On Nov. 30, Kosta Karageorge, a defensive lineman for Ohio State, was found dead of a gunshot wound — an apparent suicide. His family cited his multiple sports-related concussions (Karageorge was also a wrestler) as contributing to confusion and depression that may have led to his death.

If confirmed as a suicide, Karageorge’s death would be the latest in a series of suicides among current and former football players. As a result, players and advocates have increasingly linked depression and suicide to the long-term impact of repeat concussions.

In recent years, the NFL has struggled with a significant public relations problem around the issue of concussions. Among other things, former professional players have brought several lawsuits against the league, claiming monetary damages for negligence. CNN has a nice summary of the background and the steps the NFL has taken in response. The league now has a formal protocol to deal with concussions, acknowledging that these injuries have not always been taken seriously enough.

It is clear that concussions are dangerous and should be taken seriously. However, the explicit link with depression and suicide is much less clear. In short, the question of whether football has a real problem with depression and suicide, in addition to the other long-term health effects its players can suffer, is very much open for debate.

Evaluating the magnitude of the brain damage risks from football requires looking at much more data. We know there are a few cases where football players have committed suicide at young ages following a career with multiple concussions. This is a problem even if there are only a few cases, but the problem worsens if it is widespread. So, how widespread is it?

Traumatic brain injury — caused by violence to the head from, for example, a bullet, a car accident or an explosion — is linked to depression, dementia and other long-term neurological problems. A single concussion is typically classified as “mild traumatic brain injury,” and guidelines for how to deal with concussions have changed over time to become much more conservative. But for the most part, a single concussion is not thought to have long-term neurological consequences.

At issue for football players, however, is whether repeated concussions can add up to consequences more like a traumatic brain injury. In particular, there is a concern about “chronic traumatic encephalopathy” — long-term brain damage resulting from a career with many bad hits. Chronic traumatic encephalopathy (CTE) is closely related to a much older condition — dementia pugilistica (DP), which is typically described in boxers. Both conditions are characterized by the presence of abnormal proteins in the brain.

The best way to answer the question of whether professional (or college, or high school) football leads to long-term brain damage would be to study a large cohort of athletes, alongside a cohort of similar individuals who did not play sports with these risks. Ideally, one would look for evidence of abnormal protein structures in the athletes’ brains, as well as record data on neurological problems. This approach is made difficult by the fact that CTE, in particular, is most easily diagnosed in autopsy, which makes getting a large sample difficult.

On one side, there is significant circumstantial evidence in favor of the view that brain damage in NFL players is a serious problem. There are numerous cases of CTE among professional athletes. In one study, autopsies of 85 individuals with repeated mild traumatic brain injury found evidence of CTE in 68 of them, 50 of whom were professional, college or high school football players. The neurological damage associated with this condition is not commonly associated with others, making it clear that, at least in principle, there is damage being done.

The possibility of general long-term neurological problems is reinforced by the observation that, in a cohort of 3,300 retired professional football players, death from neurological causes (including ALS and Alzheimer’s disease) is substantially elevated.

There is also some direct evidence — again, from studies of professional players — linking recurrent concussions to depression. One study of retired professional football players showed that those with three or more lifetime concussions had three times the risk of depression relative to those with no concussions. Depression is a well-known risk factor for suicide; however, the facts here do not directly link concussions and suicide.

And when researchers have looked for the football-suicide connection more directly — asking, basically, whether suicide is more common among professional football players — the evidence does not suggest such an effect. One large study compared cause of death for about 3,500 professional football players to cause of death for the general population. Researchers found suicide was less common among professional football players than others (there were nine deaths from suicide in their sample versus an expected 21.8 based on the general population).

Further, studies of depression in this population are possibly confounded by the role of recurring pain in depression. A study of 1,600 retired professional football players found a similar level of depression in this group as in the overall population, although a high level of pain-related depressive symptoms.

Perhaps this is all best summarized by the conclusions from a recent neurological study of 45 retired football players. The researchers found evidence of trauma-related neurological problems in some of the subjects, but they also found that the majority of players had fairly normal-looking brains. The authors suggest that perhaps the view that professional football “frequently leads to chronic brain damage” is overstated.

Some professional footballers have suffered serious consequences, almost certainly linked to their play. But from an epidemiological perspective, the evidence doesn’t yet suggest that suicide risk is broadly elevated among professional football players overall.

What is clear is that more work needs to be done. The most significant holes lie in the epidemiology. There is only the single study on cause of death among football players, and it did not set out to look directly at suicide. Large-scale studies comparing the outcomes for football players — ideally, linked to their playing experiences — to those in the general population are well within reach.