New Approach Allows for Detailed Study of Schizophrenia
Schizophrenia, a disorder in which people interpret reality abnormally, affects approximately 3.2 million Americans, with 100,000 new diagnoses each year. Schizophrenia can present itself in many life-disrupting ways, including hallucinations, disorganized thinking, and delusions. Though its prevalence is low in comparison to other mental disorders, its effects can be devastating. The National Institute of Mental Health reports that individuals living with schizophrenia are at an increased risk of premature death, losing an estimated 28.5 years of potential life on average.
Despite medical advances, the current understanding of the underlying causes of schizophrenia is still limited. This is largely due to the difficulty in examining the disorder in animal models, which have been key to understanding physical diseases in recent decades. While diseases like diabetes have symptoms that can be detected and manipulated in animal models, schizophrenia presents more difficulties due to its subjective nature. Thus, knowledge and treatments of schizophrenia and other mental disorders have lagged significantly behind bodily disorders. With these challenges in mind, researchers from the Washington University School of Medicine developed an approach to detecting and manipulating schizophrenia in mice.
The researchers’ approach detected auditory hallucinations, one of the most common and disruptive symptoms of schizophrenia. In this study, humans and mice performed a similar auditory task in which subjects listened for an auditory stimulus within a constant, dull background noise, referred to as “white noise”. Human subjects were instructed to use buttons to report whether or not they heard the stimulus tone and then rate their confidence in their decision. Likewise, mice were trained to select one water port when they perceived a stimulus tone and another when they did not. The mice’s confidence was measured by the time spent at each port to earn the water reward. Hallucinations in humans and mice could then be labeled similarly when the human or mouse subjects incorrectly indicated hearing a stimulus with high confidence.
Despite medical advances, the current understanding of the underlying causes of schizophrenia is still limited. This is largely due to the difficulty in examining the disorder in animal models, which have been key to understanding physical diseases in recent decades. While diseases like diabetes have symptoms that can be detected and manipulated in animal models, schizophrenia presents more difficulties due to its subjective nature. Thus, knowledge and treatments of schizophrenia and other mental disorders have lagged significantly behind bodily disorders. With these challenges in mind, researchers from the Washington University School of Medicine developed an approach to detecting and manipulating schizophrenia in mice.
The researchers’ approach detected auditory hallucinations, one of the most common and disruptive symptoms of schizophrenia. In this study, humans and mice performed a similar auditory task in which subjects listened for an auditory stimulus within a constant, dull background noise, referred to as “white noise”. Human subjects were instructed to use buttons to report whether or not they heard the stimulus tone and then rate their confidence in their decision. Likewise, mice were trained to select one water port when they perceived a stimulus tone and another when they did not. The mice’s confidence was measured by the time spent at each port to earn the water reward. Hallucinations in humans and mice could then be labeled similarly when the human or mouse subjects incorrectly indicated hearing a stimulus with high confidence.
For centuries, lab mice have enabled researchers to understand the underlying workings of disease.
Image Source: Sandy Millar
After establishing these protocols to measure hallucination events in the lab, the researchers considered ways to increase and decrease the prevalence of hallucination events in mice. First, they found that if mice expected to hear an auditory stimulus because of an increase in the amount of tones presented, then the prevalence and confidence of false alarms increased, supporting a phenomenon noted in previous human studies. Next, they found that ketamine, a drug known to cause hallucinations in humans, among other psychedelic effects, also increased the prevalence and confidence of false alarms in mice. Then, to study the underlying neurological causes of hallucinations, the researchers used the mice models to examine the relationship between hallucination events and the neurotransmitter dopamine. They found that dopamine release increased prior to hallucinations. Knowing this, researchers then found that inducing dopamine release led to an increase in hallucination events in mice. However, administering the antipsychotic drug haloperidol, a drug that blocks dopamine activity, reduced these hallucinations. Dopamine has long been believed to play a role in causing hallucinations, and these experiments done by the Washington University researchers are the first to use animal models to support this hypothesis.
This innovative approach to examining hallucinations, a primary symptom of schizophrenia, has implications far beyond this single study. It sets up the framework for further research into the underlying processes in the brain involved in hallucinations that researchers have been unable to examine in human studies. With this, there is hope for the development of more effective treatments for schizophrenia and other psychotic disorders to significantly reduce the burden of disease for millions of people living with these mental disorders.
This innovative approach to examining hallucinations, a primary symptom of schizophrenia, has implications far beyond this single study. It sets up the framework for further research into the underlying processes in the brain involved in hallucinations that researchers have been unable to examine in human studies. With this, there is hope for the development of more effective treatments for schizophrenia and other psychotic disorders to significantly reduce the burden of disease for millions of people living with these mental disorders.
Featured Image Source: geralt
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