Researchers Gain Insight into Schizophrenia through Live Brain Imaging

A research team, including a Rutgers University professor, has enhanced the understanding of biological changes linked to schizophrenia by directly measuring synaptic connections in the living human brain. Utilizing specialized positron emission tomography (PET) imaging, the team focused on these vital communication sites between brain cells. The findings were published in the journal Molecular Psychiatry.

The study was led by Avram Holmes, an associate professor of psychiatry at Robert Wood Johnson Medical School and a core faculty member at the Center for Advanced Human Brain Imaging Research within the Rutgers Brain Health Institute, alongside Rajiv Radhakrishnan, an associate professor of psychiatry and radiology at Yale University. The first author, Sidhant Chopra, a McKenzie Research Fellow at Orygen and the University of Melbourne, was previously a postdoctoral fellow in Holmes’s lab.

Measuring the Brain’s Synaptic Connections

Synapses, critical junctions facilitating communication between brain cells, are believed to contribute to the cognitive and emotional symptoms of schizophrenia. Historically, scientists faced challenges in identifying where synaptic loss occurs in living individuals due to limitations in conventional imaging techniques like magnetic resonance imaging (MRI), which cannot specifically assess synaptic status.

In this study, 122 participants were involved, including 29 diagnosed with schizophrenia, marking it as one of the largest PET imaging studies focused on synaptic density to date. The results indicated that individuals with schizophrenia exhibited a significant and widespread reduction in synaptic connections across various brain regions, notably in the frontal and temporal lobes, as well as areas related to memory and emotion. The analysis revealed that synaptic loss was substantially greater in the left hemisphere compared to the right.

A notable finding of the study was that the observed synaptic loss patterns did not align with the changes in brain volume typically assessed via standard MRI scans. This distinction implies that synaptic loss and alterations in brain volume may reflect distinct biological processes, rather than being two manifestations of the same underlying change.

A Molecular Pattern Behind Synaptic Loss

The team also identified that the brain regions with the most significant synaptic losses were enriched with receptors for key neurotransmitters such as serotonin, gamma-aminobutyric acid (GABA), and glutamate. This discovery suggests that the molecular makeup of specific brain areas might influence their susceptibility to changes associated with schizophrenia.

To further investigate the propagation of synaptic loss throughout the brain, researchers employed computer simulations based on the brain’s structural connectivity. Their models indicated the left frontal lobe as a potential origin point for the spread of synaptic loss into adjacent regions. “These findings suggest that in schizophrenia, synaptic loss is not random,” Chopra noted. “Rather, it follows the brain’s molecular and connectivity architecture, which could eventually help identify where and how to intervene.”

Holmes added, “This detailed mapping of synaptic vulnerability could eventually help identify where and how to intervene to preserve or restore brain function, such as emerging therapies to prevent and regrow synapses.”

Toward More Precise Schizophrenia Treatments

Moving forward, the researchers aim to expand on these results by studying how synaptic loss evolves over time and its responsiveness to clinical treatments. A deeper understanding of this progression could assist in the development of more precise and personalized strategies for schizophrenia care.