A recent research effort has highlighted a distinct brain network that correlates with various patterns of brain shrinkage related to schizophrenia.
Led by researchers at Mass General Brigham, this study has uncovered a specific brain network that connects different patterns of brain atrophy – or shrinkage – seen in schizophrenia. By analyzing neuroimaging data from over 8,000 participants across several studies, the team identified a consistent pattern of atrophy connectivity that appeared in various stages and symptoms of schizophrenia, setting it apart from networks linked to other mental health disorders. These findings will aid in the upcoming clinical trial that aims to recruit patients soon to evaluate brain stimulation locations tied to the schizophrenia network. The results are available in Nature Mental Health.
“We sought to find commonalities in how schizophrenia impacts the brain,” explained corresponding author Ahmed T. Makhlouf, MD, from the Center for Brain Circuit Therapeutics and medical director of the Brigham and Women’s Hospital Psychosis Program. “We discovered that while atrophy occurs across various brain regions, they are all interlinked by a singular network.”
Despite extensive research to clarify the neuroanatomy of schizophrenia, diverse results and varying methodologies have hindered experts’ comprehension of the circuits related to brain atrophy.
“One possibility is that everyone is attempting to examine the same issue from different perspectives. If several individuals try to touch different parts of an elephant while blindfolded, they will describe various aspects,” commented senior author Shan H. Siddiqi, MD, a psychiatrist at Brigham’s Center for Brain Circuit Therapeutics. “Our aim with this study was to piece together the complete picture.”
The research analyzed data from 90 studies that focused on atrophy in schizophrenia. The data compilation consisted of 1,636 patients recently diagnosed with schizophrenia, 2,120 individuals with chronic schizophrenia, along with over 6,000 healthy participants. The study also assessed data from 927 individuals and 580 individuals who had either genetic or clinical high risk (determined by early symptoms) for developing schizophrenia, respectively.
Initially, the researchers developed a comprehensive brain map to identify the widespread areas of atrophy linked to schizophrenia. Following this, they employed a method called coordinate network mapping (CNM) to evaluate the overlap between atrophy locations and functional brain networks. The resulting map of atrophy connectivity matched regions of the brain associated with schizophrenia, such as the bilateral insula, hippocampus, and fusiform cortex. Ultimately, the researchers demonstrated that these maps were different from brain connectivity maps created for older adults or individuals with conditions like Alzheimer’s disease, major depressive disorder, or substance abuse issues, confirming the network’s specificity to schizophrenia.
The researchers found that this network appeared similar across patients with differing symptoms or at various stages of schizophrenia, and it did not noticeably change with antipsychotic treatments. Patients at high risk for developing schizophrenia exhibited shared patterns of atrophy, though a distinct connectivity pattern was observed in those who had progressed to clinical disease. The authors propose that a deeper understanding of atrophy patterns in high-risk individuals may enhance the prediction of schizophrenia onset. They also remark that future studies utilizing patient-specific connectomes could deliver personalized insights, along with plans for a clinical trial that will employ transcranial magnetic stimulation to explore the connectivity of stimulation sites within the identified schizophrenia network.
“There is ongoing discussion in the field about whether schizophrenia is a neurodegenerative disorder,” stated Makhlouf. “Our research suggests there is a unique and unified network that could serve as a fundamental aspect of schizophrenia.”
Authorship: In addition to Makhlouf and Siddiqi, other authors from Mass General Brigham include William Drew, Jacob L. Stubbs, Joseph J. Taylor, David Silbersweig, and Michael D. Fox. Additional contributors are Donato Liloia and Jordan Grafman.
