The Epigenetics Revolution

There is sometimes resistance to this approach from other disciplines, which work within different conceptual frameworks. This seems rather puzzling. If we don’t accept there is a molecular basis to a biological effect, what are we left with? A religious person may prefer to invoke the soul, just as a Freudian therapist may invoke the psyche. Both of these refer to a theoretical construct that has no defined physical basis. Moving into such a model system, where it is impossible to develop the testable hypotheses that are the cornerstone of all scientific enquiry, is deeply unattractive to most scientists. We prefer to probe for a mechanism that has a physical foundation, rather than defaulting to a scenario in which there is something which is assumed, somehow, to be a part of us, without having any physical existence.

This can generate a cultural clash, but it’s one that’s based on a misunderstanding. A scientist will expect that observable events have a physical basis. For the topic of this chapter, our proposed hypothesis is that terrible early childhood experiences change certain physical aspects of the brain during a key developmental period. This in turn affects the likelihood of mental health problems in adult life. This is a mechanistic explanation. It’s lacking in details, admittedly, but we’ll fill in some of these in this chapter. Mechanistic explanations often sit uncomfortably in our society, because they sound too deterministic. Mechanistic explanations are misinterpreted and taken to imply that humans are essentially robots, wired and programmed to respond in certain ways to certain stimuli.

But this doesn’t have to be the case. If a system has enough flexibility, then one stimulus doesn’t always have to result in the same outcome. Not every abused or neglected child develops into a vulnerable, unwell adult. A phenomenon can have a mechanistic basis, without being deterministic.

The human brain possesses sufficient flexibility to generate different adult outcomes in response to similar childhood experiences. Our brains contain one hundred billion nerve cells (neurons). Each neuron makes links with ten thousand other neurons to form an incredible three dimensional grid. This grid therefore contains a thousand trillion connections – that’s 1,000,000,000,000,000 (a quadrillion). It’s hard to imagine this, so let’s visualise each connection as a disc that’s 1mm thick. Stack up the quadrillion discs on top of each other and they will reach to the sun (which is ninety-three million miles from the earth) and back, three times over.

That’s a lot of connections, so it’s perfectly possible to imagine that our brains have a lot of flexibility. But the connections are not random. There are networks of cells within the giant grid which are more likely to link to each other than to anywhere else. It’s this combination of huge flexibility, but constrained within certain groupings, that is compatible with a system that is mechanistic but not entirely deterministic.

The child is (epigenetically) father to the man

The reason scientists have hypothesised that the adult sequelae of early childhood abuse may have an epigenetic component is that we’re dealing with scenarios where a triggering event continues to have consequences long after the trigger itself has disappeared. The long-term consequences of childhood trauma are very reminiscent of many of the effects that are mediated by epigenetic systems. We have seen some examples of this already. Differentiated cells remember what cell type they are, even after the signal that told them to become kidney cells or skin cells has long since vanished. Audrey Hepburn suffered from ill-health her whole life because of the malnutrition she suffered as a teenager during the Dutch Hunger Winter. Imprinted genes get switched off at certain stages in development, and stay off throughout the rest of life. Indeed, epigenetic modifications are the only known mechanism for maintaining cells in a particular state for exceptionally long periods of time.

The hypothesis that epigeneticists are testing is that early childhood trauma causes an alteration in gene expression in the brain, which is generated or maintained (or both) by epigenetic mechanisms. These epigenetically mediated abnormalities in gene expression predispose adults to increased risk of mental illnesses.

In recent years, scientists have begun to generate data suggesting that this is more than just an appealing hypothesis. Epigenetic proteins play an important role in programming the effects of early trauma. Not only that, they also are involved in adult depression, drug addiction and ‘normal’ memory.