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

Hector Warnes’ comment on Edward Shorter’s comment and Janusz Rybakowski’s reply to it

        I very much enjoyed reading Edward Shorter ́s skeptical remarks and Janusz Rybakowski's answer which reads: "By no means did I want to push a purinergic component of schizophrenia as a major neurochemical basis for this illness or a group of illness..." I wonder, where should I put the emphasis of Rybakowski reply? I would underline his view that there is a connection of purines (mainly adenosine) with dopaminergic and glutamatergic systems.

        Further, I would support the view that in the pathogenesis of schizophrenia there have been singled out genetic, environmental and stochastic factors which combined with epigenetic factors (Hanson and Gottesman 2005). In other words, both degenerative and/or developmental factors play a role. Based on molecular-genetic studies Hanson and Gottesman proposed a genetic-inflammatory-vascular immune dysfunction of capillary-glial-neurons triad.

        It is very interesting as well that purinergic receptors that appear to play a pathogenic role in bipolar disorder is the P2X7 receptor and that the activation of adenosine receptors is related to antidepressant activity. A higher prevalence of gout (elevated uric acid which is the end product of purines) was also observed in Bipolar Disorders. I would view the neurochemical and neurophysiological pathogenic factors as a cascade of events not unlike the process of blood coagulation.

Reference:

Hanson, DR and Gottesman II. Theories of Schizophrenia: a genetic-inflammatory-vascular synthesis. BMC Med Genet. 2005; 6:7.

February 6, 2020