A new study led by researchers from Mass General Brigham has uncovered a distinctive brain network associated with varied patterns of brain atrophy, or shrinkage, observed in individuals with schizophrenia. By analyzing neuroimaging data from over 8,000 participants across multiple studies, the research team discovered a specific connectivity pattern of atrophy that persists across different stages and symptom variations of schizophrenia. This network was found to be unique to schizophrenia and distinct from brain networks connected to other psychiatric disorders. The results were published in Nature Mental Health.
“We found that atrophy occurs in various regions throughout the brain, but these regions are connected by a common network,” said Dr. Ahmed T. Makhlouf, MD, corresponding author of the study and medical director of the Brigham and Women’s Hospital Psychosis Program.
Despite extensive research into the neuroanatomy of schizophrenia, previous efforts have yielded varied results due to methodological differences. This has hindered a clear understanding of the brain circuits linked to brain atrophy in schizophrenia. Dr. Shan H. Siddiqi, MD, a senior author and psychiatrist at the Brigham’s Center for Brain Circuit Therapeutics, compared the challenge to understanding schizophrenia to the story of several blindfolded people trying to describe an elephant by touching different parts. “Everyone might describe different things, but we aimed to reconstruct the whole picture,” Siddiqi explained.
The research team examined data from 90 studies, including a dataset of 1,636 patients with recently diagnosed schizophrenia, 2,120 individuals with chronic schizophrenia, and more than 6,000 healthy control subjects. In addition, the study considered data from 927 individuals at high genetic risk and 580 individuals with early clinical symptoms indicative of schizophrenia.
Using coordinate network mapping (CNM), the researchers created a comprehensive brain map showing areas of atrophy in schizophrenia. The map identified overlapping regions of brain atrophy, including the bilateral insula, hippocampus, and fusiform cortex, all of which are commonly associated with schizophrenia. Notably, this atrophy connectivity map differed from those seen in brain regions related to aging, Alzheimer’s disease, major depressive disorder, or substance use disorders, highlighting its specificity to schizophrenia.
The study revealed that the identified brain network remained consistent across individuals at different stages of schizophrenia and with varying symptoms. This network also did not significantly change following antipsychotic treatment. Interestingly, individuals at high risk for schizophrenia shared similar patterns of brain atrophy, but those who had progressed to full-blown schizophrenia exhibited a unique connectivity pattern. The findings suggest that analyzing atrophy in high-risk individuals could help predict the onset of the disorder.
Looking ahead, the researchers emphasize the potential of patient-specific brain connectivity maps in offering personalized insights into schizophrenia. They also noted that a clinical trial is in the works, aimed at using transcranial magnetic stimulation (TMS) to explore the connectivity of brain stimulation sites with the identified schizophrenia network.
“The debate about whether schizophrenia is a neurodegenerative disorder is ongoing,” Dr. Makhlouf commented. “However, our study suggests that a unique, unified brain network could serve as a core characteristic of schizophrenia.”
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