Little is known about the defective neural circuits that cause auditory hallucinations in patients with schizophrenia and the mechanisms of their sensitivity to antipsychotics, but evidence from a mouse study suggests a specific gene may play a role.
Stanislav Zakharenko, MD, PhD, an associate member of the St. Jude Department of Developmental Neurobiology, and colleagues created a murine model of human genetic disorder 22q11 deletion syndrome -- a known risk factor for schizophrenia -- to examine how deleted gene Dgcr8, which plays a role in the syndrome, affected the auditory thalamus.
Antipsychotic drugs are known to work by binding to D2 dopamine receptors (Drd2), but how they work to reduce auditory hallucinations is not well understood.
The researchers found that Drd2 levels were elevated in the auditory thalamus of mice with the deletion, but not in other brain regions. Mice that lacked Dgcr8 also responded to loud noise in a similar manner as schizophrenia patients. When the researchers treated mice with the antipsychotic haloperidol it restored the normal startle response in the mice, just as the drug does in patients.
Jude Children’s Research Hospital scientists have identified problems in a connection between brain structures that may predispose individuals to hearing the “voices” that are a common symptom of schizophrenia.
Researchers linked the problem to a gene deletion that leads to changes in brain chemistry which reduce the flow of information between two brain structures involved in processing auditory information. The research marks the first time that a specific circuit in the brain has been linked to the auditory hallucinations, delusions and other psychotic symptoms of schizophrenia.The findings were published in Science.