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

Janusz Rybakowski’s comment on Hector Warnes’ comment on Hans-Juergen Möller's "Kraepelinian dichotomy and beyond"


        In his first comment on Hans-Juergen Möller's 2008 paper (Möller 2008), Hector Warnes highly assesses the content and the thoughts of the article, pointing out that they are in some way opposite to the views of Kraepelin's compatriots such as Griesinger or the Wernicke-Kleist-Leonhard trio. In his second comment, Hector underlines the historical role of the French psychiatrists in describing bipolar and schizoaffective disorders.

        I concur with Hector Warnes in his praising comments of the Hans-Juergen thorough study of psychiatric classification in the wake of the Kraepelinian dichotomy. In Möller’s article it is postulated that a modified form of this dichotomy should be retained in our psychiatric mainstream. I am suggesting the same in my essay written on the 120th anniversary of this concept. Furthermore, in this essay I included the papers that appeared after Möller’s 2008 publication which speak both for and against the Kraepelinian dichotomy.

        As to the clinical aspect, I discussed three papers on the schizoaffective disorder, two of them speaking against the Kraepelinian dichotomy (Cheniaux, Landeira-Fernandez, Telles et al. 2008; Keshavan, Morris, Sweeney et al. 2011) and one in support (Kotov, Leong, Mojtabai et al. 2013). Recent genetic findings point to shared genetic make-up of schizophrenia and bipolar disorder (Lichtenstein, Yip, Björk et al. 2009) but also to different polygenic risk scores for these two disorders (International Schizophrenia Consortium, Purcell, Wray et al. 2009) and to a significantly higher frequency of the copy number variations (CNV) in schizophrenia (Green, Rees, Walters et al. 2016). As to pharmacology, the therapeutic effects of so-called atypical antipsychotic drugs in both schizophrenia and mood disorder speak against the Kraepelinian dichotomy, while the specific mood-stabilizing effects of lithium and anticonvulsants (valproates, carbamazepine, lamotrigine) could be in favor of this division (Rybakowski 2018).

        The effect of prenatal infections and immunological insults seems to be significantly stronger in schizophrenia although in some aspects more similar to bipolar disorder with psychotic features (Brown 2015). Also, a degree of cognitive impairment is higher in schizophrenia and could be a differentiating factor (e.g., Vreeker, Boks, Abramovic et al. 2016). And finally, sharing a genetic liability with bipolar disorder, patients with schizophrenia have been subjects to more additional genetic and environmental factors that impair development and are more sensitive to them. As a result of more impaired neurodevelopment, structural changes of the brain in patients with first-onset illness such as lateral ventricular enlargement and gray matter abnormalities are much more marked in schizophrenia than in bipolar illness (Demjaha, MacCabe and Murray 2012).

        Therefore, my final statement is that as of 2019 the Kraepelinian great idea is still partly valid and has been substantiated by the findings that took place in a decade after Hans-Juergen Möller's paper.



Brown AS The Kraepelinian dichotomy from the perspective of prenatal infections and immunologic insults. Schizophr Bull 2015; 41:786-91.

Cheniaux E, Landeira-Fernandez J, Telles LL, Lessa JLM, Dias A, Duncan T, Versiani M. Does schizoaffective disorder really exist? A systematic review of the studies that compared schizoaffective disorder with schizophrenia or mood disorders. J Affect Disord 2008; 106:209-17.

Demjaha A, MacCabe JH, Murray RM. How genes and environmental factors determine the different neurodevelopmental trajectories of schizophrenia and bipolar disorder. Schizophr Bull 2012; 38:209-14.

Green EK, Rees E, Walters JT,  Smith K-G,  Forty L, Grozeva  D, Moran JL, Sklar P, Ripke S, Chambert KD, Genovese G, McCarroll SA, Jones I, Jones L, Owen MJ, O'Donovan MC, Craddock N, Kirov G. Copy number variation in bipolar disorder. Mol Psychiatry. 2016; 21:89-93.

International Schizophrenia Consortium, Purcell SM, Wray NR Stone JL, Visscher PM, O'Donovan MC, Sullivan PF, Sklar P. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature. 2009; 460:748-52.

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; 133:250-4.

Kotov R, Leong SH, Mojtabai R, Erlanger AC, Fochtmann LJ, Constantino E, Carlson GA, Bromet EJ. Boundaries of schizoaffective disorder: revisiting Kraepelin. JAMA Psychiatry 2013; 70:1276-86.

Lichtenstein P, Yip BH, Björk C Pawitan Y, Cannon TD, Sullivan PF, Hultman CM. Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet 2009; 373:234-39.

Möller HJ. Systematic of psychiatric disorders between categorical and dimensional approaches: Kraepelin's dichotomy and beyond. Eur Arch Psychiatry Clin Neurosci. 2008; 258(Suppl 2):48-73.

Rybakowski JK. Meaningful aspects of the term 'mood stabilizer'. Bipolar Disord 2018; 20:391-2.

Vreeker A, Boks MP, Abramovic L, Verkooijen S, van Bergen AH, Hillegers MH, Spijker AT, Hoencamp E, Regeer EJ, Riemersma-Van der Lek RF, Stevens AWMM, Schulte PFJ, Vonk R, Hoekstra R, van Beveren NJM, Kupka RW, Brouwer RM, Bearden CE, MacCabe JH, Ophoff RA, GROUP Investigators. High educational performance is a distinctive feature of bipolar disorder: a study on cognition in bipolar disorder, schizophrenia patients, relatives and controls. Psychol Med 2016; 46:807-18.


May 14, 2020