Genetic Variants Within Molecular Targets of Antipsychotic Treatment: Effects on Treatment Response, Schizophrenia Risk, and Psychopathological Features

2017 ◽  
Vol 64 (1) ◽  
pp. 62-74
Author(s):  
Marco Calabrò ◽  
Stefano Porcelli ◽  
Concetta Crisafulli ◽  
Sheng-Min Wang ◽  
Soo-Jung Lee ◽  
...  
2016 ◽  
Vol 26 (5) ◽  
pp. 235-242 ◽  
Author(s):  
Britt I. Drögemöller ◽  
Robin Emsley ◽  
Bonginkosi Chiliza ◽  
Lize van der Merwe ◽  
Galen E.B. Wright ◽  
...  

2017 ◽  
Vol 312 (6) ◽  
pp. G606-G614 ◽  
Author(s):  
Anna Zsófia Tóth ◽  
András Szabó ◽  
Eszter Hegyi ◽  
Péter Hegyi ◽  
Miklós Sahin-Tóth

Determination of fecal pancreatic elastase content by ELISA is a reliable, noninvasive clinical test for assessing exocrine pancreatic function. Despite the widespread use of commercial tests, their exact molecular targets remain poorly characterized. This study was undertaken to clarify which human pancreatic elastase isoforms are detected by the ScheBo Pancreatic Elastase 1 Stool Test and whether naturally occurring genetic variants influence the performance of this test. Using recombinantly expressed and purified human pancreatic proteinases, we found that the test specifically measured chymotrypsin-like elastases (CELA) 3A and 3B (CELA3A and CELA3B), while CELA2A was not detected. Inactive proelastases, active elastases, and autolyzed forms were detected with identical efficiency. CELA3B elicited approximately four times higher ELISA signal than CELA3A, and we identified Glu154in CELA3B as the critical determinant of detection. Common genetic variants of CELA3A and CELA3B had no effect on test performance, with the exception of the CELA3B variant W79R, which increased detection by 1.4-fold. Finally, none of the human trypsin and chymotrypsin isoforms were detected. We conclude that the ScheBo Pancreatic Elastase 1 Stool Test is specific for human CELA3A and CELA3B, with most of the ELISA signal attributable to CELA3B.NEW & NOTEWORTHY The ScheBo Pancreatic Elastase 1 Stool Test is widely used to assess pancreatic exocrine function, yet its molecular targets have been poorly defined. We demonstrate that, among the human pancreatic proteinases, the test measures the elastase isoform CELA3B and, to a lesser extent, CELA3A. Genetic variants of the human CELA3 isoforms have no significant effect on test performance.


2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Melanie Blair Thies ◽  
Pamela DeRosse ◽  
Deepak K Sarpal ◽  
Miklos Argyelan ◽  
Christina L Fales ◽  
...  

Abstract Antipsychotic (AP) medications are the mainstay for the treatment of schizophrenia spectrum disorders (SSD), but their efficacy is unpredictable and widely variable. Substantial efforts have been made to identify prognostic biomarkers that can be used to guide optimal prescription strategies for individual patients. Striatal regions involved in salience and reward processing are disrupted as a result of both SSD and cannabis use, and research demonstrates that striatal circuitry may be integral to response to AP drugs. In the present study, we used functional magnetic resonance imaging (fMRI) to investigate the relationship between a history of cannabis use disorder (CUD) and a striatal connectivity index (SCI), a previously developed neural biomarker for AP treatment response in SSD. Patients were part of a 12-week randomized, double-blind controlled treatment study of AP drugs. A sample of 48 first-episode SSD patients with no more than 2 weeks of lifetime exposure to AP medications, underwent a resting-state fMRI scan pretreatment. Treatment response was defined a priori as a binary (response/nonresponse) variable, and a SCI was calculated in each patient. We examined whether there was an interaction between lifetime CUD history and the SCI in relation to treatment response. We found that CUD history moderated the relationship between SCI and treatment response, such that it had little predictive value in SSD patients with a CUD history. In sum, our findings highlight that biomarker development can be critically impacted by patient behaviors that influence neurobiology, such as a history of CUD.


2018 ◽  
Vol Volume 14 ◽  
pp. 2981-2987 ◽  
Author(s):  
Raul Escamilla ◽  
Beatriz Camarena ◽  
Ricardo Saracco ◽  
Ana Fresán ◽  
Sandra Hernández ◽  
...  

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