What Accounts for Link Between Allergy and Suicide?

Although seasonal affective disorder (SAD) occurs most often in winter, the incidence of suicide peaks in spring. Growing evidence is emerging to suggest possible biochemical connections between allergy and both suicidal behavior and mood symptoms (see Original article: Cytokines Could Play a Role).

The phenomenon of a spring peak in suicide rate has been observed in both hemispheres and in various climates. The epidemiological evidence from countries such as the United Kingdom, Taiwan, Finland, and the United States has puzzled many researchers. A smaller spike in suicide rate in late summer and early fall has also been observed.

In a study published in the March 2005 Molecular Psychiatry, Teodor Postolache, M.D., director of the Mood and Anxiety Program and an associate professor of psychiatry at the University of Maryland, and colleagues identified a significant association between tree-pollen peaks in spring and nonviolent suicide in women. They used U.S. suicide data and pollen counts from 1995 to 1998.

The rate of nonviolent suicide in women younger than age 65 during peak tree-pollen periods was twice the rate in the periods before pollen season. The nonviolent suicide rate in women aged 65 or older during the peak pollen periods was as high as 4.6 times that of the pre-pollen period, they found.

Postolache and Leonardo Tonelli, Ph.D., an assistant professor of psychiatry at the University of Maryland, have been investigating the biological mechanisms for the neuropsychiatric effects of allergy since 2004 with grant support from the National Institute of Mental Health, NARSAD, and the American Foundation for Suicide Prevention.

“Ongoing epidemiological studies from Denmark, the U.S., and other places are currently investigating a connection between the seasonal trends of allergy and suicide,” Postolache told Psychiatric News.

Allergy Changes Animal Behaviors

Tonelli and colleagues have been testing the effects of upper-respiratory-tract allergy on the behaviors of mice and rats in the laboratory. “There is no animal model for suicidal behaviors,” Tonelli said in an interview with Psychiatric News. “We have to use surrogate behavioral indicators to model the known suicide risk factors, such as anxiety, depression, and aggression.”

In a series of experiments, Tonelli and colleagues artificially induced allergy in rats and mice that are allergic to pollen or chicken egg. One experiment is the open-field test, in which an animal is placed in an open arena, which is analogous to “an empty basketball court at night to a human.” The total times it runs along the wall and ventures into the center of the open field are recorded.

It has been established that the more anxious an animal is, the less time it spends in the center of the open field and the more it stays by the walls. After controlling for physical function (measured by the time spent running along the walls), animals with induced allergy showed significantly higher anxiety levels than those without allergy, Tonelli said.

Other behavioral tests, such as the elevated “plus” maze test used to evaluate anxiety, confirmed that allergies can induce anxiety. Tonelli and colleagues have also found that induced allergy is associated with increased social isolation when the rodent is placed in a group. Curiously, animals with allergy did not show signs of increased depression in behavioral experiments.

Also interesting is their discovery that although induced allergy alone does not significantly increase aggression, it does provoke increased aggressive behavior if the animal is subjected to a stressful condition. In other words, the interaction between the environment and the physiological reaction to allergens can lead to observable behavioral changes, which reflect increased anxiety, isolation, and aggression, in both rats and mice.

Indirect Links Seen in Humans

Postolache, Tonelli, and colleagues have been seeking biochemical evidence to explain this possible association between worsening mood and allergy in humans. A study they published in the August 2007 Journal of Affective Disorders indicated that people who reported mood worsening when exposed to pollen had also reported a greater range of seasonal mood variation and were more likely to have the nonwinter type of SAD.

“Epidemiological studies have repeatedly shown some kind of connection between depression and allergy,” said Postolache. In addition to the worldwide evidence of suicide rate peaking in spring, a recent large, observational study in Norway, published in the March Journal of Affective Disorders, showed that the prevalence of comorbid depression and anxiety peaks in spring.

In addition to nasal allergy, a study in the May Annals of Allergy, Asthma, and Immunology by Diana Clarke, Ph.D., and colleagues found that asthma was significantly associated with suicide attempts, but was not associated with suicidal ideation without attempts.

To further complicate the picture, the biological factors contributing to the act of suicide remain unclear. The vast majority of people with suicidal ideation do not act on it. Suicide research has suggested that aggression is a key ingredient in pushing some people into making attempts. Tonelli and Postolache believe that the combination of heightened anxiety and aggression, induced by a stressful environment, seen in animal models, may be relevant to research on human suicidology.

Beware of Nonwinter SAD

Regardless of the actual neuroimmunological links that may be in play, Postolache recommends that psychiatrists be mindful of any seasonal variations in patients' mood and provide closer monitoring in spring if mood is thought to be linked to the season.

“[A psychiatrist] should ask about the patient's allergy history ... and explore the allergic patient's exposure to pollen, the most important seasonal aero-allergen, and dust-mite feces, the most important perennial allergen,” he said. Patients who have many allergy symptoms should be referred for appropriate diagnosis and treatment.

Similarly, allergists and general practitioners should ask their patients about symptoms of depression, anxiety, and suicidal ideation and refer them to psychiatrists for specialized care if necessary.

Meanwhile, Postolache, Tonelli, and colleagues plan to continue searching for the biological connection between seasonal allergies and psychiatric disorders in clinical and animal studies. “We are nowhere near knowing what these connections are,” Postolache said. ▪