The striking similarity between schizophrenia and ageing

A natural part of healthy ageing is to experience mild cognitive impairment. It might mean that we suffer a slight decline in our ability to remember certain things or complete certain tasks as we get older.

Interestingly, scientists from the Broad Institute of MIT and Harvard have observed a striking similarity in a sequence of gene changes that leads to mild cognitive impairment in those who are ageing, and those living with schizophrenia - a psychiatric condition which can have much more debilitating symptoms. The University of Cambridge’s Stephanie Brown has been looking at the study for James Tytko.

Stephanie - Schizophrenia is a serious mental health disorder that affects 1 in 300 people globally and symptoms can be quite debilitating. These include things like hallucinations, hearing voices, and believing things that are not reflected in reality. Cognitive impairment is also quite a common symptom and people can have trouble remembering or learning new things or concentrating and making decisions, but it can also include things like subtle personality changes or just difficulty in general doing the tasks of the day.

James - Is schizophrenia a genetic condition?

Stephanie - So that is a very interesting question and the answer is yes and no. It does tend to run in families, but there's no one gene that's thought to be responsible. This actually relates to something known as polygenic risk where a collection of small changes in the genome can contribute to a higher overall increased risk of developing the condition. But it's also very important to recognise that the environment can also play an important role and factor into triggering or increasing risk for developing schizophrenia.

James - Interesting. But it's this cognitive impairment symptom of the condition we are thinking about for the purposes of this study. In the news recently, there's been quite a lot of coverage hasn't there of the cognitive functions of the presidential candidates in the US and people have been pointing to their age as a contributing factor as to why they might not be where they should be. What's the science there?

Stephanie - So firstly, it's normal that cognition will get a bit slower or less effective as we age. That's actually healthy ageing, that's completely normal. But as people get older, they also become more at risk for something called mild cognitive decline and this can affect memory and the ability to perform tasks. It doesn't necessarily have to be debilitating, but it can develop into more serious neurodegenerative diseases like Alzheimer's disease. And similarly to schizophrenia, cognitive impairment in old age can also be inherited and some specific genes can increase risk, but there's no one gene that's responsible.

James - So what have these scientists found out about how cognitive impairment happens in these two groups of people: those with schizophrenia and those who are ageing?

Stephanie - So this has to do with the way that certain genes are expressed and the discovery that they are coordinated in two brain cell types called neurons and astrocytes. Neurons connect with other neurons at synapses and carry messages from one part of the brain to another and, thanks to previous studies, we actually knew that genetic factors related to synapses and neurons were linked with schizophrenia. And astrocytes are really the kind of support cells of the brain.

James - Yes. Astrocytes are the most numerous cell types in the brain, aren't they, performing lots of jobs in keeping our nerve cells working the way they should?

Stephanie - Yeah, that's right. So, in this study that was published in Nature, the team describes how they analysed gene expression in more than a million individual cells from postmortem brain tissue from 191 people. They found that in individuals with schizophrenia and in older adults, astrocytes and neurons reduced their expression of genes that support the synapses compared to healthy or younger people. They also discovered that when neurons decrease this expression of certain genes related to the synapses, astrocytes similarly changed their expression of a distinct set of genes that support the synapses.

James - So the expression of these genes is somehow synchronising in these fundamental cells in the brain. That's really interesting.

Stephanie - The team called this coordinated set of changes the 'synaptic neuron and astrocyte program' i.e. 'SNAP.' And even in healthy young people, the expression of these SNAP genes always increased or decreased in a coordinated way in their neurons and astrocytes.

James - What sort of doors does this open research wise for the understanding of cognitive impairment? Could this be a really important step for mitigating the impact of it for whomever is impacted by it?

Stephanie - With a better understanding of SNAP the authors are hoping that it might possibly be useful to identify life factors that could positively influence SNAP and develop medicines that could help stimulate SNAP as a way to treat cognitive impairments of schizophrenia or help maintain cognitive flexibility in people as they age. And, as you say, it could have wider implications as well.