Stress and Balance

Our responses to threatening situations depend on two fear-regulation circuits, a recent study shows.

"I wish this job wasn't so heavy on the glutamate."

A well-balanced sense of fear is crucial to our survival: too much, and we’d descend into panic attacks every time we were startled. Too little, and we might not react when survival is crucial. As it turns out, this balance is maintained by two opposing brain circuits, both involving corticotropin-releasing hormone (CRH) and its type 1 receptor (CRHR1).

The body releases CRH in response to stressful stimuli. This substance creates some pretty interesting effects in different parts of the brain – in areas like the forebrainhippocampus, and thalamus, it triggers the release of the excitatory neurotransmitter glutamate, which contributes to anxiety behavior.

But as a new paper in the journal Science shows, CRH helps with a completely different set of responses in the midbrain - it directly triggers the release of dopamine, which reduces fear and increases confidence. This means CRH and its type 1 receptors are involved in a self-regulating circuit that can both spread and reduce feelings of stress:

These results define a bidirectional model for the role of CRHR1 in anxiety and suggest that an imbalance between CRHR1-controlled anxiogenic glutamatergic and anxiolytic dopaminergic systems might lead to emotional disorders.

In other words, these two CRH-triggered systems exist in a delicate balance – and a disruption of that balance could lead to excessive fear reactions on the one hand, or to indifference on the other.

This means it’s probably time for psychiatrists to take another look at anti-anxiety drugs that target the brain’s CRH circuits:

The over-activity of the CRH system in patients with mood disorders is not general but probably limited to certain regulatory circuits in the brain, thus causing imbalanced emotional behavior.

This means that instead of just thinking of CRH as a “stress hormone,” we should probably be looking at these regulatory circuits as whole systems, and examining their interactions with one another.

So the next time you’re feeling panicky, try to remind yourself that it’s just your glumatergic neurons acting up – and those lovely dopaminergic circuits should kick in any second.

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