If you have ever jumped at a loud noise and felt an adrenaline rush, you have experienced the effects of corticotropin-releasing hormone (CRH). In the body, this hormone triggers the familiar fight-or-flight response—racing heart, shortness of breath, sweaty palms. In the brain, however, it acts as a chemical messenger, playing a role in anxiety and depression. That role, a new study suggests, is more complex than anyone expected.
Because animal research from the past decade found that CRH contributes to anxiety and depression, drugs were developed that would block its actions in the brain. Clinical trials of these antianxiety and antidepressant drugs in human patients, however, have been disappointing. The new study, published last September in Science, shows why. Jan M. Deussing, a molecular biologist at the Max Planck Institute of Psychiatry in Munich, and his colleagues genetically altered mice so that some of their brain cells would be unable to detect the presence of CRH because they lacked the proper receptors. When the receptors were missing from neurons that produce the neurotransmitter glutamate, the mice displayed less anxiety, as expected. Yet when the receptors were missing from neurons that produce dopamine, the mice became more anxious.
These two different neuron types, when interacting with CRH, “have exactly opposite effects in terms of anxiety-related behavior,” Deussing says. Because the unsuccessful drugs limited the amount of the hormone available to all types of neurons, they ended up blocking its actions at neurons that both produce and prevent anxiety. The finding reaffirms scientists’ growing understanding that mood disorders do not result from a simple chemical imbalance—too much or too little of one neurotransmitter—but rather from subtle changes in many systems in the brain. “The network is much more complex than we thought before,” Deussing says.
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This article was published in print as "Double-Edged Hormone."