Martin M. Katz’s comment on Jose de Leon’s article “Focusing on drug versus disease mechanisms and on clinical subtyping to advance personalized medicine”


Jose de Leon’s editorial on “Focusing on drug versus disease mechanisms and on clinical subtyping to advance personalized medicine”, published in Acta Neuropsychopharmacologica, in 2014, is a very thoughtful piece and an eloquent case for the importance of sophisticated clinical experience and judgment in advancing the science of psychopathology. The author wishes to rescue psychiatry from its need to emulate other specialized areas in medicine and its conception of its disorders as “diseases”. Schizophrenia and the affective disorders are not as far as we now know, based on established brain neuropathology and thus, do not qualify as diseases. If we adhere to the tenets of descriptive psychopathology, they are syndromes. Reliance on the DSM undermines that approach, and consequently, is viewed as an obstacle to progress in advancing the science. He would, in his long term goal for “personalized medicine”, propose the syndrome approach in place of the conventional diagnostic system. In advocating this approach, he points to the neglected early work of Leonhard in characterizing the syndromes and the efforts of others to apply a more empirical analysis to the issues of classification.
I believe with De Leon that psychiatry should cease trying to emulate other medical specialties. It does not have diseases, based on defined neuropathological processes, to target. It has, at best, syndromes with continuing disagreement about their borders and somewhat resistant to quantification that makes progressing in the science difficult. Even where we have “disease”, such as with Alzheimer’s, the disease approach, as the author notes, has not been very successful in uncovering new treatments.

The author would have us step back, rely more on “descriptive psychopathology”, the basic science for psychiatry as Ban (2007) and others have proposed. It will permit taking advantage of sophisticated clinical judgment as against the present obsession with controlled trials and the DSM. It is clinical judgment that led to the discovery of the new drugs. It should be made easier for “clinical experts” to continue to make their mark in this field.

Regarding goals and personalized medicine, I would, however, propose taking an even further step back from the syndrome approach. The prime goal should be to further advance the science of psychopathology. To do that one has to adopt an even more elemental approach to the more complex syndromal, which in itself can be difficult to quantify. It is necessary to start with identifying and validating the emotional, cognitive and behavioral components and the dimensional constructs, already demonstrated quantifiable entities, upon which the science can be built. There is already much evidence that this approach is capable of opening new pathways in the science, resulting in uncovering the structural nature of the depressive disorders and in elaborating the nature, timing and mechanisms of actions of established drug treatments. My own effort in advancing this approach is one example (Katz 2013). The componential system needs to be more widely applied and the atmosphere for the kind of thinking De Leon is encouraging more quickly developed.

Ban TA. Towards a clinical methodology for neuro-psychopharmacological research. Neuropsychopharmacologia Hungarica 2007; 9: 81–90.
De Leon J. Focusing on drug versus disease mechanisms and on clinical subtyping to advance personalized medicine. Acta Neuropsychopharmacologica  2014; 26: 327-33.

Katz MM. Depression and Drugs: The Neurobehavioral Structure of a Psychological Storm. New York: Springer; 2013.


Martin M. Katz

August 25, 2016