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At 71, Arthur Prange Jr., M.D., is tickled to be the corecipient of the $50,000 Selo Prize for Outstanding Achievement in Depression Research conferred last month by the National Alliance for Research on Schizophrenia and Depression at its annual symposium in New York City.
Prange, who just retired from the position of director of the Mental Health Clinical Research Center at the University of North Carolina in Chapel Hill, plans to relax a little. His $25,000 share of the Selo Prize is a nice way to conclude his formal career, he commented.
He is confident that his corecipient, Charles Nemeroff, M.D., Ph.D., will carry the torch. Their work in elucidating how thyroid function and the adrenal axis affect depression has provided clinicians with practical insights about how to help some of the millions of people who struggle with this debilitating disorder.
Prange spoke with Psychiatric News about his research and what first sparked his interest in the relationship between thyroid function and depression. (Nemeroff was unavailable to speak with Psychiatric News.)
It was in 1960, he recalled, that he examined a woman who was receiving what was then a new antidepressant drug—imipramine. This patient, however, was also getting thyroid replacement therapy. The combination of imipramine and thyroid hormone was causing cardiovascular problems, which led Prange to wonder whether the interaction reflected by the cardiovascular system might also be impacting the brain.
He and his colleagues decided to switch the woman from the less potent but longer-acting T4 thyroid hormone to the more potent but shorter acting T3 thyroid hormone. In addition to controlling the cardiovascular side effects, they found that augmenting imipramine with T3 achieved antidepressant results in three to four days rather than 10 days to two weeks.
Intrigued, the investigators continued experimenting with the combination of imipramine and T3. They discovered that about two-thirds of nonresponders to imipramine became responders with coadministration of T3. This has since been "widely confirmed," he noted, and has been incorporated into the clinical practice of thousands of physicians.
Some psychiatrists have yet to employ thyroid compounds as ancillary therapeutic agents, said Prange. "Unfortunately, psychiatrists often do what drug companies tell them to do," he added.
Nemeroff and Prange joined forces in the late 1970’s as they investigated the behavioral effects of the brain peptide thyrotropin-releasing hormone (TRH). When a synthetic version of TRH became available, they were able to expand their research. They found that TRH had "profound behavioral effects" in rodents, recalled Prange.
"What we found, which was very important," was that by giving rats sedated with barbiturates a very small amount of TRH, the rats awakened in about half the time they normally did.
This led to investigation of other brain peptides, in which Nemeroff "took the lead," according to Prange. Nemeroff has increasingly focused on the relationship between brain peptides and the adrenal axis, Prange said.
"In general all of this shows that there is a relationship between the endocrine systems and the regulation of affective states by the brain," Prange commented.
They subsequently investigated anterior pituitary peptide (TSH), finding that it is elevated "in as many as 10 percent of otherwise normal adult women," said Prange. "It’s becoming the common view that [this elevation is] evidence of stress and possible incipient failure in the thyroid axis," which may result in hypothyroidism, Prange noted. They also found that those with elevated TSH have three times the lifetime prevalence of depression compared with women with normal TSH levels, Prange observed.
The public health issue is, "Is it cost-effective to find these women?," asked Prange. He thinks so. Ten percent is "a very large number," he pointed out. It is about the same as the incidence of left-handedness, he commented.
"We’ve talked about 40 years of work in 10 minutes," he concluded. "But I think what you can say is that the thyroid axis is dynamically involved, in one way or another, with the depression process. We’ve found now that even slight degrees of hypo-thyroidism can predispose to depression, and that the addition of even tiny amounts of thyroid hormone can help relieve depression by being used in an ancillary way with standard drugs."