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While some researchers were trying to get into the mind-set of the lonely, others were trying to get into their brains. One of them was John Cacioppo, PhD, currently a professor at the University of Chicago's department of psychology. "When I became interested in the topic in 1994, loneliness was thought to be a gnawing, chronic disease with no redeeming qualities," says Cacioppo, quoting Weiss on the subject. "As a neuroscientist, that didn't make sense to me. Everything has evolved for a purpose, or it doesn't stick around."

The way Cacioppo sees it, loneliness is what propelled the solitary Neolithic hunter-gatherer back into the fold, where the group shares its meager supplies and survives, while his impervious buddy carries on only to die high in the Italian Alps and be discovered as a subzero mummy by 20th-century hikers. The implication of this theory is that loneliness is handed down, and with the help of the Netherlands Twin Register Study, Cacioppo estimates that, unlike eye color (100 percent inheritable), loneliness is only 48 percent inheritable. Cacioppo likens it to a pain threshold: If you're born with a low social-pain threshold but raised in a caring and supportive environment and taught techniques for managing your discomfort, you might never become lonely. Alternatively, if you're continually bruised throughout your formative years, no matter what your genetic setting, you might plunge into lonely episodes repeatedly.

Cacioppo knew epidemiologic evidence showed that social isolation is comparable to sedentary lifestyles, poor diet, and high blood pressure as a cause of morbidity and mortality, but he didn't know why. In the past 12 years, he's done a number of studies on physiological differences between the lonely and nonlonely, paying close attention to two groups—college students and 50- to 68-year-old Chicago adults. His team's findings on stress and perceived stress pointed out some interesting differences between the socially isolated and the socially connected.

For example, lonely and nonlonely young adults were faced with approximately the same number of negative and positive life events, but the nonlonely group coped better with stressors. (In the older group, the lonely had slightly more negative life experiences.) To the lonely, the same irritation felt like a bigger hassle than it did to the nonlonely, while a happy coincidence wouldn't lift their spirits as much as it would the nonlonely. Cacioppo's team also did a brain-imaging study with the young adults, and the preliminary results suggest physiological reasons for the different outlooks. Researchers scanned lonely and nonlonely people while certain images flashed before them. When the nonlonely looked at positive pictures of people (happy, smiling folk), they showed greater activation in the reward center of the brain than when viewing an equally positive photo of an object (a cake). A lonely person, however, showed no difference in that part of the brain, suggesting that he intuitively associates connecting with others as a less rewarding experience than the nonlonely do.

Faced with negative pictures, the nonlonely person didn't react differently to an object (a dirty toilet) and a person (a battered woman). But the lonely did; they showed a much stronger response in the threat surveillance part of the brain to the negative picture of a person than to the object. The finding indicates that when a lonely person has a negative interaction, or even sees a negative interaction, he'll feel more threatened than the average person.

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