Normal Cognition, Neurodevelopmental Disorders Share the Same Brain Space

A research team has identified a network of genes in the brain that regulates normal cognitive abilities but is also implicated with a range of neurodevelopmental disorders, such as autism, epilepsy, intellectual disability, and schizophrenia.

In several neurodevelopmental disorders, cognitive difficulty is reported as a core symptom. However, no explanation had been provided for this association, until now. The findings offer an alternate starting point for scientists to develop therapies for these debilitating disorders.

The team from Duke-NUS Medical School (Duke-NUS) and Imperial College London (ICL) began their study by observing all genes that are active in the human hippocampus — a part of the brain that plays an important role in the formation and consolidation of our memories.

They identified one significant network of 150 genes which has a major influence on general cognitive abilities. They found that these genes are already highly active following birth, which is a clue that the genes play a role in brain development and neurodevelopmental disease.

Analysing all data available to date, the team observed that about one-third of the genes in this network are mutated in various neurodevelopmental disorders. Their findings were quite surprising as the majority of these genes that were known to cause neurodevelopmental disease had never been connected to each other before.

The identification of this gene network provides the starting point to develop precision medicine strategies to target the entire pathway or genes specific to neurodevelopmental disorders. All gene network data generated from this study have been made accessible online for other researchers and scientists.

“We believe that studying gene networks in the brain can give us extra clues about the genetic cause of neurodevelopmental disorders and of their neurological comorbidities,” said Associate Professor Enrico Petretto, senior co-author of the study and head of the Systems Genetics of Complex Disease Laboratory at Duke-NUS.

“The results of our study in the human brain show a previously unappreciated functional relationship between cognition and neurodevelopmental disorders’ genes. This gives us the first explanation to why the two seem to be related.”

Petretto explained that the team’s approach to understand the genetic causes of complex disease could be compared to developing a strategy to beat a rival football team. To outplay a rival team, the focus cannot lie on a single player, even if it happens to be a key player such as Lionel Messi.

Instead, understanding how the eleven players cooperate, with or without Messi’s contribution, and figuring out their coach’s game strategy, which in this study is comparable to the regulatory factors of the gene network, is vital to achieving a long-term winning strategy.

The findings are published in the journal Nature Neuroscience.

Source: Duke- NUS Medical School