Stress versus depression.

Abstract

1. Exhaustive evidence is quoted showing that uncontrollable (uncoping) stress provoked in experimental mammals leads to depletion of central noradrenergic activity+ adrenomedullary-cortical gland hyperactivity. These physiological disorders cause the typical neuroendocrine peripheral profile: a) raised catecholamines (CA) in plasma [noradrenaline (NA)+adrenaline (Ad)+dopamine (DA), b) reduced NA/Ad ratio in plasma and c) raised plasma cortisol. 2. Exhaustive evidence is quoted which indicates that severely ill humans show peripheral neuroendocrine profile similar to that found in mammals submitted to uncontrollable stress situation. Further, the NA/Ad ratio does not increase but decreases during orthostasis and exercise stress challenges, as well as oral glucose stress (tolerance) test. 3. Exhaustive evidence is quoted which indicates that endogenous depressed subjects show a neuroendocrine profile opposite to that observed in stressed mammals and severely ill humans. This profile consists of central NA (neural sympathetic) hyperactivity+ adrenomedullary glands hyporresponsivity. These disorders are reflected in a three to ten fold increase of the NA/Ad ratio in plasma. 4. Exhaustive evidence is also quoted showing that dysthymic depressed patients show low plasma catecholamines+low NA/Ad plasma ratio (< 2) during supine-resting condition, it is normalized at orthostasis and exercise periods. 5. It is quoted evidence showing that whereas platelet serotonin is increased in dysthymics, the same is reduced in both endogenous depressed and stressed mammals as well as severely ill humans. 6. It is quoted evidence showing that free serotonin in plasma is greatly raised in uncoping stressed mammals and severely ill humans. The same parameter is normal or slightly increased in dysthymic and endogenous depressed humans. These findings are consistent with the increased platelet aggregability observed in "uncontrollable" stressed mammals and in severely ill, but not depressed patients. 7. It is also quoted evidence showing that whereas parasympathetic activity is absent in uncontrollable stressed mammals and severely ill humans, the same is increased in both types of depressed humans. 8. According to the above, the authors postulate the existence of 3 distinct central+ peripheral neuroendocrine profiles for endogenous depression, dysthymic depression and maladaptation to stress syndrome. These different profiles should lead researchers to attempt different therapeutical approach. 9. In view of the fact that the authors found much clinical overlap among the three syndromes (endogenous depression, dysthymic depression and severely ill patients), they believe that a differential diagnosis should be based on neurochemical, neuroendocrine, physiologic, metabolic and neuropharmacological grounds. 10. The experimentally induced uncontrollable stress (behavioral despair) syndrome in mammals should not be used as a valid model of human depressive syndrome.