Although sadness may appear to be a much more subdued primary emotion than fear or anger, it ranges just as widely, from mild melancholy to uncontrollable crying. Sadness probably evolved to emphasize and underscore losses of all kinds; it takes us off-line so that we can regroup and reevaluate. It may even cause us enough “pain” that we are motivated to change. In the brain, sadness seems to be related to an increase in activity in the left amygdala and the right frontal cortex and a decrease in activity in the right amygdala and the left frontal cortex.

Prolonged sadness can cause sustained overactivity in the amygdala and frontal lobe. Some speculate this can cause neuronal “burnout” in these areas, either by depleting their stores of neurotransmitters or crippling the ability of these chemicals to transmit messages. When this occurs, sadness can slip into depression, which is characterized by emotional numbness rather than intense feeling. This is distinct from depression that is accompanied by anxiety, which can cause a person to become feverishly active, even suicidal. In classical depression, typified by a person sitting motionless in a chair with no intention of getting out, the numbness may be adaptive, granting relief in the case of a terrible loss or giving a person some “down time” to prepare for the next stage in life or to incorporate a major change.

That’s what happened to a patient we’ll call Bobby Jack. B.J. was a happy-go-lucky guy who generally responded positively to most everything. He tended to see the world as full of answers, structures, and stories that were positive and had good endings. His left hemisphere was working all the time, fitting everything into what he would have predicted. The ongoing story of life generated by his left hemisphere was accurate and upbeat. Events had closure.

But one September, after his company had conducted its annual job reviews, B.J. was told he wasn’t going to get a promotion he was expecting. He hadn’t failed to work hard; he just wasn’t right for the job. This upset him. He was sad. It was one of the first times real life didn’t square with the story he had running in his mind. And no promotion meant no raise, which meant that he couldn’t leave his apartment and finally buy a house, which he had wanted for so long.

B.J. tried to put matters back in order in his mind, but he couldn’t because there was no resolution. He didn’t get the job, period, for no reason that he could change. The spin he put on it was, “They made a mistake. They are fools. They will promote me later.” He tried to act differently, plan differently, do something to fit the situation back into his internal story line. In doing so, his left hemisphere may have started to overactivate, trying to deal with the new reality, trying to impose logic on the illogical set of circumstances, trying to get back to happiness.

Meanwhile his stomach had begun to act up. He got diarrhea and became physically exhausted. He began to worry that his physical condition was deteriorating. This steady anxiety commanded even more attention from his left hemisphere, which tried to find a way to explain his physical maladies as well. But there was no story that gave him control. He got sadder, more tired. He started to feel hopeless.

In all the discomfort B.J. had also stopped exercising. He gained a few pounds, which hurt his self-image. He became preoccupied with his failings, convinced that he was no longer fun to be with. He stopped talking to his friends and spent more time alone. He withdrew into himself, running his left hemisphere nonstop in trying to solve what were now all these huge problems. His left hemisphere could no longer take it. It got worn down, then burned out. There were no solutions. B.J. became clinically depressed. Now that his left hemisphere was completely inactive, his harsher, more realistic right hemisphere was free to take over. He chased people away. He didn’t have words anymore. He sank into a real blue funk.

Finally, B.J. went to a therapist. The counselor got him talking again. He had been stuck trying to explain events to himself, and it was extraordinarily helpful to thresh it out with someone else. As he did, he was able to put his experience into a bigger story line that could include a future. He saw that he hadn’t made egregious mistakes in the past and that he wasn’t a bad worker, but that someone else was in fact more suited to this particular job and that the choice was indeed his boss’s. His future was still in front of him. He could still work effectively and make a few changes that would make life more interesting and more fun.

B.J. put the loss into perspective by activating the talking brain, then recruited even more of the talking brain to plan and get into thinking about the future again. This prompted him to start taking walks, and to talk a bit to one of his siblings, which reactivated his left hemisphere. But it wasn’t quite enough, so the therapist prescribed an antidepressant, imipramine, which helped change the chemistry of his limbic system. He began to accomplish new tasks at work, to exercise, and to look forward to attaining new goals again. Bobby Jack was back.

Depression may be characterized by feelings of despair, guilt, helplessness, and hopelessness. People with depression may have symptoms such as less ability to concentrate, impaired memory, weight loss or gain, fatigue, sleep disturbances, and loss of interest in everyday activities. The onset of this disorder is typically in early adulthood, although it can occur with anyone at one time or another, especially if someone experiences a significant life trauma. Depression affects 3 to 5 percent of the population at any given time, and about 20 percent of people will experience major depression in their lifetimes. Even children only five or six years old can experience symptoms clinically similar to adult depression.

Depression is less genetically based than any other mental illness, and is the one most dependent on environmental factors. Life events can affect brain biology in even the most naturally cheerful people, like Bobby Jack. Mark George, a psychiatrist and neuroscientist at the University of South Carolina Medical School, has done PET scans of the brains of clinically depressed individuals and maintains that scanning technology can open up new treatment options by identifying subtypes of depression and differences in responses to medication. Helen Mayburg and her colleagues at the University of Texas recently used PET scans to locate an area of the brain that is different in depressed people who do not react positively to antidepressant drug therapy. In these people the front tip of the cingulate gyrus has below-normal glucose metabolism. Being able to separate out a subgroup of patients for whom current medications are not effective is an important step toward finding the right treatment for the group.

The traditional approach to treating depression-talk therapyshould still be pursued. It is helpful because it opens a straightforward connection to another person. Talking helped Bobby Jack create a palatable story of the past and a new story for the future. It connected him to his therapist; he felt understood and was encouraged. This allowed him to break free from the loop of self-hate and recrimination. At the same time, it helped break the lock in this pattern in his brain. Also, the physical act of talking itself may have been helpful, forcing the language centers in the left hemisphere to work more, reactivating other structures.

For years, the last resort for people who did not respond to talk therapy or antidepressant drugs has been electroconvulsive therapy (ECT)-shock treatments. Electrodes are placed on the scalp and a strong electric current is sent through the skull to the brain. To be effective, the current must be so strong that it triggers a seizure. Because ECT succeeds in a majority of cases, some 50,000 people a year turn to it.

Like antidepressant drugs, ECT works by changing the chemistry in the brain, elevating mood. However, the side effects are significant. The typical regimen is three shocks a week for several weeks. To prevent pain and injury during each seizure, patients are put under general anesthesia. By the end of the cycle patients can suffer confusion and memory loss, some of which may be irreversible, and their mood may improve for only 3 to 6 months.

A new technique that has been found useful for treating severely depressed people is transcranial magnetic stimulation (TMS), which appears to have many of the advantages of ECT without the nasty side effects. A coil of magnets placed against the patient’s scalp sets up a magnetic field inside the brain, which excites neurons, also inducing heightened levels of a number of neurotransmitters. No anesthesia is needed, and there seems to be no loss of memory or disturbance of other brain functions. Unlike ECT, this technique can target a specific region of the brain, notably the left prefrontal cortex, where activity is often lower than normal in depressed people.

TMS is still experimental, but early results are encouraging. In one study patients showed a 50 percent improvement on a commonly used depression rating scale-better than that seen in most antidepressant drug or ECT treatments. TMS may also be useful in treating PTSD and OCD, as well as Parkinson’s disease.


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