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
- Auburn couple says social isolation has caused wife's Alzheimer's disease to progresson June 24, 2020 at 9:37 pm
Whether they’re living at home or in long term care facilities, families of Alzheimer’s patients say they’re seeing the disease progress faster in isolation.
- Indirect adverse effects of COVID-19 on children and youth's mental, physical healthon June 24, 2020 at 9:21 pm
Despite reports that children and young people may be less likely to get coronavirus disease 2019 (COVID-19) than older adults, there may be substantial indirect adverse effects of the disease on ...
- Dementia May Develop 7 Years Earlier for Adults with Inflammatory Bowel Diseaseon June 24, 2020 at 5:00 pm
Older adults with chronic inflammation of the gastrointestinal tract may develop dementia more than seven years earlier than those without the condition.
- Mental health spending may be up because of COVID-19on June 24, 2020 at 3:38 pm
The COVID-19 pandemic has upended health care spending by employers who offer health insurance. They may save money this year, as some employees put off care because of the pandemic. But they appear ...
- COVID's Drain on Mental Health; Struggle for New Momson June 24, 2020 at 11:02 am
And such unique pandemic-related stressors and isolation have proved particularly difficult for new moms, as more than 70% of pregnant and new moms reported anxiety and more than 40% reported ...
- Well-being and mental health amid COVID-19: Differences in resilience across minorities and whiteson June 24, 2020 at 10:19 am
The COVID-19 pandemic was an exponential shock to much of the U.S. population and also exposed deep vulnerabilities associated with our fragmented health care system and our extreme income inequality.
- Genomind Mental Health Map: First-Ever Consumer DNA Test to Unlock the Connection Between Genetics and Mental Wellness-Related Behavioral Tendencies, Offers “How-To ...on June 24, 2020 at 5:56 am
Genomind®, a leading mental health company, today announced the official launch of Genomind® Mental Health Map™. This unique product is the most compr ...
- How To Protect Your Mental Health Even While Watching The Newson June 23, 2020 at 8:11 pm
Balancing staying informed by watching the news and protecting your mental health, especially during a crisis, can feel challenging. How do you know if you have a problem and, then, if you do, how do ...
- MS Disease Activity Tied to Comorbiditieson June 23, 2020 at 1:34 pm
Of 959 trial participants included in the analysis, 55.1% had comorbidities at enrollment, they wrote in Neurology. "Even though trials often exclude people with serious comorbid ...
- California woman who fatally stabbed a Grafton man has been found not guilty by reason of mental diseaseon June 19, 2020 at 6:23 am
A California teenager who fatally stabbed a Grafton man in May 2019 will be sentenced to a psychiatric facility, after being found not guilty by reason of mental disease or defect. Crystal Gutierrez, ...
via Bing News