Magazine article The Saturday Evening Post

Mood Swings: A World-Renowned Expert on Bipolar Disorder Discusses the Latest Research Demonstrating That Thyroid Hormone Can Have a Positive and Profound Effect on Mood in Bipolar Patients

Magazine article The Saturday Evening Post

Mood Swings: A World-Renowned Expert on Bipolar Disorder Discusses the Latest Research Demonstrating That Thyroid Hormone Can Have a Positive and Profound Effect on Mood in Bipolar Patients

Article excerpt

An Interview with Peter Whybrow, M.D.

The Post continues its series on mood disorders in an interview with Dr. Peter Whybrow, who published his recent findings in the journal Molecular Psychiatry. The Post also spoke with his collaborators, Dr. Michael Bauer, in Berlin, and with Dr. Edythe London, who performed the PET scans included in this article.

Post: Could you discuss your research into the link between thyroid function and bipolar disorder, particularly recent findings published in Molecular Psychiatry?

Dr. Whybrow: The study is the most recent piece of a lot of work that attempts to understand how thyroid hormones modulate brain function and mood disorders. In this report specifically, how thyroid hormone may modify severe unremitting depression.

It has always intrigued me that people with severe hypothyroidism develop a syndrome that is very similar to depression, a finding that is historically well-known.

I first started studying the syndrome about 30 years ago. This recent study clearly shows that the addition of high-dose thyroxine in some individuals actually shifts the physiological activity in the brain, as measured by blood flow with positron emission tomography (PET) scans, to the areas which we know usually become active in recovery from depression. In these resistant depression patients, it mimics the same activity you see in other depressed individuals during recovery usually achieved just with antidepressant drugs.

The findings validate the idea that thyroid hormones have a powerful effect upon brain physiology. When that shift occurs in chronically depressed people, it associates with behavioral changes that we recognize as improvement in the depression.

Post: Were you impressed with the results of the study, or did you anticipate improvements in the patients when you supplemented standard treatment with high-dose thyroid?

Dr. Whybrow: We anticipated the results because we've seen this happen many times before in our research over the past ten years. But the magnitude of the findings was very encouraging.

Post: In the study, you administered supraphysiological doses of levothyroxine. What does "supraphysiological" mean, and what is an ordinary dose?

Dr. Whybrow: The doses that we have been using clinically lie between 0.2 and 0.4 rag, which produce blood levels of the hormone that are higher than the usual, hence the term "supraphysiological." My colleague in Germany, Michael Bauer, M.D., Ph.D., who's the first author on the recent paper in Molecular Psychiatry, has used up to 0.5 rag, but we haven't done that in the U.S. These doses are much higher than ones used simply for thyroid hormone replacement in individuals with hypothyroidism or myxedema, usually following Hashimoto's disease, or secondary to the treatment of Grave's disease. But the doses are not quite as high as one might imagine from an historical viewpoint.

If you look through the scientific literature, you'll see that 25 to 30 years ago it was routine for individuals to be replaced with about double the dose they receive now. Most people today receive somewhere around 0.1 mg and 0.15 mg. Earlier, the doses given were in the 0.2 to 0.25 mg range. Thus, although we're using higher doses in our studies today, the fact is that they're not extraordinary. And certainly we've done extensive studies looking at bone metabolism, which, of course, every endocrinologist, including myself, worries about when administering thyroid hormone. I'm glad to say that we haven't found any significant shifts in bone metabolism, even in longitudinal studies of individuals who receive these doses.

Post: This may be a naive question, but are thyroid problems more common in certain forms of bipolar disorder, such as in mixed states or rapid cycling?

Dr. Whybrow: That's not a naive question at all. In fact, that is where the research into bipolar illness began. …

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