Built-in ‘brain calendar’ provides insight into schizophrenia

Image credit: jgmarcelino via Wikimedia Commons.

As we age, the brain coordinates the responses of thousands of cells to new psychological and social stimuli. This coordination becomes particularly relevant when considering psychiatric disorders such as schizophrenia. Until a few years ago, the onset of schizophrenia was thought to be due to environmental stress or damage. But many studies have now shown that the majority of schizophrenia patients start showing symptoms in their late 20s, and the exact age of onset is highly heritable. This supports the hypothesis that there is a genetic brain ‘calendar’ that coordinates neural activity.

Last month, scientists from the Centre for Clinical Brain Sciences at the University of Edinburgh published a paper that sheds some light on this phenomenon. The authors of the paper set out to determine how the brain’s clock works, by studying genes related to ageing of the brain. Genes are regions of DNA that control each cell’s behavior. If a gene is turned on, it induces the cell to produce specific molecules that reshape structure and behavior. By drawing a graph of how genes in the brain are turned on and off over time – otherwise known as gene expression – the authors defined a series of ‘Trajectory Turning Points’, i.e. the points in time when many genes significantly change their expression. Previous studies tell us that these turning points synchronise gene activity through aging, allowing the body to age uniformly.

They found that most gene synchronisation occurs early in life and peaks in early adulthood, consistent with the idea that this is an important age of brain stabilisation and maturation. The turning point distribution was extremely specific and consistent with age, allowing the scientist build a virtual ‘brain age map’, much like counting the rings of a tree to calculate its age.

To determine what causes these changes in the brain of a twenty-something, they looked at the functions of the genes that change the most. One of their major functions turned out to be synaptic transmission. Synapses are the regions at the ends of brain cells that are essential for cell communication and functionality, and are fundamentally responsible for all brain activity. Faulty synaptic transmission has been implicated in many neurodevelopmental and neurological conditions, including schizophrenia. The data suggests that the synaptic network of the brain is highly fluid during early adulthood. The authors then hypothesised that the fluidity of the synaptic network at this stage of life could be linked to the age of onset of schizophrenia. Indeed, when they looked at genes that are known to be involved in schizophrenia, they found that their trajectory in the brain changes drastically in the early adulthood years. To reinforce this evidence, they looked at the differences between male and female samples: in males, the turning points were concentrated at an earlier timepoint than in females – consistent with males typically having an earlier onset of symptoms than females.

Overall, the researchers work tells us that brain functions are not hard-wired, but change dynamically as we age. Their approach is comprehensive and unbiased, and sets a large database for studying brain aging. Disruptions in the brain’s biological clock might explain why people with neurological disorders respond differently to environmental stimuli. This also opens possibilities for new therapeutic approaches, with the aim of developing age-appropriate drugs to better target mental disorders.


This article was written by Benedetta Carbone and edited by Bonnie Nicholson.

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