Magda Malewska-Kasprzak, Agnieszka Permode-Osip and Janusz K. Rybakowski: Disturbance of the purinergic system in affective disorders and schizophreniaJanusz K. Rybakowski’s response to Hector Warnes’ response
The issue is about 1) a deficit of glutamatergic system in schizophrenia and 2) an excess of this system in depression. Let me explain these two points.
1. The glutamatergic hypothesis of schizophrenia was formulated 25 years ago by Olney and Farber (1995). They postulated a decrease of the activity in the glutamatergic N-methyl-D-aspartate (NMDA) receptor in this illness. Also, Arvid Carlsson (1923-2018), the 2000 Nobel Laureate in Physiology or Medicine, became a follower of the role of glutamatergic deficit in the pathogenesis of this illness (Carlsson, Hansson, Waters and Carlsson 1999). In subsequent years, the glutamatergic concept has been confirmed in numerous molecular-genetic studies (Carter 2006). It made also a basis for therapeutic attempts, mainly the use of inhibitors of the glycine site, a part of the NMDA receptor, for augmentation of neuroleptic drugs in the treatment of negative symptoms (Balu 2016).
2. The concept of an increased NMDA activity in depression arose after showing a rapid antidepressant effect of the infusion of ketamine, an NMDA antagonist (Zarate, Singh, Carlson et al. 2006). In our study, we demonstrated that ketamine augmentation rapidly improves depression scores in inpatients with treatment-resistant bipolar depression (Rybakowski, Permoda-Osip and Bartkowska-Sniatkowska 2017). As Hector Warnes noticed in his response of March 12, the antidepressant effect of lithium could be also connected with a NMDA receptor blockade (Ghasemi, Raza and Dephour 2010). It would be desirable if lithium could maintain the rapid antidepressant effect following ketamine infusion. However, the studies on this topic have brought about controversial results (Papakostas 2020).
Balu DT. The NMDA receptor and schizophrenia: from pathophysiology to treatment. Adv Pharmacol 2016; 76:351-82.
Carlsson A, Hansson LO, Waters N, Carlsson ML. A glutamatergic deficiency model of schizophrenia. Br J Psychiatry Suppl. 1999; (37):2-6.
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Papakostas G. Maintaining rapid antidepressant effects following ketamine infusion: a major unmet need. J Clin Psychiatry. 2020; 81(2).
Rybakowski JK, Permoda-Osip A, Bartkowska-Sniatkowska A. Ketamine augmentation rapidly improves depression scores in inpatients with treatment-resistant bipolar depression. Int J Psychiatry Clinical Pract 2017; 21:99-103.
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August 6, 2020