New study links placebo effect to TPH2 gene allele
A new article in the Journal of Neuroscience links the placebo effect to a specific gene.
In the study, summarized here, researchers measured amygdala activity by PET scan in individuals with Social Anxiety Disorder while they recited speeches in front of an audience. Subjects gave the speech both before and after an eight week trial of SSRI or sugar pill. A subset of the subject population demonstrated reduced anxiety and attenuated amygdala activity after the eight-week treatment period, even if they received the placebo. Notably, eight of the ten subjects who responded to the placebo had a unique allele at the tryptophan hydroxylase-2 promoter (TPH2), a gene involved in serotonin metabolism that has been ” linked to heightened amygdala activity in healthy people.”
The authors note that TPH2 is “the first genetic marker tied to any placebo response.”
Anthropologist Nicholas Humphrey has written a book chapter about the evolution of the placebo effect in Psychology at the Turn of the Millennium, Vol. 2: Social, Developmental, and Clinical Perspectives, and it’s available online.
Humphrey reviews the power of the placebo effect here:
Indeed experimental studies have shown that placebos, as well as being particularly effective for the relief of pain and inflammation, can for example speed wound healing, boost immune responses to infection, cure angina, prevent asthma, lift depression, and even help fight cancer. Robert Buckman, a clinical oncologist and professor of medicine, concludes that “Placebos are extraordinary drugs. They seem to have some effect on almost every symptom known to mankind, and work in at least a third of patients and sometimes in up to 60%. They have no serious side-effects and cannot be given in overdose. In short they hold the prize for the most adaptable, protean, effective, safe and cheap drugs in the world’s pharmacopoeia.” Likewise, another medical authority, quoted in a recent review in the British Medical Journal, dubs placebos “the most effective medication known to science, subjected to more clinical trials than any other medicament yet nearly always doing better than anticipated. The range of susceptible conditions appears to be limitless.”
He continues:
And there’s the puzzle: the puzzle that I’ll try to address in this paper from the perspective of evolutionary biology. If placebos can make such a contribution to human health, then what are e waiting for? Why should it be that we so often need what amounts to outside permission before taking charge of healing our own bodies? I can illustrate the paradox with one of Weil’s case histories. He describes the case of a woman with a metastatic cancer in her abdomen who refused chemotherapy and relied instead on dieting, exercise and a regime of “positive thinking” including “regular meditation incorporating visualization of tumour shrinkage” – following which, to the physicians’ astonishment, the tumour completely disappeared.
Weil asks: “What happened in this woman’s abdomen that eliminated widely disseminated cancer and restored her internal organs to good health? Her healing system, probably making use of immune mechanisms, was surely responsible; but why did it not act before?” Precisely. Why? Why should her bodily immune system be prepared, apparently, to let her die unless and until her mind decided otherwise? Weil asks the question as a doctor, and his “why?” is the why of physiological mechanism: “what happened?”. But I myself, as I said, want to take the perspective of an evolutionist, and my “why?” is the why of biological function: “why are we designed this way?”
There are two reasons for thinking that evolutionary theory may in fact have something important to say here. One reason is that the human capacity to respond to placebos must in the past have had a major impact on people’s chances of survival and reproduction (as indeed it does today), which means that it must have been subject to strong pressure from natural selection. The other reason is that this capacity apparently involves dedicated pathways linking the brain and the healing systems, which certainly look is if they have been designed to play this very role. I’d say therefore it is altogether likely that we are dealing with a trait that in one way or another has been shaped up as a Darwinian adaptation – an evolved solution to a problem that faced our ancestors. In which case, the questions are: what was the problem? and what is the solution?
After reviewing the significant evidence for evolutionary pressures that could select for the placebo effect, Humphrey concludes:
To start with, given that there are certain universals in how people fare in different situations, there are presumably general rules to be found linking global features of the physical and psychological environment to changes in the costs and benefits of health-care – features such as where you live, what the weather is like, the season of the year, what you can see out the window, how much you feel at home here, and, especially important, what social support you’ve got.
Generally speaking any such features that make you feel happy and secure – success, good company, sunshine, regular meals, comforting rituals – are going to be associated with lower benefits to having the symptoms of illness (e.g. feeling pain) and lower costs to self-cure (e.g. mounting a full scale immune response). By the same token any of them that make you feel worried and alone – failure, winter darkness, losing a job, moving house – are going to be associated with higher benefits to continuing to show the symptoms and higher costs to elfcure.
Now, appreciating these cost/benefit changes, and switching health-care strategy accordingly, would bring clear advantages in the competition for biological survival. So it’s a fair bet that natural selection will have discovered these general rules and that humans will now be genetically designed to make good use of them – with the appropriate environmentally-activated switches being wired into the brain. And indeed there is lots of evidence that this is actually the case. People’s health does respond quite predictably to global environmental factors of the sort just listed. Much of the science of “health psychology” is now concerned with charting just how important these global effects are.