A significant discovery emerged from a study spearheaded by investigators at Mass General Brigham. They identified a distinct brain network that ties together the varying patterns of brain atrophy, or shrinkage, related to schizophrenia. By pooling neuroimaging data from over 90 studies encompassing more than 8,000 participants, the research team unearthed a particular connectivity pattern of atrophy. This pattern was consistent across different phases and symptoms of schizophrenia and set it apart from brain networks associated with other psychiatric disorders. The findings are set to steer a clinical trial that will commence patient recruitment shortly, aiming to evaluate brain stimulation sites connected to the schizophrenia network. The results have been published in Nature Mental Health.
“We searched for commonalities among reports on how schizophrenia impacts the brain. We discovered atrophy in multiple regions across the brain, yet they all converge on a single network,” stated Ahmed T. Makhlouf, MD, the corresponding author from the Center for Brain Circuit Therapeutics and the medical director of the Brigham and Women’s Hospital Psychosis Program.
Despite extensive efforts to decipher the neuroanatomy of schizophrenia, inconsistent results and methodological disparities have hampered experts’ comprehension of the circuits linked to brain atrophy.
“One possible explanation is that everyone has been observing the same phenomenon from diverse perspectives. It’s like several people attempting to describe an elephant by feeling different parts of it with their eyes closed; they’ll end up with different descriptions,” explained senior author Shan H. Siddiqi, MD, a psychiatrist at the Brigham’s Center for Brain Circuit Therapeutics. “Our strategy in this study was to piece together the whole elephant.”
The research scrutinized data from 90 studies focused on atrophy in schizophrenia. The dataset comprised 1,636 newly diagnosed schizophrenia patients, 2,120 individuals with chronic forms of the disease, and just over 6,000 healthy controls. Additionally, it examined outcomes from 927 people at genetic high risk and 580 individuals at clinical (based on early symptoms) high risk of developing schizophrenia.
Initially, the investigators crafted a common brain map by integrating the widespread locations of atrophy in schizophrenia. Subsequently, they employed a technique known as coordinate network mapping (CNM) to gauge the overlap between atrophy sites and functional brain networks. The resultant atrophy connectivity map intersected with schizophrenia-associated brain regions, such as the bilateral insula, hippocampus, and fusiform cortex. Finally, the researchers demonstrated that these maps differed from those developed for aging patients or those with conditions like Alzheimer’s disease, major depressive disorder, or substance use disorders, highlighting the network’s specificity to schizophrenia.
The researchers ascertained that the network remained comparable among patients with disparate symptoms or at varying stages of schizophrenia and didn’t undergo significant alterations with antipsychotic treatments. High-risk individuals exhibited similarities in atrophy, but patients who had progressed to clinical disease displayed a unique connectivity pattern. The authors propose that further exploration of atrophy patterns in high-risk individuals could enhance the prediction of schizophrenia onset. They also note that future studies leveraging patient-specific connectomes could offer individualized insights. Moreover, a planned clinical trial will utilize transcranial magnetic stimulation to assess the connectivity of stimulation sites to the identified schizophrenia network.
“There’s an ongoing debate in the field regarding whether schizophrenia qualifies as a neurodegenerative disorder,” remarked Makhlouf. “Our study suggests the existence of a unique and unified network that could potentially be a central hallmark of schizophrenia.”
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