Evidence for connectivity-based grey matter loss in schizophrenia

What is it about?

Many studies have shown that people with schizophrenia have reduced grey matter compared to healthy people, and they tend to lose more grey matter as their illness progresses. Some researchers have proposed that the progressive loss of grey matter in schizophrenia might be related to brain connectivity – that is, grey matter loss actually ‘spreads’ through the brain between regions that are connected to one another. Our study set out to test this theory by investigating whether brain regions that showed grey matter reductions in people with schizophrenia were those that were more strongly connected to each other. We used MRI brain scans to measure the amount of grey matter in 148 brain regions in three groups of people with schizophrenia: those in the early stages of the disease, those with established schizophrenia, and those with an established form of schizophrenia that doesn’t respond to treatment (treatment-resistant schizophrenia). We also took brain scans for three groups of healthy controls, who were matched to our patient groups. The first step in our research was to find out how many brain regions showed grey matter loss in each of our three groups. What we found was that, the more serious the illness, the more grey matter loss that was present – in early schizophrenia only 34 regions were affected, whereas in established illness and treatment-resistant schizophrenia there was grey matter loss in 79 and 106 regions, respectively. We then used a novel analysis technique called structural covariance to measure the strength of brain connectivity between each of these 148 grey matter regions. Once we knew how strongly each brain region was connected to every other brain region, we could then compare connectivity strength in regions with grey matter loss to that of randomly selected brain regions. Connectivity in this context means the extent to which a pair of regions is likely to be interconnected by nerve fibres, which enable communication and integration of information between distant brain regions. When we compared connectivity strength in brain regions with grey matter loss to that of randomly selected brain regions, we found that regions with grey matter reductions were more strongly connected than randomly selected regions. What this tells us is that brain regions with grey matter loss in schizophrenia are more strongly interconnected than would be expected by chance. These findings suggest that, even though grey matter loss in schizophrenia occurs in brain regions that are distant from each other, this loss of grey matter does not occurring randomly or in isolation in each of these regions. Rather, it is likely that connective tissue in the brain, which is called white matter, is actually helping grey matter loss to spread between brain regions that are connected to one another.

Featured Image

Photo by Robina Weermeijer on Unsplash

Photo by Robina Weermeijer on Unsplash

Why is it important?

While this network-based grey matter loss has been established in neurodegenerative disorders such as dementia and Alzheimer’s disease, our study is the first to provide evidence for network-based grey matter loss in schizophrenia. Our findings indicate that it may not be sufficient to consider grey matter abnormalities in schizophrenia in isolation, without also taking into account the underlying white matter connectivity that helps to shape our brain’s grey matter. This research could provide a new model for understanding progressive grey matter loss in schizophrenia.