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cross-posted hi all this is the most important finding i've seen about clinical depression (cd) in years let's kiss that old stigma goodbye so long yer history! janet -------------------------------------------------------- Decade of Work Shows Depression Is Physical Bethesda, Md - Psychiatrist and brain imaging researcher Wayne C. Drevets, MD, recalls a patient dealing with breast cancer and unrelated episodes of major depression. The woman found it easier to talk about the cancer because, Drevets said, "with the depression there was nothing tangible to point to or explain to people, even herself." It turns out that there is something tangible. A decade of unusually collaborative research by Drevets and a number of other researchers dramatically illustrates that chronic major depression is as physical as diabetes or heart disease. Dysfunctional metabolism and blood flow in the brain's emotional centers mark two physical manifestations of the mental disorder. Charted with magnetic resonance imaging and positron emission tomography scans, these findings have been replicated in dozens of studies. More recently, Drevets and colleagues have detailed even more startling findings: certain brain regions shrink in volume by nearly 40% during depressive episodes, losing gray matter, mainly glial cells (Nature. 1997;386:824-827). Neurons in these "emotion zones" also change, by cropping dendritic connections to other parts of the brain, in effect short-circuiting an individual's ability to deal with strong negative feelings (Nat Med. 2001;7:541-547). A decade of imaging research points to specific, possibly irreversible, changes in brain structures during and after episodes of major depression. Here, transverse PET scans illustrate a recent finding, that brain structures in individuals at nadir of depression cannot properly listen to the neurotransmitter serotonin (5-hydroxytryptamine [HT]). A series of scans using a radioactive tracer synthesized at the University of Pittsburgh uncovered marked deficiency in 5-HT type 1A receptor activity in depressed individuals. The most pronounced deficits were seen in brain areas critical to emotional stability, including the mesiotemporal cortex (home of the amygdala and the hippocampus) and the midbrain raphe nucleus, which is densely packed with serotonin-producing neurons (Biol Psychiatry. 1999;46:1375-1387). Current antidepressant drugs, such as selective serotonin reuptake inhibitors, appear to compensate for this effect in depressed individuals. Other reports from this realm - namely, that these changes tend to persist - explode the myth that people with serious depression "can just snap back out of it," said Drevets, who is chief, Section on Neuroimaging in Mood and Anxiety Disorders, Mood and Anxiety Disorders Program, at the National Institute of Mental Health, during a recent "Director's Seminar Series" talk here at the National Institutes of Health. "It may be that ... it's not good enough to just 'tough it out,' avoid treatment, and just hope for it to go away. You may be doing damage to some structures." AMYGDALA ABNORMALITIES In particular, researchers describe physical abnormalities and functional problems in the amygdala, part of the limbic system, and in the orbital prefrontal cortex, a network above the eyes that receives signals from the senses and helps regulate emotions. While other areas of the brain have been implicated in depression, much research has focused on these two, which together help orchestrate emotions and subsequent behavior via a tangled web of connections with other vital brain areas. The amygdala plays a particularly stellar role in assigning emotional significance to stimuli. Monkeys with intentionally placed lesions in the amygdala, as well as people with naturally occurring ones, cannot recognize facial expressions; happy, sad, fearful, or ecstatic faces all look the same to them (Nature. 1994;372:669-672). Electrical stimulation of the amygdala provokes strong reactions, instantly triggering vivid recall of emotionally charged life events (Cortex. 1985;21:7-24). And as shown in a well-known series of experiments by Antonio Damasio, MD, PhD, at the University of Iowa College of Medicine, Iowa City, the amygdala lights up with activity after mentally healthy individuals see a fearful or sad face (Neuropsychologia. 1999;37:1111-1117). In depressed individuals, these reactions are more pronounced, as seen on various types of brain scans. The amygdala may even get stuck in an overactive state, as it consumes more glucose (a general sign of brain activity) in chronically depressed patients than in controls (Pharmacol Biochem Behav. 2002;71:431-447). Drevets said this hyperactivity apparently triggers symptoms via the amygdala's extensive links with other parts of the brain, which originate in a dense pack of output neurons called the central outflow nucleus. "You can get a good idea of what depression syndrome looks like by going through the list of what's impacted by [the central outflow] nucleus," said Drevets, ticking off an inventory of symptoms including social withdrawal, slowed metabolism, inactivity, decreased motivation, gastrointestinal disturbances, and wakefulness in the middle of the night. ROLE OF ORBITAL CORTEX After the amygdala generates a strong emotion and the accompanying autonomic reactions - say, fear followed by perspiration, tachycardia, and a spike of adrenalin - the nearby orbital cortex keeps these mental and physical manifestations from spiraling out of control. It does this via its own network of connections, which stretch into nearly all of the brain regions linked to the amygdala. Together, the two areas comprise the yang (orbital cortex) and yin (amygdala) of emotional responses, the existence of which were elucidated 5000 years ago in the founding text of traditional Chinese medicine, The Yellow Emperor's Classic of Medicine: "Yang stands for peace and serenity; Yin stands for confusion and turmoil. . . ." (Ebrey P. Chinese Civilization: A Sourcebook. 2nd ed. New York, NY: Free Press; 1993:77). Or as Drevets put it, "The more you activate your orbital cortex, the less depressed you feel. The more you activate your amygdala, the more depressed you feel." Studies on healthy individuals in various emotional states, for example, from the verge of tears to delighted, confirm the seesaw effect. Curiously, though, imaging studies show that depressed individuals do have more orbital cortex activity than healthy controls; it looks as if the area is straining to suppress the emotional sparks thrown off by the amygdala. Add that finding to the pathologic data that show the orbital cortex to be shrunken in those who are depressed and "you get a sense that [the orbital cortex] may not be working right," said Drevets. "So, after looking at all of the data, the hypothesis is that dysfunction of this area, rather than too much or too little activity, is responsible for the depression." More generally, these findings hold for other involved areas of the brain. The regions responsible for regulating emotion have lost glial cells and dendritic connections, rendering them dysfunctional. In contrast, the regions that generate or express emotion are uninhibited and overactive. "ALL IN THE HEAD" Exactly how or why these physical changes occur is unknown. Most patients in imaging studies of major depression come from families with a history of the disorder. This has led some brain researchers on a search for genes that heighten risk through, perhaps, a hypersensitivity to certain hormones or other stimuli. What is known is that once a person has survived his or her first bout with depression, more will likely follow. Drevets thinks that the odds for repairing the brain damage decrease with each episode, making treatment with antidepressants, most of which appear to confer some neuroprotective benefits, even more crucial. "You still have this concept floating around ... that people must have deep-seated psychological problems that they aren't dealing with, that's why they're depressed," he said during a phone interview. "Some clinicians think that the medicines just mask the underlying problem." An ever-growing number of research reports refutes that notion, at least for those with a family history of major depression. The recent evidence also supports clinical impressions that go back to earlier times. Even Sigmund Freud, in his 1917 essay, Mourning and Melancholia, noted that some forms of depression suggest "somatic rather than psychogenic affections." The new brain imaging research thus gives a very different meaning to the idea that the disorder is "all in the head." Brian Vastag 2002 American Medical Association. All rights reserved. http://jama.ama-assn.org/issues/v287n14/ffull/jmn0410-1.html janet paterson: an akinetic rigid subtype, albeit perky, parky pd: 55/41/37 cd: 55/44/43 tel: 613 256 8340 email: [log in to unmask] smail: 375 Country Street, Almonte, Ontario, Canada, K0A 1A0 a new voice: http://www.geocities.com/janet313/ ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn