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

Larry Stein’s response to Victor Peralta’s reply

            The second part of Victor Peralta’s carefully-considered response strongly confirms within his own data set a curious observation.  This finding had originally provided the unanticipated and “presumably paradoxical” basis for my own Comment.  Reported here — now on one and the same large population of affected subjects — are Peralta’s measurements both of familial load and responsivity to antipsychotic drugs for Leonhard’s systematic and unsystematic schizophrenias.  Contrary to the expectation of positive correlation, Peralta finds again that the genetics and pharmacology go in opposite directions in Leonhard’s classification, i.e., the less-familial unsystematic schizophrenia diagnosis is substantially more responsive to antipsychotic drugs than is the more-familial diagnosis of systematic schizophrenia. This unexpected observation, if correct, may have some interesting implications for the biology and genetics of schizophrenia, as I had previously noted in my Comment.

            But complicating the arguments above is an unsettling prior issue—raised by various commentators as a simple matter of fact—in regard to the actual familial load of systematic and unsystematic schizophrenias. Others, including Leonhard himself, are at odds with Peralta and report contrariwise that, in fact, unsystematic schizophrenias exhibit more familial aggregation than systematic schizophrenias. Several factors that might explain this disagreement with Leonhard and his followers are thoughtfully reviewed in the first part of Peralta’s response.  The opposed findings, Peralta concludes, may be due more “to sample representativeness and family study methodology than to diagnosing. Regardless, our findings will need to be corroborated by other investigators using representative samples of psychotic disorders in the general population.”  These considerations bear on suggestions (Peralta et al., 2015; Ban, 2015) that Leonhard’s classification of psychotic disorders may be better suited for molecular genetic studies than other diagnostic systems. Perhaps the disagreements on basic issues of fact within Leonhard’s classification, as noted above, might first be resolved.



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/sbv192.

Ban TA. In historical perspective. Peralta, Cuesta and their associates’ findings of the highest familiality of Leonhard’s classification in polynosologic study. Historical Perspective. March 31, 2016.


Larry Stein

December 29, 2016