Schizophrenia is one of the top 15 leading causes of disability in the world, with psychotic symptoms such as hallucinations, delusions, and disordered thinking, as well as decreased emotional expression, decreased motivation to achieve goals, difficulty in social relationships, motor impairment, and cognitive impairment, according to the National Institute of Mental Health.
Though cognitive impairment and strange behaviors can occasionally show up in childhood, symptoms often begin in late adolescence or early adulthood.
Antipsychotic medications are being used to treat schizophrenia, although these medications only treat the symptoms of the disorder.
“One of the major side effects of the drugs used to treat schizophrenia is lack of pleasure and joy,” said author Dr. Jennifer Erwin. “In theory, if we could target the dopamine receptor specifically with drugs, that could be a new strategy for treatment that would not limit a patient’s joy as much.”
Dopamine is a type of neurotransmitter. It sends messages between neurons, which are nerve cells in the brain, to change how they work and act. Dopamine is the neurotransmitter that makes people feel good when they do something they enjoy.
Scientists have long recognized that abnormal dopamine levels play a key role in schizophrenia, Alzheimer’s disease, and other neuropsychiatric illnesses, as well as having some connection to psychosis.
Amphetamines and other drugs that make the brain make more dopamine are known to cause psychosis. Psychosis-treating medications reduce dopamine activity.
Scientists have tried for many years to figure out if and how an imbalance of dopamine is really linked to schizophrenia based on these observations. Dopamine sends messages in the brain by interacting with proteins called dopamine receptors that are on the surface of brain cells. The Lieber Institute’s groundbreaking research into those receptors has led to new findings demonstrating that dopamine contributes to the development of schizophrenia.
The researchers looked at hundreds of brains that had been donated to the Lieber Institute after the deaths of more than 350 people. Some of the brains were from people with schizophrenia, while others were from people without mental illness.
They opted to concentrate on the caudate nucleus because it contains the highest concentration of dopamine in the brain and is crucial for learning how to make complicated concepts and behaviors more automatic and intuitive.
Additionally, they looked at a region of the human genome that has been linked to the risk of schizophrenia in numerous large-scale international genetic investigations. The genes for dopamine-responsive protein receptors are located in this area, suggesting a possible link between this neurotransmitter and schizophrenia. But genetic data only shows that dopamine receptors may play a role in the risk of schizophrenia.
The data are not conclusive and don’t show what the real link is.
Researchers at the Lieber Institute went one step further in figuring out how dopamine receptors make people more likely to get sick.
The mechanism is unique to the autoreceptor subtype of the dopamine receptor, which is found on the “male” side of the presynaptic terminal, the junction between neurons.
This autoreceptor controls the amount of dopamine released from the presynaptic neuron. If autoreceptors are damaged, it’s hard to control how much dopamine flows through the brain, so too much dopamine flows for too long.
The researchers showed that the genetic evidence of risk for sickness might be explained by reduced expression of this autoreceptor in the brain. This fits with the idea that too much dopamine causes psychosis and is strong evidence that the dopamine-schizophrenia puzzle has finally been solved.
Dr. Sol Snyder, a pioneering neuroscientist, lauded the discovery as a significant advance that had been decades in the making. Dr. Snyder founded the department of neuroscience at the Johns Hopkins University School of Medicine, which bears his name. He is a distinguished service professor of neuroscience, pharmacology, and psychiatry. He was the researcher who found that dopamine in the brain is reduced by antipsychotic medications.
Dr. Snyder, who was not engaged in this study, stated that there is a lot of conflicting evidence supporting the role of dopamine and dopamine receptors in schizophrenia.
“The key thing these researchers have done is,” Dr. Snyder added, “to collect data that puts it all together and in a fashion that is persuasive in establishing that dopamine systems are out of kilter in schizophrenia, and that is causal to the disease.”
“For decades, people have debated the dopamine connection to schizophrenia.
“They used to say, ‘Well, this is interesting to speculate about, but there’s no solid evidence.’ But now that we have much more rigorous data available, we keep coming back to the same story. You don’t have to call it a hypothesis anymore.”
Source: 10.1038/s41593-022-01182-7
Image Credit: Getty
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