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Headlines*: May 2006

* Newsletter of NISAD (Neuroscience Institute of Schizophrenia and Allied Disorders)

Two Genetic Keys to Schizophrenia

1: Gene Profiling for Tailored Treatment

The symptoms of schizophrenia have long been separated into negative and positive types, and individual sufferers usually show a predominance of one type. Some patients, for example, show a diminution or loss of normal functions (negative symptoms), whereas others tend towards an excess or distortion of normal functions expressed in hallucinations and delusions (positive symptoms). Some scientists have proposed that a 'disorgan­ised' or 'cognitive' type, indicating thought disorder, disorientation, and memory problems, be added as a third category ­but this has yet to be generally accepted.

NISAD's Nikola Bowden and a team of Newcastle scientists designed a prelimi­nary investigation to discover if an individual's schizophrenia type could be identified from a genetic profile obtained from a simple blood sample. 14 patients and 14 matched controls took part in the study', which identified 18 brain-related genes significantly altered by schizophre­nia (Fig. 1). When individual gene profiles were classified by age, distinct gene expression profiles for subgroups of schizophrenia were identified for the first time.

Such gene expression profiling from blood samples may in the future provide a template for individually 'tailored' treat­ments, and larger scale studies on the same lines may lead to a diagnostic tool to assess at-risk status in the early phases of the illness.

Fig.2: The billions of neurons in the brain communicate by sending chemical messages to each other across synapses.

2: Genetic Abnormalities Found in the Amygdala

The amygdala is a part of the brain of special interest to' schizophrenia researchers due to the key role it plays in emotion processing. While some studies have reported reduced tissue volumes and neural differences in the amygdala in schizophrenia, the genes involved in its dysfunction have yet to be identified.

Judith Weidenhofer and the NISAD affiliated team at the University of Newcastle examined gene expression in the amygdala' in postmortem brain tissue of seven matched pairs of schizophrenia and normal control subjects.

Among other differences, genes involved in presynaptic function (Fig.2) were found to be consistently dysregulated in the schizophrenia samples.

These results are the first evidence that genes involved in presynaptic mechanisms in the amygdala are implicated in the pathophysiology of schizophrenia.

I. Bowden A, Weidenhofer J, Scott R, Schall U, Todd J, Michie P, Tooney P. Preliminary investigation of gene expression profiles in peripheral blood lymphocytes in schizophrenia. Schizophrenia Research 2006; 82: 175-183.

2. Weidenhofer J, Bowden A, Scott R,Tooney P. Altered gene expression in the amygdala in schizophrenia: Up-regulation of genes located in the cytomatrix active zone. Molecular and Cellular Neuroscience 2006; 31: 243.250.