L ike bacteria multiplying in a moist laboratory culture, investigations of the link between psychological factors and immune function proliferated during the 1980s. Particular interest centered on probes of disturbed immunity among people experiencing either clinical depression or some type of severe stress, such as bereavement. As data accumulated, a seemingly incurable optimism infected scientists in this relatively new discipline, known as psychoneuroimmunology Perhaps, they mused, we can show that well-chosen psychological treatments shore up immunity and slow the spread of infectious diseases, from the common cold to virally induced cancers. But the field with the long name and high hopes now finds itself dealing with a sense of hard-boiled skepticism. Some researchers say studies of stress, depression and immunity contain flaws that render them inconsistent and inconclusive. Others see the data in a better light but acknowledge that depression may have received premature billing as a powerful immunity-buster. And everyone admits that so far no solid evidence connects psychological states to any specific immune disease. Investigations of stress, depression and immune measures have mainly generated findings in search of meaning, concludes a team led by psychiatrist Marvin Stein of the Mount Sinai School of Medicine in New York City, writing in the February ARCHIVES OF GENERAL PSYCHIATRY. In the mid-1980s, Stein's group conducted a study of bereaved men and severely depressed individuals, finding that infection-fighting white blood cells known as lymphocytes displayed stunted proliferation when chemically stimulated to reproduce (SN: 2/16/85, p.100). In a follow-up study, the researchers observed that while younger depressed patients retained normal immune responses, many middle-aged or older depressed patients suffered declines in two types of lymphocyteshelper T-cells and natural killer cells and in the overall lymphocyte proliferation rate (SN: 5/23/87, p.328). This suggested that depression and immunity dance a complex waltz, not a straightforward two-step. Depression may simply sit the dance out in cases of HIV infection, according to a report in the February ARCHIVES OF GENERAL PSYCHIATRY. For six months, psychologist Judith G. Rabkin of Columbia University in New York City and her coworkers tracked a group of 124 homosexual men who tested positive for HIM the immunity-weakening virus that can lead to AIDS. Those enduring the most depression, emotional distress or stressful life events showed no greater drop in the number of helper T-cells and no more advanced symptoms of HIV infection than the others, the researchers found. Psychiatrist Samuel Perry of Cornell University Medical College in New York City directed a similar HIV investigation last year. Together, Perry's and Rabkin's results suggest that depression and stress do not have a measurable or substantial effect on the immune system in relation to physical disorders such as AIDS, Stein and his colleagues argue. Even when a depression-immunity link turns up, its implications prove murky, observe psychiatrist Denis E Darko of the Veterans Administration Medical Center in San Diego and his colleagues. Among a group of 43 severely depressed men, those with the fewest symptoms of depression displayed lower rates of lymphocyte proliferation than healthy controls, while the most depressed men compared favorably with controls on this lymphocyte measure, Darko's team reports in the March AMERICAN JOURNAL OF PSYCHIATRY. The view that all depressed patients possess stunted lymphocyte function must be reexamined, they conclude. Several problems plague psychoneuroimmunology, according to Stein's group. First, the relationship of laboratory measures, such as lymphocyte proliferation and numbers of T-cells and natural killer cells, to actual infectionor tumor-inspired immune responses remains fuzzy Also, studies of depression and immunity often rely on small samples, lack comparisons with ageand sexmatched controls, and lump depressed patients together regardless of the nature or severity of their mood disorder. Mounting evidence documents extensive two-way communication between the central nervous system and the immune system, Stein and his coauthors note. Further research may show that depressive disorders somehow participate in the chemical correspondence between brain and immune cells, they contend.