New insight into schizophrenia from post mortem tissue

The company's results showed that the expression levels of genes encoding for energy metabolism and protein processing are selectively and consistently decreased in the brains of patients with schizophrenia.

In the first study of its kind, scientists from Psychiatric Genomics microdissected neurons from the hippocampus of post-mortem brain samples of psychiatric patients and, using microarray technology, compared them to those same neurons from people not affected by the disease.

The integrity of the findings was supported by their high statistical significance, their replication in two different groups of schizophrenia patients, and the lack of such changes in neurons either from non-afflicted subjects or from patients with bipolar disease or depression.

Fuller Torrey, associate director for laboratory research at the Stanley Medical Research Institute in the US, said the findings represent a paradigm shift in our understanding of the disease.

"Previously, schizophrenia was thought to be caused by changes in brain neurotransmitter receptors. These new results re-direct our focus to even more fundamental processes that could radically alter the way the disease is treated in the future,"​ he said.

Psychiatric Genomics claims to be the only biotechnology company that is basing drug discovery for psychiatric diseases on postmortem human brain samples. Through relationships with various institutions, the company accesses the central nervous system tissue of normal controls and patients afflicted with illnesses such as bipolar disorder, schizophrenia, autism, and depression.

The company's scientists analyse these tissues using microarrays to identify their distinctive gene expression patterns, known as disease signatures.

In addition, using human neuronal cell culture systems, Psychiatric Genomics identifies drug signatures, which are the gene effects of clinically relevant therapeutics. This information is combined with the knowledge of the disease signatures to select a set of critical genes that are used as the endpoint for the company's drug discovery engine - called the Multi-Parameter High Throughput ScreenSM (MPHTSSM).

The MPHTSSM simultaneously determines the action of new chemical entities on the function of multiple genes, thus using the power of genomics to discover the next generation of psychotherapeutics. The drugs developed through this approach have the potential for improved efficacy, reduced side effects and earlier onset of action.

Schizophrenia affects approximately 1-2 per cent of the world's population, but the available pharmacological armamentarium -based on neurotransmitter-modulating drugs - treats only the symptoms of the disease.

The data were presented at Neuroscience 2004, the Society for Neuroscience's 34th Annual Meeting, currently being held in San Diego, California, US.