Manning returned after missing a season to recover from delicate neck surgery. Tedy Bruschi came back after a stroke. Seau un-retired three times so he could play four more seasons.

Such passion for football illustrates why a definitive connection between CTE and suicide cannot be drawn, at least not yet. Like Duerson, Seau had other risk factors, and losing one’s athletic identity at middle age was a major one. Seau’s parents were from Samoa, which has a high suicide rate. He was dealing with business problems. In 2010, he was arrested for domestic violence against a 25-year-old girlfriend. After he was released, he inexplicably drove off a cliff in Carlsbad, Calif., on his way home.

Duerson, 50, who put forth a cigar-smoking, motorcycle-riding, back-slapping front as a successful businessman, was divorced and bankrupt.

Chronic pain also causes depression, according to Kevin Guskiewicz, chief of the University of North Carolina’s Center for the Study of Retired Athletes.

The brains studied at BU were from symptomatic people whose families wanted answers for their behavior. Much more research on a bigger sample is needed, said Dr. Robert Cantu of BU’s Center for the Study of CTE and the Sports Legacy Institute.

“With ex-athletes we see a perfect storm for depression,” Cantu said. “They are no longer on a pedestal, hearing the roar of the crowd, feeling the camaraderie of the locker room. There is no question CTE plays a role, but it’s not the only factor.”

A new longitudinal study at CSTE involves 100 NFL players undergoing interviews, spinal taps and imaging tests.

As the NFL playoffs continue and hockey season commences, Cantu understands why athletes embrace risk.

“Smoking is dangerous but 20 percent of the population still smokes, and they are not being paid millions and receiving adulation,” Cantu said. “My advice is don’t play through injury. Take yourself out.”

Seau couldn’t take himself out, and that quality made him a Hall of Fame player. He will have to be inducted posthumously.