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Developing therapies for troubled brains

Dr. Horacio Capote is enamored with the troubled brain. The medical director of the Division of Neuropsychology at the Dent Neurologic Institute has a patient load that includes those with Alzheimer’s and Parkinson’s diseases, as well as a variety of mood disorders.

Depression alone is perplexing, he said, and so different from a condition like diabetes, which can be diagnosed with a simple blood test.

“We’re getting there,” he said, “but we don’t have it yet, so we lump different symptoms together and put them in these categories and make believe to ourselves that the DSM (mental health disorders guide) is the bible. In reality, underneath any one diagnosis, there’s a lot of heterogeneity. It’s not homogeneous. So as we begin to parse out the different subgroups of mental illness … I think we’ll be able to direct our treatments toward those subgroups.”

Capote, 54, of Amherst, is Cuban-born and grew up in Miami. He met his wife, Eileen, a Poughkeepsie native, while the two were in medical school at Universidad Autonoma de Guadalajara, in Mexico. They came to Buffalo for their residencies and stayed. His wife is an Amherst-based pediatrician.

Capote spends workdays at the Dent building in Amherst, conducting research and treating patients. He and his staff of two fellow doctors and four physician assistants use several ways to tackle depression untouched or barely helped by prescription medications. They include Electroconvulsive Therapy (ECT), a procedure that produces controlled seizures in a patient’s brain to clear the dark clouds of the disorder, and Transcranial Magnetic Stimulation (TMS), which uses focused magnetic pulses to stimulate key neurons to do the same.

“We also have probably two dozen patients with vagul nerve stimulators,” he said. “It’s a little pacemaker connected to the vagus nerve (that goes from your brainstem to your chest) and every five minutes electrical impulses get sent to the brain for 30 seconds. It’s like a pacemaker for the brain. We have a couple of patients with deep brain stimulators, who have electrodes inside the brain bilaterally. They have depression that is very difficult to treat. And we are working on an intravenous ketamine program.

Q. What will the ketamine program be like?

Ketamine is an anesthetic. There have been studies at the National Institutes of Health where they’ve seen that you can acutely reverse suicidal thoughts and depression. It’s a 45-minute IV. It’s a little bit like ECT. The beauty of ketamine seems to be that folks will or won’t respond in one or two treatments. If you’re a responder, the full course typically takes six treatments (about half as many as with ECT). If not, you stop right there, which is really impressive.

In the future, techniques like genotyping and ways of differentiating the subgroups within depression will be valuable to us in terms of steering patients into one or all of these differing modalities.

Q. How does the Mexican health care system differ from what you’ve experienced in the U.S.?

We were exposed to it but in a way, we were sequestered. We were in a program made for North Americans. There were Canadians there, as well. We didn’t get the complete effect but were able to sort of observe it. If you have money, it works. If you don’t, it doesn’t. There’s a lot more parasitic infections. I ran a free student-run clinic called Our Lady of Guadalupe and we had jars of different worms that had been taken out of different people. Yucky, but when you’re a medical student you’re interested in that stuff.

Q. Why psychiatry?

One of the most unique human activities is to think and to feel, so to me the brain is the most fascinating area. It’s certainly the area that I discovered I had the most facility in. I originally thought I wanted to be a surgeon and realized I’d probably be run of the mill. Here’s an area I can excel and really have passion and involve myself in. I’m sure an orthopedist might argue with me, but after a while, one broken arm looks like the next. Five different people with depression are five worlds. There are so many factors involved, so many intracacies on micro and macro levels that it keeps it challenging and certainly interesting.

Q. What is the difference between psychiatry and neuropsychiatry?

There are special boards and certifications. I have certification in behavioral neurology and neuropsychiatry. It is a more brain-based approach to behavioral health and sometimes we would tend to get more of the combined patient – for instance, the brain tumor patient who happens to be hallucinating as a result.

Q. Any other patients and what might be the range of the caseload?

A good quantity are mood disorder patients, whether they be unipolor or bipolar depression. A great many of all of these people have comorbid generalized anxiety, worrying. Somewhere between a fifth and a quarter have some sort of dementia or cognitive issue. In between you’d fit in psychosis, whether it be schizophrenia or something else. It turns out that Parkinson’s related psychosis is an important issue. One of the interesting things about Parkinson’s is that, although we focus on the movement disorder as the major feature of the disease, when you talk to Parkinson’s patients they will tell you it’s the non-movement issues that really impact their quality of life: the comorbid depression, the hallucinations.

Q. For anybody who’s been living under a rock, your work seems to demonstrate that mental illness is a medical issue.

Yes. Studies at the NIMH show you can have a person with bipolar depression, a person with unipolar depression and a gifted actor and you can look at their PET scans and tell who’s who. An actor would have an increase in brain activity because it takes all that mental energy to put on a facade.

Q. What’s the staff like?

We have two other docs. God willing, another will be coming soon. And we have four physicians assistants, along with support staff. We have two doctorates of pharmacology who are invaluable. Their major role is coordinating all the research but clinically they can be invaluable, especially with the elderly, but it could be anyone. Say you’ve got a patient on 20 meds and you’re wondering, “Do we really need all this and what is the interaction between all these medications?” You can have a consultation with a doctorate in pharmacology who can help parse all these things out.

Q. There are two parts to treatment of mental illness: behavioral therapy and medication/medical procedures. Should they work together?

Absolutely. Up to now, we’ve referred out for behavioral therapy but we’re in the process of beginning to establish our own psychotherapuetic services right here. Hopefully by next year that should be in place. It’s certainly been shown that psychotherapy is a drug. Eric Kandel, when he won the Nobel prize for (biology for) his work with dopamine and learning, stated that one day we’d be able to do a scan and show that good therapy was working. Subsequent to that, in obsessive compulsive disorder, for instance, with half the people treated with medication, half the patients treated with cognitive behavioral therapy, the ones who improved in both groups had equal changes in their caudate nucleus metabolism and equal changes in their brain scans. But both together should be synergistic.

I like to make the comparison with diabetes. Do you have a guy who takes his insulin and is OK? Sure. But the guy who takes the insulin, learns nutrition, does exercise, does yoga or tai chi, and puts it all together, that person thrives. I like to say, “If it’s good for the ticker, it’s good for the noggin.” A Mediterranean diet, which is very high in antioxidants, is good for the brain. We talk about psychotherapy. We talk about neuroplasticity: engaging the brain in new activity that forces it to make new connections. That could be learning to play the harmonica or learning to brush your teeth with your non-dominant hand. Things that are different for you challenge the brain a little bit. It forces the brain to make new synaptic connections and that makes it more resilient.

Q. You have feet both in addictions and mental health treatment. How do these differ and how are they similar?

Addiction is a behavioral disorder. Quite often it’s there in the background and we can choose to see it or ignore it in many disorders. For instance, in bipolar disorder, 65 percent of the time, a person will have an issue of abuse at some point in their life. It’s there to be dealt with and certainly can throw a monky wrench into someone’s overall treatment. It could be the sole subject of treatment. So it’s ubiquitous. If it’s there, we have to be honest and open our eyes to it and see it for what it is, hopefully without judgement, and address it.

Q. How do you treat someone with addiction who also has a mental disorder?

It varies from person to person. For instance, if you have severe mental illness plus an addiction or abuse problem, we should employ a different timeline. A patient with schizphrenia but definition will be cognitively fragmented. A lot of addiction treatment is cognitively taxing. So rather that expect an individual to start to show some results and get better in six months, we should really be thinking two years. We could spend several months just establishing trust and rapport.

Q. What are the long-term prospects for people treated for addiction and mental illness? What must they do to make sure they help themselves after significant episodes?

Regular maintenance activities. Not letting themselves be lured into the idea that everything is OK again. To remember that this is much more like diabetes than an infection. An infection you treat with antibiotics and it’s over. Your done. This is very typically an ongoing illness that you manage and don’t cure. Understanding this is an issue of management for the long haul is important.


On the Web: Read about a promising new Alzheimer’s treatment trial at