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

Hector Warnes’ comment


        Professor Rybakowski published this essay under the title "The 120th Anniversary of the Kraepelinian Dichotomy of Psychiatric Disorders" in Current Psychiatry Reports (Rybakowski 2019). I am amazed at his capacity for synthesis and clarity of exposition: "It can be stated that, as of 2019, this great idea has been still partly valid." The words "partly valid" conjured up the continuous disagreements and changes in our psychiatric nosology up to date. Rybakowski, citing Keshavan MS, Morris DW, Sweeney (2011), wrote about a Schizo-Bipolar scale stating: "The majority of cases had ratings close to prototypic schizophrenia or bipolar disorder, however a large group (45% of cases) fell on the continuum between these two prototypes." We are well aware that diagnostic reliability is not the same as diagnostic validity, nor that a positive response to a given treatment (ex-juvantibus) points out necessarily to the precise etiology.

        The 45% number of endogenous bipolar, major depressive, schizophrenic or schizo-affective disorder are supported by Rybakowski's referral to a "substantial overlap of common polygenic variation between these two illnesses (‘a genetic overlap’)... Since both disorders shared common genes a specific polygenic risk score was created for each of these two conditions." The gold standard would thus be to identify a pharmacogenetic profile for each diagnostic category (personalized medicine). We are also aware though that the introduction of many "spectrum disorders," based on dimensional frames and ultimately catamnestic studies, has blurred the boundaries of the Kraepelinian dichotomy further.

        I am surprised that based on few studies Rybakowski asserts that infusion of ketamine, an NMDA antagonist, "appears to show that ketamine improves treatment resistant bipolar depression." As far as I am aware the risks are higher and the results last a few days. We must wait for confirmability testability, refutability, falsifiability and verifiability in Popper's sense before inflicting more casualties that our long standing "trial and error" history has shown abundantly.

        Using as the bridge the "spectrum disorders," the poor validity of psychiatric diagnosis, the 45% or more of blurred boundaries between them (even dysthymic disorders may develop into a bipolar disorder or many major depression in long term follow up may trigger a neurodegenerative, an auto-immune, cancer, accelerated aging, or a cardiovascular illness). Brian Leonard (2007), based on many studies in animals and humans carried out for at least a decade, indicated that a process of chronic inflammation is central in the pathogenesis of chronic depression and dementia (and many other illnesses) both share a neuronal loss, the activation of macrophages in the blood and microglia in the brain and release of proinflammatory cytokines which in turn stimulate a cascade of inflammatory changes along with hypercortisolemia. It is known that cortisol reduces the synthesis of neurotrophic factors (BDNF). We are aware that the positive response to anti-depressants facilitates neuroplasticity, neurogenesis in the hippocampus (CA3) and decreased cortisol levels. As Leonard writes: “the tryptophan (a precursor of serotonin) largely produced in the gut may be deviated via a toxic pathway: kynurenine, quinolinic acid which accumulates in astrocytes and neurons in depression and dementia.”

        We have all had the experience of changing diagnosis and treatment of psychiatric patients over decades or reviewing old clinical histories which have different diagnosis in longitudinal studies.

        I would support Timothy J. Crow (1980) in so far as he divides schizophrenia into two types: I and II. The former has positive symptoms, good response to anti-psychotics, affective symptoms, increased dopaminergic activity, normal Magnetic Resonance findings in the brain and better prognosis. The latter has an insidious onset, mostly negative symptoms, cognitive impairment, atrophy of gray matter in the prefrontal lobes, enlarged ventricles, hypodopaminergic activity and of course poor prognosis.

        I am inclined to put forward the pre-Kraepelinian view of an Einheit Psychose (Unitary Psychosis or Mischpsychose) viewing most psychotic states in a continuum, which is another word for a spectrum ranging from genetic, epigenetic and environmental factors with various degrees of brain lesions as shown by imagenology (particularly functional PET) and molecular biology.

        Thomas A Ban (2018) has written an insightful history of psychiatry where with great historical accuracy he develops the concept of Einheit Psychose with Albert Zeller, Joseph Guislain, Heinrich Neumann (1859) and Wilhelm Griesinger (1861), the latter influenced by Jesse Bayle's findings on neurosyphilis, supporting this view: " Das Irresein hat nicht vershiedene Formen wohl aber verschiedene Stadien" (Insanity does not have different forms but different stages). A more specific paper on the subject was published by G. E. Berrios and D. Beer (1994).




Ban T. Bulletin 29. Wilhelm Griesinger and Unitary Psychosis (Einheitpsychose). Thomas A. Ban: Neuropsychopharmacology in Historical Perspective, Education in the Field in the Post-Neuropsychopharmacology Era. inhn.org.education. August 2, 2018.

Berrios GE, Beer D. The notion of a unitary psychosis: a conceptual history. Hist Psychiatry. 1994;5(17 Pt 1):13-36.

Crow TJ. Molecular pathology of schizophrenia More than one disease process. British Medical Journal. 1980;280(6207):66-8. 

Keshavan MS, Morris DW, Sweeney JA, Pearlson G, Thaker G, Seidman LJ, Eack SM, Tamminga C. A dimensional approach to the psychosis spectrum between bipolar disorder and schizophrenia: the Schizo-Bipolar Scale. Schizophr Res. 2011;133(1-3):250-4.

Leonard BE. Inflammation, depression and dementia: are they connected? Neurochem Res. 2007;32(10):1749-56.

Rybakowski JK. 120th Anniversary of the Kraepelinian Dichotomy of Psychiatric Disorders. Curr Psychiatry Rep. 2019;21(8):65.


February 20, 2020