Janusz Rybakowski: 120 years of the Kraepelinian dichotomy of "endogenous psychoses" in historical perspective


Samuel Gershon’s comment


        I reread the entire thread of these articles. Janusz Rybakowski has opened the discussion in assembling evidence to support the Kraepelinian dichotomy. Other authors have raised questions about clarity and the functional utility of this separation. Edward Shorter has pressed other concerns based on subsequent genetic and pharmacological studies.

        I would like to enter the discussion at this point and refer to other pharmacological reports. The catecholamine hypothesis was introduced and was presented with a case for low catecholamine that could cause depression and elevated levels associated with mania.

        Looking at psychiatric drug usage more broadly the picture becomes very unclear with one example: Quetiapine being marketed as an antipsychotic for schizophrenia and then marketed for depression and then it being ideally useful for schizoaffective disorders.

        Also, in recent contributions to this network, Janowsky and Davis (1979) and Angrist and Gershon (1971) have both shown that physostigmine given to manic patients can induce a return to a stable normal baseline. Also, Gershon and Shaw in 1961 reported that acetylcholinesterase inhibitors can induce a depressive illness. So, I think our search for resolution of some of these issues is still an ongoing project.



Angrist B, Gershon S. A Pilot Study of Pathogenic Mechanisms in Amphetamine Psychosis Utilizing Differential Effects of D and L Amphetamine. Pharmacopsychiatry 1971; 4(2):64-75.

Gershon S, Shaw FH. Psychiatric sequelae of chronic exposure to organophosphorus insecticides. Lancet. 1961; 1(7191):1371-4.

Janowsky DS, Davis JM. Psychological Effects of Cholinomimetic Agents. In: Davis KL, Berger PA, editors. Brain Acetylcholine and Neuropsychiatric Disease. Springer, Boston, MA. 1979.


September 3, 2020