In our study, CRH-BP variation showed the same direction of relationship to alpha power in two independent populations. Moreover, CRH-BP variation was significantly associated with AUD in the U.S. Caucasians and anxiety disorders in the Plains Indians. CRH-BP codes for a high affinity binding protein for corticotrophin releasing hormone (CRH), the primary mediator of the mammalian neuroendocrine and behavioral response to stress. In humans, CRH-BP is widely distributed throughout the body and is found in several brain regions including the cerebral cortex, the hippocampus, amygdala, lateral septal nucleus and a variety of midbrain structures [31]. Although its function in the brain is largely unknown, CRH-BP is thought to modulate CRH activity because a large proportion (65–90%) of total CRH is complexed with CRH-BP and is therefore unavailable for receptor activation [32], [33]. Centrally administered CRH increases anxiety-like behavior in rats across a wide range of paradigms [34]. Although CRH-BP deficient mice have normal baseline and stress-exposed HPA axis function they show increased anxiety-like behavior indicating an important role for CRH-BP in the CNS extra-hypothalamic stress response system [35]. CRH-BP located
