Friday, 07.08.2020

Magda Malewska-Kasprzak, Agnieszka Permode-Osip and Janusz K. Rybakowski: Disturbance of the purinergic system in affective disorders and schizophrenia 

Hector Warnes’ further comment


        Professor Rybakowski’s outstanding research left me wondering about the underlying Ding-an-sich or the causal connection between noumena and phenomena. The latter implies the sensible intuition which appears in our consciousness within a spacio-temporal order and regularity. Since the great break-through of phenomenology we are able to observe clusters of phenomena which share the same features. We were even allowed to use our sixth sense or intuition to confirm it, as was the felicitous paper of H.C.Rümke (1942), Das Kern symptom der Schizophrenie und das "Precox Gefühl." There were brilliant clinicians who surpassed us in using minute observations and sensory data (semiological signs) such as olphatory (a peculiar odor in particular diseases) and acoustic (sapere aude).

        About half a century ago there was an over-diagnosis of schizophrenia which later shifted to an over diagnosis of bipolar disorder. Rating scales cannot replace the clinical experience of a good clinician. Validity studies have demonstrated that not infrequently the original diagnoses were wrong and even major depression which became refractory to treatment has been called a neurodegenerative disorder because of the cognitive and imagenological brain changes over time. The many factors involved in the inexorable process of aging, including the second law of thermodynamics, have also been implicated.

        The above can be easily related to the necessary and sufficient conditions for an illness to develop. The obvious is that every person with the Koch bacillus of tuberculosis does not develop the disease nor does every person with HIV develop AIDS; HIV is not sufficient to cause AIDS. The physiopathology of stress and distress, including diet, lifestyle, predisposing factors, childhood traumatic events (shown in the earliest care in raising monkeys, rats and so on) are invoked as sufficient, but HIV must be found. The thousands of research papers written on the physiopathology of stress, including the cumulative allostatic burden (life events) on the homeostatic organismic system, has been demonstrated. Stress is now widely accepted in medicine as one of the risk factors for any pathology. Nowadays, one hardly uses the term psychosomatic medicine which essentially reached the same conclusions many, many decades ago.

        Further, Professor Rybakowski himself has noticed the overlap in genetic susceptibility across schizophrenia and bipolar disorders with associated findings, i.e., DAOA (G72), DISC 1 and NRG1 (genetic polymorphisms). Both diseases share DAOA (G72) but only the bipolar disorder has BDNF.

        There are, however, many diseases that are associated with the mutation of only one gene, such as Huntington disease, which gene is both necessary and sufficient for the development of the illness. The HTT gene provides instructions for making a protein called huntingtin. The HTT mutation involves a DNA segment known as a CAG trinucleotide repeat. If they repeat more than 40 times the illness appears.

        In medicine we often deal with the relation of parts and wholes and continuity and discontinuity which often confuses us in the clinical course of psychiatric disorders.

        Finally, I would like to cite the concept of the "Occam's razor": Entities are not to be multiplied without necessity. As far as I understand, it is the essence of the reductionist aspect of most ground-breaking discoveries. We find out by meticulous research activity or by serendipity a factor that is undeniably involved. Thereafter we must relate every statement in terms of this particular finding. Unfortunately, the human body and later findings are continually changing and not infrequently we may be led astray by our original findings. I am not aware of how many hundreds of drugs have been taken off the market after having been hailed as the latest advances for the treatment of various diseases which later proved false or toxic or superseded by better drugs.

        It is always a pleasure to read Professor Rybakowski’s papers.



Rümke H.C. Kernsymptom der Schizophrenie und das "Precox Gefühl." Zentralblatt für die Gesamte Neurologie und Psychiatrie, 1942; 102:168-9.


March 19, 2020