New research conducted at Northwestern’s Feinberg School of Medicine is providing the scientific community with a fresh understanding of what goes on in the brain of a schizophrenic.
This rare psychiatric disorder plagues about one-half a percent of the population, causing an altered perception of reality. It can manifest with symptoms such as hallucinations, paranoia, delusions or disorganization of thoughts and speech. Patients also tend to exhibit “negative” symptoms that include social withdrawal, lack of emotionality and a tendency to stray away from very strong, vibrant stimuli such as paintings or bright colors, said Dr. Jelena Radulovic, an associate professor in Feinberg’s department of psychiatry and behavioral sciences and co-author of the study.
“(Schizophrenia) is one of the most difficult mental disorders because its main abnormalities are in the perception or expression of reality,” Radulovic said. “It’s more or less like a split mind between actual reality and the patient’s inner reality.”
Scientists discovered that these symptoms of schizophrenia may be set off by the lack of kalirin, a crucial protein normally found in both human and mouse brains. The research team, headed by Feinberg graduate student Michael Cahill, created a genetically modified mouse model lacking the kalirin-producing gene. The model later began to exhibit symptoms consistent with the mental disorder once it turned about two months old. This delayed onset seen in the mouse model mimics the disease’s behavior in humans, as schizophrenia does not appear until adolescence for some or during early adulthood for others.
According to Cahill, a shortage of kalirin in the brain’s frontal cortex – an area that plays a role in a number of higher level functions like memory, social interaction and decision-making – resulted in a loss of dendritic spines, which are necessary for fluid communication between brain cells.
“The change in number of the protrusions…has been linked to neuropsychiatric diseases (such as schizophrenia),” wrote co-author Maria Barbolina, an associate professor in the department of biopharmaceutical sciences at the University of Illinois at Chicago, in an e-mail.
Without kalirin, these neurons struggle to talk to one another – a problem that, when occurring in the frontal cortex, may play a role in the onset of schizophrenia’s symptoms.
“There is a big abnormality in (dendritic) spine generation in schizophrenic patients,” Radulovic said. “Kalirin helps to form and maintain these spines, so if there is a loss of kalirin there are fewer spines formed…which makes processing information more difficult; you lose the speed and efficacy of the brain.”
Today’s treatments for schizophrenia revolve extensively around potent anti-psychotic drugs and social interventions, both of which provide some help for patients in managing their symptoms and reintegrating themselves into society.
However, these new findings may open up avenues for more sophisticated, gene-based medicines to help treat the disease’s cognitive impairments, like viral injections or nanoparticles to introduce kalirin into organisms that lack the protein.
“Overall, this research has a tremendous significance for both basic science and translational research,” Barbolina said. “(In the future), kalirin…could be used as a target for the development of gene-specific therapeutics.”
