John T. Cacioppo, whose research into human bonds and connections expanded the horizons of psychology, generating an entirely new discipline — social neuroscience — and key insights into loneliness, died March 5 at his home in Chicago. He was 66.

The cause was not immediately known, said his wife, Stephanie Cacioppo, a fellow University of Chicago scholar with whom he shared an office desk and strikingly divergent research interests. While he studied loneliness, examining its neural, hormonal, cellular and genetic roots, she studied love and its effects on human health.

An unlikely academic who became the first member of his family to graduate from college, Dr. Cacioppo (pronounced cass-ee-OH-POE) was president of a dizzying array of psychological societies, the founder of several research journals and a scholastic pillar of the University of Chicago. In addition to serving as a professor of psychology, he directed the university’s Center for Cognitive & Social Neuroscience, led its social psychology program and was the founding faculty director of Arete, a program that helps Chicago professors find funding for large-scale research projects.

“John was an absolute force of nature,” said Jay Van Bavel, a social neuroscientist at New York University who described Dr. Cacioppo as “one of the most prolific and creative psychologists alive.” In a four-decade career, he wrote more than 500 articles and several books, including “Loneliness: Human Nature and the Need for Social Connection.”

Co-authored with William Patrick in 2008, the book presented Dr. Cacioppo’s theories on loneliness to a popular audience, describing the state of mind partly as a disease — it is contagious, inheritable and quite literally damaging to the heart — and partly as a biological signal akin to hunger.

“His research on the causes and consequences of loneliness was rigorous, deep, and impactful,” Daniel Gilbert, a Harvard University psychology professor, wrote in an email. “Anyone who tells you that being lonely is as bad for your health as smoking a pack of cigarettes a day is quoting John Cacioppo without knowing it.”

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Dr. Cacioppo was sometimes jokingly referred to as “Dr. Loneliness,” and his research coincided with, and perhaps to some extent spurred, a wave of international interest in the subject. Vivek H. Murthy, U.S. surgeon general in the Obama administration, has described loneliness as a health epidemic, and two months ago British Prime Minister Theresa May appointed a “minister for loneliness” to address what she called “the sad reality of modern life.”

Yet Dr. Cacioppo’s career extended far beyond the study of social isolation, to include major contributions to the psychology of decision-making and the ways in which people form opinions about the world.

While at Ohio State University in the 1980s, he and psychologist Richard Petty developed what is known as the elaboration likelihood model, which distinguished between decisions that are made thoughtfully and deliberately, and those that are made because of environmental cues such as a catchy but superficial television jingle.

The theory anticipated the work of scientists such as Daniel Kahneman, a Nobel Prize-winning psychologist whose book “Thinking, Fast and Slow” (2011) outlined two similar systems of logical and emotion-driven thought.

Broadening his research, Dr. Cacioppo later joined Gary Berntson in developing a model for how people make one of the most fundamental decisions of all — determining whether they like or dislike something, whether it’s a head of lettuce or an electric car.

“Prior to this theory, most psychologists treated positivity (liking) and negativity (disliking) as reciprocal,” his former colleague Petty wrote in an email. “That is, it was believed that as you came to like something more, you came to dislike it less. John, however, focused on how these two dimensions were actually independent in that liking and disliking could both go up or down simultaneously. In some elegant studies and mathematical analyses, he demonstrated the importance of treating each separately.”

Dr. Cacioppo began moving toward the study of loneliness in 1992, when he and Berntson coined the term “social neuroscience” to describe a new merger of psychology and biology, one that would study the underlying mechanisms of human or animal interactions.

It was an interest that had consumed Dr. Cacioppo for years, his wife said, recalling that he sometimes referenced a car accident that nearly killed him as a young man. In the aftermath of the crash, “he realized what really matters in life — love and social connection.”

The latter, Dr. Cacioppo often said, was his true interest. It was only by studying its absence — loneliness — that he believed he could begin to understand its importance in human life.

To that end, he and his colleagues utilized a vast array of experimental methods, studying brain activity and the effects of hypnosis as well as the loneliness of stroke patients, Army veterans, rodents and monkeys. Crucially, he observed that loneliness was not necessarily tied to the number of human connections in a person’s life.

“In fact, often times, fewer is better,” he told the Guardian in 2016. “The classic case is the billionaire who sees that everyone wants to be their friend, but in the billionaire’s eyes none of those are effective, because they are seen as being motivated by material gain.”

Dr. Cacioppo estimated that about one quarter of the population regularly feels lonely, and reported that “chronic loneliness increases the odds of an early death by 20 percent” — about as much as obesity.

He also developed techniques for reducing loneliness. Perhaps surprisingly, he reported that social engagement, improved social skills and increased social support did relatively little to ease the pain of a lonely person. Instead, he argued that loneliness was best treated by retraining the way a lonely person looks at others, helping them see the world in an open, relaxed way, rather than with a sense of fear or vulnerability.

John Terrence Cacioppo was born in Marshall, Tex., on June 12, 1951. According to a report by the American Psychological Association, he planned to become a lawyer and studied economics at the University of Missouri, but changed careers after meeting a social psychologist, Lee Becker.

Dr. Cacioppo received a master’s degree from Ohio State in 1975 and, remarkably, received his doctorate in psychology from the school just two years later. He taught at the University of Notre Dame, University of Iowa and Ohio State before joining the University of Chicago in 1999.

He met Stephanie Ortigue when she was seated next to him at a research conference in Shanghai, and they married in 2011. Four years later, he was diagnosed with salivary gland cancer but effectively cured, his wife said.

In addition to his wife of Chicago, survivors include two children from a previous marriage, Anthony Cacioppo of Columbus, Ohio, and Christina Cacioppo of San Francisco; two brothers; and a sister.

While Dr. Cacioppo was keen to note that chronic loneliness could and should be treated, he also insisted that loneliness played an important role, and was not something to lament altogether.

“The purpose of loneliness is like the purpose of hunger,” he told the Atlantic in 2017. “Hunger takes care of your physical body. Loneliness takes care of your social body, which you also need to survive and prosper. We’re a social species.”