Objective: Occurrences of early-life stress (ELS) are associated with the severity of psychotic symptoms and working memory (WM) deficits in patients with psychosis (PSY). This study investigated potential mediation roles of WM behavioral performance and glutamate concentrations in prefrontal brain regions on the association between ELS and psychotic symptom severity in PSY.
Method: Forty-seven patients with PSY (established schizophrenia, n = 30; bipolar disorder, n = 17) completed measures of psychotic symptom severity. In addition, data on ELS and WM performance were collected in both patients with PSY and healthy controls (HC; n = 41). Resting-state glutamate concentrations in the bilateral dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) were also assessed with proton magnetic resonance spectroscopy for both PSY and HC groups. t tests, analyses of variance, and regression analyses were utilized.
Results: Participants with PSY reported significantly more ELS occurrences and showed poorer WM performance than HC. Furthermore, individuals with PSY displayed lower glutamate concentrations in the left DLPFC than HC. Neither ELS nor WM performance were predictive of severity of psychotic symptoms in participants with PSY. However, we found a significant negative correlation between glutamate concentrations in the left DLPFC and ELS occurrence in HC only.
Conclusion: In individuals with PSY, the current study found no evidence that the association between ELS and psychotic symptoms is mediated by WM performance or prefrontal glutamate concentrations. In HC, the association between ELS experience and glutamate concentrations may indicate a neurometabolite effect of ELS that is independent of an illness effect in psychosis.
Bibliographical noteFunding Information:
The author SML has received financial support for research, in the past 3 years, from Janssen, in relation to research. He has also received fees for advisory panels and/or educational meetings from Janssen and Sunovion. HCW is supported by a JMAS SIM Fellowship from the Royal College of Physicians of Edinburgh and by an ESAT College Fellowship from the University of Edinburgh. SML and HCW have also previously received support from Pfizer (formerly Wyeth). These received funds do not present a conflict of interest with the present study.
We acknowledge Douglas Blackwood, Barbara Duff, Andrew Watson, Neil Roberts, Nicholas J Brandon, and John Dunlop for their assistance with study design, recruitment, and data collection. We also acknowledge the Scottish Mental Health Research Network ( http://www.smhrn.org.uk ) for providing further assistance with participant recruitment and cognitive assessments. We would like to thank both the participants who took part in the study and the radiographers who acquired the MRI scans. Scans were collected at the Clinical Research Imaging Centre ( http://cric.ed.ac.uk ). This work was funded by an award from the Translational Medicine Research Collaboration (NS EU 166)—a consortium consisting of the Universities of Edinburgh, Aberdeen, Dundee, and Glasgow, the four associated NHS Health Boards (Grampian, Tayside, Lothian, and Greater Glasgow and Clyde), Scottish Enterprise, and Pfizer. However, the funder had no role in study design, data collection, analysis, or interpretation or the writing of the report. The Dr Mortimer and Theresa Sackler Foundation also offered financial support for imaging aspects of this study.
© 2020 The Authors. Brain and Behavior published by Wiley Periodicals, LLC.
- early-life stress
- left dorsolateral prefrontal cortex
- working memory
ASJC Scopus subject areas
- Behavioral Neuroscience