Scientists and mental health professionals have made major strides in understanding and treating major depression, including the discovery of the role played by imbalances in brain chemicals such as serotonin and noradrenaline. But there is increasing evidence that there is more to the story: depression also involves structural changes in areas of the brain that are involved in mood, memory, and decision-making.
Depression is often precipitated by stressful experiences. The brain interprets our experiences and decides if they are threatening, and then controls our behavioral and physiological responses to them. Data obtained from animal experiments show that harmful physiological changes result from the inability of the brain and body to respond to repeated stress with adaptive modifications in structure and function. Three brain areas - the hippocampus, the prefrontal cortex, and the amygdala - are particularly susceptible to pathological changes in size and function.
These areas are instrumental in interpreting what is stressful and in determining appropriate responses. Many chemical mediators are involved, including cortisol and adrenalin from the adrenal glands, other hormones and neurotransmitters (such as serotonin and noradrenalin), and responses from the autonomic and immune systems. Depression thus leads to changes in the rest of the body, owing to long-term chemical imbalances in the systems that control the heart, the immune system, and metabolism.
The hippocampus, a key structure in the formation of memories of events and contexts, expresses receptors that enable it to respond to stress hormones in the blood. We now know that it atrophies in a number of psychiatric disorders.