CRH: Role In Anxiety

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Hello, I wanna bring up CRH, I don't think it gets enough recognition , it has involvement in all types of anxiety/fear disorders. CRH trough CRHR1 receptor increases anxiety. CRHR1 is activated by CRH. CRH is always created and running but some people have increased of it running due to mutations,which leads to more anxiety. You don't want too much CRH but not too little either but it is better to have less obviously. CRHR2 receptor decreases anxiety so it does the opposite of CRHR1. CRHR1 and CRHR2 are increased together, becuase they both can only be activated via CRH. CRH has effect on how well you handle stress, and that is crucial to well-being and health.
CRH is first created in the PVN (paraventricular nucleus) of the hypothalamus, Stress induces the hypothalamic production and release of CRH, which then causes the activation of the CRH receptor (CRHR) type 1 (CRHR-1). It then is sent throughout the brain to take effect (mainly increase anxiety) and also activates its receptors (CRHR1/CRHR2 and on).
In terms of anxiety, the central factor regulating that axis, CRH, seems to increase anxiety via acting at the amygdala and BNST.
Chronic stress increases CRH receptors in the PVN, which makes you even more susceptible to the harmful effects of stress
Early life stress causes heightened neuronal activity in response to stress-induced CRH release. With repeated exposure to stress, you’ll continue to hyper-secrete CRH. Over time, CRH receptors in the anterior pituitary will become down-regulated, producing depression and anxiety symptoms
Local repeated corticotropin-releasing factor infusion exacerbates anxiety- and fear-related behavior: differential involvement of the basolateral amygdala and medial prefrontal cortex.

Here is a study proving my point: Researchers discover how the brain turns chronic stress into pathological anxiety
''The researchers focused on the endogenous cannabinoid (endocannabinoid or eCB) system, which include natural lipid signaling molecules that bind to cannabinoid receptors in the brain. Cannabinoid (type 1) receptors control stress-mediating circuits by inhibiting neurotransmitter release — a sort of gating mechanism to keep anxiety in check.


In contrast to the stress-reducing properties of endocannabinoids, a peptide molecule called corticotropin-releasing factor (CRF) activates the stress response and promotes increased sensitivity to stress and anxiety when activated over and over again.''


Basically, CRF and CB1 receptors in the Amygdala plays a huge part in the stress response. It also goes on to say ''These rats exhibit a mutation in a gene called CRHR1 that increases CRF (type 1) receptor signaling''. So basically high CRH-CRHR1 signaling (becuase CRHR1 can only be activated with CRH) is the majory key player in anxiety.

So I was looking for a way to decrease CRH which in turn will decrease the CRHR1 receptor, and the best thing I have found is a drug by the name of Clomipramine, it is an old TCA drug but it lowers CRH mRNA expression by 74% in the hypothalamus PVN. So basically stops CRH from being made.

(BTW CRF and CRH is the same thing just different name, same with CRF1 and CRHR1 receptor same thing different name)
 

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