VIENNA — A diagnosis of generalized anxiety disorder (GAD) is associated with a significantly increased risk for cancer mortality in men, but not in women, new research shows.

In the largest study to date to look at the link between anxiety and cancer mortality, Olivia Remes, a PhD student in the Department of Public Health and Primary Care, University of Cambridge, United Kingdom, and colleagues found that a diagnosis of GAD more than doubled the risk for cancer mortality in men.

Crucially, this association held after adjusting for factors known to be associated with cancer mortality risk, such as smoking, alcohol intake, physical activity level, and chronic physical conditions.

The study was presented here at the 29th European College of Neuropsychopharmacology (ECNP) Congress.

Early Warning Sign?

Remes told Medscape Medical News that although the findings do not explain why GAD may increase cancer mortality risk, there are some potential explanations for the association.

"Some studies have shown that men tend to wait a while to go to the doctor when they have a health problem, and they go when the disease tends to be in later, more advanced stages compared to women.

"So if they have anxiety, which we think could an early warning signal for poor health, then they might not think that it's a big deal, not anything that needs to be seen by a doctor. But if it is this underlying signal for poor health, then it could be triggering negative health consequences, like cancer development, and therefore men might be more likely to die earlier from cancer."

Remes pointed out that anxiety has been shown to trigger inflammation as well as immunosuppression and overactivation of the stress systems, "and this could trigger diseases like cancer down the road.

"So it's not just you have an anxious personality, it's something more serious." As a consequence, the study authors are calling for researchers, policy makers, and clinicians to focus greater attention on anxiety as a major health problem, she added.

Although some previous studies indicate that anxiety is linked to an increased risk for death from major causes of mortality, others have not shown such an association or have even found negative associations between anxiety and mortality.

Lifestyle Factors at Play?

The researchers noted that there are several mechanisms through which anxiety may be associated with pathogenesis and premature mortality. They used a large, longitudinal population study to determine that GAD is associated with excess cancer deaths.

The investigators examined data on 8799 women and 7139 men older than 40 years who took part in the European Prospective Investigation of Cancer in Norfolk, the United Kingdom, and who had completed a baseline health check between 1993 and 1997. During follow-up, the participants were given a series of questionnaires on demographic characteristics, social class, medical conditions, psychiatric disorders, and behavioral risk factors.

Between 1996 and 2000, study participants completed a health and life experiences questionnaire, which was used to establish a diagnosis of GAD in line with DSM-4 criteria. The vital status of the participants was then ascertained from the UK Office of National Statistics for the period 1996 to 2015.

A diagnosis of GAD during the past year was made in 2.4% of women and 1.8% of men.

Women with past-year GAD were more likely to be younger than 65 years, to have a high disability level, and to be current smokers than those without GAD, and they were substantially more likely to have been diagnosed with major depression in the past year.

Like their female counterparts, men diagnosed with GAD during the past year were also more likely to be younger than 65 years than those without such a diagnosis. However, they were also more likely to be single, to have a high level of disability, and a higher body mass index. They were also more likely to be physically inactive and to be current smokers.

Men with a diagnosis of GAD were markedly more likely to have been diagnosed with major depression in the past year than men without GAD.

Twice the Risk

After adjusting for age, marital status, educational level, social class, major depressive disorder, chronic physical conditions, disability, smoking, alcohol intake, and physical activity level, the team found that in men, GAD was associated with a significant increase in cancer mortality (hazard ratio, 2.14).

There was no significant association between GAD and cancer mortality in women (fully adjusted hazard ratio, 1.03).

Remes said the findings need to be replicated in further studies. She noted that although the current investigation is the largest study to date to examine the impact of GAD on cancer mortality risk, the absolute numbers of individuals with GAD were relatively small.

She said that it is "a large sample, but I don't think it's large enough.

"The next step that we will be doing is to look at anxiety symptoms, because a lot more people have anxiety symptoms rather than meet this strict definition for GAD, based on criteria set out by the DSM," she added.

An issue with previous studies that have looked at more general anxiety symptoms is that they have been inconsistent in their approach.

"A lot of these studies that have looked at anxiety and mortality have assessed a general proneness to anxiety, which isn't clinically meaningful or relevant. It's not useful for physicians," Remes said.

"There are so many ways that people have looked at it. There isn't a consistent definition. Some studies asked, on a scale of 1 to 5, how anxious do you feel? That's not really an anxiety disorder. That could be just a more stressed-out personality type," she added.

No Surprise

Commenting on the findings, David Nutt, MD, PhD, Edmond J. Safra Professor of Neuropsychopharmacology at Imperial College London, United Kingdom, and former president of the ECNP, noted, "As a psychiatrist who used to run one of the very few clinics in the UK that specialized in the treatment of people with severe anxiety disorders, these results do not surprise me.

"The intense distress that these people suffer often on a daily basis is usually associated with a great deal of bodily stress. That is bound to have a major impact on many physiological processes, including immune suppression of cancerous cells," he said.

"I fully support the authors' statement that much more information and investment need to be given to the diagnosis and treatment of anxiety disorders," Dr Nutt added.

The study was funded by the Medical Research Council and Cancer Research UK. Olivia Remes has received funding from the National Institute for Health Research. The other authors and Dr Nutt have disclosed no relevant financial relationships.

29th European College of Neuropsychopharmacology (ECNP) Congress. Abstract P.4.a.012. Presented September 20, 2016.