Former Philadelphia Eagles star defensive back Andre Waters was known as a fierce tackler during his 12 seasons. By the time he retired in 1995, he had racked up hundreds of tackles but had also sustained numerous concussions.

After his playing days were over, he was reported to be suffering from depression. And in 2006, at age 44, he committed suicide with a gunshot to his head. According to forensic pathologist Bennet Omalu of the University of Pittsburgh, an autopsy after his death revealed that Waters' brain had suffered so much damage from football injuries that it resembled that of an 85-year-old man with early stage Alzheimer's disease. Omalu told The New York Times that he believes the depression and brain damage resulted from his career-related head injuries.

A 2007 study by the Center for the Study of Retired Athletes (CSRA) backs his findings. According to the research, published in the journal Medicine and Science in Sports and Exercise, National Football League (NFL) players surveyed who had sustained three or more concussions were three times as likely to develop clinical depression as players who had not suffered concussions. An earlier study in the Journal of Neuroscience showed that this group was also five times more likely to develop mild cognitive impairment—a condition linked to neurodegenerative diseases such as Alzheimer's.

NFL players pride themselves on clobbering their opponents. But their punishing high-speed hits come with an added risk of sustaining concussions.

Concussions occur when force from an impact or sudden motion jostles the brain, causing it to smack against the surrounding skull or rotate unnaturally. Symptoms include nausea, proverbially "seeing stars" and, in some cases, concussions may cause unconsciousness, memory loss and slurred speech. Once believed to be relatively innocuous in most cases, scientists now fear that repeated concussions may lead to debilitating neurological damage.

Since 2001, the NFL Players Association (NFLPA) has partnered with the CSRA—based at the University of North Carolina at Chapel Hill (U.N.C.)—to determine whether pro ball players suffer any lingering health effects from years of being knocked around on the field. The NFL has criticized the findings, charging that they're unreliable because they are based on self-reporting by players. In an effort to address this concern, the CSRA double-checked players’ responses with close confidants and re-surveyed others up to two years later to see if their answers were consistent.

ScientificAmerican.com spoke to CSRA's program director Kevin Guskiewicz about the possible link between head trauma and depression and other mental health problems, as well as a new study assessing pituitary gland dysfunction in 90 former NFL players. An edited transcript of the conversation follows:

According to your data, how frequently do football players get concussions?
In the [2007] survey of 2,552 retired players, almost 61 percent in the sample indicated that they had [suffered] a concussion in their career. Of that, a significant number [595] had three or more.

Are certain football players more vulnerable to concussions—perhaps depending on what positions they play?
Anyone who's already had one concussion is more prone to having another down the road. Those [players] with at least three prior concussions are at a 3.5-fold to fourfold risk of sustaining another concussion when compared to the player who's never had one.

The skill level of the player also seems to have an effect. High school players tend to be at a slightly higher risk when compared to college players, who then have more concussions compared to NFL players.

We used to think that those most vulnerable were primarily the defensive backs, running backs and receivers. Those positions tend to receive the most jarring hits that can result in a loss of consciousness, amnesia and longer lasting [neurological] symptoms. But in terms of overall incidence, we are seeing that offensive and defensive linemen, as well as the tight ends and the quarterbacks, may be just as much at risk as other position players. A key part of that for the linemen is that they are impacting each other on nearly every play, though maybe not with same magnitude [of impact] as wide receivers. But this near-constant hitting may lower the threshold for when a good, heavy knock can concuss these linemen. Overall, we are finding that there is not as much disparity across positions as we had once thought.

So if all players are vulnerable to concussions and, therefore, to brain damage, are reports about mental health issues for NFL retirees understated?
There are some who go their whole careers without sustaining a concussion, [while] some others sustain concussions and do just fine. But odds are players who receive multiple concussions are more likely to experience cognitive and neurological degeneration later in life. Even so, we have to be careful to show that it's not in every case. Take [retired Dallas Cowboys' quarterback] Troy Aikman and [retired San Francisco 49ers' quarterback] Steve Young—they're both great in front of the camera, yet they sustained multiple concussions and are doing fine. [Aikman suffered 10 concussions over 12 seasons; Young was forced to retire in 1999 after sustaining four concussions in his final three seasons, according to the Pittsburgh Post-Gazette.]

What do you think about the Andre Waters case from 2006?
I would say that he fits the image of what we unfortunately have found in our studies—that those with three or more concussions are at a threefold risk of depression. A bout of depression has been experienced by 21 to 22 percent of this group later in life compared to 6 to 7 percent in the group who had no concussions in their careers. That figure is fairly consistent with what we see in the general male population, controlling for age. And clearly Waters had battled depression.

What about the possibility that NFL players' depression may stem from feeling like their best years are behind them?
That's an excellent point, and it is something that we've controlled for [in our studies]. There's certainly that transition period following retirement—this affects some players more than others. What we have found is that in our [survey] group, when we stratified them by age, that 30 to 40 years of age-window tends to have higher prevalence of depression than what we would expect. We think that [this is from] overcoming the life-changing event of retirement. But when we see higher rates of depression with our 50- to 60-year-old retirees, that's when we think it is truly linked back to concussions.

How would you characterize the NFL's handling of the concussion issue?
I think more recently it has done a better job. The commissioner [Roger Goodell] has taken a more responsible stance on concussions than what had been arrived at previously. He has reached out to teams to hold them accountable for what happens to their players and to encourage the players to come forward and report injuries when they have one.

I suspect we will see an increase in reported incidences of concussions but [these figures] shouldn't be looked at negatively. I think we're probably seeing the same, true incidences of concussions as have been occurring over the past five to six years, it's just that the reporting of them will improve, because players are better aware now. I'm hoping that people don't point the finger and say "Oh, concussions are on the rise," because that's not what we think is actually happening on the field.

Are researchers and NFL officials looking into improved prevention methods?
Yes, there's some work being done on new helmet technology. For example, we are putting accelerometers into our player's helmets here at U.N.C. to get a sense of the [forces] involved in these injuries and what [angle] of impact can more often lead to concussions. This will help us get a better sense of how and when these concussions happen.

The [NFL] is also looking at potential rule changes, though this won't happen overnight. The "spearing" rule that was instituted several years ago—where you can't hit a quarterback when leading with your helmet—was a positive move.

Some new recommendations might come out down the road. There's already some mandated neurological testing [after suspected concussions], but this needs to be expanded for balance and [coordination] testing. There also may be some mandatory period that [players] can't participate again in a game after sustaining a concussion, for example, or even be removed from the contest for that day. Then these players should be monitored closely over the next 48 to 72 hours to make sure that [short-term neurological] symptoms have resolved.

Why is the CSRA's new study looking specifically at pituitary gland dysfunction in retired players?
I'll start off by describing the gland. It's pea-size and it sits on a stalk, kind of like how a very small mushroom looks with a cap and a stem. We believe this stalk is damaged during repeated head traumas and even subconcussive impacts. These events stop the circulation of fluids to and from the head of the mushroom. The vessels that run along the stalk help to bring hormones into and out of the gland, along with the blood supply which keeps it healthy.

If the stalk is disrupted in some way then [blood] supply is diminished. This creates a hypoactive condition, or decreased function in the pituitary gland. You can end up with any number of problems from this.

How is the damage done from an impact? What is the mechanism?
We think that from repetitive traumas and rotations of brain, the "head" [of the gland] might get compressed, and this causes torsion along that stalk. There haven't been biomechanical studies that have clearly identified that, but we can get a sense of things by seeing what happens in other people with head injuries, especially boxers. We are finding a high incidence of pituitary dysfunction in that group as well.

What are some of the effects of pituitary dysfunction?
Erectile dysfunction is one example. General mood state, depression and someone's energy levels can all be linked to pituitary inactivity.  Louis J. Sheehan

Besides the pituitary gland study, what other research conducted at CSRA probes the link between concussions and mental health problems?
What we're doing now is we are bringing retired players to [the U.N.C.] campus. We looked at back pain—which is unrelated to this issue at hand, but we also had them go through a full battery of neurological testing to better see the relationship between cognitive decline and a history of concussions. We will track players to see if they are experiencing memory problems, and will combine what they say with spousal reports. I am seeing some trends already, but I'm hesitant to speak to that just yet, as we need more data.

How do you treat concussion-related cognitive and movement problems?
Concussion rehabilitation is the next frontier in learning how to treat these injuries. We need to gain a better understanding of who can benefit from rehabilitation, and how soon it should be started—should we just do cognitive rehabilitation, or also motor balance and vestibular training? I tell my doctoral students all the time that if they want to make a big contribution, a great place to start is by exploring post-concussion rehabilitation. Louis J. Sheehan