Thursday, January 09, 2014

The Brain and depression.

Though depression involves an overall reduction in brain activity, some parts of the brain are more affected than others. In brain-imaging studies using PET scans, depressed people display abnormally low activity in the prefrontal cortex, and more specifically in its lateral, orbitofrontal, and ventromedial regions. And the severity of the depression often correlates with the extent of the decline in activity in the prefrontal cortex.
The prefrontal cortex is known not only to be involved in emotional responses, but also to have numerous connections with other parts of the brain that are responsible for controllingdopamine, norepinephrine, and serotonin, three neurotransmitters that are important in mood regulation. More specifically, the lateralprefrontal cortex seems to help us choose a course of behaviour by letting us assess the various alternatives mentally. The orbitofrontalcortex seems to let us defer certain immediate gratifications and suppress certain emotions in order to obtain greater long-term benefits. And theventromedial cortex is thought to be one of the sites in the brain where we experience emotions and the meanings of things. 
1) orbitofrontal cortex
2) lateral prefrontal cortex
3) ventromedial cortex
4) limbic system
The two halves of the prefrontal cortex also seem to have specialized functions, with the left half being involved in establishing positive feelings and the right half in establishing negative ones. And indeed, in depressed people, it is the left prefrontal cortex that shows the greatest signs of weakness. In other words, when people are depressed, they find it very hard not only to set goals in order to obtain rewards, but also to believe that such goals can be achieved. 

In healthy people, the left prefrontal cortex might also help to inhibit the negative emotions generated by limbic structures such as the amygdalae, which show abnormally high activity in depressed patients. In patients who respond positively to antidepressants, this overactivity is reduced. And when the amygdalae remain highly hyperactive despite antidepressant treatment, the likelihood of a patient's relapsing into depression is high.

It is also interesting to note that when someone's left prefrontal cortex is operating at full capacity, the levels of glucocorticoids in their blood are generally very low. This follows logically, considering the harmful effects that high levels of glucocorticoids have on mood.

Brain-imaging studies have also shown that in patients with severe depression, the volume of the two hippocampi is reduced. This atrophy may be due to a loss of neurons that is also induced by the toxic effects of the high levels of glucocorticoids associated with recurrent episodes of depression.The extent of atrophy in the hippocampus even seems to be proportional to the sum of the durations of the episodes of depression, and depressions that are treated rapidly do not seem to lead to this reduction in hippocampal volume (see sidebars).
In an experiment using functional magnetic resonance imaging (fMRI), a group of healthy people and a group of depressed people were shown clips from sad films. Both groups were asked to try to suppress any feelings of sadness that the films elicited.

The image here represents the arithmetical difference between the brain activity levels of healthy subjects and of depressed subjects. It shows that the healthy subjects had more activity in the lateral portion of the orbitofrontal cortex (Brodmann area 11), which plays a major role in regulating emotions. This is not surprising: since depressed people have a lot of trouble in inhibiting their negative emotions, it makes sense that their orbitofrontal cortexes would be less active than those of healthy people.
Experiment: A Protocol for Functional Brain Mapping by Functional Magnetic Resonance Imaging and Positron Emission Tomography
Source: Mario Beauregard, Centre de recherche de l'Institut universitaire de gériatrie de Montréal

Why would evolution have allowed the human brain to develop and maintain circuits that can cause depression? Some potential answers can be found in the animal kingdom. When an animal is faced with a disagreeable situation and can neither fight nor flee, it responds with inhibition of action, a state that resembles depression. The status of the most subordinate animals in a hierarchy may also have an adaptive value, by preventing them from engaging in fights that could be very costly, or even fatal. This would also explain why in human beings today, depression is often triggered by events that undermine self-confidence—the equivalent of being defeated by a more dominant animal.