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Scientists have found a genetic mechanism that hyperlinks mind chemical substances to schizophrenia

Scientists have found a genetic mechanism that hyperlinks mind chemical substances to schizophrenia

Brain activity Excited nerve cells Illustration

Researchers have decided how the mind chemical dopamine is linked to schizophrenia.

Researchers inspecting postmortem brains are confirming a long-standing speculation that explains the neurotransmitter’s connection to the debilitating illness.

How is the mind chemical dopamine linked to schizophrenia? This query has plagued scientists for greater than 70 years, and now researchers on the Lieber Institute for Mind Growth (LIBD) consider they’ve solved the complicated puzzle. This new understanding may result in higher remedies for schizophrenia, an usually devastating mind dysfunction characterised by delusional pondering, hallucinations and different types of psychosis.

By inspecting gene expression within the caudate nucleus—a mind area related to emotional decision-making—scientists discovered bodily proof that neuronal cells are unable to precisely management dopamine ranges. Additionally they found a genetic mechanism that controls the stream of dopamine. Their outcomes have been revealed as we speak (November 1) within the journal Neuroscience of nature.

In response to the World Well being Group (WHO), roughly 1 in 300 folks worldwide endure from schizophrenia, which is about 24 million folks. This determine will increase to 1 in 222 folks if solely adults are thought of.

“Till now, scientists haven’t been capable of decipher whether or not the connection to dopamine is a causative issue or only a solution to deal with schizophrenia,” mentioned Daniel R. Weinberger, MD, co-author of the research. “We’ve got the primary proof that dopamine is a causative think about schizophrenia.” Weinberger is the manager director and director of the Lieber Institute.

Dopamine, a kind of neurotransmitter, acts as a chemical messenger that sends alerts between neurons—nerve cells within the mind—to vary their exercise and habits. Dopamine is the reward neurotransmitter that permits folks to expertise pleasure.

In response to the Nationwide Institute of Psychological Well being, schizophrenia is among the 15 main causes of incapacity worldwide. Individuals with this situation endure from psychotic signs similar to hallucinations, delusions, and thought issues, in addition to diminished expression of feelings, diminished motivation to realize objectives, difficulties in social relationships, and motor and cognitive impairments. Signs often seem in late adolescence or early maturity, though cognitive impairment and weird habits generally seem in childhood. Present remedies for schizophrenia embrace antipsychotic medication, which handle the signs of psychosis however don’t handle the trigger.

“One of many fundamental uncomfortable side effects of the medication used to deal with schizophrenia is the shortage of delight and pleasure,” mentioned Dr. Jennifer Erwin, a researcher on the Institute and one of many authors of the report. “Theoretically, if we may goal dopamine receptors particularly with medication, that could possibly be a brand new therapy technique that would not restrict the affected person’s pleasure as a lot.”

Scientists have identified for many years that irregular dopamine ranges have some connection to psychosis and are a crucial think about schizophrenia.[{” attribute=””>Alzheimer’s disease, and other neuropsychiatric disorders. Drugs that increase dopamine in the brain, such as amphetamines, are known to cause psychosis. Drugs that treat psychosis do so by reducing dopamine activity.

These observations have inspired generations of scientists to try to understand whether – and how – an imbalance of dopamine actually relates to schizophrenia. Dopamine transmits information in the brain by interacting with proteins on the surface of brain cells, called dopamine receptors. By studying those receptors, scientists at the Lieber Institute have come up with novel evidence confirming that dopamine is a causative factor for schizophrenia. 

The investigators examined hundreds of post-mortem specimen brains donated to the Lieber Institute from over 350 individuals, some with schizophrenia and others without psychiatric illness. They chose to focus on the caudate nucleus, a part of the brain that is critically important for learning how to make complex ideas and behaviors more automatic and intuitive, but also because it has the brain’s richest supply of dopamine. They also studied a region of the human genome that large international genetic studies have identified as being connected with the risk of schizophrenia. This region contains the genes for the protein receptors that respond to dopamine, which points to the dopamine-schizophrenia connection. But while genetic data suggest at most a role of dopamine receptors at risk for schizophrenia, the data are not conclusive and do not identify what the relationship actually is. The investigators at the Lieber Institute went critically further in discovering the mechanisms that make dopamine receptors a risk factor.

The mechanism exists specifically in a subtype of the dopamine receptor, called the autoreceptor, which lies on the “male” side of the connection between neurons, the presynaptic terminal. This autoreceptor regulates how much dopamine is released from the presynaptic neuron. If autoreceptors are compromised, the flow of dopamine within the brain is poorly controlled, and too much dopamine flows for too long.

The investigators found that decreased expression of this autoreceptor in the brain explains the genetic evidence of risk for illness. This is consistent with the prevailing hypothesis that too much dopamine plays a role in psychosis, and strong evidence that the dopamine-schizophrenia riddle has at last been solved.  

The pioneering neuroscientist Dr. Sol Snyder hailed the study as a breakthrough many decades in the making. Dr. Snyder is a distinguished service professor of neuroscience, pharmacology, and psychiatry and founder of the Department of Neuroscience at the Johns Hopkins University School of Medicine, which bears his name. He was the scientist who discovered that antipsychotic drugs work by reducing brain dopamine.

“There’s lots of muddled data indicating the relevance of dopamine and dopamine receptors in schizophrenia,” said Dr. Snyder, who was not involved in this research project. “The key thing these researchers have done is 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,” Dr. Snyder said. “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.” 

Reference: “Analysis of the caudate nucleus transcriptome in individuals with schizophrenia highlights effects of antipsychotics and new risk genes” 1 November 2022, Nature Neuroscience.
DOI: 10.1038/s41593-022-01182-7




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