A brain circuit important for working memory may be influenced by genes suspected to be involved in the development of schizophrenia, according to a study published in the Proceedings of the National Academy of Sciences on June 16th. Activity in the working memory circuit functions when a person holds multiple items in mind before answering a question; working memory is known to be disrupted in schizophrenia.
Disruption in interactions between the dorsolateral prefrontal cortex (DLPFC) region of the brain and the hippocampus (HC) region are believed to be associated with this impairment in working memory. Prior studies have shown disruptions in patients, their unaffected siblings, and carriers of common genetic variants associated with schizophrenia, but the global genetic architecture of the disruption is unclear.
To examine the genetic basis of DLPFC-HC connectivity, a research team led by two-time NARSAD Grantee Andreas Meyer-Lindenberg, M.D., Ph.D. (2000 Young Investigator and 2009 Distinguished Investigator), from the University of Heidelberg in Germany, combined gene set enrichment analysis with whole-genome genotyping and functional magnetic resonance imaging (fMRI) data from 269 healthy German volunteers. They report that this technique offers a new approach for a biologically driven analysis of imaging and genetic data.
The team’s findings highlight genes involved in synapse (the junction between two neurons across which information flows in the brain) organization as well as those involved in brain development and plasticity processes throughout life. The researchers report that the identified genes are dysfunctional in schizophrenia and linked to DLPFC-HC functional interactions. The results, they say, identify gene sets in which genetic variation may contribute to risk of developing schizophrenia by altering DLPFC-HC functional interactions that may also be linked to both ongoing and developmental synaptic plasticity.