Scientists have identified a new schizophrenia biomarker and potential peptide treatment that could target cognitive symptoms caused by the condition.
A newly identified biomarker could lead to the first effective treatment targeting the cognitive symptoms of schizophrenia, according to new research from Northwestern University.
Current medications for schizophrenia are effective at managing hallucinations and delusions but have little impact on cognitive difficulties such as disorganised thinking and impaired decision-making. These symptoms often prevent patients from working or living independently, leaving many reliant on long-term support.
Tackling the hidden burden of schizophrenia
Schizophrenia affects around 0.5 percent of the global population, including roughly two million people in the United States. While antipsychotic drugs can control some symptoms, cognitive impairment is still a huge issue.
Schizophrenia affects around 0.5 percent of the global population, including roughly two million people in the United States.
“A lot of people with schizophrenia cannot integrate well into society because of these cognitive deficits,” said corresponding author Peter Penzes, Professor of Neuroscience, Pharmacology and Psychiatry and Behavioural Sciences at Northwestern University Feinberg School of Medicine. “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.”
Discovery of a new biomarker
By analysing cerebrospinal fluid from more than 100 people with schizophrenia and healthy controls, researchers identified a circulating form of a brain protein known as Cacna2d1.
The study found that levels of this protein were significantly reduced in patients with schizophrenia. This deficiency appears to lead to overactive brain circuits, which may contribute to the disorder’s cognitive symptoms.
Synthetic protein shows promising results
To test a potential treatment, the team developed a synthetic version of the protein, called SEAD1, and evaluated it in a mouse model of genetic schizophrenia.
A single injection of SEAD1 corrected abnormal brain activity and improved behaviour linked to the disorder.
A single injection of SEAD1 corrected abnormal brain activity and improved behaviour linked to the disorder. Importantly, the researchers reported no observable negative side effects, such as sedation or reduced movement.
“Our treatment reopens a crucial window to rewire connections in adult brains,” said first author Marc Dos Santos, Research Assistant Professor of Neuroscience at Feinberg. “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.”
Towards more precise treatments
The researchers say the discovery could transform how schizophrenia is treated by pairing a diagnostic biomarker with a targeted therapy.
Unlike conditions such as diabetes or heart disease, psychiatric disorders lack clear biological markers, making diagnosis and treatment more difficult. The identification of Cacna2d1 as a biomarker could help pinpoint patients most likely to benefit from the new 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,” said Penzes. “The next step for us would be to develop a blood biomarker to identify a subset of schizophrenia patients who can respond to this treatment and then we can give them this peptide – almost like Ozempic for schizophrenia, an injection that you can give once a week.”
Next steps and future potential
Researchers are now working to refine the synthetic protein and assess how long its therapeutic effects last. Future studies will also explore its use in people with 16p11.2 duplication syndrome, a genetic condition linked to a significantly increased risk of schizophrenia.
If successful in clinical trials, the approach could help in treating not only schizophrenia but potentially other psychiatric disorders linked to impaired brain plasticity.