Thomas A. Ban: In historical perspective - Peralta, Cuesta and their associates’ findings on the highest familiality of Leonhard’s classification in polynosologic study 

Thomas A. Ban’s reply to Larry Stein’s comment

Thank you for your comment. I wonder why you find it “paradoxical” that a different sub-population of schizophrenia shows high “familiality” than high response rate to neuroleptics? For me, the findings of Frank Fish (1964) and Peralta and his associates (2015) indicate that the patient population identified by the diagnostic concept of schizophrenia is heterogeneous pharmacologically and genetically. Probably, what is even more important is that the findings from these two studies also indicate that by diagnosing patients on the basis of Leonhard’s (1957) classification, one can identify pharmacologically and genetically more homogenous subpopulations of schizophrenia than by diagnosing patients on the basis of some other classifications.


As genetically homogenous populations are a prerequisite for successful molecular genetic research (association studies-linkage analysis) and pharmacologically homogenous populations for successful neuropsychopharmacological research, findings in these studies imply that patient populations identified on the basis of diagnoses derived by Leonhard’s (1957) nosology would provide more suitable populations for genetic and neuropsychopharmacological research, in general, and in schizophrenia, in particular, than patient populations identified by diagnoses in  some other classifications.

If patients diagnosed with schizophrenia were diagnosed on the basis of Leonhard’s nosology, it would become evident that “positive symptoms” and “negative symptoms” do not provide a natural divide in the population (Crow 1980), as in some of the16 forms and sub-forms of schizophrenia “positive symptoms“and “negative symptoms” are present simultaneously all the time and in some other forms, some of the time. It would also focus attention on the fallacy of the commonly held view that “positive symptom” in schizophrenia as a rule, are responsive, to treatment with neuroleptic drugs whereas negative symptoms are less so. In the “paraphrenias”, one of the three forms of “systematic schizophrenia”, the clinical picture is dominated by “delusions”, a “positive symptom”, yet in Fish’s (1964) study, only 40.3% (58) of 144 patients diagnosed with “paraphrenia” showed a marked to moderate therapeutic response to neuroleptics. Furthermore, if diagnoses based on Leonhard’s (1964) nosology were adopted at the time they were introduced, in the late 1950’s, we probably would never had a “dopamine hypothesis schizophrenia”, but a “dopamine hypothesis of affect-laden paraphrenia”, as in Fish’s (1964) study, 84.4% (43) of 51 patients with “affect-laden paraphrenia” showed a marked to moderate therapeutic response to neuroleptics.

In so far as Sekar et al’s (2016) re-analysis of the data from a study is concerned, it would have been be carried out with consideration that patients with the diagnosis of schizophrenia, represent a genetically heterogeneous population.


Crow TJ.  Positive and negative schizophrenic symptoms and the role of dopamine.The British Journal of Psychiatry 1980; 137 (4) 383-6.

Fish F. The influence of the tranquilizers on the Leonhard schizophrenic syndromes. Encephale  1964; 53: 245-9.

Leonhard K. Aufteilung der endogenen Psychosen. Berlin: Akademie Verlag; 1957.

Peralta V, Goldberg X, Ribeiro M, Sanches-Torres AM, Fananas L, Cuesta MJ. Familiality of psychotic disorders: A polynosologic study in multiple families. Schizophrenia Bulletin Advance Access 2015 doi: 101093/schbul/sbv

Sekar A, Bialas AR, de Rivea H, et al. Schizophrenia risk from complex variation of complement component 4.  Nature 2016


Thomas A. Ban

May 5, 2016