Seasonal allergies linked to depression, suicide.

PHILADELPHIA -- Seasonal allergies might be associated with fatigue and mood disorders, including depression, in certain patients, Dr. Tedor T. Postolache reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

These possible associations are suggested by a series of observational studies documenting the correlation of a spike in suicides during the spring months and the sudden release of tree pollens after the relatively pollen-free winter, said Dr. Postolache, a psychiatrist and director of the mood and anxiety program at the University of Maryland, Baltimore.

Allergies that occur at other times of the year might have the same effect, but the impact of tree pollen on suicide rates can be seen in large populations because it is so dramatic after winter. Dr. Postolache and his associates first reported on a possible link between the tree pollen season and an increased suicide rate in women several years ago (Mol. Psychiatry 2005;10:232-5).

"Allergens may generate an immune response in vulnerable individuals, with inflammatory processes reaching brain centers involved in modulation of risk factors for suicide," he said at the meeting.

Among the evidence that links allergy and depression is a 1999 study of more than 6,800 adults that showed that patients with hay fever were twice as likely to have been diagnosed with major depression in the past 12 months. And in the same group, patients with a history of receiving allergy shots or having a positive skin test reaction were more than three times as likely to have been diagnosed with major depression in the preceding 12 months.

A population-based study of an unselected group of more than 12,000 Finns born in 1966 found that maternal atopy was linked with a nearly twofold increased risk for depression in women at any time in life. Women who themselves were diagnosed with atopy and also had a mother with atopy had a fourfold increased risk of developing depression, compared with nonatopic women with nonatopic mothers (J. Allergy Clin. Immunol. 2003;111:1249-54).

A link between allergy and suicide was recently explored more directly by Dr. Postolache and Danish collaborators (including Dr. Ping Qin, an epidemiologist at Aarhus [Denmark] University) in a study of more than 21,000 Danes who committed suicide during 1981-1997. The medical data were obtained through the National Patient Register in Denmark. In this case-control analysis, data were obtained for 20 control individuals for every suicide case by randomly finding people from Danish records who lived at the same time, and matching for gender and age.

Preliminary analysis of these data indicated that men and women had a similarly increased risk for suicide that was linked to having allergies. Among all people in the study, those with an allegry were about two times more likely to have committed suicide, compared with similarly aged people without history of an allergy, Dr. Postolache said.

Dr. Postolache suggested some possible physiological mechanisms that could mediate the link between allergies, especially aeroallergen allergies, and psychiatric effects, based on evidence from animal studies. Cytokines released in the nose because of an allergic reaction can activate indoleamine 2,3-dioxygenase, which inhibits serotonin production. Cytokines in the nose also may upset the hypothalamic-pituitary-adrenal axis. Nasal cytokines can affect the brain through signals sent via the vagus and olfactory nerves.

In addition, sleep impairment, a suicide risk factor, can result from allergic rhinitis and from the decongestants often used by patients with active allergies.

Certain medications used to treat allergic rhinitis will produce symptomatic improvement, but will not reduce cytokine production or effects. It is possible that the best way to interrupt the cytokine process is by using an intranasal corticosteroid, which will reduce or stop cytokine production and subsequent effects, Dr. Postolache said in an interview.

Among the agents that might not be effective for disrupting the allergy and mood disorder link is montelukast (Singulair), a leukotriene receptor antagonist that has indications for allergic rhinitis and asthma. In late March, the Food and Drug Administration said it was investigating a possible link between the use of montelukast and behavior/mood changes, suicidality, and suicide.

Dr. Postolache cautioned that it was premature to make any firm link between montelukast use and suicidality. "The relationship could be spurious. For example, montelukast may be given selectively to a more refractory population with allergies. In addition, montelukast may not reduce cytokine production or [the effects of cytokines] because cytokines act via a parallel, leukotriene pathway. So it might be that montelukast may not itself induce suicidal behavior; instead, it might prevent suicidal behavior less than other medications."

Dr. Postolache emphasized the importance of differentiating between depression and fatigue, a common symptom of allergy. The differential diagnosis can be helped by asking patients about their views of the future (their level of hopelessness), the past (a gauge of guilt), and their self-image (their sense of worthlessness).

Based on epidemiologic estimates, at least 20% of women and about 10% of men with allergies also have a depressive disorder, an anxiety disorder, or both, he noted.

BY MITCHEL L. ZOLER

Philadelphia Bureau