Current medications for schizophrenia treat symptoms such as hallucinations and delusions, but have little effect on cognitive symptoms such as disorganized thinking and executive dysfunction. As a result, many patients are unable to work, rely on their families for lifelong support, become homeless, and in some cases experience suicidal thoughts and behaviors.
A new Northwestern University study in humans and mice has discovered a novel biomarker for schizophrenia that may also serve as a potential drug to treat the disease’s cognitive symptoms. Schizophrenia affects 0.5% of the world’s population, including approximately 2 million people in the United States
“Many people with schizophrenia have trouble integrating into society because of these cognitive deficits,” said corresponding author Peter Penseth, professor of neuroscience, pharmacology, psychiatry, and behavioral sciences at Northwestern University Feinberg School of Medicine. “Our findings have the potential to address these challenges by establishing the basis for innovative and entirely new therapeutic strategies through a tandem biomarker and peptide therapeutic approach.”
The study will be published in the journal Neuron on March 19th.
Penseth is also director of Feinberg’s Center for Autism and Neurodevelopment.
Addition of synthetic proteins corrects abnormal brain circuit activity
Scientists identified a previously unknown free-circulating brain protein called Cacna2d1 by examining the cerebrospinal fluid of more than 100 schizophrenia patients and healthy controls. Studies have found that levels of this protein signal are reduced in schizophrenia patients compared to controls, resulting in overactive or overexcited brain circuits.
The research team created a synthetic version of the protein (named SEAD1) and tested it in a mouse model of genetic schizophrenia. A single injection of SEAD1 into the animals’ brains corrected both the abnormal brain circuit activity and the behavioral problems associated with the disorder. Importantly, the study authors said the treatment did not cause any observable negative side effects, such as sedation or decreased locomotor activity.
“Our treatment reopens an important window for rewiring connections in the adult brain,” said lead author Mark Dos Santos, research assistant professor of neuroscience at Feinberg. “Lack of brain plasticity is thought to be an important factor in the development of symptoms in schizophrenia. Synaptic reshaping may also be beneficial in other psychiatric disorders such as depression.”
Dos Santos said the team does not yet know how long the treatment’s effects last, but they plan to study this in future experiments. The research team is currently optimizing the protein for future clinical trials in patients with 16p11.2 duplication syndrome, who have a 10-fold increased risk of developing schizophrenia, Penseth said.
Why biomarkers for mental illness are so important
While there are biomarkers for diagnosing diseases, such as blood sugar levels for diabetes and cholesterol for heart disease, diagnosing mental illness is much more subjective, Penseth said.
Furthermore, due to the biological diversity of people, many potential drugs do not perform well in clinical trials or fail later. By identifying specific schizophrenia biomarkers in this study, scientists were able to identify the subgroups of people most likely to respond well to this SEAD1-based peptide drug.
Combining biomarkers and therapies is revolutionary because biomarkers are used to identify patients most likely to benefit from this treatment and biomarker-related peptide drugs are used to treat those same patients.
“Clinical trials will have a much higher success rate, and the treatment will be much more effective because you can give the new drug to the exact people who will actually respond to it,” Penseth said. “Our next step is to develop blood biomarkers to identify the subset of schizophrenia patients who will respond to this treatment, so we can give them this peptide, sort of like Ozempic for schizophrenia, as an injection that can be given once a week.”
The title of the study is “Soluble α2δ-1 altered in disease CSF modulates network homeostasis and rescues deficits in neuropsychiatric mouse models.” Other Northwestern study authors include Mark P. Forrest, Ewa Bomba-Warzak, Soumil Day, Euan Parnell, Jessica M. Christiansen, Sebby L. Edassery, Blair L. Eckman, Katherine R. Lammert, M. Dolores Martin de Saavedra, Marco Martina, Jeffrey N. Sabas, and others.
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Reference magazines:
Dos Santos, M. and others. (2026). Soluble α2δ-1 altered in disease CSF modulates network homeostasis and rescues defects in a neuropsychiatric mouse model. neuron. DOI: 10.1016/j.neuron.2026.02.004. https://www.cell.com/neuron/fulltext/S0896-6273(26)00087-5
