Can aspirin fight anger?

"Keep calm and carry an aspirin to beat your temper," reports The Daily Telegraph's front page.

This risible headline comes from a study that did not look at aspirin or at people who have a "quick temper".

In fact, the study investigated whether people with a condition called "intermittent explosive disorder" (IED) had higher levels of two proteins that indicate inflammation.

Researchers compared people with IED to two groups of people who did not have aggressive outbursts – one group with a different diagnosis of mental illness and the other with no mental illness.

They found that levels of C-reactive protein (CRP) and interleukin 6 (IL-6) were significantly higher in people with IED. Higher levels of CRP and IL-6 in any group were also associated with increased levels of aggression.

But as this was a case-control study, it can only show that there is an association between these inflammatory markers and aggression. It does not tell us that inflammation causes aggression or that reducing the levels of inflammation would have any effect on aggression.

Where did the story come from?

The study was carried out by researchers from the University of Chicago and the University of Colorado. It was funded by the National Institute of Mental Health and a grant from the University of Colorado, Denver.

The study was published in the peer-reviewed medical journal, JAMA Psychiatry.

The Telegraph coverage has made the huge and misguided assumption that simply taking aspirin could be the answer to both treating intermittent explosive disorder and calming people with a quick temper.

What kind of research was this?

This was a case-control study looking at the level of two inflammatory markers in people with and without a history of aggression and impulsivity. This study can only show an association. We cannot tell whether aggression and impulsivity occur before or after inflammatory markers are raised merely from the results of this study.

Further research in the form of a randomised controlled trial would be required to determine whether aspirin or other anti-inflammatory drugs are effective treatments for intermittent explosive disorder or calming a quick temper, as suggested by the Telegraph.

What did the research involve?

Researchers measured the levels of two markers of inflammation in three groups of people to see if they were related to aggression and impulsivity.

Participants were recruited from clinical settings and through newspaper advertisements. People were excluded if they suffered from bipolar disorder, schizophrenia or mental "retardation". They were medically examined, screened for any drug abuse, and mental illness was diagnosed using the standard DSM-IV criteria (read more about the DSM).

The participants were put into three groups:

• 69 had intermittent explosive disorder
• 61 had a current mental illness – depression, anxiety, non-IED impulse control disorder, eating disorder, somatoform disorder or personality disorder ("psychiatric" controls)
• 67 had no mental illness ("healthy" controls)

Eight standard questionnaires and a structured interview were used to assess:

• the number of times a person had engaged in aggressive or impulsive behaviour in their life
• a person's disposition to act aggressively or impulsively as a personality trait
• life history of suicidal behaviour
• symptoms of depression
• the number of stressful life events over the previous six months
• personality
• psychosocial functioning

Participants did not take any medication for at least four weeks and then had a blood test for C-reactive protein (CRP) and interleukin-6 (IL-6).

Statistical analyses were performed to look for differences between the groups and the levels of CRP and IL-6.

They also analysed the results to see if any of the following could account for any differences seen:

• body mass index (BMI)
• age
• depressive symptoms
• psychological stress
• history of psychiatric treatment

What were the basic results?

People with IED had higher inflammatory marker levels than either "healthy" controls or "psychiatric" controls. The results did not change when BMI, age, depression or recent psychological stress were taken into account.

People with IED and a current or previous mental illness or personality disorder had significantly higher levels than the "psychiatric" control group, and previous history of psychiatric treatment did not change these results.

Across all participants, higher levels of aggression and impulsivity increased the levels of CRP and IL-6, even after BMI, age, depression or recent psychological stress were adjusted for.

How did the researchers interpret the results?

The researchers concluded that, "These data suggest a direct relationship between plasma inflammatory processes and aggression in humans."

Conclusion

This study showed that aggression and impulsivity were associated with slightly – but significant – increased levels of two inflammatory markers. It does not explain why this association is present.

There are a number of limitations of this study. These include:

• The highest CRP reported in this study was 5mg/l, which is well within normal levels.
• Although all participants were reported to be physically healthy, no other blood tests were performed to look for causes of the difference between the levels of inflammatory markers, such as a mild infection.
• The researchers only performed the blood test once, when in fact inflammatory markers go up and down according to whether there is an infection or inflammatory process going on.
• There was no attempt to record when the last outburst of aggression was compared to the timing of the blood test.
• The study was heavily reliant on self-reporting, using eight questionnaires. There is also the possibility that "questionnaire fatigue" caused inaccurate reporting.
• It is not clear what kind of treatment anyone was receiving for their mental health problems. All participants were not on any medication for four weeks prior to the blood test, but it's not clear if they were told to stop medication for the study or if people who were on medication were excluded.
• All people in the IED group also had a diagnosis of a personality disorder, and most had a current or previous history of depression, anxiety or substance dependence. This makes any interpretation of the results complex.

Use of anti-inflammatory medication such as aspirin was not assessed in this study, and nobody should follow the Telegraph's advice to pop an aspirin if you've got a bad temper.