August and September are rarely a favorite time of year for the some 36 million Americans who suffer from ragweed allergies. During these weeks, ragweed pollen moves their immune systems into high gear and leads to sneezing, a runny or congested nose, and swollen, itchy eyes.

Many of these ragweed sufferers may also experience a sense of malaise and even depression, suggests a study reported in the July-August Psychosomatic Medicine.

The study was conducted by Paul Marshall, Ph.D., director of the neuropsychology section and the department of psychiatry at Hennepin County Medical Center in Minneapolis; Christine O’Hara, R.N., a research nurse coordinator with the Hennepin County Medical Center; and Paul Steinberg, M.D., director of the division of allergy and immunology at Bassett Healthcare in Cooperstown, N.Y.

Allergists have occasionally reported that persons with ragweed allergies may feel fatigued and mentally "down" during ragweed season. Two large epidemiological studies have also suggested an intriguing link between ragweed allergy and depression.

In one study, of some 700 randomly selected children, those with hay fever were found to be twice as likely to develop a major depressive episode over the next few years than those without hay fever. In the other, of approximately 7,000 adults, those with hay fever were twice as likely to have been diagnosed with major depression within the previous year than those without hay fever.

So Marshall and his coworkers set out to determine whether there is truly a connection between ragweed allergy and fatigue or between ragweed allergy and depression.

They recruited 57 subjects who were either allergic to ragweed or served as controls. Both allergic and control subjects were similar with respect to age, sex, intelligence, and years of education. None was preselected because of complaints about fatigue or depression. They then tested the subjects for fatigue and depression during ragweed season 1996, winter 1997, ragweed season 1997, and ragweed season 1998.

During the testing periods, subjects filled out the Multidimensional Fatigue Inventory, a 20-item, self-report instrument that measured both mental and physical fatigue. They also rated their moods with the Positive Affect Negative Affect Scales, which measured positive mood states such as high energy and full concentration, and negative mood states such as sadness and lethargy. Allergy subjects used no allergy medications to avoid confounding test results. Findings for the allergy subjects per season were compared, as were findings for control subjects per season.

Allergy subjects, the researchers found, reported more mental and motivational fatigue, but not more physical fatigue, during ragweed season than in winter, and the differences were statistically significant. These subjects also reported statistically significant changes in mood between ragweed season and winter, their moods being more negative during the former.

As for controls, there was no statistically significant difference between their mental and physical energy levels in ragweed season and in winter. The same held true for their moods.

Several hypotheses might explain why ragweed sufferers endure more negative moods during allergy season. One possibility, of course, is that people who have allergies to ragweed feel mentally depleted because of the physical suffering that their allergies impose on them. Another is that their mental distress comes from allergy-induced sleep loss. And yet a third explanation—the one Marshall and his colleagues favor since ragweed allergy seems to sap mental but not physical energy—is that ragweed allergy provokes its negative mental effects by acting directly on the brain.

For instance, as the researchers pointed out in their study report, ragweed is known to be capable of forcing nose and lung cells to release cytokines—little proteins that play a role in immune responses. Severely depressed patients have been found to have higher concentrations of such cytokines in their cerebrospinal fluid.

Thus, ragweed might prompt, in persons allergic to it, the release of cytokines from lung cells. The cytokines in the lung cells might then excite the vagus nerve, which innervates the lungs, and the excited vagus nerve might then signal the brain, thereby unleashing malaise and depression.

The study was partly funded by Pfizer Inc.

An abstract of the study, "Effects of Seasonal Allergic Rhinitis on Fatigue Levels and Mood," can be accessed at www.psychosomaticmedicine.org by clicking on "Search an Issue from the Archive" and then the "July-August 2002 issue." ▪