May 23, 2004
Depressed People Have Fewer 5-HT2A Serotonin Receptors

Mark A. Mintun, M.D., professor of radiology and of psychiatry at Washington University School of Medicinem and colleagues have found that depressed people have fewer 5-HT2A serotonin receptors.

To get a look at how the brain works differently in depressed patients, Mintun and colleagues studied 46 people with active depression and compared positron emission tomography (PET) scans of their brains to scans from 29 people who were not depressed. The team was measuring levels of a particular type of serotonin receptor called the 5-HT2A serotonin receptor.

Mintun has been on the trail of serotonin receptors for years. "The 5-HT2A receptor in this study is the most common of several types of serotonin receptors, so we thought this would be a good place to start," he says.

Almost a decade ago at the University of Pittsburgh, Mintun and radiochemist Chester Mathis, Ph.D., developed a method of labeling the 5-HT2A serotonin receptor with a chemical called altanserin. The altanserin sticks to the serotonin receptors and allows the PET scanner to take pictures of them.

Because most people with depression get better when their serotonin levels increase after treatment with SSRIs, Mintun initially believed the PET scans would reveal high levels of serotonin receptors in brain structures linked to depression. The hypothesis was that because less serotonin was available, the brain would try to compensate by making more receptors.

But that's not what they found. In the February issue of the journal Biological Psychiatry, Mintun and colleagues report that the depressed people actually had fewer serotonin receptors throughout the brain and significantly fewer receptors in a key structure called the hippocampus, an area that acts as a gateway between memory and mood, among other processes.

Anti-depressant drugs seem to protect the hippocampus and make it bigger.

Meanwhile, in a parallel series of depression studies, co-author Yvette I. Sheline, M.D., associate professor of psychiatry, radiology and neurology, was learning from magnetic resonance imaging (MRI) scans of depressed patients that the hippocampus is smaller in patients with depression. Sheline also has found that antidepressant drugs seem to have a protective effect and prevent some of the volume loss she has observed.

Putting it all together, Sheline says the volume loss in the hippocampus might be to blame for the low number of serotonin receptors, rather than the other way around.

"Although it's clear that serotonin is involved in depression, it may be that the volume loss we have observed is due to damage in cells in the hippocampus, which then cannot process serotonin effectively," Sheline says. "Perhaps the low number of serotonin receptors is related to cell damage in the hippocampus rather than the damage and volume loss being caused by problems in the serotonin system."

A longitudinal study started with a population that is not depressed and then followed hippocampus size at the onset of depression and after an extended period of being depressed would go a long way in answering the question of what comes first and causes depression and what changes are a consequence rather than causes of depression.

The anti-depressant drugs known as selective serotonin reuptake inhibitors (SSRIs) such as Zoloft (sertraline), Paxil (Paroxetine), and Prozac (fluoxetine) are known to take a few weeks to cause a beneficial effect and also we know that only after taking them a few weeks hippocampal stem cell division is increased. So it might be that taking them leads to an increase in neuron formation for neurons that have serotonin receptors and that part of the benefit of the SSRIs is that they increase the number of serotonin receptors by causing neural stem cell division.

This report is another indication that depression is gradually being figured out piece by piece. We will some day reach the point where depression becomes reliably curable in the vast bulk of the populace with treatments that have little or no side effects. Given that the rate of advance of biological science and biotechnology are accelerating my guess is that depression will be curable for the vast bulk of the population within an absolute maximum of 30 years and probably more like 20 years.

Also check out some of my other serotonin-related posts: Serotonin Transporter Gene Linked To Depression, Binge Drinking, Serotonin Receptor Concentration Varies Inversely With Spirituality, Excess Serotonin 5-HT1A Receptor Increases Depression, Suicide, Serotonin Receptor Concentration Correlates With Anxiety , and Serotonin Receptor Variation Causes Worse Short Term Memory.

Share |      Randall Parker, 2004 May 23 08:27 PM  Brain Emotion Alteration

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