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 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.
The focus of a lot of research in this field has been a hormone called cortisol. This is produced from the adrenal glands which sit on top of the kidneys. Cortisol is produced in response to stress. The more stressed we are, the more cortisol we produce. The average level of cortisol production tends to be raised in adults who had traumatic childhoods, even if the individuals are healthy at the time of measurement[205][206]. What this shows is that adults who were abused or neglected as children have higher background stress levels than their contemporaries. Their systems are chronically stressed. The development of mental illness is, in many cases, probably a little like the development of cancer. A lot of things need to go wrong at the molecular level before a person becomes clinically ill. The chronic stress levels in the abuse survivors push them closer to that threshold. This increases their vulnerability to disease.
How does this over-expression of cortisol happen? It’s a consequence of events that happen far from the kidneys, in our brains. There is a whole signalling cascade involved here. Chemicals produced in one region of the brain act on other areas. These areas in turn produce other chemicals in response and the process continues. Eventually a chemical leaves the brain and signals to the adrenal glands and cortisol is produced. During an abusive childhood, this signalling cascade is very active. In many abuse survivors, this system keeps signalling as if the person is still trapped in the abusive situation. It’s as if the thermostat on a central heating system has malfunctioned, and the boiler and radiators continue to pump out heat in August, based on the weather from the previous February.
The process starts in a region of the brain called the hippocampus, which gets its name from the ancient Greek term for seahorse, it being shaped a little like this creature. The hippocampus acts as a master switch in controlling how much the cortisol system becomes activated. This is shown in Figure 12.1. In this figure, a plus symbol indicates that one event acts to stimulate the next link in the chain. A minus symbol shows the opposite effect, where one event decreases the level of activity of the next event in the chain.
Figure 12.1 Signalling events in response to stress set up a cascade of events in selected regions of the brain that ultimately result in release of the stress hormone cortisol from the adrenal glands. Under normal circumstances, this system is controlled by a set of negative feedback loops that act to dampen down and limit the activation of the stress response pathways.
Because of changes in the activities of the hippocampus in response to stress, the hypothalamus produces and releases two hormones, called corticotrophin-releasing hormone and arginine vasopressin. These two hormones stimulate the pituitary, which responds by releasing a substance called adrenocorticotrophin hormone which gets into the bloodstream. When the cells of the adrenal gland take up this hormone, they release cortisol.
There’s a clever mechanism built in to this system. Cortisol circulates around the body in the bloodstream, and some of it goes back into the brain. The three brain structures shown in our diagram all carry receptors that recognise cortisol. When cortisol binds to these receptors, it creates a signal that tells these structures to calm down. It’s particularly important for this to happen at the hippocampus, as this structure can send out signals to dampen down all the others involved in this signalling. This is a classic negative feedback loop. Production of cortisol feeds back on various tissues, and the final effect is that the production of cortisol declines. This stops us from being constantly over-stressed.
But we know that adults who suffered traumatic childhoods are actually over-stressed. They produce too much cortisol, all the time. Something must be going wrong in this feedback loop. There are a few studies in humans that show that this is the case. These studies examined the levels of corticotrophin-releasing hormone in the fluid bathing the brain and spinal cord. As predicted, the levels of corticotrophin-releasing hormone were higher in individuals who had suffered childhood abuse than in individuals who hadn’t. This was true even when the individuals were healthy at the time of the experiments[207][208]. Because it’s so hard to investigate this fully in humans, a lot of the breakthroughs in this field have come from using animal models of certain conditions and then correlating them where possible with what we know from human cases.
A useful model has been based around the mothering skills of rats. In the first week of their lives, rat babies love being licked and groomed by their mothers. Some mothers are naturally very good at this, others not so much so. If a mother is good at it, she’s good at it in all her pregnancies. Similarly, if she’s a bit lackadaisical at the licking and grooming, this is true for every litter she has.