Schizophrenia is linked to iron and myelin deficits in the brain, neuroimaging study finds

Schizophrenia is a severe and debilitating psychiatric disorder characterized by hallucinations, disorganized speech and thought patterns, false beliefs about the world or oneself, difficulties concentrating and other symptoms impacting people's daily functioning. While schizophrenia has been the topic of numerous research studies, its biological and neural underpinnings have not yet been fully elucidated.

While some past brain imaging studies suggest that schizophrenia is associated with abnormal levels of iron and myelin in the brain, the results collected so far are conflicting. Iron is a metal known to contribute to healthy brain function, while myelin is a fatty substance that forms a sheath around nerve fibers, protecting them and supporting their conduction of electrical signals.

Researchers at King's College London, Hammersmith Hospital and Imperial College London recently set out to further explore the possibility that schizophrenia is linked to abnormal levels of iron and myelin in the brain. Their findings, published in Molecular Psychiatry, uncovered potential new biomarkers of schizophrenia that could improve the understanding of its underlying brain mechanisms.

"Iron is essential for many neuronal processes but excess causes oxidative damage, so brain levels are kept in a delicate balance," Dr. Luke J. Vano, first author of the paper, told Medical Xpress. "Iron-sensitive MRI studies focusing on schizophrenia have yielded conflicting results, with both increases and decreases reported. As myelin—which increases brain signal transmission—influences iron-sensitive MRI, myelin variation could complicate interpretation."

As part of their study, Dr. Vano and his colleagues examined the brains of 85 individuals diagnosed with schizophrenia and 86 matching control subjects. To study the brains of the study participants, they used iron-sensitive and myelin-sensitive magnetic resonance imaging (MRI), imaging techniques that allow researchers to detect iron and myelin levels in specific regions of the brain.

"We scanned patients with schizophrenia and matched controls using quantitative susceptibility mapping (QSM) to measure magnetic susceptibility (increases with iron and decreases with myelin), and diffusion MRI, to calculate mean diffusivity and magnetic susceptibility anisotropy (which decrease and increase with myelin, respectively)," explained Dr. Vano. "We compared these measures to test whether iron or myelin alterations accounted for patient differences in magnetic susceptibility and correlated the regional patterns with postmortem gene expression maps to identify potential cell-type contributions."

Using these experimental techniques, the researchers' results suggested iron and myelin anomalies that affected specific regions in the brains of individuals diagnosed with schizophrenia, including the caudate, putamen, and globus pallidus. Their findings are aligned with those of some earlier studies and could help to paint a clearer picture of disease pathophysiology.

"We found that patients with schizophrenia had lower magnetic susceptibility, higher mean diffusivity, and lower magnetic susceptibility anisotropy, suggesting that both iron and myelin brain levels are lower in schizophrenia," said Dr. Vano. "This was most significant in regions rich in oligodendrocytes. As oligodendrocytes utilize iron to synthesize myelin, this links oligodendrocyte dysfunction to schizophrenia, highlighting the mechanism underlying this as an important research area."

The recent work by Dr. Vano and his colleagues could soon pave the way for further investigations exploring how iron and myelin deficiencies might play a role in the various symptoms of schizophrenia. In the future, it could also potentially contribute to the development of alternative treatments for the disorder, which could, for instance, promote myelin repair or try to raise iron levels.

"Next, we'll test the same markers in bipolar disorder and in people at risk of developing schizophrenia," added Dr. Vano. "Additionally, we will evaluate whether they predict response to psychiatric treatments."