Molecular signaling pathways underlying schizophrenia

Show full item record



Permalink

http://hdl.handle.net/10138/333921

Citation

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 . https://doi.org/10.1016/j.schres.2021.05.011

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: University of Helsinki, Neuroscience Center
University of Helsinki, Department of Psychology and Logopedics
University of Helsinki, HUS Psychiatry
University of Helsinki, University of Eastern Finland (UEF)
University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
Date: 2021-06
Language: eng
Number of pages: 9
Belongs to series: Schizophrenia Research
ISSN: 0920-9964
URI: http://hdl.handle.net/10138/333921
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
hiPSc
Pathway
ABNORMALITIES
GLUTAMATE
DOPAMINE
NEURONS
MICE
3124 Neurology and psychiatry
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
1_s2.0_S0920996421001717_main.pdf 1.974Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record