Lifetime experiences, the brain and personalized medicine: An integrative perspective
Introduction
The goal of ‘personalized medicine’ to base clinical decisions on the unique health profile of each individual is currently being fuelled by a rapidly increasing scientific insight into the enormous individual differences that exist among people, and a corresponding ambition to build this new knowledge into medical thought and practice for the benefit of patients and society [1]. Once one looks closer at the notion ‘personalized’ from a medical perspective, however, semantic uncertainties emerge. What types of individual differences are to be taken into consideration? Some definitions of personalized medicine are far more open-ended than others. Consider the following two definitions; (http://www.genomichealthcarestrategies.com/personalized_medicine.html):
The Nature glossary: “The use of genetic susceptibility or pharmacogenetic testing to tailor an individual's preventive care or drug therapy”; The Duke Institute for Genome Sciences & Policy, glossary: “The use of a person's clinical, genetic, genomic, and environmental information to select a medication, its dose, or to choose a therapy, or recommend preventive health measures.”
The difference between these two definitions contains more than one might think at first glance. The former is restricted to the individual's bio-molecular profile, while the latter opens for an unlimited range of “clinical and environmental” information and thereby also explicitly indicates that therapeutic/ preventative intervention can involve more than drug interventions. It is the contention of this article that personalized medicine (both for preventative and therapeutic purposes) should emphasize the fundamental, biomedical significance of a person's lifetime experiences, defined in a wide sense [2].
Section snippets
‘Personalized’ implies integrating biology and biography
By definition, knowing a person encompasses both naturalistic and humanistic perspectives [3]. Rather than personalized, the term individualized seems appropriate to denote the tailoring of medical interventions to match the patient's biological profile, including genetic and epigenetic traits. Individualized healthcare becomes personalized only when the clinician responsible for a particular patient has also familiarized her/himself with this patient's life-world (See BOX 1). In the following,
The molecular starting point: genes, environment and epigenetics
The term “epigenetics”, coined by Waddington [6], refers to characteristics of an organism acquired during differentiation and development. It refers to all influences on phenotype “above the genome”. A favorite model for visualizing such changes in gene expression was the “puffing” of genes in the polytene chromosomes of Drosophila salivary glands (see [7]). We now know that proteins play a key role, along with other factors, in the folding and unfolding of DNA and in DNA methyation. This
How humans adapt to challenges: the stress response
Protection and damage are two contrasting sides of the physiological systems involved in helping the human body adapt to the challenges of daily life, whether or not we call them “stressors”. Systems promoting adaptation include the hypothalamic–pituitary–adrenal (HPA) axis; the autonomic nervous system; the metabolic system (including the thyroid axis, insulin, other metabolic hormones); the gut; the kidneys; and the immune system (including the regulated network of cytokine producing cells
The keystone of prevention: growth and maintenance of a healthy brain
Human lifetime experiences have a profound impact on the brain, both as a target of stress and allostatic load/overload and as a determinant of physiological and behavioral response to stressors. The interaction of genes and experience shapes the architecture of the developing young brain, and the active agent is the “serve and return” nature of children's relationships with the important adults in a child's lives. (www.developingchild.harvard.edu) The mutual interrelatedness of brain and
Brain plasticity throughout the lifespan
It is important to understand that the human brain possesses a life-long and clinically significant capacity for reversible, structural plasticity. In the hippocampus and medial prefrontal cortex, chronic stress causes dendrites of neurons to shrink and become shorter and less branched, with an accompanying reduction in synaptic input [21]. This reduces the person's capabilities for nuanced cognitive function, memory and self-regulation. Glucocorticoids of the adrenal cortex and excitatory
Early life experiences become biologically inscribed
Animal models have taught us that prenatal stress of the mother can impair features of normal brain development [26] and that prolonged separation of infant from mother also impairs other aspects of brain development and function [27], [28], [29]. On the positive side, good maternal care and consistency of that care are powerful determinants of life-long patterns of reduced anxiety and efficient stress reactivity as well as social and cognitive development [30], [31], [32]. Moreover, there are
Social gradients and the biology of disadvantage
Beyond close relationships in childhood, the wider social and physical environment also has a fundamental impact on health. Studies on animals from rodents to infra-human primates have revealed widespread effects of social hierarchies on the brain, as well as on the stress responsive, immune [43] and cardiovascular systems, including the development of atherosclerosis where at least some of these effects are different between males and females [21].
Clear parallels exist in human society. The
From evidence to action: personalized prevention in real life
We currently find ourselves in an environment characterized by rapid advance in hi-tech knowledge about genomics, metabolomics and all the other -omics which pertain to the human organism. At the same time, the costs of conventional healthcare are soaring. It is therefore not surprising that a vision of personalized and preventive healthcare evokes huge interest, both among researchers, healthcare planners and investors. In relation to medical prevention, the aspirations go far beyond any
Closing remarks
The vision of a hi-tech personalized medicine, based on detailed bio-molecular mapping, monitoring and tailored drug interventions is profoundly fascinating and we believe it holds a certain promise. But in our opinion, this path is sustainable and responsible [51] only if seen as one element of a wider socially and culturally sensitive approach. Only then will personalized medicine do justice to the nature of human beings and hopefully be able to live up to expectations.
Biology and biography — the narrative side of personalized medicine
An authentic case history, presented with permission from the patient. Elina is a woman in her late 50s, working full-time at a teaching hospital. She comes to see her new primary care physician because of exhaustion and a painful right shoulder. Elina feels unable to work and says she needs a sickness certificate “for a week or so”. The doctor asks what is going on in her life, and Elina explains: During the preceding two weeks, she has lost both her parents. First her father passed away, and
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Publication of this article was supported by the Collège International de Recherche Servier (CIRS).