The Epigenetics Revolution

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.