A Northwestern University study published on March 19 has identified a new protein biomarker for schizophrenia and developed a potential treatment that targets the disorder's cognitive symptoms. The research, conducted in both humans and mice, could lead to improved therapies for patients who struggle with disorganized thinking and executive dysfunction.
Cognitive symptoms of schizophrenia often prevent patients from working or living independently, leaving many reliant on family support or at risk of homelessness. Current medications primarily address hallucinations and delusions but do little to improve these cognitive challenges.
Peter Penzes, professor of neuroscience, pharmacology, psychiatry, and behavioral sciences at Northwestern University Feinberg School of Medicine, said, "A lot of people with schizophrenia cannot integrate well into society because of these cognitive deficits. Our discovery could solve these challenges by establishing the basis of a revolutionary and completely novel treatment strategy through a tandem biomarker-peptide therapeutic approach."
The researchers examined cerebral spinal fluid from more than 100 individuals with schizophrenia and healthy controls. They discovered lower levels of a previously unknown form of the brain protein Cacna2d1 in patients with schizophrenia. This reduction was linked to overactive brain circuits. The team then created a synthetic version called SEAD1 and tested it in mice with genetic schizophrenia traits. A single injection corrected abnormal brain activity and related behaviors without causing negative side effects such as sedation or reduced movement.
First author Marc Dos Santos said, "Our treatment reopens a crucial window to rewire connections in adult brains. The lack of brain plasticity is believed to be a key factor in the development of symptoms in schizophrenia. Reforming synapses could also be beneficial for other mental disorders, such as depression." Dos Santos added that further studies are needed to determine how long the therapeutic effects last.
Penzes explained that identifying this specific biomarker allows scientists to target subgroups most likely to benefit from SEAD1-based therapy: "The clinical trials would have much higher success rate, and the treatments would work much better because you would give the new drug to the exact people who actually could respond to that drug." He said future steps include developing a blood test for this biomarker so eligible patients can receive peptide injections similar to weekly treatments used for other conditions.
The findings offer hope for more precise diagnosis and effective treatment options for those affected by schizophrenia's cognitive symptoms.
