Large Study Confirms Major Hypotheses in Schizophrenia Research

Large Study Confirms Major Hypotheses in Schizophrenia Research

Posted: June 16, 2015

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Although researchers don't yet have a good picture of what causes schizophrenia, they do know that both genetics and environment play a role. A small minority of people with the illness have missing or extra chunks of DNA known as copy number variants (CNVs). Researchers have turned to these large spans of altered DNA in the search for gene changes that contribute to schizophrenia.

The largest study of CNVs in schizophrenia so far reports the first strong genetic evidence that molecules involved in neuronal communication with GABA, one of the brain's major neurotransmitters, may play a role in schizophrenia. The new findings, published in the June 3rd issue of Neuron, are consistent with a large amount of non-genetic research from people with schizophrenia as well as animal models that also point to changes in GABA signaling as underlying the cognitive problems of the illness. The research also confirms previous evidence implicating the other major neurotransmitter, glutamate.

CNVs aren't only found in schizophrenia; they're also found in healthy individuals. The current study was led by researchers Andrew Pocklington, Ph.D., along with 2012 Brain & Behavior Research Foundation Lieber Prize Co-Winners for Outstanding Achievement in Schizophrenia Research Michael O'Donovan, M.D., Ph.D., and Michael Owen, M.D., Ph.D., of Cardiff University in the United Kingdom. They examined CNVs in a total of 11,355 people with schizophrenia and 16,416 healthy individuals, looking for genes that are found more often in schizophrenia CNVs than in control CNVs. To compile a list of possible genes relevant to schizophrenia to look for in the CNVs, the researchers combed through a database of genes and their functions, settling on 134 sets of related genes involved in brain development and function. Based on earlier studies suggesting cellular communication problems in schizophrenia, they also added gene sets involved in neuronal signaling.

When the research team, which also consisted of 2012 Sidney R. Baer, Jr. Prizewinner for Innovative and Promising Schizophrenia Research James T.R. Walters, M.D., Ph.D. (and 2009 NARSAD Young Investigator Grantee), compared the CNVs from people with schizophrenia to those from healthy individuals, they found that six different gene sets were significantly more common in the schizophrenia CNVs compared to the healthy control CNVs. Many of the gene sets had previously been linked to schizophrenia in earlier genetic studies, but this study is the first to find that genetic changes in GABA signaling are associated with schizophrenia.

Unlike some genetic abnormalities that involve changes to single building blocks of DNA, CNVs encompass large chunks that include many genes, so pinpointing exactly which of the many changed gene(s) lead to the development of schizophrenia is a challenge for future studies.

Learn more about this research from the Schizophrenia Research Forum

Read the abstract of this research.