What is the latest on genetic inheritance of obsessive-compulsive disorder?

-An undergraduate from California

June 23, 2010

Some people feel like they need to wash their hands over and over. Or they might be afraid of odd numbers. Or maybe they are always worried they left the stove on and have to check it twelve times.

These people have something called obsessive-compulsive disorder (OCD). And they aren't alone. Experts think that around 3% of people in the world have it.

Many of these people also have something else in common. They were predisposed to getting OCD because of the DNA they got from their parents.

Scientists have found that OCD tends to run in families. Somewhere between 20 and 35% of kids diagnosed with OCD are related to someone with OCD.*

The fact that a kid with OCD is more likely to have a relative with OCD suggests that having OCD is at least partly genetic. In fact, scientists agree that 45-65% of OCD is due to the genes we have.

What I want to do with the rest of the answer is to talk about how scientists sort out how genetic a particular disease is. Then I'll talk about what has been found about the genes involved in OCD.

Studying OCD in Twins and Families

One way scientists figure out whether something is genetic is by studying identical twins. These twins have the exact same DNA. So if a disease is 100% due to genes, it means that if one twin has it, the other will twin always have it too. (Click here for more on twin studies.)

It's not quite that simple for OCD though. If one twin has OCD, her identical twin sister only has an 80-87% chance of also having OCD. So it looks like genes are likely a big part of OCD, but they aren't the whole story. The rest of the story is probably things like environment and upbringing.

But wait, you might say, don't identical twins usually grow up in the same house? And eat the same food? And get treated the same by their parents? How do we know for sure that the 87% chance isn't all because of non-genetic things?

Scientists answer these questions by also studying fraternal twins. These twins only share about half their DNA (the same amount as any two siblings), but have the same environment. If environment is the whole story, then the identical and fraternal twin studies should give about the same result. But they don't!

Scientists found that in fraternal twins, if one twin has OCD, the other twin only has a 47-50% chance of having it. If environment was all that mattered, that number would be closer to the identical twin numbers. So OCD must depend on both genetic and other factors.

How do we find out what genes are involved, then? One way is to compare the DNA of family members with and without OCD. If a particular difference in DNA is found more often in family members with OCD than in those without it, then that difference might be involved with OCD. (Click here for some details on how this kind of study is done.)

Sure enough, a few genes look like good suspects, since changes to those genes tend to be found more often in people with OCD. It turns out that a couple of these genes are involved in how nerve cells talk to each other. Which makes sense, since messing with the connections between nerve cells in your brain can cause changes in thoughts or behavior.

Your Brain Plays "Telephone"

The job of your nerve cells is to send messages back and forth like a telephone wire. But nerves aren't a single string -- they're made of lots of interconnected cells. So they act more like the game telephone, where one person whispers a message to the next, and it's passed down to the end of the line one person at a time.

Nerve cells don't actually whisper to each other, but they have lots of ways of communicating. Instead of words, the "message" is passed by chemicals called neurotransmitters that are sent by one cell to the next in line.

These chemicals are sent out by one nerve cell into the space between it and the next cell. The next cell in line gets the message once those chemicals get to it from across the gap. Then that nerve cell releases a chemical toward the next nerve cell so it gets the message. And so on.

It's important that the right amount of chemical is sent or the message might be heard wrong. Think whispering "fire" when the house is on fire, or shouting during silent reading in school.

A key chemical involved in OCD is called serotonin. And a key gene for this process is hSERT.

hSERT has the instructions for making a serotonin transporter. The transporter's job is to sop up extra serotonin after a nerve spits it toward the next nerve cell in line. In some people with OCD, hSERT works too fast, and may collect all the serotonin before the next cell has even heard the signal! Their nerves are whispering when they should be speaking out loud.

One type of drug used to treat people with OCD slows down the collection of serotonin by transporters like hSERT. This means that serotonin stays in the space between the cells longer and increases the chances that the second cell will get the message. Which helps prevent some OCD symptoms.

OCD Is Very Complicated

As it turns out, not all people with OCD are helped by this kind of drug. Scientists don't know exactly why that is, but as usual they have lots of ideas.

It could be that there is more than one way to get OCD. In other words, serotonin may not be the only culprit.

Scientists have found that another gene called SLC1A1 might be involved. This gene is similar to hSERT, but is in charge of soaking up a different neurotransmitter called glutamate. A drug that targets serotonin won't have much effect in people who have OCD because of certain differences in this gene.

And there could be lots of other reasons. OCD isn't like chicken pox, where the disease is diagnosed because we know what causes it and what it looks like. A person is diagnosed with OCD because of certain things they do and think. So there's no physical evidence like a specific gene or a change in how they look.

So it's possible that there are different types of OCD that have different causes. There may be lots of different things that cause the same symptoms! Some types could depend more on genes (or on different genes), and others could depend more on environmental causes. And each of these different types could need different kinds of drugs or treatment.

Scientists have made a lot of progress in figuring out what might cause OCD, but it doesn't look like they've found "The Answer" just yet. But they're still hard at work learning more about OCD and about how to help people with OCD to improve their lives.

*Of course, these statistics are based on diagnosed cases. There may be a lot more people in the world who have OCD but don't know it, so these numbers could be much higher in reality


A great explanation of OCD.

Robin Trujillo, Stanford University

Studying twins can help tell if something is genetic, environmental or both.

OCD may come from some nerves whispering when they should be shouting.








Neurotransmitters take a message from one nerve cell to the next in line.