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Schizophrenia hope as genetic secrets revealed

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The risk of developing schizophrenia has been linked to genes associated with essential brain functions including memory and signalling, as well as those active in the immune system.

In a major step toward the development of new and effective treatments for the common and debilitating psychiatric disorder, researchers worldwide have collaborated on a project that has led to the identification of 108 locations on the human genome associated with the risk of developing schizophrenia.

The massive undertaking, which involved examining 80,000 gene samples from schizophrenia patients and healthy volunteers, has confirmed earlier findings identifying around 24 genomic regions associated with the condition and expanded knowledge of its genetic basis and underlying biology.

Lead author of the study, Stephan Ripke of the Broad Institute at Massachusetts General Hospital, said the identification of so many genetic loci for schizophrenia meant researchers were able to distinguish patterns, so that “we can group them into identifiable pathways – which genes are known to work together to perform specific functions in the brain. This is helping us to understand the biology of schizophrenia”.

The study, “Biological insights from 108 schizophrenia-associated genetic loci”, published in the journal Nature, found the disorder was linked to many genes expressed in brain tissue, particularly those related to the function of neurons and synapses.

Some were found to be active in pathways that control the plasticity of synapses – a function essential to learning and memory – while other govern post-synaptic activity, particularly signalling between cells in the brain.

In a discovery that lends some support to theories that schizophrenia may be linked to immunological processes, several of the schizophrenia-linked genes identified by the study are active in the immune system.

Building hope that the study could lead to a new generation of drugs to treat schizophrenia, researchers found that the disorder was also associated with the gene that produces the dopamine receptor targeted by current medications.

“The fact that we were able to detect genetic risk factors on this massive scale shows that schizophrenia can be tackled by the same approaches that have already transformed our understanding of other disease,” senior author Michael O-Donovan of the MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff University said. “The wealth of new findings have the potential to kick-start the development of new treatments in schizophrenia, a process which has stalled for the last 60 years.”

Currently, treatments for schizophrenia are primarily to treat psychosis, just one of the symptoms of the disorder, rather than its debilitating cognitive symptoms, and treatment options have been limited by a lack of understanding of the condition’s underlying biological mechanisms.

They said the sole target for existing treatments was found serendipitously, and “no medications with fundamentally new mechanisms of action have been developed since the 1950s”.

The researchers said their discoveries provided many more possible avenues for therapeutic action and investigation.

Adrian Rollins

 

 

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