Pinpointing genetic links to schizophrenia may open doors to better treatment

JUDY WOODRUFF: Finally tonight: understanding the connections between human genetics and schizophrenia.

It's part of our series on the science of the brain. Tonight, we look at a study published this week, the largest ever of schizophrenia patients. There are more than three million of them in the U.S. The study found that perhaps more than 100 genes were associated with the condition. Genetics has long been assumed to play a role.

But for the first time, researchers found genes in the immune system are among those involved. Patients have long awaited better treatments.

Dr. Steven Hyman is the director of the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard. His center was involved in this study. And I spoke with him yesterday.

Dr. Steven Hyman, welcome to the NewsHour.

First of all, tell us what it is like to have schizophrenia. We know that something like three million Americans suffer from this.

DR. STEVEN HYMAN, Broad Institute: That's right. It affects about 1 percent of people worldwide, including the United States.

And what patients experience is extremely distressing and also disabling. There are three kinds of symptoms. Most famously, people have what are called psychotic symptoms, hallucinations, most often hearing voices that aren't there, delusions, which are fixed false beliefs that are not culturally appropriate.

But also less well recognized are two other symptoms which contribute to disability. People have declines in their cognitive functions, things like memory, ability to pay attention, and ability to use their thoughts to control their emotions and behavior.

And then there's another cluster of symptoms called deficit symptoms, where people have what is called blunted affect. That is even something very sad might not elicit a response or something very happy. They lose motivation.

The drugs we have today only treat the psychotic symptoms, and do that incompletely, and really don't touch the other two sets of symptoms, leaving patients very disabled and great costs and challenges of course to families and society.

JUDY WOODRUFF: Well, we know this was a large study, as they go. What are the main findings here?

DR. STEVEN HYMAN: So the most important finding is that this is the beginning of identifying specific variations in genes that contribute to the causes of schizophrenia.

And I think it's really important, just to put in context, that not very many years ago, schizophrenia was considered an absolutely mysterious disease. When I began my psychiatric training, there were many people who thought that the way parents, especially mothers, behaved toward children psychologically was the cause of this illness.

We now know that it is largely caused by genes. Genes are not fate for any of these diseases, but genes are very influential. But there's a big step between knowing that genes are important and actually finding the genes that are involved. And in this study, which was a large international study, 108 separate locations in the genome were with certainty associated with the causes of schizophrenia.

JUDY WOODRUFF: So, you're saying a connection, but not in every case.

For example, you're saying the genes — I know the studies show that genes that affect the immune system also show up in individuals with schizophrenia. So that means these genetic markings don't in every case indicate causation.

DR. STEVEN HYMAN: Right. So, that's exactly right.

Like most chronic common human illnesses, where genes are highly influential — and they're influential in everybody — it's just as you suggest. Different combinations of genes matter in different individuals, and we're not yet in a stage — in a state to say, you know, these 20 genes or these 30 genes matter to this person.

But what we can do is begin to say, you know, in the population, there are now 108 known places in the genome which point us towards genes that are involved in causation. And, as you suggest, while most are in the nervous system, some of them, very intriguingly, point to the immune system as being involved.

JUDY WOODRUFF: And you were saying earlier that it's been difficult to find medications to successfully treat schizophrenia, so why then are these findings so important?

DR. STEVEN HYMAN: Well, that's what — that's really — the whole reason to do these studies is ultimately to improve diagnosis and to develop treatment.

The first drugs to treat schizophrenia and, in fact, to treat, you know, depression and other psychiatric illnesses were discovered by serendipity, by prepared minds seeing unexpected effects of drugs on human beings. And the antipsychotic drugs that we use to treat schizophrenia stemmed from the discoveries made in the 1950s.

Tragically, there's been no fundamental improvement on these drugs. So, we have been using, with improvements in terms of side effects and safety, fundamentally the same kinds of medications for more than half-a-century. And, indeed, it's been so difficult because the human brain is not well modeled in animals, because it's hidden behind our hard and opaque skulls. It's been very hard to get real clues.

And drugs companies have been existing psychiatry, leaving patients with less and less hope. The key here is, if as a gene is involved causing an illness, in some sense, it's a clue to what is going wrong, in this case in the brain, maybe the immune system, in the disease processes.

And, ultimately, as we add up these clues, people developing therapies, ultimately pharmaceutical companies, can say, OK, we're going to target this gene, we're going to target this pathway. And we hope, we very much hope that these clues will begin to bring industry back into the game, because, ultimately, we academics are going to do a lot of research, but it's industry that has got to make the medicines.

JUDY WOODRUFF: But, just quickly, I hear you saying, Dr. Hyman, it may be several years before these finding translate into new treatment.

DR. STEVEN HYMAN: Yes, unfortunately, because we're all impatient, but no one is more impatient than those affected by these terrible illnesses and their families.

But the reality is that these are very early clues. They are real clues. They are not going to go away. They are going to lead us to — in important directions, but it will take many, many years to turn these into more useful treatments.

JUDY WOODRUFF: Dr. Steven Hyman, we thank you very much for talking with us.

DR. STEVEN HYMAN: My pleasure.

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