In the mid-1980s, the neuropsychiatrist Peter Whybrow, who has died aged 86, and his colleague Marc Bauer encountered a strange case involving a 41-year-old doctor. Ten years previously he had had a suspected pre-cancerous cold thyroid nodule surgically removed. After eight years he began to behave extremely erratically, going out at night and not coming home despite being married with children. Then he would go to bed for a week and not get up, and lost his job.
His family forced him to see a psychiatrist, who diagnosed him with manic depression and put him on lithium. However, his rapid cycling between depression and mania did not improve, and withdrawing from lithium made him wildly manic.
He was referred to Whybrow’s Malignant Bipolar Illness Clinic at the University of Pennsylvania, in Philadelphia. There a high dose of thyroxine – the hormone created in the thyroid gland, which controls how much energy the body uses – was added to the lithium the patient was given. This immediately led to a cessation of rapid mood cycling and to long-term stability in managing his bipolar disorder.
Whybrow and Bauer’s treatment has since been replicated in many bipolar patients suffering from rapid cycling and other variants of severe and intractable bipolar illness. Many, but not all, of these patients are pre-menopausal women, where their bipolar disorder is driven by oestrogen-thyroid hormone interaction in the brain. In bipolar disease, too little thyroxine is circulating, and when a woman is pre-menopausal, the oestrous cycle fosters rapid cycling.
This is particularly difficult for some vulnerable, still menstruating young women, whose thyroid axis collapses when given lithium. Whybrow and colleagues’ clinical trials showed that when these young women were given high doses of thyroxine, about 75% of them became much better.
Born in Hatfield, Hertfordshire, Peter was the son of Doris (nee Abbott) and Charles Whybrow. His father was an excellent oboist who became a tank commander in the second world war, and lost his embouchure, and so his ability to play. Peter watched his father deal with the trauma of war with the help of the 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 especially enjoyed surgery, and studied thyroid carcinoma with Eric Pochin, head of the Medical Research Council Unit. When the thyroid was removed, patients were given radioactive iodine to kill cancer cells. This treatment works well for six months, but deprives the body of thyroxine. In those days, doctors did not have T3 (triiodothyronine), which is now used now as a substitute. So patients would become profoundly hypothyroid during their six to seven months of treatment.
At the end of this treatment, the patients often became altogether different people, but no one knew why. A diplomat confided to Whybrow that when deprived of thyroxine in the phase after surgery, he was unable to calculate anything and became completely dependent on his staff. In fact, many patients complained of being unable to think and becoming melancholic. This conundrum of whether hypothyroidism could masquerade as a mood disorder kickstarted Whybrow’s lifelong interest in research on the brain-thyroid axis.
In 1962, while still a medical student, he published his first scientific article in University College Hospital magazine, on peyote, the psychedelic cactus. It demonstrated how medicine not only works through its pharmacology but is always rooted in beliefs and cultural context. He went on to pursue a different kind of psychiatry, focused on treating patients in an integrative fashion, rooted in fundamental medical research but always using evidence from interdisciplinary social and anthropological research.
In 1965 Whybrow took a psychiatry residency 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 rather ill before diagnosis. The researchers found that hypothyroidism can indeed mimic psychiatric illnesses, particularly cognitive dysfunction and mood disturbances, and that sometimes patients can become quasi-psychotic, a condition referred to as “myxedema madness”.
After Whybrow returned to the Medical Research Council Depression Unit in the UK in 1968, Prange joined him on a sabbatical. They showed that supplementing antidepressant treatments with thyroid hormone medication was particularly useful for women, and that the level of thyroid hormone circulating in the bloodstream is correlated with how quickly people recover from depression. Depressed patients with elevated levels of thyroid hormone in their bloodstream are much more likely to benefit from antidepressant drugs. Because women’s thyroid function deteriorates as they age, and because they have poorer thyroid function than men, women are much more likely to be helped by adjunctive thyroid hormones. These findings have significantly helped clinicians treat mood disorders, especially in women.
In 1969 Whybrow moved with his wife, Ruth (nee Steele), whom he had married in 1962, and their daughters, Kate and Helen, to New Hampshire for an assistant professorship at Dartmouth Medical School.
By the age of 31 he was chairman of the department of psychiatry, and went on to be executive dean of the whole medical school. In 1984 Whybrow went back to psychiatry at the University of Pennsylvania, and developed his insights into mood cycling.
In 1997 he moved to the University of California, Los Angeles, and for 23 years combined the three roles of executive chair of psychiatry, director of the Semel Institute for Neuroscience and Human Behavior, and chief executive of the Resnick Neuropsychiatric hospital. Thus he was able to create one of the world’s leading centres for psychiatric research and treatment, combining neuroscience, genetics, and behavioural science with patient care and training.
From the late 1990s, he and Michael Bauer took the brain-thyroid work forward, notably with applying novel brain imaging technology to demonstrate that thyroxine modulates metabolism in limbic brain regions that are responsible for regulating human emotions.
Another important outcome of their collaboration was the development of ChronoRecord, the first electronically based daily self-rating system through which patients may follow the course of their illness and recovery in accurate correlation with treatment, thus facilitating long-term therapeutic management of affective illness.
In his book A Mood Apart: A Thinker’s Guide to Emotion and Its Disorder (1997), he explores the subject of human emotion and the widely misunderstood illnesses of depression and mania, guiding the reader in how to identify mood disorder and what to do when it emerges.
It was the first of a trilogy exploring the impact of modern-day culture on human behaviour. American Mania: When More Is Not Enough (2005) and The Well-Tuned Brain: Neuroscience and the Life Well Lived (2015) explore the link between neuropsychiatric research on health and illness to larger cultural themes, such as making a connection between “manic” behaviour and America’s history as a migrant culture, and proposing potential solutions.
In 2020 Whybrow collaborated with me in founding the Centre for Eudaimonia and Human Flourishing at Oxford University, eudaimonia being the classical Greek concept of living well. Its research expands his ideas of balancing brain and body with the use of whole-brain models of malign brain states that may in time benefit neuropsychiatric patients.
His first marriage ended in divorce, as did his marriage to Eva Redei in 1998. In 2014 he married his long-term 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.
