UCLA researchers, in global collaboration, gain new understanding of brain architecture of autism, schizophrenia
Since the completion of the groundbreaking Human Genome Project in 2003, researchers have discovered changes to hundreds of parts of DNA, called genetic variants, that are associated with autism spectrum disorder, schizophrenia and other psychiatric diseases. Now, a new, large-scale study has linked many of those changes in DNA to their molecular effects in the brain, revealing for the first time mechanisms behind those diseases.
In 10 studies published today in Science and two related journals, UCLA researchers and collaborators from more than a dozen other institutions around the world provide a comprehensive data set on the molecular workings of the brain. The findings offer a roadmap for development of a new generation of therapies for psychiatric conditions.
“This work provides several missing links necessary for understanding the mechanisms of psychiatric diseases,” said Dr. Daniel Geschwind, a senior author of two of the papers, and the Gordon and Virginia MacDonald Distinguished Professor of Human Genetics at the David Geffen School of Medicine at UCLA.
During the past decade, scientists have compared the genetics of people with psychiatric diseases with those of healthy individuals, seeking genes that have different sequences between the two groups. Often, however, the findings raised more questions than answers. Scientists not only discovered genes linked to the diseases, but they also uncovered hundreds of areas of DNA found in between genes, called regulatory DNA, that also seemed to have an association.
Scientists know those sections of DNA can control when, where and how genes are turned on and off. But figuring out which regulatory region affect which genes — and therefore the RNA and proteins encoded by those genes — is not straightforward.
In 2015, researchers from UCLA and other institutions from around the world came together in a multidisciplinary group called the PsychENCODE Consortium to study in more detail the brain’s regulatory DNA. An earlier project, known as ENCODE, already had uncovered the roles of sections of regulatory DNA, but it was clear that those roles might be different in the brain than in other organs.
To date, PsychENCODE has analyzed not just genetic variants linked to psychiatric diseases, but also patterns of RNA and proteins in 2,188 brain tissue samples from people with and without psychiatric disorders.
In one of the new papers, Geschwind and collaborators write that the new data helps explain the roles of tens of thousands of sections of regulatory DNA in affecting RNA and proteins in the brain. The data also reveals which genes are most often expressed at the same time as each other, suggesting new biological processes and pathways. The data set — essentially a detailed model of the molecular workings of the human brain — is now available to other scientists as a starting point for research on the mechanisms of disease and potential drug targets.
“This resource is so vast that you can start by choosing an interesting disease-associated genetic variant and begin digging into that and discovering how it impacts molecular networks in the brain,” Geschwind said. “Having robust data of this scope provides a foundation for countless new studies.”
In a second paper, Geschwind, first author Dr. Michael Gandal, assistant professor of psychiatry and biobehavioral sciences at the Geffen School of Medicine, and other collaborators studied nearly 1,700 samples of brain tissue from multiple brain banks around the country; they discovered thousands of RNA molecules that are either spliced differently — with different sections of genetic material — or present at higher or lower levels in the brains of people with autism spectrum disorder, schizophrenia and bipolar disorder.
“You can’t look at the brain under a microscope and see substantial differences in these disorders,” Gandal said. “But we’ve now shown that if you look finely at patterns of how genes are expressed, you see pathways [the communication paths that neurons travel] that are clearly dysregulated.”
Among the surprises in the data is that altered levels of RNA appear to be linked to changes in the brain’s immune system in people with schizophrenia, autism spectrum disorder and bipolar disorder.
The study also showed the importance of considering which individual cell types within the brain were involved when parsing the RNA data. In some cases, alternately spliced RNA was linked to disease but only when the RNA was found in certain cell types and not others. Finally, new genes were implicated in the diseases based on the RNA results; five were linked to autism spectrum disorder, 11 to bipolar disorder, and 56 to schizophrenia.
In addition to the compelling findings already revealed based on the new data, Gandal said he is even more optimistic about what the data will help researchers do in the future.
“This is the tip of the iceberg,” Gandal said. “The ability to compile together 2,000 brains has been revolutionary in terms of revealing new genetic mechanisms, but it also points to how much we don’t know.”
The Latest on: Psychiatric diseases
via Google News
The Latest on: Psychiatric diseases
- Destigmatizing mental health for women of color on February 18, 2019 at 12:49 pm
“Anyone can experience mental illness. There is no group ... at higher rates than most other illnesses, including heart disease, diabetes and cancer.” That’s especially alarming for minority ... […]
- Zane Trace working to break the mental health stigma on February 18, 2019 at 12:09 pm
Now, after educating himself, King knows that depression and other mental health disorders are a disease. To him, the Signs of Suicide program is a directed step by the school to assist kids with unde... […]
- How Mental Health Charity Strongminds Is Disrupting Depression In Africa on February 18, 2019 at 4:44 am
I have one final consideration: I certainly don’t want to make a “ranking” of mental diseases but depression seems relatively less debilitating than schizophrenia. And I guess that people in the schiz... […]
- Looking behind a rare brain disease for clues to treat more common mental disorders on February 18, 2019 at 3:08 am
Researchers have reported for the first time the mechanism behind a very rare brain syndrome called disproportionate pontine and cerebellar hypoplasia (MICPCH), which causes microcephaly. […]
- The need for more in-patient psychiatric beds on February 17, 2019 at 3:15 pm
This IMD (Institutions of Mental Disease) exclusion has made it financially beneficial for states to have as few public psychiatric beds as possible and to push our most ill toward insufficient outpat... […]
- KT for Good: How lifestyle diseases take a toll on mental health on February 17, 2019 at 12:20 am
A healthy you means a healthy society. Khaleej Times' latest campaign under the 'KT For Good' umbrella highlights common lifestyle diseases. In Part 8 of our series, Dr Anil Kumar P N tackles how chro... […]
- Cudahy man accused of killing landlord over $30 rent increase found not guilty by mental disease/defect on February 15, 2019 at 1:59 pm
Cudahy man accused of killing landlord over $30 rent increase found not guilty by mental disease/defect The Cudahy man accused of killing his landlord possibly over a $30 rent increase in March 2018 w... […]
- US Life Expectancy: The Mental Health Perspective on February 15, 2019 at 6:32 am
More recently however, the body of literature related to life expectancy of patients with mental illness has been increasing. In particular, there has been growing concern surrounding opioid abuse, su... […]
- The psychiatric implications of thyroid disease on February 15, 2019 at 5:44 am
Both hypothyroidism and hyperthyroidism can cause psychotic symptoms such as delusions and hallucinations, plus depression Psychiatric conditions such as depression and anxiety disorders are often mis... […]
- Facing Heart Disease: A Guide for Psychiatric Clinicians on February 12, 2019 at 1:54 pm
Heart disease is a chronic condition that affects millions of people worldwide. Research has led to improvements in treatment and increased longevity for patients. Heart disease is comorbid with many ... […]
via Bing News