Subtle differences identified in brains of people with schizophrenia

Schizophrenia might be among the most intensely studied mental illnesses. However, its causes—and the way those causes manifest in the brain—remain frustratingly elusive. A new study published February 26 in the American Journal of Psychiatry examines physical differences between the brains of people who experience schizophrenia and those who do not.

Wolfgang Omlor, a study co-author and psychiatrist from the University of Zurich in Switzerland, tells Popular Science that “while schizophrenia may have its own mechanisms shaping brain structure and function, these processes remain far from fully understood.” 

To identify trends in physical features common to the brains of people with schizophrenia, Omlor and his team combed through data from the global Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) database covering 6,037 people. They saw two potential features: an increased uniformity of folding patterns in a part of the brain called the right caudal anterior cingulate region, and an increased variability in the thickness of the cerebral cortex.

An immediate question is whether these features could contribute to causing schizophrenia, or whether they’re caused by the condition. Similarly, it’s not clear whether these features are innate, or develop over the course of a person’s life. Omlor explains that because this study is “comparing individuals already diagnosed with schizophrenia to controls,” it can’t address the question of causation. 

As far as whether these features are something with which a person is born, or whether they develop over the course of life, he says, “It’s likely a combination of both. Some features may be present from early development, while others can emerge later, influenced by factors like medication or chronic stress that reshape the brain through neuroplasticity.”

According to Omlor, cortical folding appears to fall into the category of features present from early development and is mostly established before birth and into early childhood. However, schizophrenia itself tends to manifest in late adolescence/early adulthood. This raises the possibility that these folding patterns represent some sort of predisposition to schizophrenia; whether or not this results in the onset of the actual condition, however, will depend on any number of other factors.

The folding of cerebral tissue is one of the brain’s most distinctive features. In general, “folding increases the brain’s surface area in limited space and is thought to influence how neurons connect,” Omlor says. Subtle differences in the nature of the way that brain tissue is folded are also a feature of other conditions, although it’s difficult to identify what exact effect such differences have. 

“Some neurodevelopmental conditions (e.g., autism) also show altered cortical folding,” he says. “The implications of such differences aren’t fully understood, but the more uniform folding in schizophrenia’s anterior cingulate could point to a more constrained developmental process in that region.”

Exactly how these folding patterns might interact with the development and nature of the condition remains an open question, but Omlor theorizes that “the uniform folding patterns may reflect a less flexible interplay between genes and environment at these earlier stages [of development].”

It certainly seems notable that the folds manifest in the right caudal anterior cingulate region, a part of the brain that integrates cognitive and emotional processes. However, a single role should not be given part of the brain.

“Brain regions generally work together in complex networks.So while we do see more uniform folding [in the right caudal anterior cingulate region] in schizophrenia, it’s best not to think of [that region]  as solely ‘responsible’ for any single task,” he says.“Rather, it’s part of a broader circuit linking thought and emotion.”

The study’s second finding is a “greater variability in cortical thickness” in individuals with schizophrenia. As an example of how nothing related to the brain is ever simple, this isn’t merely a question of people with schizophrenia having “bigger” or “smaller” cerebral cortices. Instead, one person’s cortex might be thinner in some parts and thicker in others, while another might be just the opposite—so even though those two people’s cortices might have the same overall volume, their internal make-up might be quite different. In people with schizophrenia, there is a broader spread of such variation in thickness.

The subtleties involved here reflect the fact that the brain’s dizzying complexity means it’s rarely possible to draw simple conclusions. Even in this case, where a basic interpretation might be that schizophrenia is linked to the volume of the cerebral cortex, the answer is not that straightforward. 

“Greater variability of cortical thickness in schizophrenia reflects a broader range beyond a ‘more’ or ‘less’ pattern, underscoring the disorder’s complexity,” says Omlor.

However, it does appear possible to correlate these differences with the myriad ways in which schizophrenia presents. 

“We also found that variations in specific brain regions correlate with schizophrenia symptom domains, suggesting these structural differences mirror the diverse presentations of the condition,” Omlor says.

Ultimately, one key takeaway from this study is that the way in which schizophrenia presents in a person is as unique as that person themselves. Similarly, it appears that there’s no single way in which schizophrenia can be reflected in a person’s brain. If anything, there’s perhaps a set of regions in which the condition manifests, but the ways in which it can do so appear to be many and varied. 

Approaching schizophrenia in this individualistic manner isn’t merely an abstract consideration. Instead, a better understanding of how and why the condition varies from person to person could “guide more individualized precision-medicine efforts… by recognizing these differences early on, clinicians and researchers can work toward treatments better suited to each person’s unique profile,” according to Omlor.

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