Schizophrenia linked to “distinctively different” neuron size and shape

A new study published in Psychiatry Research provides evidence that certain brain cells are physically smaller in individuals with schizophrenia and that this size difference is related to the severity of hallucinations. By examining tiny structures in a specific region of the brain using advanced imaging techniques, researchers found that the neurons in people with schizophrenia were shorter and narrower than those in people without the condition.

Previous brain imaging studies have shown that people with schizophrenia tend to have less gray matter volume, particularly in the anterior cingulate cortex. This brain region is known to play an important role in cognitive and emotional processing. However, while large-scale imaging methods like MRI have repeatedly detected these differences, they do not provide a clear picture of what is happening at the level of individual cells.

To understand the biological basis for the shrinkage in gray matter, the research team focused on the structure of individual brain cells. Specifically, they looked at the soma, or cell body, of neurons. This is the part of the cell that contains the nucleus and serves as the main processing hub for neural activity.

“Psychiatric disorders are long thought to accompany no obvious neuropathological signs. It means there is no change in neurons, but this sounds somehow strange. Identifying neuronal changes in psychiatric disorders should provide clues for curing them. This idea led us to analyze neuronal 3D structure of schizophrenia sufferers with the synchrotron radiation nano-CT,” said study author Ryuta Mizutani, a professor at Tokai University and visiting researcher at RIKEN SPring-8 Center.

Previous studies by the researchers had already found that the threadlike extensions of neurons, called neurites, tend to be thinner and more twisted in schizophrenia. With this new work, the researchers aimed to determine whether the cell bodies themselves also showed signs of change.

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The study involved post-mortem brain tissue from eight individuals diagnosed with schizophrenia and eight individuals without the disorder. Using a specialized imaging method called synchrotron radiation nano-CT, the team was able to generate three-dimensional images of the neurons in extremely fine detail.

They focused on a particular type of neuron found in the anterior cingulate cortex known as pyramidal neurons. These cells are thought to be important for communication between different areas of the brain. In total, they analyzed 263 neurons across all participants.

The analysis revealed that the average length of the neuron cell bodies in people with schizophrenia was about 80 percent of that seen in the control group. The width was also reduced to around 90 percent.

When looking specifically at pyramidal neurons, the length reduction was even more pronounced, with cells measuring only 79 percent as long as those from the control group. Interneurons, another type of brain cell, did not show a clear size difference, but they were found in lower numbers and not in every case, limiting the conclusions that could be drawn about them.

The researchers also examined how the shape of the neurons related to other known features of schizophrenia. One analysis looked at the relationship between soma length and neurite curvature. Neurites that are more twisted tend to be less efficient at transmitting signals. The combination of shorter soma and more twisted neurites was able to distinguish schizophrenia cases from controls in their sample.

In another part of the analysis, they found a negative correlation between soma length and hallucination scores. In other words, the shorter the neuron cell body, the more severe the hallucinations tended to be. This relationship held even after controlling for medication use, suggesting that the physical brain changes were not simply due to treatment effects.

Overall, the team calculated that the reduced size in both the soma and neurites could explain much of the previously observed volume loss in the anterior cingulate cortex. They estimated that the total volume of neurons in this region might be reduced to about 50 to 60 percent of that seen in people without schizophrenia.

The findings indicate that the “neurons of schizophrenia sufferers are distinctively different from those of healthy people,” Mizutani told PsyPost. “If a drug to restore the neuronal change is developed, we can cure the disorder. I hope some company develop such a drug from our findings.”

Although the findings are based on precise measurements and advanced imaging techniques, the sample size was small, with only 16 individuals. This makes it difficult to generalize the results to all people with schizophrenia. The brain tissue used in the study came from individuals who had been living with chronic schizophrenia, so it remains unclear whether these changes develop early in the illness or evolve over time. Another limitation is that the analysis was based only on post-mortem samples, which means it cannot track how these changes might develop throughout a person’s life.

The researchers plan to continue studying additional brain samples to see whether the same patterns hold in larger and more diverse groups. They also expressed interest in exploring how their findings could contribute to the development of treatments that target the physical structure of neurons. If therapies could be developed to restore neuron size or shape, it might be possible to reduce some of the symptoms of schizophrenia.

The researchers emphasized that their work provides a starting point for understanding how physical changes in brain cells relate to psychiatric symptoms. While the results suggest a possible biological marker for hallucinations, much more research is needed before such findings could be applied in a clinical setting.

The study, “Pyramidal soma size in the anterior cingulate cortex is small in schizophrenia and correlates with hallucination score,” was authored by Ryuta Mizutani, Rino Saiga, Yoshiro Yamamoto, Chie Inomoto, Hiroshi Kajiwara, Yu Kakimoto, Yuki Sada, Masahiro Yasutake, Masayuki Uesugi, Akihisa Takeuchi, Kentaro Uesugi, Yasuko Terada, Yoshio Suzuki, Viktor Nikitin, Francesco De Carlo, Youta Torii, Itaru Kushima, Norio Ozaki, Shuji Iritani, Ken-ichi Oshima, and Masanari Itokawa.