THE OPIOIDERGIC SYSTEM AND PANIC
There is compelling evidence suggesting a connection between panic disorder and deficits in endogenous opioids, which are naturally produced by the brain and contribute to our sense of well-being. Studies have indicated that the sensitivity to carbon dioxide (CO2) is modulated by the opioidergic system. Endogenous opioids appear to reduce respiratory sensitivity, enabling increased survival in conditions of hypoxia (insufficient oxygen) and hypercapnia (excessive CO2 in the blood).
This argument gains support from the physiological differentiation between fear and the panic response. While fear activates the hypothalamic-pituitary axis (HPA), the panic response inhibits it. This inhibition is crucial as HPA activation would increase catabolic activity and oxygen demand, which is undesirable during panic. Neuroimaging studies further substantiate this viewpoint by implicating the cerebellum in the generation of air hunger and suggesting its role in regulating the overriding emotional activation associated with suffocation alarm in oxygen-deprived conditions.
SEPARATION ANXIETY AND PANIC DISORDER
Moreover, the opioid system also regulates the response to separation anxiety, which correlates with panic disorder. Research indicates that panic often arises from severe early separation or bereavement experiences. The association between early separation anxiety and adult panic disorder is particularly strong, to the extent that separation anxiety seems to be more linked to panic disorder than agoraphobia. This connection can be explained by the relationship between separation anxiety and respiratory dysregulation, which is also observed in panic disorder.
For instance, studies reveal that children with separation anxiety disorder exhibit significant respiratory sensitivity to 5% CO2, whereas this sensitivity is lower in generalized anxiety disorder and nonexistent in social phobia. Additionally, the finding that the endogenous opioid system is the first neurochemical system to inhibit separation distress contributes to the development of the brain opioid theory of social attachment.
Reference:
Preter, M., & Klein, D. F. (2008). Panic, suffocation false alarms, separation anxiety and endogenous opioids. Prog Neuropsychopharmacol Biol Psychiatry, 32(3), 603-612. doi:10.1016/j.pnpbp.2007.07.029