Brain circuit problem likely sets stage for the 'voices' that are symptom of schizophrenia

June 5, 2014
Functional magnetic resonance imaging (fMRI) and other brain imaging technologies allow for the study of differences in brain activity in people diagnosed with schizophrenia. The image shows two levels of the brain, with areas that were more active in healthy controls than in schizophrenia patients shown in orange, during an fMRI study of working memory. Credit: Kim J, Matthews NL, Park S./PLoS One.

St. 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. The work appears in the June 6 issue of the journal Science.

Researchers linked the problem to a gene deletion. This leads to changes in chemistry that reduce the flow of information between two brain structures involved in processing .

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 . The disease is a chronic, devastating brain disorder that affects about 1 percent of Americans and causes them to struggle with a variety of problems, including thinking, learning and memory.

The disrupted circuit identified in this study solves the mystery of how current antipsychotic drugs ease symptoms and provides a new focus for efforts to develop medications that quiet "voices" but cause fewer side effects.

"We think that reducing the flow of information between these two brain structures that play a central role in processing auditory information sets the stage for stress or other factors to come along and trigger the 'voices' that are the most common psychotic symptom of schizophrenia," said the study's corresponding author Stanislav Zakharenko, M.D., Ph.D., an associate member of the St. Jude Department of Developmental Neurobiology. "These findings also integrate several competing models regarding changes in the brain that lead to this complex disorder."

The work was done in a mouse model of the human genetic disorder 22q11 . The syndrome occurs when part of chromosome 22 is deleted and individuals are left with one rather than the usual two copies of about 25 genes. About 30 percent of individuals with the deletion syndrome develop schizophrenia, making it one of the strongest risk factors for the disorder. DNA is the blueprint for life. Human DNA is organized into 23 pairs of chromosomes that are found in nearly every cell.

Earlier work from Zakharenko's laboratory linked one of the lost genes, Dgcr8, to brain changes in with the deletion syndrome that affect a structure important for learning and memory. They found evidence that the same mechanism was at work in patients with schizophrenia. Dgcr8 carries instructions for making small molecules called microRNAs that help regulate production of different proteins.

For this study, researchers used state-of-the-art tools to link the loss of Dgcr8 to changes that affect a different , the auditory thalamus. For decades antipsychotic drugs have been known to work by binding to a protein named the D2 dopamine receptor (Drd2). The binding blocks activity of the chemical messenger dopamine. Until now, however, how that quieted the "voices" of schizophrenia was unclear.

Working in mice with and without the 22q11 deletion, researchers showed that the strength of the nerve impulse from neurons in the auditory thalamus was reduced in mice with the deletion compared to normal mice. Electrical activity in other brain regions was not different.

Investigators showed that Drd2 levels were elevated in the auditory thalamus of mice with the deletion, but not in other brain regions. When researchers checked Drd2 levels in tissue from the same structure collected from 26 individuals with and without schizophrenia, scientists reported that protein levels were higher in patients with the disease.

As further evidence of Drd2's role in disrupting signals from the auditory thalamus, researchers tested neurons in the laboratory from different of mutant and normal mice by adding haloperidol and clozapine. Those drugs work by targeting Drd2. Originally nerve impulses in the mutant neurons were reduced compared to normal mice. But the nerve impulses were almost universally enhanced by antipsychotics in neurons from mutant mice, but only in neurons from the auditory thalamus.

When researchers looked more closely at the missing 22q11 genes, they found that mice that lacked the Dgcr8 responded to a loud noise in a similar manner as schizophrenia patients. Treatment with haloperidol restored the normal startle response in the mice, just as the drug does in patients.

Studying schizophrenia and other brain disorders advances understanding of normal brain development and the missteps that lead to various catastrophic diseases, including pediatric brain tumors and other problems.

Explore further: Rare genetic disorder points to molecules that may play role in schizophrenia

More information: "Specific disruption of thalamic inputs to the auditory cortex in schizophrenia models," by S. Chun et al. Science, 2014. www.sciencemag.org/lookup/doi/ … 1126/science.1253895

Related Stories

Rare genetic disorder points to molecules that may play role in schizophrenia

October 9, 2012
Scientists studying a rare genetic disorder have identified a molecular pathway that may play a role in schizophrenia, according to new research in the October 10 issue of The Journal of Neuroscience. The findings may one ...

Altered brain activity responsible for cognitive symptoms of schizophrenia

March 20, 2013
Cognitive problems with memory and behavior experienced by individuals with schizophrenia are linked with changes in brain activity; however, it is difficult to test whether these changes are the underlying cause or consequence ...

Improving the search for new schizophrenia treatments

April 5, 2013
(Medical Xpress)—Controlling the symptoms of schizophrenia is the job of antipsychotic drugs which block a set of specific neural signals. But the way these drugs work can lead to a host of severe and debilitating long-term ...

Rhythmic bursts of electrical activity from cells in ear teach brain how to hear

May 21, 2014
A precise rhythm of electrical impulses transmitted from cells in the inner ear coaches the brain how to hear, according to a new study led by researchers at the University of Pittsburgh School of Medicine. They report the ...

Brain wiring quiets the voice inside your head

September 3, 2013
During a normal conversation, your brain is constantly adjusting the volume to soften the sound of your own voice and boost the voices of others in the room.

These blind mice hear like Stevie Wonder

February 11, 2014
Want to hear as well as Stevie Wonder or the late Ray Charles? A blindfold not only might help, it could rewire your brain in the process, a new study suggests.

Recommended for you

The neural codes for body movements

July 21, 2017
A small patch of neurons in the brain can encode the movements of many body parts, according to researchers in the laboratory of Caltech's Richard Andersen, James G. Boswell Professor of Neuroscience, Tianqiao and Chrissy ...

Faulty support cells disrupt communication in brains of people with schizophrenia

July 20, 2017
New research has identified the culprit behind the wiring problems in the brains of people with schizophrenia. When researchers transplanted human brain cells generated from individuals diagnosed with childhood-onset schizophrenia ...

Scientists reveal how patterns of brain activity direct specific body movements

July 20, 2017
New research by Columbia scientists offers fresh insight into how the brain tells the body to move, from simple behaviors like walking, to trained movements that may take years to master. The discovery in mice advances knowledge ...

Scientists discover combined sensory map for heat, humidity in fly brain

July 20, 2017
Northwestern University neuroscientists now can visualize how fruit flies sense and process humidity and temperature together through a "sensory map" within their brains, according to new research.

Team traces masculinization in mice to estrogen receptor in inhibitory neurons

July 20, 2017
Researchers at Cold Spring Harbor Laboratory (CSHL) have opened a black box in the brain whose contents explain one of the remarkable yet mysterious facts of life.

Speech language therapy delivered through the Internet leads to similar improvements as in-person treatment

July 20, 2017
Telerehabilitation helps healthcare professionals reach more patients in need, but some worry it doesn't offer the same quality of care as in-person treatment. This isn't the case, according to recent research by Baycrest.

2 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

RobertKarlStonjek
not rated yet Jun 06, 2014
Auditory hallucination is not the most common symptom of schizophrenia. It is, in fact, the holding of false beliefs.

Everybody hears voices in their head, the voice heard when you are reading or thinking or recalling a conversation but we do not believe that these voices hold any special significance or independence.

Does the study differentiate between schizophrenic and non-schizophrenics who experience seemingly independent voices?

"A common form of auditory hallucination involves hearing one or more talking voices. This may be associated with psychotic disorders such as schizophrenia or mania, and holds special significance in diagnosing these conditions. However, individuals may hear voices without suffering from diagnosable mental illness."
http://en.wikiped...cination
sighwren
not rated yet Jun 08, 2014
"St. Jude's Children's Hospital has found that the auditory hallucinations or "voices" associated with schizophrenia could be linked to a chemical imbalance that interferes with communication between the thalamic inputs and auditory cortex, the sections of the brain that interpret audio stimuli." So instead of fixing the chemical imbalance, most likely caused by mercury poisoning, and subsequent copper toxicity from mercury amalgam fillings, they come up with another synthetic drug to control symptoms.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.