Molecular signaling pathways underlying schizophrenia

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Tiihonen , J , Koskuvi , M , Lähteenvuo , M , Trontti , K , Ojansuu , I , Vaurio , O , Cannon , D T , Lönnqvist , J , Therman , S , Suvisaari , J , Cheng , L , Tanskanen , A , Taipale , H , Lehtonen , S & Koistinaho , J 2021 , ' Molecular signaling pathways underlying schizophrenia ' , Schizophrenia Research , vol. 232 , pp. 33-41 .

Title: Molecular signaling pathways underlying schizophrenia
Author: Tiihonen, Jari; Koskuvi, Marja; Lähteenvuo, Markku; Trontti, Kalevi; Ojansuu, Ilkka; Vaurio, Olli; Cannon, D. Tyrone; Lönnqvist, Jouko; Therman, Sebastian; Suvisaari, Jaana; Cheng, Lesley; Tanskanen, Antti; Taipale, Heidi; Lehtonen, Sarka; Koistinaho, Jari
Contributor organization: Neuroscience Center
University of Helsinki
Department of Psychology and Logopedics
Faculty of Medicine
HUS Psychiatry
Department of Psychiatry
Date: 2021-06
Language: eng
Number of pages: 9
Belongs to series: Schizophrenia Research
ISSN: 0920-9964
Abstract: The molecular pathophysiological mechanisms underlying schizophrenia have remained unknown, and no treatment exists for primary prevention. We used Ingenuity Pathway Analysis to analyze canonical and causal pathways in two different datasets, including patients from Finland and USA. The most significant findings in canonical pathway analysis were observed for glutamate receptor signaling, hepatic fibrosis, and glycoprotein 6 (GP6) pathways in the Finnish dataset, and GP6 and hepatic fibrosis pathways in the US dataset. In data-driven causal pathways, ADCYAP1, ADAMTS. and CACNA genes were involved in the majority of the top 10 pathways differentiating patients and controls in both Finnish and US datasets. Results from a Finnish nation-wide database showed that the risk of schizophrenia relapse was 41% lower among first-episode patients during the use of losartan, the master regulator of an ADCYAP1, ADAM'S, and CACNA -related pathway, compared to those time periods when the same individual did not use the drug. The results from the two independent datasets suggest that the GP6 signaling pathway, and the ADCYAPI, ADAATTS, and CACNA-related purine, oxidative stress, and glutamatergic signaling pathways are among primary pathophysiological alterations in schizophrenia among patients with European ancestry. While no reproducible dopaminergic alterations were observed, the results imply that agents such as losartan, and ADCYAP1/PACAP -deficit alleviators, such as metabotropic glutamate 2/3 agonise MGS0028 and 5-HT7 antagonists-which have shown beneficial effects in an experimental Adcyapl(-/-) mouse model for schizophrenia - could be potential treatments even before the full manifestation of illness involving dopaminergic abnormalities. (C) 2021 The Authors. Published by Elsevier B.V.
Subject: Schizophrenia
Stem cell
3124 Neurology and psychiatry
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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