PsychEducation.org (home)

GRK3 and CRF

The following passage is lifted from a newsletter produced by Janice and Demitri Papalos, in this case their recent summary of anxiety and its relationship to bipolar disorder (here's the whole article).  I've clipped the segment below because it summarizes the research on this topic.  Here's a more basic summary of stress mechanisms in the brain, if needed. 

 

CRF and the Much-Talked-About GRK3 Gene

CRF is the neuropeptide in the brain that participates in the generation of the stress response. It also has important influences on the systems that regulate arousal, sleep/wake transitions, appetite, energy production, and the experience of pleasure and pain.

GRK3—a G-protein-coupled-receptor kinase plays an important role in the regulation of CRF receptors by turning them off at a certain point after they have been stimulated.

We spoke with Dr. Richard Hauger, professor of psychiatry at the University of California San Diego and a leading author of the recently reported study: “Evidence that a single nucleotide polymorphism in the promoter of the G protein receptor kinase 3 gene is associated with bipolar disorder,” and he explained:

We hypothesize that activation of brain neural networks by CRF during stress may require rapid counterregulation by the GRK3-mediated mechanism.

It has been established that exposure to severe stress can induce a long-term sensitization to anxiety-inducing stimuli. Therefore, a deficiency in GRK3 expression (caused by a different sequence of nucleotides that makes the promotor gene less capable of promoting transcription of the protein) may render brain CRF receptors incapable of being turned off when chronically exposed to high levels of CRF. This excessive degree of CRF receptor activation could contribute to the development of anxiety and depression.