Obituary of Peter Whybrow | Psychiatry
In the mid-1980s, neuropsychiatrist Peter Whybrow, who has died aged 86, and his colleague Mark Power encountered a strange case involving a 41-year-old doctor. Ten years ago, he had surgery to remove a pre-cancerous cold thyroid nodule. After eight years he started behaving very strangely, going out at night and not coming home even though he was married and had children. Then he goes to bed for a week and doesn’t wake up, and loses his job.
His family forced him to see a psychiatrist, who diagnosed him with manic depression and put him on lithium. However, his rapid swings between depression and mania did not improve, and withdrawal from lithium left him severely manic.
He was referred to the Whybrow Clinic for Malignant Bipolar Illness at the University of Pennsylvania in Philadelphia. A high dose of thyroxine – the hormone created in the thyroid gland, which controls the amount of energy the body uses – was added to the lithium that was given to the patient. This immediately resulted in a cessation of the rapid mood cycle and long-term stability in the management of bipolar disorder.
Wipro and Power therapy have since been replicated in numerous bipolar disorder patients with rapid cycling and other variants of severe and intractable bipolar illness. Many, but not all, of these patients are premenopausal women, whose bipolar disorder is driven by an interaction between estrogen and thyroid in the brain. In bipolar disease, too little thyroid hormone is circulating, and when a woman is premenopausal, the estrous cycle promotes rapid menstruation.
This is especially difficult for some frail young women who are still menstruating, and whose thyroid axis collapses when taking lithium. Clinical trials conducted by Wibrow and colleagues showed that when these young women were given high doses of thyroid hormone, their condition improved significantly by 75%.
Peter was born in Hatfield, Hertfordshire, the son of Doris (née Abbott) and Charles Whybrow. His father was an excellent flute player, then became a tank commander in World War II, and lost his ornament, and thus his ability to play. Peter watched his father deal with the trauma of war with the help of a local family doctor, and felt drawn to a life in medicine.
From Welwyn Grammar School he went to University College London to train as a doctor. He particularly enjoyed surgery, and studied thyroid cancer with Eric Beauchaine, head of the Medical Research Council unit. When the thyroid gland was removed, patients were given radioactive iodine to kill the cancer cells. This treatment works well for six months, but it deprives the body of thyroid hormone. In those days, doctors did not have T3 (triiodothyronine), which is now used as a substitute. So patients will develop severe hypothyroidism within six to seven months of treatment.
At the end of this treatment, patients often became completely different people, but no one knew why. One diplomat told Whybrow that when he was deprived of thyroid hormone post-operatively, he could not count anything and became completely dependent on his staff. In fact, many patients complained of not being able to think and became sad. This mystery of whether hypothyroidism could masquerade as a mood disorder sparked Wibrow’s lifelong interest in research on the brain-thyroid axis.
In 1962, while still a medical student, he published his first scientific article in the University College Hospital Journal, on peyote, a psychedelic cactus. He showed how medicine does not work solely through pharmacology, but is always rooted in cultural beliefs and context. He went on to pursue a different kind of psychiatry, focusing on treating patients in an integrative way, rooted in basic medical research but always using evidence from interdisciplinary social and anthropological research.
In 1965, Whybrow did a residency in psychiatry at the University of North Carolina, where he met Arthur Prange. They collaborated on how an individual experiences hypothyroidism and whether this experience overlaps with depression. In those days, chemical tests for thyroid disease were not widely available, and in rural North Carolina people became ill somewhat before diagnosis. The researchers found that hypothyroidism can actually mimic psychiatric illnesses, especially cognitive dysfunction and mood disorders, and that sometimes patients can become quasi-psychotic, a condition referred to as “myxedema insanity.”
After Whybrow returned to the UK Medical Research Council Depression Unit in 1968, Prang joined him on sabbatical leave. They showed that supplementing antidepressant treatments with thyroid hormone medications was particularly beneficial for women, and that the level of thyroid hormone circulating in the bloodstream correlated with how quickly people recovered from depression. Depressed patients who have high levels of thyroid hormone in their bloodstream are more likely to benefit from antidepressant medications. Because women’s thyroid function declines as they age, and their thyroid function is weaker than men’s, women are more likely to get help from ancillary thyroid hormones. These results have greatly helped doctors in treating mood disorders, especially in women.
In 1969, Whybrow moved with his wife Ruth (née Steele), whom he married in 1962, and their daughters Kate and Helen, to New Hampshire to work as an assistant professor at Dartmouth Medical School.
By the age of thirty-one, he was chairman of the Department of Psychiatry and then became executive dean of the entire medical school. In 1984, Whybrow returned to psychiatry at the University of Pennsylvania, and developed his ideas about the mood cycle.
In 1997, he moved to UCLA, where for 23 years he held the three roles of chief executive officer of psychiatry, director of the Semel Institute for Neuroscience and Human Behavior, and CEO of the Resnick Neuropsychiatric Hospital. He was thus able to establish one of the world’s leading centers for psychiatric research and treatment, combining neuroscience, genetics, behavioral science, and patient care and training.
Since the late 1990s, he and Michael Bauer have advanced brain and thyroid work, in particular by applying new brain imaging technology to demonstrate that thyroid hormone regulates metabolism in areas of the limbic brain responsible for regulating human emotions.
Another important outcome of their collaboration is the development of ChronoRecord, the first electronic daily self-assessment system through which patients can track the course of their illness and recovery in precise correlation with treatment, thus facilitating long-term therapeutic management of emotional illnesses.
In his book Detached Moods: A Thinker’s Guide to Emotion and Its Disorder (1997), he explores the subject of human emotion and the widely misunderstood pathologies of depression and mania, and instructs the reader on how to recognize a mood disorder and what to do when it appears.
It was the first of a trilogy exploring the influence of modern-day culture on human behavior. American Obsession: When More Isn’t Enough (2005) and The Well-Tuned Brain: Neuroscience and the Good Life (2015) explore the relationship between neuropsychiatric research on health and illness and larger cultural themes, such as the link between “obsessive” behavior and America’s history as an immigrant culture, and suggest potential solutions.
In 2020, Whybrow collaborated with me to establish Center for Eudaimonia and Human Flourishing At Oxford, eudaimonia was the classical Greek concept of living well. His research expands his ideas about balancing the brain and body using whole-brain models of malignant brain conditions that may benefit neuropsychiatric patients over time.
His first marriage ended in divorce, as did his marriage to Eva Reddy in 1998. In 2014, he married his partner, Nancy Main; She died in 2017.
He is survived by Kate and Helen, four grandchildren, Chase, Gavin, Willa and Wren, and his brother John.