Facing Darkness

For decades, scientists believed the main cause of depression was low levels of the neurotransmitters serotonin and norepinephrine. Newer research, however, focuses on the nerve cells themselves and how the brain8217;s circuitry can be permanently damaged by hyperactive stress responses, brought on by genetic predisposition, prolonged exposure to stress or even a single traumatic event. 8220;When the stress responses are stuck in the 8216;on8217; position, that has a negative effect on mood regulation overall,8221; says Dr. Michael C. Miller, editor of the Harvard Mental Health Letter. A depressed brain is not necessarily underproducing something, says Dr. Thomas Insel, head of the National Institute of Mental Health 8212; it8217;s doing too much.

These discoveries have opened up broad new possibilities for treatment. Instead of focusing on boosting neurotransmitters the function of antidepressants in the popular SSRI category such as Prozac and Zoloft, scientists are developing medications that block the production of excess stress chemicals, hoping to reduce damage to otherwise healthy nerve cells. They are also looking at hormones. In a recent study, DHEA, an over-the-counter hormonal therapy, was shown to be effective in treating major and minor midlife-onset depression. And Canadian scientists have had success with deep brain stimulation8212;a procedure in which two thin electrodes are implanted in the brain to send a continuous electrical current to Area 25, a tiny, almond-shaped node thought to play a role in controlling emotions. In recent trials involving patients who got no relief from other forms of treatment, all the subjects reported mood improvements within six months and, remarkably, most said they were completely cured of depression.

Researchers at the NIMH are also experimenting with the idea of fast-acting antidepressants that would relieve symptoms in a few hours instead of the eight weeks or more needed for most antidepressants to take effect. In clinical trials, scientists found that a single dose of ketamine, an animal tranquiliser, reduced the symptoms of depression in just two to three hours and had long-lasting effects. Because of its hallucinogenic side effects, ketamine can never be used out of controlled environments. But the success of the trial is giving scientists new ideas about drugs and methods of administering them.

The most effective remedy remains a combination of medication and therapy, but finding the right drug and dosage is still more art than science. STARD, a three-year NIMH-funded project, found that 67 percent of patients who complete from one to four treatment steps, such as trying a different medication or seeking counseling, can reach remission. The process can be onerous and frustrating, and the potential side effects, including a low libido, can be hard to take especially for men.

Social attitudes toward depression are changing, thanks in part to men themselves. John Aberle is a sales and marketing consultant, retired Air Force security specialist, part-time radio talk-show host, devoted husband, active father and a 6-ft-4, 250-pound body-builder who twice faced a depression so deep, he cried on his knees. He readily tells other men it8217;s their duty to get better. 8220;There8217;s no crime in having a disorder, whatever it is,8221; says Aberle, 38. 8220;The crime is not dealing with it. It8217;s your responsibility to be at the top of your game.8221; Taking care of yourself physically, mentally and emotionally maybe that8217;s the real definition of what it means to be a man.

JULIE SCELFO