Most Common Psychiatric Disorders Share Genetic Roots

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Illustration of the double helix structure of DNA; suagr phosphate backbones in antiparallel coil with coding nucleobases attached in between

Diverse mental illnesses may actually represent variations on a common theme rather than separate disorders.

A quiet autistic child is certainly unlike a manic adult with bipolar disorder, or a person suffering a bout of paranoia due to schizophrenia, but new research suggests that these varied conditions may be more alike than previously thought.

Researchers analyzed genetic data from some 33,000 people of European descent who had either autism, schizophrenia, major depression, bipolar disorder or attention deficit/ hyperactivity disorder (ADHD).  They were compared with nearly 28,000 unaffected controls. Scanning the entire genome, the scientists found variants in four different regions that affected risk for all or most of these conditions.

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The results suggest that it may be possible to move away from classifying psychiatric disorders primarily based on profiles of symptoms and focus on biological causes of mental illness, according to the study’s lead author, Dr. Jordan Smoller of Massachusetts General Hospital.

“This was a really well done study and the best yet at trying to address the question of whether there might be common processes underlying what we have long though to be very different psychiatric conditions,” says Dr. Bryan King, director of child and adolescent psychiatry at the University of Washington and Seattle Children’s Hospital, who was not associated with the research.

“It’s really very exciting to see scientists from 19 countries bringing together data on tens of thousands of different patients to ask questions about the genetic architecture of these various mental illnesses,” says Dr. Thomas Insel, director of the National Institute on Mental Health (NIMH), which provided some of the funding for the research that was published in The Lancet.

Two of the four variants are involved in regulating calcium channels, which are crucial for the proper functioning of nerve cells.  “They are fundamental to the working of neurons,” says King. “Calcium and chloride balance is critical to the proper electrical activity of the neuron.”

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The findings could help explain many apparently odd connections between psychiatric disorders.  For example, autism was once known as childhood schizophrenia, in part because people with both conditions seem to be mesmerized by their own internal worlds.  Conversely, some of the adults labeled as having schizophrenia in the past might have been diagnosed with autism instead if their childhood history had been known.

“In families with bipolar disorder, the risk of schizophrenia is increased, so we knew that there was some overlap, but it was not clear to what extent,” says Thomas Lehner, a co-author of the study and branch chief of genomics for the NIMH.

The new knowledge of the common gene-based roots could help to tease apart some of these overlapping symptoms and diagnoses. Some of the variants the researchers found are more common in patients with depression, for example, while others are more prevalent among those with schizophrenia. But without biological tests to differentiate between disorders, until now, symptoms have been the only guide to classifying psychiatric conditions. To make matters worse, many people have symptoms of more than one disorder and many disorders share some of the same symptoms.

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Insel compares the situation to diagnosing people with malaria, the flu and a bacterial infection as having the same disease.  “All of them have a fever of about 103 and they look really miserable, with sweating and muscle aches. Under the DSM, they’d all have same thing,” he says, noting that this does not mean that psychiatric disorders are any less real, just that we don’t yet have precise ways of characterizing them.

The genetic revelations are only a first step, however. Scientists still have to figure out why a problem with calcium channels might lead to autism in one case and bipolar disorder in another. And the knowledge may lead to a re-thinking of at least the five psychiatric conditions found to share some genetic changes.

“When we say with the DSM that this person has ADHD and autism [together],  at some level we’re saying those two entities are somehow distinct,” says King, “Instead, the truth may very well be, at least in some instances, that ADHD manifestations and autism manifestations are part of some overarching problem that’s neither one nor the other.”

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Insel and Lehner stress that none of the genetic variants the scientists identified are a major cause of any of the disorders.  “This confers a very small amount of risk,” says Insel, “If you went out and had your genotype looked at and you had this particular variant, does that mean that you have a greater likelihood of schizophrenia? Only in a very, very tiny way, maybe a 10% increase in risk.”

But understanding the places where development may be going astray or how circuitry may be disrupted could eventually provide leads for better treatments. “The shared biology opens the door to the exploration of novel treatment approaches and early interventions,” says King.

To capitalize on such approaches, the NIMH is developing the Research Domain Criteria (RDoC), an alternative system for classifying psychiatric illness that considers symptoms in many different ways. Anxiety, for example, may involve a problem with a fear circuit that in turn is related to variants of a specific gene that is activated, or triggered by an early childhood experience of terror.  Genetic studies that identify common genes that psychiatric conditions share could help to fill in such multi-dimensional views of mental illness.  “RDoc is saying let’s build in many levels of information,” says Insel, “We know that the DSM approach is not the way to understand these disorders. It may be a way to bill for them, but it’s not a way to develop science or even identify who should get what treatment.”

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That understanding could lead to a more biology-based understanding that psychiatric disorders that many experts welcome. Factoring in the effect that genes have in dialing up or turning down risk may prove invaluable in improving our understanding of how the brain develops, and how we might intervene when that process goes awry.

20 comments
bordermindejavu
bordermindejavu

@time @timehealthland This is new news? Maybe it's family structure and old news...

WIBeetle
WIBeetle

@TIME @timehealthland so pretty much everyone probably has some degree! #stopthestigma

megzinki
megzinki

“@TIME: Most common psychiatric disorders share genetic roots | http://t.co/W7EWuLCjqw (via @TIMEHealthland)” ...really interesting article!

ian_ondine
ian_ondine

@TIME @TIMEHealthland Really?! I'd never have guessed.

raygibbs1
raygibbs1

@TIME @TIMEHealthland fated we . important post . thanks friends .

Kokyu5
Kokyu5

@TIME @TIMEHealthland If mental disorders are caused by faulty genes, then they are not mental disorders, they are genetic/bodily disorders.

JujuCosta
JujuCosta

so, there should be no law, if everyone is responsible for their own brain

people can deal with anything if they r HEATHY and robotic unpredispositionated to any circumstances

JujuCosta
JujuCosta

now people r gonna blame the victims

JujuCosta
JujuCosta

everyone have potentions,,, but circunstances mold them

i think when its about kids, you cant expect them to be responsible for how they feel

for solving situations out of their reach, without letting it affect their growing brain

its not just predisposition

plus, they shouldve done it to babies, an thenlater in adulhood compare the genes

because genes can transform, and everyone knows it

because we r not only how we r born, bout the enviroment molds us in a way too, even without predispositions

like cancer, cancer is not there, is it in the genes? it can appears.. if u have a certain lifestyle or for genetic reasons

even without non historical in the family

MillyLanders
MillyLanders

This published finding? really disturbs me because I am a grandmother to a now five year old grand daughter that is autistic. I never thought of autism being  psychiatric related. She is nonverbal and has a seizure disorder. She has gastrointestinal issues, transitional issues...the usual issues associated with a child with autism. The scientists that publish this research do a disservice to themselves and to the millions of parents and grandparents that love these children.

ellenbep
ellenbep

This is an interesting study.

Current advances in neurobiology keep revealing new knowledge about the human genome.

I can remember when mental illnesses and their causes were considered environmental.

Now, it seems that the long standing nature/vs./nurture debate is leaning 

to neurobiological causes. This is exciting news if proven conclusively since it

may mean gene remediation will render these debilitating illnesses to history.


Peace_2_All
Peace_2_All

@MillyLanders 

First... let me say how sorry I am about your Grand daughter's condition.  It must be really tough.  I have a cousin who has been autistic all his life.  So I understand to a certain extent.

Respectfully, however, I don't understand your posting in how science is starting to target even further many of these disorders, that you find it disturbing and doing "millions of parents and grandparents a a disservice, etc..." ??

Please elaborate as to where you are coming from on this.

Peace...