October 4, 2023, reading time: 3 minutes.
Clarity in psychotic illnesses: Researchers have discovered where psychoses begin to change the brain and into which brain regions these changes spread. The study also shows brain damage caused by antipsychotic medications. From this, the scientists developed an algorithm that can be used to predict the course of psychoses of varying degrees of intensity. The results also open up new therapeutic options.
In psychoses such as schizophrenia, the volume of gray matter in the brain is reduced, which can have a massive impact on the lives of those affected. Psychotic people sometimes have difficulty communicating and thinking logically and lose touch with reality. As the disease progresses, these changes spread to the brain. Undesirable side effects of the medication are also suspected due to the cost-intensive treatment.
The causes of psychoses are diverse and have only been partially researched. The mechanism through which the psychotic changes spread in the brain is also currently unknown. It is also difficult for doctors to precisely separate the effects of the medication from those of the disease, as so far most of the studies have been carried out on people who are already taking antipsychotic medication.
Look into the brains of those affected
That’s why researchers led by Sidhant Chopra from Monash University in Melbourne have now specifically examined the brains of psychosis patients with and without treatment and analyzed in detail in which regions of the brain the effects of the disease and the medication appear over the course of the disease. For the study, Chopra and his colleagues created multiple MRI images of the brains of 534 people who had suffered from a psychotic illness such as schizophrenia for varying lengths of time. MRI images from healthy people served as controls.
The research team compared the data from the different groups and individuals after three and twelve months. They primarily documented the changes in the gray matter of the brain, which lies on the outside of the brain and contains the cell bodies of the neurons. Using mathematical-statistical models, Chopra and his colleagues calculated from the comparative data how the volume of the gray matter had changed and could develop further.
Gray matter in the brain progressively shrinks
The result: “Our network-based model was able to explain and differentiate between drug-related and disease-related brain changes,” says Chopra, describing one of the results. According to the recordings, the psychosis is manifested by a significant and progressive decrease in the volume of the gray matter of the brain. At the same time, taking antipsychotic medications also leads to measurable reductions in this layer of the brain, as the team found.
However, the changes in gray matter caused by psychosis are not randomly distributed across the brain. Rather, where they spread is determined by a complex network of structural connections in the white and gray matter – “very similar to what we observe in the progression of neurodegenerative diseases in the brain,” says Chopra.
Hippocampus is the epicenter of psychoses
Using these analyses, the team also identified the area of the brain where the psychotic changes are likely to occur first. The central starting point is the hippocampus, the area that plays an important role in memory processes but is also known to be associated with schizophrenia. This area is the first to be affected by a psychosis-related decrease in gray matter.
From the hippocampus, the disease then spreads over time to the brain via the nerve connections in the white matter. At the beginning of psychosis, this leads to damage in the posterior cortex; as the disease progresses, according to the study, the prefrontal cortex is also affected – the seat of self-control, action control and reason.
New starting points for therapies
These new findings also open up new opportunities for the treatment of psychoses: According to the researchers, the hippocampus in particular, as the epicenter of psychotic development, is a potential starting point for the development of future medications that can stop or reduce the spread. “These therapies could limit the effects of the disease or perhaps even reduce the risk of psychosis outbreaks,” says Chopra.
Overall, his team’s findings help understand the causes of brain changes in psychotic disorders and open up new possibilities for predicting how they might develop in individual patients. Chopra and his colleagues want to further expand their models to identify possible additional treatment targets and predict the course of the disease in individual people. (Journal of the American Medical Association Psychiatry/ JAMA Psychiatry, 2023; doi: 10.1001/jamapsychiatry.2023.3293)
Source: Monash University
October 4, 2023 – Claudia Krapp