The study of anxiety is fast merging with the science of memory. No longer focused just on symptoms like social isolation and depressed mood, scientists are turning to the disorder’s neural roots, to how the brain records and consolidates in memory the frightening events that set off long-term anxiety. And they are finding that it may be possible to blunt the emotional impact of even the worst memories and fears.
Enlarge This Image

The war in Iraq has lent a new cultural urgency to this research. About one in eight of the troops returning from combat show signs of post-traumatic stress disorder, or P.T.S.D., which is characterized by intrusive thoughts, sleep loss and hyper-alertness following a horrifying experience. Many are so traumatized that they fail utterly to respond to anti-anxiety medications, talk therapy and other conventional treatments.

P.T.S.D. is one of the most worrisome of the generally recognized anxiety disorders. There are four others: generalized anxiety disorder (G.A.D.), obsessive-compulsive disorder, phobias and panic disorder. G.A.D. is the most common, but all are familiar complaints in doctors’ offices: more than 20 million Americans will suffer one of these during his or her lifetime.

Genetics and the environment play roles in the development of anxiety disorders, but the point where these influences intersect is clearly the brain. The biology of anxiety has been very difficult to untangle in part because it is so familiar, so integral to our survival.

Most people can and do cope with many causes of anxiety, including demanding jobs, rocky relationships, second mortgages and even combat. Every day uncounted millions are beset by the sudden, heart-pounding dizziness of panic. It is normal, even necessary, to feel fear and stress. The brain’s anticipation of threats is an invaluable survival tool. The question for scientists is: Why can’t some people turn down the voltage?

When mammals sense threat, at least two important brain circuits swing into action. One pathway runs through the frontal lobe of the cerebral cortex, the layer of the brain that regulates consciousness, thinking and decision-making functions.

The other circuit is more primal, running deep into the unconscious brain and through the amygdala, a pair of lozenge-sized nubs of neural tissue (one on each side of the brain) specialized to register threats. This unconscious circuit is “quick and dirty,” a primal survival instinct that increases blood pressure, heart rate and alertness well before the thinking cortex is fully aware of what is happening.

The difference between the two may be crucial to understanding how an irrational fear forms. The amygdala records sights and sounds associated with a harrowing memory, and it is capable of sending the body into high alert before a person consciously processes the stimuli.

Most drugs currently prescribed for anxiety, like benzodiazepines and antidepressants, work to ease the symptoms of anxiety and have little effect on the underlying trigger. But scientists are now taking tentative first steps toward altering the brain’s age-old dynamic.

Researchers have been experimenting with a heart disease drug called propranolol, for instance, which interferes with the action of stress hormones like epinephrine. Stress hormones are central to the human response to threat; they prime the body to fight or run, and appear to deepen the neural roots of a terrifying memory in the brain. When the memory returns, these hormones flood again into the bloodstream.

But in one series of studies, people with P.T.S.D. who took propranolol reacted more calmly — on measures of heart rate and sweat gland activity — upon revisiting a painful memory than did similar subjects who took a dummy pill. By blocking receptors on brain cells that are sensitive to stress hormones, experts theorize, the drug may have taken the sting out of the frightening recollections.

Propranolol has not been proved to reliably ease the effects of trauma, but the investigation of such drugs is only beginning. Another candidate, an antibiotic called D-cycloserine, may help severely anxious patients alter the way they think about and react to current everyday concerns.

In one experiment, 28 people who were terrified of heights received so-called exposure therapy, including computer simulated rides in a glass elevator. The therapy helped all the subjects cope with their anxieties. But the participants who also took D-cycloserine learned to override their fears far more quickly than those who did not.

The drug may speed up a process that researchers call fear extinction, the unlearning of frightening associations. In theory, a successful fear-extinguisher might even complement analytic talk therapy in which patient and therapist work to understand how symptoms might be linked to loss, poisoned relationships or childhood traumas. The anxieties that flow from these events flourish deep in the brain, but now there is evidence that they can be rooted out.