The opioid receptor can sensitize neurons in LC to corticotropin-releasing factor (CRF), a potent psychological mediator regulating stress-induced behaviors.272 Chronic or persistent acute stress can alter LC functions.273 Hyperactive LC is associated with psychiatric disorders.274 Dysregulation of the opioid receptors affects emotion processing in patients with major depressive disorders.275 Opioid receptor levels are related to neurocognitive deficits.276 Elevated opioid receptors level might elicit symptoms of schizophrenia resulting in treatment resistance.276. This evidence concerns the gene CRH and major depressive disorder.