A Mount Sinai stem cell model may be able to shed light on the complex biology behind certain psychiatric disorders.
In order to map disease risk variants in human neurons, researchers from the Icahn School of Medicine at Mount Sinai used a unique stem cell model. This work may help shed light on the biological mechanisms behind neuropsychiatric diseases such as autism and schizophrenia.
The group’s in vitro cellular model, which was recently published in the journal Cell Reports, was created to make it easier for future researchers to understand the disease mechanisms involving genome-wide association studies (GWAS) that characterize various risk alleles (common genetic variants conferring risk) for psychiatric disorders. This study could help develop better diagnostic methods for spotting mental problems years before patient symptoms manifest.
The research focuses on identifying cis-regulatory elements in human neurons that could be related to the heritability of psychiatric disorders. Cis-regulatory elements, which include enhancers and promoters, are non-coding DNA regions that control the expression of genes and are essential parts of the genetic regulatory network. A considerable enrichment of common variants in the cis-regulatory elements, including those linked to bipolar disorder, schizophrenia, and autism spectrum disorder, has been found in previous genetic investigations.
“While common risk variants can shed light on the underlying molecular mechanism, identifying causal variants remains challenging for scientists,” says Nan Yang, Ph.D., Assistant Professor of Neuroscience at the Icahn School of Medicine of Mount Sinai, and senior author of the study. “That’s because cis-regulatory elements, particularly the enhancers, vary across cell types and activity states. Typically, researchers can only use postmortem brain samples where the neurons are no longer active. As a result, they are likely to miss enhancers that only respond to stimulation. Our approach is to map cis-regulatory elements in human neurons derived from pluripotent stem cells. That allows us to replicate neurons in the human brain that can be affected by different types of neuropsychiatric disease, and conduct mechanistic studies of human genetic variants that are inaccessible from other types of human samples.”
Functional Genomics and the Pathophysiology of Psychiatric Diseases
In recent years, GWAS have identified hundreds of gene regions associated with psychiatric disease, though understanding disease pathophysiology has been elusive. The functional genomics approach Dr. Yang and her team developed uses stem cell models that can help resolve the impact of patient-specific variants across cell types, genetic backgrounds, and environmental conditions. This unique approach effectively lays a foundation to translate risk variants to genes, genes to pathways, and pathways to circuits that reveal the synergistic relationship between disease risk factors within and between the cell types in the brain.
“Our research attempts to decode and transfer highly complex genetic insights into medically actionable information,” says Dr. Yang, who is a member of the Black Family Stem Cell Institute, The Friedman Brain Institute, and The Ronald M. Loeb Center for Alzheimer’s Disease within the Mount Sinai Health System. “That means improving our diagnostic capabilities, predicting clinical trajectories, and identifying presymptomatic points of therapeutic intervention for psychiatric disorders.”
By characterizing cell-type specific and activity-regulated gene expression patterns in human cell-derived neurons, Dr. Yang believes her team’s study can greatly benefit the research community. “Our data can guide choosing relevant cell types of experimental conditions to further elucidate molecular mechanisms of disease across the genome,” she points out. “And that could lead to the development of biomarkers that might detect neuropsychiatric disorders years before they manifest themselves in patients, while there is still time to delay or possibly prevent them.”
Reference: “Mapping cis-regulatory elements in human neurons links psychiatric disease heritability and activity-regulated transcriptional programs” by Carlos Sanchez-Priego, Ruiqi Hu, Linda L. Boshans, Matthew Lalli, Justyna A. Janas, Sarah E. Williams, Zhiqiang Dong and Nan Yang, 31 May 2022, Cell Reports.
DOI: 10.1016/j.celrep.2022.110877
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16 Comments
Multiple Vaccine Administration in an immunocompromised Immunodeficient infant with an underdeveloped Central Nervous System and Brain, accumulative Viral/toxin ( multiple adjuvants) associated neurological infection and accumulative toxic degenerative injury- Demylinating Neuropathy.
Although it is diagnosed by a psychologist, autism is not a psychiatric disease. Autistic people can suffer psychiatric illness through repeated exposure to ableist and exclusionary environments, and this can be prevented by a change in society’s approach to disability and accessibility. Autism cannot be prevented by early intervention methods, and diagnosis can effectively be achieved by a knowledgeable and sensitive clinical practitioner who keeps aware of modern diagnostic methods, without the need for genetic testing.
Vaccines can damage genetic regulatory mechanisms but so can toxic chemicals, such as psychiatric drugs. These can not only alter the expressions of genes, but they can also alter the genes themselves.
Frank, you put that quite eloquently. Thank you
Frank, your thoughtful response is appreciated. I don’t fully agree with your conclusion, though. Having two very-late-diagnosed children on the spectrum, for whom I was not able to access services until after dx, I have often bemoaned the lack of biological testing that could potentially have assisted us sooner. Not to “prevent” the autism, but certainly to enable us to more knowledgeably advocate for the better environments you mention. Schools do not usually have such insightful professionals available, nor does it benefit them to intervene and/or assess students to end up with a dx that results in their obligation under an unfunded mandate to provide an education to such dx’d students. They get more benefit from claiming the kids are a “discipline problem”.
Autism is not a disease. This article is poorly written and coming off as not only ignorant, but also ableist.
Detecting it in our genes serves little to no purpose other than confirming diagnoses. Is the ultimate goal to detect it in fetuses and end pregnancy when detected, or perhaps to stop people who carry the genes from having children? What is the end goal?
Another unfortunate example of ignorance are the antivaxxers commenting here.
Vaccines do not cause autism, nor do they make it worse. That is a long disproven myth, and one that has caused me a lifetime of suffering. My mother was swindled into thinking vaccines would somehow make me more autistic, so I was not correctly vaccinated as a child, and now have permanent nerve damage from getting chickenpox three times. You people are absolutely disgusting and ought to keep your mouths shut before you cause any more harm to society.
Sincerely, an autistic person.
So how would you prevent Schizophrenia and autism if you discover them ahead of time before they become apparent?
As Frank said above, autism is not a psychiatric disorder. It is classed as a developmental disorder, which is different. Autistic people, especially undiagnosed adults, can end up with inappropriate psychiatric labels because of lack of understanding and, as Frank also said, develop psychiatric problems for the same reason. There is no excuse for the original paper making this confusion and little excuse for the article perpetuating it.
Are we again to argue the point of Nature or nurture? I believe all the answers to human evolution will be found just as fast as all the answers to nature and the planet have been found! And in order to solve the question of whether any disease of the brain is genetic or developed, you must first answer the ever-changing question of human Evolution! (We bring this on ourselves ALWAYS)
Autism is not a disease.
Autism is not a psychological disorder. It is neurological, it is not an illness or a disorder.
My 17 year old son has Autism. And for all who keep commenting, Autism is a nervous system disorder. I’d like to know how they intend to predict Autism years in advance when some start to show symptoms very early on. My sons Autism is on the more severe side. He started showing signs at age one and was diagnosed at age two and a half. And for the comment from the person with Autism, each case is different. The doctors I have seen, which includes a highly decorated immunologist, say autoimmune disease in the mother is the actual cause of autism. The role a vaccine plays is the severity. Because vaccines are designed to create a strong immune response a mother with an autoimmune disease should never receive one while pregnant. The vaccine can cause the mother’s immune system to produce a high number of autoantibodies that can cross the placenta and damage the developing fetuses central nervous system. I received a flu vaccine while pregnant with my autistic son, and at the time had undiagnosed Graves disease. I did not receive any vaccine with any of my other three children and they developed with no known issues. The immunologist I’ve seen has been trying for decades to get autoimmunity screening added to prenatal labs, and if a mother tests positive she should absolutely not receive any vaccines while pregnant. There is nothing that shows vaccines directly cause Autism. There is no reason an autistic person can’t receive them. My son is fully vaccinated. And as I stated before, his Autism was present at birth. Before he received the majority of his vaccines.
The Key to the Universe;
Revelation One Nineteen
Write down a brief account of your day, your problems that day, and a list of tasks to do the next day.
©1985 Paul Noblin
Read Rev.1:19 (KJV).
“Write the things which thou hast seen, and the things which are, and the things which shall be hereafter;”
Write down the past, present, and future.
Align your inside mind with the outside world (reality including Christ), and you will be one with All.
This how you fix a person’s bio-computer, like de-bugging FORTRAN.
I concur with those who are speaking from experience, as Science statistically has null factors and several other things that fall out of “normal” range to suffice as explanation in support of concept to context, or to refute such findings concerning any truth assigned to any claim in this world made by Science. Aside from those with direct inherit or direct psychological connection to the disease, (via self or close loved one) findings through a collective understanding without professional insight is intuitively distinct in our collective conscious of understanding, and those who are gifted with the intuitive insight clearly seeing the environmental causation of societal effects on every psychological condition, begin to open the minds of those who only believe “facts” through modeled tests to grand problems that can not be described under a handful of common diagnoses. Some of us can just see solutions to problems long before others can even know what is beginning to happen. My son has autism, another boy I was a live-in for had severe autism, the environmental cause of snap in developmental circuitry is found in bonding that occurs from womb to birth up until 3 years of age. The vaccines, alcoholism, so forth being blamed are only a booster to the already developing mind and dependent upon when these snaps in the child’s brain are occurring in relation to the important process of bonding and the outside introduction of foreign reactants. Mom, who has the 17 year old, do you recall any hitch in your bonding process with your child in which a strong separation with the child or significant event you recall happening in the time frame specified that could have assigned itself as a hinder to your child’s development? Individual who has autism, are there events that were occurring during the specified time frame that could have substantially affected the process of bonding with your mother? This is also true if you are a single mother, my case is more defined in that a child does need both a mother and a father to be able to prepare themselves with the correct balance of outlook on their life path, in order to balance the scales of adult life and all that the environment will deal to them. Other person’s may suffice in place during this bonding process, but once the snap has occurred who will believe that the reason ultimately lies within the parent, do we want to know this and admit that it may have been our fault? No, no, no, and our decisions we made as a parent? In the best interest of our child? Period. The answers are there, in the truth of things, not hidden in some depths of biology. Look again at every psychological factor. The development of a psychiatric, neuropathic, pathology of mind of any sort, all stems back to self and interaction with the environment, society, and expectation of self and ability of self to fulfill selfs perception. Pathologies become genetic due to the predisposition of thought processes in the host entity, it is only transmissions into the cell and DNA of the new lifeform. It will no longer be genetic when the lifeform no longer is trying to adapt to systematical early environmental disruption and is able to outgrow the intruding disposition that is changeable in it’s form at the point of learning. The genetics of this correction will no longer exist guaranteed. When in our specific DNA lineages significant disruption occurs, it assigns and codes for this disruption only because it has occurred enough times in the DNA pool to make or cause a change. The same introduction is the same pathway to reduction. Autism is to the case number it is at this current time, not becoming an issue, until it became enough of an issue that constantly would cause a disruption for the DNA to code with the easily broken transmission lines to even the smallest degree of learning and bonding introduction into the world. As a virus will mutate, our DNA adapts. Frank, you know what’s up.
As an Autistic professional, I deem this article as very poorly written and clearly the author has not updated themselves with current research. We are not in the 1940s anymore…..
Just to also add in the comments, everyone’s replies are very informative and points have been very well mentioned. However it is important to point out that labelling Autism as either mild or severe can cause generalisation of how each Autistic person present themselves, which may result in those who may not have sufficient understanding of Autism to either minimise struggles or to ignore individuals strengths.