Researchers have identified distinct biological markers and cellular mechanisms linked to schizophrenia and neurodevelopmental disorders, potentially opening new therapeutic windows. Recent studies point to a missing protein in cerebrospinal fluid and abnormal brain cell activity as promising targets for treating cognitive and behavioral symptoms that current medications often fail to address.
The Role of α2δ-1 Protein in Cognitive Deficits
A collaborative team from Northwestern University and Johns Hopkins University has identified a significant molecular signature associated with the cognitive challenges of schizophrenia. Researchers discovered that a protein known as α2δ-1 is found at lower levels in the cerebrospinal fluid of patients with the disorder. This protein, which is typically part of a calcium-channel complex on neurons, is released into the surrounding fluid by brain cells.
In experiments published in Neuron, scientists engineered a soluble version of the protein, dubbed SEAD1, and administered it to mice with a genetic alteration linked to schizophrenia. The treatment successfully restored excitatory connections on inhibitory neurons—specifically parvalbumin interneurons—and improved performance in memory and social behavior tests.
“A lot of people with schizophrenia cannot integrate well into society because of these cognitive deficits.”
Peter Penzes, study senior author and neuroscientist at Northwestern University
Targeting Brain Cell Activity in 15q13.3 Microdeletion Syndrome
Separate research from the University of Copenhagen’s Biotech Research and Innovation Center suggests that cognitive symptoms in neuropsychiatric disorders may stem from developmental disruptions that reach a “snapping point” during the transition to adolescence. By studying mice with 15q13.3 microdeletion syndrome—a condition associated with autism, epilepsy, and schizophrenia—researchers monitored sleep patterns as a behavioral marker for brain function.
The study, also published in Neuron, found that a rare, specific type of brain cell showed abnormal activity in these mice. Using chemogenetics to reduce the activity of these cells restored normal sleep patterns, suggesting a precise target for future therapies.
“Our study shows that until a specific point, brain development is largely unaffected by changes. The period leading up to that point may represent a treatment window where we can prevent functional impairment.”
Katarina Dragicevic, one of the study’s first authors and researcher at the University of Copenhagen
Experimental Strategies for Rett Syndrome
At the Texas Children’s Duncan Neurological Research Institute (NRI), scientists are exploring a method to treat Rett syndrome by increasing levels of the MeCP2 protein. Rett syndrome, which typically affects girls, is caused by mutations in the MECP2 gene that result in a lack of functional protein.
In experiments with mouse models and patient-derived cells, increasing the levels of mutant MeCP2 provided proof of concept for therapeutic benefit.
“Working with mouse models and cells derived from patients with Rett syndrome, our study provides proof of concept that increasing the levels of mutant MeCP2 in patients with the condition could provide therapeutic benefit.”
Harini Tirumala, graduate student and first author, Zoghbi lab
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