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DISCOVERING THE BRAIN
sites, as did binding sites for the barbiturates, a class of sedative or hypnotic drugs. The discovery that makes sense of this arrangement is that both the benzodiazepines and the barbiturates work by means of the GABA receptors: they open the chloride ion channel so that negatively charged chloride ions enter the cell. The result is to hyperpolarize the cell membrane, thereby reducing the excitability of the neuron; this brings about a lower level of response to stimuli, which is experienced as a sedating or tranquilizing effect.
This mechanism in turn points back toward panic disorder, in which some patients apparently have a lower than usual sensitivity in their receptors to the benzodiazepines and an increased sensitivity to substances that block the action of those compounds. Animal models of panic disorder all show evidence of abnormality around the hippocampus, where the benzodiazepine-antagonist receptor sites are densely concentrated. Thus, from the perspective both of cell biology and of genetics, a general outline of panic disorder is being filled in with increasing detail.
So far we have considered several illnesses that interfere with the effective functioning of specific cells, usually at the level of chemical signal transmission. Not all mental disorders fall into this category, however. Another category, known as the dementias, arises from progressive degeneration of brain structures. Often, these illnesses pass through several stages of increasing severity.
Alzheimer's disease is the major form of dementia known in the United States today, affecting an estimated 4 million people. The progressive changes in mental functioning that it causes—disturbances of memory, a lessening ability to take in new information or to coordinate it with what is already known, and sometimes subtle changes in personality—may be slight at first but can soon become most distressing. The toll taken by Alzheimer's is clearly associated with advancing age: it afflicts less than 5 percent of the population below the age of 75, about 20 percent of those aged 75 to 84, and more than 40 percent of