University Times

If you catch a cold, you can treat it with a general, multi-symptom medication or you can take different drugs for specific symptoms: a cough suppressant, aspirin for a headache, an antihistamine for sneezing and congestion.

Or, you can simply rest and drink plenty of liquids, and the cold eventually will go away.

Treatment options aren’t nearly so precise or predictable for the debilitating mental illness of schizophrenia, which afflicts an estimated 1 percent of the population of the United States alone.

“Our approach toward treating schizophrenia, which is far more complex and severe than a common cold, has been almost unbelievably naïve,” says Bita Moghaddam, a Pitt professor of neuroscience. “Basically, we’re still using the same one-size-fits-all, anti-psychotic drugs that we’ve been using since the late 1950s.”

These medications, called neuroleptics, block the actions of dopamine, one of the neurotransmitters that relay messages between neurons in the brain. Typically, neuroleptic drugs reduce paranoia and hallucinations but offer little or no relief from other symptoms of schizophrenia such as jumbled thoughts and social withdrawal.

Moreover, neuroleptics often cause severe side effects, including uncontrollable tremors, huge weight gains and dangerous increases in patients’ blood lipids.

Moghaddam is among a growing number of researchers who suspect that schizophrenia is, in fact, linked to disruptions in the brain’s most pervasive neurotransmitter, glutamate, and that the illness may one day be treated by glutamate-targeting drugs.

In experiments at Yale University, where Moghaddam worked before joining Pitt’s faculty this fall, she and her co-researchers showed that treating rats with a compound called LY354740 blocked schizophrenia-like behaviors that would otherwise be induced by the hallucinogenic drug phencyclidine (PCP) -— “angel dust” — while also reducing the excess release of glutamate that PCP normally elicits.

Eli Lilly & Co., which produces LY354740, plans to seek approval from the U.S. Food and Drug Administration for the compound in the next couple of years, the journal Science reported this summer. A limited clinical trial indicated that LY354740 is just as effective as benzodiazapines (a group of drugs that includes Valium) in treating generalized anxiety disorder, without the side effects or withdrawal associated with benzodiazapines.

“Even if this particular drug doesn’t prove to be effective in treating schizophrenia, I personally feel very excited that we’re experimenting with this class of [glutamate-targeting] drugs,” Moghaddam says. “Because, in order to improve the treatment of schizophrenia we need to go beyond these older medications that have a lot of bad side effects and don’t treat many of the devastating symptoms of the disease.”

Moghaddam predicts that, in the next decade, scientists will gain greater understanding of the biological sources of schizophrenia’s various symptoms and begin treating them individually. “Many people with schizophrenia suffer from delusions and hallucinations, but some of these people exhibit serious cognitive symptoms” — such as poor short-term memory and inability to make decisions — “and others do not. It makes no sense to be giving those people the same, identical drugs, but that’s exactly what we’ve been doing.”

Moghaddam is the first faculty member that Pitt’s neuroscience department has recruited as a full professor. N. John Cooper, dean of the School of Arts and Sciences, notes: “Our Department of Neuroscience was founded in 1986, but this marks the first time that they have gone outside for a major senior person. It’s a sign of the department’s quality and maturity that they were able to attract somebody of Dr. Moghaddam’s stature.”

According to neuroscience chairperson Alan F. Sved, Moghaddam’s expertise “fits in beautifully” with that of other researchers in his department, particularly professors Anthony Grace and Susan Sesack.

Grace records the electrical activity of nerve cells in the brain believed to be linked to schizophrenia. Sesack studies how these cells are connected to one another. Moghaddam “fills a gap by adding expertise at both the neurochemical and the behavioral levels,” says Sved. “All three researchers are working on questions related to the neurobiology and neurochemistry of schizophrenia.”

They also collaborate with other colleagues from Pitt’s neuroscience and psychiatry departments through the University’s Center for the Neuroscience of Mental Disorders, which is supported by the National Institute of Mental Health.

Moghaddam is the latest distinguished neuroscientist and/or psychiatrist to leave Yale for Pitt in recent decades. Others have included Thomas P. Detre, David J. Kupfer and Edward Stricker.

“Although Yale has a tradition of excellence in the neurosciences, in the last 10 or 15 years, especially, people have been leaving out of frustration that not enough resources were being made available to them,” says Moghaddam.

“As a neuroscientist, I saw Pitt as being one of the most prestigious places I could have gone,” she says. “Between the arts and sciences and the medical school, this university has one of the largest and most prestigious groups of neuroscientists in the country, if not the world.”

And, Pitt neuroscience researchers will gain additional space in a planned addition to the Clapp-Langley-Crawford halls complex. “Nothing like that is happening at Yale,” Moghaddam points out.

And yet, she might easily have missed out on coming here. “I knew that neuroscience faculty positions were available at Pitt, but I had assumed they were for junior people,” Moghaddam recalls. However, during a scientific meeting last January a Pitt professor happened to overhear her talking about an upcoming interview at another university; the professor urged Moghaddam to visit Pittsburgh, too.

At Yale, Moghaddam didn’t do much teaching. Pitt neuroscience chairperson Sved says: “Often times, the most prominent scientists are too busy in their labs to want to be bothered about undergraduate teaching, but teaching is a real focus of our department.” Pitt is one of the few universities that offer an undergraduate degree in neuroscience.

Sved says, “I was a little hesitant about broaching the teaching question with Bita when I first met with her” for fear of discouraging her from joining his department’s faculty.

But, to Sven’s relief, Moghaddam welcomed the opportunity to teach undergrads here. “Neuroscience, I think, is the most exciting field in the sciences now,” she says. “To be able to interact with young people who want to specialize in this field is very exciting. It’s one of the things that made Pittsburgh even more special for me.”

When Moghaddam left her native Iran in the late 1970s to enroll at the University of Kansas, she planned to major in chemistry. “One day,” she says, “I happened to walk into the laboratory of a professor named Ralph ‘Buzz’ Adams, who was one of the best-known analytical chemists in the world. He had just started applying his knowledge of analytical chemistry to brain chemistry. He was very interested in schizophrenia and how thought processes work, and it was really his influence that led me to pursue research in this field.”

While doing post-doctoral work at Yale, Moghaddam came under the influence of another mentor: Patricia Goldman-Rakic, who investigated neural mechanisms in the brain that control thought and planning, reasoning and attention. Goldman-Rakic was killed in a car accident last summer; Adams died in 2002.

“My heroes are passing away one after another,” says Moghaddam, wistfully. She recognizes that she’s reached the point in her career where it’s her turn to mentor students and younger colleagues.

“I’ve traveled a lot, and it’s been amazing to me how similar people are all over the world. If more people traveled, I think we would have less conflict!” Moghaddam says, with a laugh. “It’s been very moving for me to meet young people and see in them the same aspirations, the same excitement about pursuing science, that I felt at their age.”

Moghaddam’s father is a retired judge from a small town in western Iran. Her mother, who attended college but quit working after marrying, is from Tehran. Both parents saw no conflict between the family’s Shiite Muslim faith and seeing that their two daughters got the best educations possible.

“Growing up in such a family, it was never an issue for me that you can’t accomplish something just because you’re a woman,” Moghaddam says. “My favorite line about that is something that Ann Richards, the former governor of Texas, liked to say: ‘Ginger Rogers danced as well as Fred Astaire. It’s just that she had to do everything in reverse, wearing high heels.’ In other words, anything is possible for a woman if she’s willing to put in a little more effort than a man” — although that’s not true in all countries, Moghaddam regretfully adds.

While she’s capable of describing herself, jokingly, as “a product of the Axis of Evil,” Moghaddam says seriously that she feels more American than Iranian today. She wears no headscarf, dresses stylishly and admits, “I’m about as non-religious as they come.”

As a Yale professor, Moghaddam was living in New Haven, Conn., in the aftermath of the Sept. 11, 2001, terrorist attacks but says she was never harassed for being a Middle Easterner. “One reason is that New Haven is a pretty tolerant place. Another reason,” Moghaddam suggests, smiling broadly, “is that New Haven is full of Italians, and I can kind of pass for an Italian.”

Moghaddam originally in-tended to return to Iran after completing her studies in the United States. “But then the revolution happened and I ended up staying, getting my doctorate, getting married, having children — and now, 26 years later, here I am.”

Moghaddam didn’t return to Iran until the early 1990s, when the ruling mullahs began to tolerate limited political reforms and loosening of rigid restrictions on women’s roles.

“Things are definitely getting better there,” says Moghaddam, who now visits Iran about once a year. “Of course, they could still be a lot better….”

She admits to feeling mixed emotions when she visits Iranian universities and meets women science students. “On one level, it’s very sad because I meet these very driven, hard-working young women who aspire to be first-rate scientists. But resources and opportunities are limited, and their lives are very frustrating because there’s not much they can do to get faculty positions or do laboratory work.”

And yet, there’s something in the eyes of these young Iranian women that Moghaddam finds uplifting. “It’s the same look that I’ve seen in the eyes of young women here in America and around the world. You can see that they share the same aspirations, the same hope of controlling their destinies and becoming whatever they want to be.

“It’s just unfortunate that in some countries there are plenty of opportunities, and in other places there are not.”

—Bruce Steele