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RESEARCH BRIEFSMost People with Major Depression Lack TreatmentMillions of Americans suffer from major depression each year, and most are not getting proper treatment for this debilitating disorder, according to a two-year nationwide study reported in the June 18 Journal of the American Medical Association. The study, led by HMS researchers, found high rates of major depressive episodes (MDE) in all segments of the U.S. population. "This is the first study to assess clinical severity of depression in a community sample," said survey leader Ronald Kessler, HMS professor of health care policy. "Critics have suggested that depression was overestimated in earlier studies because of many people with mild depression being included even though they really don't need treatment. But we built in a state-of-the-art clinical severity assessment, and we found that the majority of people with MDE are severe cases and only a small minority are mild cases." The average person with MDE in the past year reported an average of 35 days he or she was unable to work or carry out other normal activities because of depressive episodes. "These findings confirm that depression is an enormous societal problem, both in terms of the number of people involved and in terms of clinical severity," Kessler said. Although most people reporting depression in the past 12 months got some treatment--an improvement over earlier findings--only one in five received treatment that met minimum standards established by the Agency for Health Care Policy and Research. The study found that inadequate treatment was due to inappropriate dosing of antidepressants on the part of physicians, patient discontinuation of treatment, and the use of unproven treatments outside the medical and mental health systems. "While recently increased treatment is encouraging, inadequate treatment is a serious concern," Kessler and his co-authors write. "Emphasis on screening and expansion of treatment needs to be accompanied by a parallel emphasis on treatment quality improvement."
Disruption of Immune Function in Mice Leads to GlaucomaScientists at Schepens Eye Research Institute have shown that mice with an abnormal immune response in their eyes go on to develop a form of glaucoma. Pigmentary glaucoma occurs when pigment particles disperse from the iris and clog the eye's drainage system. This causes pressure to build up, potentially damaging the optic nerve and affecting vision. The normal eye is an immune privileged site, which suppresses inflammatory immune responses that could lead to blindness. The study, published in the May 19 Journal of Experimental Medicine, describes a disruption of immune privilege in the eyes of mice that go on to develop pigment dispersion and, finally, pigmentary glaucoma. This loss of immune suppression suggests that "maybe there is an abnormality in immune privilege that is an underlying basis for the pigment dispersion syndrome," said Wayne Streilein, the Charles L. Schepens professor of ophthalmology at Schepens Eye Research Institute and senior author of the study. Streilein, Jun Song Mo, HMS instructor in ophthalmology at Schepens, and their colleagues found both pigment and a mutated form of Gpnmb, a gene associated with pigment production, in bone marrow-derived cells in diseased eyes of the mice. The discovery suggests that the mutation in these immune cells may prevent proper elimination of dispersed pigment from the eye and may generate an inflammatory response that would normally be suppressed. To verify the link between this response and pigment dispersion, the researchers transplanted bone marrow cells from healthy mice into irradiated mice with the mutated Gpnmb gene. These mice did not develop inflammation or pigment dispersion in their eyes, strengthening the argument that the mutant bone marrow-derived cells did, indeed, play a role in disease pathogenesis. Appreciating that an immune abnormality may contribute causally to pigmentary glaucoma opens the door for new glaucoma and other blinding eye-disease treatments, said Streilein. "If this truly is an inflammatory eye disease, and we can work out its pathogenesis, then we might have an approach to that vast number of people with inflammatory eye diseases for which nothing works." --Gaia Remerowski
Heightened Activity in Brain Region Tied to Inhibited TemperamentPsychologists have brooded for centuries over why some individuals seek out new people, things, and places while others shun them. Researchers have suspected that the difference between shy and outgoing people lies to some extent in their biological makeup, in particular their brains. But they have been unable to locate where the neurological roots lie. Now, a team of HMS scientists reports that the amygdala, an almond-shaped cluster of neurons buried below the prow of the brain, may provide clues to this fundamental human distinction. Carl Schwartz and his colleagues found that adults who had been identified as having shy, inhibited temperaments when they were two years old exhibited greater amygdalar activity when shown pictures of unfamiliar faces than did adults who had been classified as uninhibited or outgoing. The findings, which appear in the June 20 Science, are of more than theoretical interest. Inhibited temperament is a risk factor for generalized social anxiety disorder and, indeed, a better understanding of how biological structures such as the amygdala interact with environmental factors could lead to a better understanding of the causes and treatments of this destructive psychiatric disease. "There is no way to intervene early in the life of a child to prevent suffering without understanding these developmental risk factors," said Schwartz. An HMS assistant professor of psychiatry at Massachusetts General Hospital, Schwartz began to explore the possibility that the amygdala might play a role in temperament nearly 15 years ago while working with Jerome Kagan, the Daniel and Amy Starch research professor of psychology at Harvard University. Kagan and his colleagues had shown that inhibited children exhibit striking physiological features. Their heart rate is faster and more variable; their pupils dilate more when solving problems; and they produce more cortisol than uninhibited individuals. "The question was, what part of the brain had to be hyperactive to produce those physiological effects?" said Schwartz. Though the amygdala is best known for its role in emotion, it also regulates autonomic responses. Kagan and Schwartz became intrigued by the possibility that the structure might play a role in temperament. But it was years later, after becoming trained in functional magnetic resonance techniques, that Schwartz would have a chance to explore the idea along with Kagan and colleagues. While their findings appear to add another feather to the amygdala's hat, they raise questions about its old image as a master of emotion. For example, this nerve cell cluster is often associated with the fear response. Yet the unfamiliar faces shown to Schwartz's subjects were neutral, not threatening. He thinks that the amygdala's real function may be to detect new and ambiguous stimuli and that fearful stimuli might fall into that broader category. "So a wider role for the amygdala could be that it is involved in the detection of novelty and ambiguity," he said. He and his colleagues made yet another pot-stirring discovery, one that could have implications for the diagnosis and treatment of generalized social anxiety. As it turned out, two of the inhibited subjects in the study were diagnosed with the disorder. Yet they displayed the same pattern of amygdalar activity as the inhibited subjects who did not have a psychiatric diagnosis. "If I had started with people with anxiety disorder, we would have found a difference in the amygdala. I might have gone on to say this is a marker for the disease. Wrong," he said. "This a marker for the risk factor of inhibited temperament." Schwartz believes the rush to discover new drug targets could lead some to confuse disease markers with risk factors, not just in the case of social phobias but in other psychiatric disorders. "If nature is being that subtle in this case--well, she is usually kind of consistent in that way." --Misia Landau |
