February 20, 2007

Stress and the Cellular Response to Dopamine

Although stress is an inevitable fact of life and most people show remarkable resiliency to it, people with schizophrenia tend to be particularly sensitive to stress. Stress can elevate dopamine levels in the prefrontal cortex (PFC) of the brain. New research into the cellular response to dopamine in the prefrontal cortex, reported in the Schizophrenia Research Forum, is adding to our understanding of how genes, dopamine, and cellular response interact. Scientists hope this understanding will lead to effective treatment for alleviating cognitive difficulties in schizophrenia.

As dopamine levels increase in the prefrontal cortex, cognitive performance improves, reaching a peak and then when dopamine levels become too high performance declines. This type of response, when graphed, forms a "bell-curve" - an inverted "U" shape. Research had already suggested that people with some psychotic ilnesses have different baseline levels of dopamine, and that baseline position on the bell-curve is related to variations in the gene encoding catechol-O-methyltransferase (COMT), an enzyme that degrades dopamine.

Researchers Vijayraghavan and colleagues investigated the response to dopamine levels at the level of the brain cell. Coauthor A. Arnsten explained their study results,

“What we saw is that dopamine D1 suppresses the response to irrelevant information; in other words, it increases the signal-to-noise, but if you have too much dopamine, then it erodes the signal as well as the noise.”

“Under stressful conditions, there is more dopamine released, and those people with the methionine substitution are now on the downward part of the inverted U and their cognition is less than optimal.”

Research findings also indicated that the messenger cyclic-AMP (cAMP) is involved in the bell-curve shaped response to dopamine seen in the prefrontal cortex - previously, cAMP has been shown to mediate dopamine responses in various neurons and experimental settings.

Arnsten believes these findings help to explain the link between stress and schizophrenia symptomatology, and states,

“Our lab has shown for years that stress profoundly impairs cognitive functioning of the prefrontal cortex and, of course, stress can precipitate symptoms of the disease in young people. If we understand why the cortex goes offline in normal people and why people with schizophrenia are particularly sensitive to this, then we may have clues to protect against it.”

Read the Article: The New "Inverted U”—Cellular Basis for Dopamine Response Pinpointed

Source Journal Article: Inverted-U dopamine D1 receptor actions on prefrontal neurons engaged in working memory Nature Neuroscience

Thanks goes to Copper Kettle for pointing out this article to us.

For background information on dopamine, check out these links:
Dopamine - Wikipedia
My Rhymes Are So Dop… amine
Dopamine for Dummies

Related Reading:

Stress Harms Baby's Brain While in Womb

Stress, Dopamine and Unusual Experiences in Everyday Life

The Impact of Stress on the Brain, and Schizophrenia

Trauma Link to Schizophrenia is Strengthened by New Research

Social Stress Has Link to Psychotic Disorders

How Stress Can Worsen Schizophrenia Symptoms


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