Maria Nemchuk/Broad Institute

WHO

Dr. Steven E. Hyman

WHAT

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Hyman, a neuroscientist and former Harvard provost, now directs the Stanley Center for Psychiatric Research at the Broad Institute, which is trying to better understand and develop treatments for conditions like depression, anxiety, schizophrenia, bipolar disorder, ADHD, obsessive-compulsive disorder, and autism.

Q. There haven’t been a lot of drugs developed recently to treat these conditions.

A. The modern era of neuropsychopharmacology began brilliantly in the early 1950s. There has been enormous progress in making drugs safer and more tolerable. [But effectiveness has not improved substantially.] We’ve reached a fairly unsatisfactory place in the treatment of these devastating illnesses.

Q. Big drug companies are now getting out of the business of developing new medications for these conditions.

A. The pharmaceutical industry is basically giving up and throwing in the towel. Their exit is both a symptom of the difficulty and a problem.

Q. What does this mean for someone with one of these conditions?

A. I don’t want to be inappropriately negative. If somebody has OCD or panic disorder or depression, the combination of cognitive behavioral therapy and a well chosen SSRI-like drug [like Prozac] will, for a reasonable fraction of those patients, markedly improve their lives, although there will be side effects and residual symptoms.

Q. But it’s not good enough?

A. For people with schizophrenia and bipolar, the typical life is periods of benefits from medicines, sometimes [unmanageable symptoms] and lots of side effects. Again, it’s better than the era when symptoms were uncontrollable and people were locked away in snake-pit mental hospitals, which is still the case in too much of the developing world.

Q. Why is it so difficult to make progress against these conditions?

A. The human brain is the most challenging object that human science has ever undertaken in its complexity, diversity person-to-person; it is relatively unique in nature and hidden inviolably behind a bony skull. When we see the human brain, it is indirectly through imaging. And animal models of human behavior, the classic rodent models, have been poor as real disease models. That’s one of the reasons the pharmaceutical industry is exiting [drug development for these conditions]. They don’t believe there’s an animal model of schizophrenia or depression that would predict the efficacy of a new class of compounds.

Q. So, what progress can you make at the Broad Institute, which is known for its expertise in genetics?

A. One of the clues to these disorders is that they run with great strength in families. You’ll have a family with schizophrenia, but there will be people in the family who also have mood disorders. What we are learning is that the genetic contributors to autism, to schizophrenia, to bipolar, to ADHD, to abnormal brain development, result from many, many different genes – maybe many hundreds of genes in aggregate. Many of these genes are shared across different diagnoses.

Q. The environment plays a role, too, right?

A. The genes do not act alone. In schizophrenia, your genes are not your fate. Probably the factors which influence [brain development] are environmental, but probably relatively physical parts of the environment, like maternal nutrition. Some people think that the immune system may play a role. And some of it may just be bad luck.

Q. You’ve had quite a varied career, from basic neuroscience to head of the National Institute of Mental Health, to Harvard provost, and now back to science.

A. I think this is what I should be doing. This is what I believe in – these kinds of interdisciplinary institutions in engagement with the private sector. To be surrounded by such brilliant young people is an enormous tonic. One of the reasons I’m so interested in these disorders is because these are the great destroyers of human potential.

Karen Weintraub