Treatments for Depression, Part 2

Stress has been discussed many times on this blog. The dangers and benefits of stress are widely discussed in the scientific community as well as in the lifestyle industry concerning productivity and behavior. In part 1, we talked about early research on mental health issues and some current treatment options for those suffering with depression.

The stress hormone cortisol cycles daily to help when we need to pay attention to what's going on around us. Many studies find that in rodents and humans a mild increase in stress is good for the brain, particularly for memory. For example, students who get stressed while studying are more alert and remember more than those who feel no urgency - up to a point. Stress becomes a problem when there is too much at one moment such as in a rape or violent attack or too sustained as in long-term poverty, neglect, or abuse.

Stress changes the brain's architecture and the effect of hormones on the brain. For example, in a case of chronic stress, neurons in the hippocampus and the prefrontal cortex (mood and impulse control) start to shrink, while those in the amygdala (fear and anxiety) expand. However, everyone has different levels of vulnerability depending on genes and prior life experience. According to Maurizio Popoli, a professor of pharmacology at University of Milan, "it is because they perceive the stress differently." Image Credit

The role of the stress hormone is to flood parts of the brain with glutamate, the brain's "go" signal. Glutamate triggers neurons to generate sudden bursts of electricity that release more glutamate, which can trigger electrical bursts in nearby neurons. This function is called excitation and is fundamental to how information is processed in the brain. It ebbs and flows, meaning there is a "refractory period" following each neural firing during which the neuron cannot be excited.

Other neurotransmitters, like serotonin, are called "modulatory," because they change the sensitivity of neurons that secrete glutamate. As Popoli puts it, these modulators are "very important for fine-tuning the machine. But the machine itself is an excitatory machine," driven by glutamate.

Stress hormones affect the glutamate system along its journey through the brain. Stress causes more glutamate to be released, then block glial cells from removing the glutamate from the synapse, and block the glutamate from reaching its destination on the other side of the synapse. All of these changes increase the amount of glutamate in the synapse, flooding the cell with aberrant signals. A depressed person's brain, or at least animal models of depression, shows that all three of these problems lead to long-lasting excess glutamate in key portions of the brain. This makes a neuron fire sooner than it should and triggers a cascade of signals inside the cell damaging its structure. An overdose of glutamate causes the neurons and their dendrites (branches of the neuron) to shrink and after a time whole branches recede.

This dangerous process, called excitotoxicity, is thought to be involved in bipolar disorder, depression, epilepsy, and neurodegenerative diseases like Alzheimer's, Huntington's, and Parkinson's. In depressed brains, many area are shrunken and underactive.

Usually the brain's ability to adapt is considered a good thing; however in the case of mental disorders the human brain's flexibility allows regeneration, but also renders it vulnerable to being altered by stress. A traumatic event or a time of homelessness could cause a person with a genetic predisposition to find his mind stuck in a loop of chronic fear or depression.

In part 3 we'll discuss how drugs can be used to modify the effect of stress.