Seau, 43, died in May after shooting himself in the chest at his beachfront house in his hometown of Oceanside, California. He played mostly for the San Diego Chargers and two other teams in a 20-year career in the National Football League.
A study of Seau's brain by a team of independent researchers found he suffered from chronic traumatic encephalopathy, or CTE, likely brought on by two decades of blows to the head as a football player, the report said.
CTE can be diagnosed only after death.
Tissue from his brain was sent to the National Institutes of Health for analysis in July, at the request of Seau's family, amid growing concern over the long-term effects of football-related head injuries.
"The final diagnosis was findings consistent with chronic traumatic encephalopathy," Dr. Russell Lonser, the lead researcher on the case, told Reuters. Lonser is chairman of the Department of Neurological Surgery at Ohio State University and led the study of Seau's brain while he was at NIH.
Patients with CTE may display symptoms "such as impulsivity, forgetfulness, depression, (and) sometimes suicidal ideation," Lonser said in the report.
Five neuropathologists - two who work for the government and three who were independent and not informed they were examining Seau - came to a consensus on the diagnosis by studying the accumulation of a protein called tau in certain areas of the brain, Lonser said.
The distribution of tau discovered in Seau's brain "is unique to CTE and distinguishes it from other brain disorders," the NIH said in a statement about the study.
It was unclear what effect the study would have on a class action suit brought by several thousand former NFL players who claim the league has not done enough to protect players from brain injuries.
Just weeks before Seau shot himself, former Atlanta Falcons safety Ray Easterling committed suicide, and family members described a long descent into dementia following his retirement from the NFL. An autopsy revealed indications of CTE.
In February 2011, four-time Pro Bowl safety Dave Duerson, who played most of his career with the Chicago Bears, shot himself in the chest. In a suicide note, he donated his brain for study, and it was found to exhibit signs of CTE.
The NFL said the result of the examination of Seau's brain underscored "the recognized need for additional research to accelerate a fuller understanding of CTE."
"The NFL clubs have already committed a $30 million research grant to the NIH, and we look forward to making decisions soon with the NFL Players Association on the investment of $100 million for medical research that is committed in the Collective Bargaining Agreement," the NFL said in a statement. "We have work to do, and we're doing it."
CTE, once known as boxer's dementia, is caused by repeated impacts to the brain, and has been found in athletes who suffered head injuries as well as members of the armed forces with concussive injuries from blast waves.
Because the mild and moderate brain injuries do not show up on CT scans or other imaging, the condition can be definitively diagnosed only through an autopsy.
The so-called "invisible injury" causes dramatic behavioral and cognitive changes. It can cause depression, aggression, impulsivity and memory loss and has been linked to suicide.
Research led by scientists at Boston University and the Veterans Administration in 2012 showed, through microscopic analysis of the brains of military veterans and young athletes, exactly how repeated head injuries cause CTE and impair mental function.
The trauma strangles blood vessels, diminishing blood flow within the brain, the scientists reported last May. It also breaks components of brain neurons called axons. Axons carry signals between neurons, so when they are damaged, brain signals peter out and thinking is impaired. CTE litters the brain with the chewed-up remnants of neurons and other cells so extensively that the brain seems to be eating itself alive.
CTE also stretches neurons, scientists led by Boston University's Ann McKee found. That stretching damages them so severely that they resemble neurons in the brain of Alzheimer's patients and are no longer functional.
The Institute of Medicine, which advises the federal government, has also begun an extensive study on sports-related concussions in youth that will in part examine the long-term consequences from such blows to the head.
That review, requested by several U.S. senators and jointly funded by the government along with private sponsors, was expected in late 2013. The panel was due to meet next Feb. 25 to gather more data, institute spokeswoman Christine Stencel said.