Searching for new answers to the puzzle of schizophrenia

While we know that schizophrenia is a hereditary disease, we do not know its precise genetic causes. As a Wallenberg Scholar, Jens Herling-Leffler will be hoping to identify biological mechanisms in the brain driving the development of the disease.

Schizophrenia is a hereditary, polygenic disease, which means that no one single gene is involved in the pathological process. Instead, for most patients the risk of developing the disease is the result of small mutations in many different genes. 

Schizophrenia often onsets in late adolescence or early adulthood, a stage of life in which our brain and behaviour undergo considerable changes. However, knowledge of how the brain changes during this period is still rather rudimentary. 

What we do know, however, is that the part of the brain called the prefrontal cortex is still maturing at this age, and one of the main aspects of this process is synaptic pruning and rewiring.

Reattract pharmaceutical companies 

Jens Herling-Leffler and his research team will now be studying what happens in the prefrontal cortex in late adolescence and the biological mechanisms driving these changes. Their hypothesis is that schizophrenia develops when something goes wrong in these processes.

“The first signs of disease often appear at the age of 16 or 17,” says Dr Herling-Leffler. “If the symptoms can be detected then and the important processes understood, it would be possible to develop drugs able to retard its progress.” 

Their research will involve experiments on mice in order to examine which genes might be involved and what parts they play. They have also studied the brains of deceased patients to see which genes are up- and downregulated in schizophrenia.

Dr Herling-Leffler hopes that the results can be used to reattract the major pharmaceutical companies that have pulled out of psychiatric research in the past 20 years due to the lack of knowledge about the biological mechanisms of the diseases. 

“Schizophrenia is a terrible disease,” he says. “The patients suffer terribly and most are stuck in the healthcare system for the rest of their lives. If we can find drugs to treat the disease, it would help many people.”