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“Mr. Thomas (not his real name) is a very successful 55-year-old businessman, who built his small investment company into a multi-million dollar business. He has been happily married for almost 30 years and has three children who are happy and love him. About two months after his last birthday, Mr. Thomas began complaining of insomnia; he would wake up at three or four in the morning and then toss and turn without returning to sleep until the alarm clock went off. He began to lose weight and suffered from various aches and pains including headaches and stomachaches. His family doctor performed a through physical examination; Mr. Thomas was the picture of physical health. Then, he started to make mistakes at work, looked dreary and distracted to his co-workers, and lacked energy. His wife noticed that his usually robust sex drive has dwindled to complete lack of interest and that nothing, including visits from his children, favorable financial news, and his favorite hobbies, seemed to cheer him up.” (from a New York psychiatrist, Dr. Gorman’s journal)
Mr. Thomas suffers from Depression. Depression is the most common emotional disorder and a devastating psychiatric illness, which can lead to suicide in as many as 15 percent of those who suffer from the condition. Good scientific studies indicate that about 8 percent of Americans will develop depression serious enough to warrant treatment sometime in their lifetime.
Depression is a deceptive illness—with many faces. Sometimes, patients complaining of heartburn or chronic fatigue eventually end up knocking on a psychiatrist’s office by her physician’s referral who, after a series of thorough examination, could not find anything wrong with the patient yet had an insight into the various seemingly unrelated symptoms of depression. In a worse instance, misdiagnosis leads patients to clinic-hopping one place after another, and by the time the patient visits a psychiatrist finally, she may become seriously suicidal.
There is the DSM-IV (Statistical and Diagnostic Manual of Mental Disorders, published by American Psychiatric Association), which is a bible for psychiatrists, and to which physicians refer as a diagnostic tool for various mental disorders, including depression. However, the nature of the illness and its manifestation of symptoms in seemingly irrelevant parts of the body often makes a diagnosis not an easy job.
Even though the right diagnosis of depression is reached, choosing an antidepressant drug is another problem for a physician. Today, psychiatrists still have to exercise intuition and rely on conflicting scientific literature, in selecting appropriate antidepressants that would “work” for a patient. It takes anywhere from one week to three months until an antidepressant drug’s efficacy begins to manifest itself, depending on individuals. Such situations can put suicidal patients in jeopardy for weeks or months until the right compound is selected.
As white blood cells are an indicator for pneumonia, and as insulin for diabetes, if there is a simple biological “marker” for depression, many of the fatal outcomes of depression may be prevented. Those markers could consist of, for example, elevated or reduced levels of selected molecules in the blood.
Approximately 15 years ago, platelets were proposed and found to be a useful model. Platelets are a component of blood, involved in clotting. (This is what makes you stop bleeding when you accidentally cut your hand, instead of an onion!) Platelets are found to store and transport the now famous serotonin, a chemical playing a key role in depression and other mood disorders. Remarkably, it has been also discovered that platelets share the same embryological ancestry with serotonergic neurons. The serotonin transporter molecule, which literally transports serotonin back to where it is released, differs only in the extent of glycosylation (the addition of sugar group to the molecule) between platelets and the brain. In other words, platelets may be regarded as comparable to serotonin neurons in the brain.
The platelet idea is fascinating because it suggests that now we have a “window into the brain.” The brain serotonin neurons are situated in the brain stem region called raphe nuclei. The only way to get there and take a few tissues out is postmortem. That is, only after a person dies. However, then, it would be too late to cure depression! Instead, we may now have an indicator in the blood that tells us what goes on in the brain. And that's the whole idea.
The theory is based on the observation that the density of brain serotonin transporter binding sites in postmortem brain tissues decreased, while the same remarkably consistent findings with platelets were reported. Many laboratories across the United States have been able to replicate such observation, using radiolabeled ligand, a molecule that binds to a receptor specific to serotonin. One of them is paroxetine. Paroxetine is an antidepressant drug, working as the same mechanism as fluoxetine (known by the trademark Prozac). Both Prozac and paroxetine are called Selective Serotonin Reuptake Inhibitor (SSRI) drugs. Literally, these drugs have their effects by blocking serotonin molecules going back to their released sites, called presynaptic terminal, and thus prolonging their effects in the body. Depressed people were found to have a lower concentration of the serotonin transporters in their platelets compared to normal people. The same finding was discovered in the brains of individuals who committed suicide after suffering from severe depression.
Currently, an expansive study is in progress, led by a research group at Emory University in Atlanta. The Emory’s psychiatry team is working specifically with women at risk of postpartum depression. Postpartum depression occurs in a woman who has recently had a baby. While the common "baby blues" is a relatively mild form of sadness and anxiety that dissipate without any need for intervention, postpartum depression is more severe and lasts long, with symptoms that can be debilitating and often require medical treatment.
Postpartum depression is an intriguing model for the researchers to choose because it provides a well-characterized patient group. A clear marker, first of all, precedes the illness, that is, birth; there is a defined period of risk for illness onset; and high-risk samples of women (those with episodes of mood disorder) are identifiable.
So far, Michael Owens and his colleagues at Emory have been looking at whether platelet serotonin transporter binding, Bmax, is altered in postpartum depressed mothers compared to control groups. However, measuring Bmax value is what other researchers in different institutions have been interested in as well. What differentiates Emory group from others is that they are at this time also looking at Bmax values in an individual over a period of timeprepartum, pregnancy, and postpartum. This expansive approach is expected to provide whether depression is state-dependent (present only during episodes), or trait-dependent (uniquely present in depressed patients independent of episode occurrence).
While reductions in the density of brain serotonin transporter binding sites have been previously demonstrated in depressed suicide victims, Yale University’s Robert Malison’s group, an Emory’s collaborating team, was recently able to confirm the same reductions for the first time in living depressed patients. These findings, using SPECT (Single Photon Emission Computed Tomography), provide further support for a prominent role for alterations in serotonergic neurons in the pathophysiology of depression. The dual study of postpartum depression in blood platelets and SPECT study in the living brain, would present comparable data between the two, and decisively indicate whether platelets represent a “window into the brain.”
As with any illness, in depression it is crucially important to obtain treatment as soon as possible, otherwise symptoms may linger and often worsen . The current researches at Emory and Yale may embark on a new horizon of depression study and provide a useful and easily available laboratory “marker” to aid in the diagnosis and selection of medication treatment.
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