophrenia are recognised as the single largest contributor to their inability to retain a fully functional role in society. Effective drugs for treating this aspect of the disorder could potentially revolutionise the long term outcomes for people with schizophrenia. Moreover, the psychological benefits of being able to function within the parameters of society would be immense.  Such treatments would reduce the estimated annual cost of $3,000,000,000 – 49% of which is due to lost productivity.

* Brodmann’s area 9 is part of the frontal cortex of the human brain