Abstract
ObjectiveOccurrences 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.MethodForty‐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.ResultsParticipants 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.ConclusionIn 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.
Highlights
Psychotic disorders are debilitating conditions that are primarily characterized by positive symptoms, negative symptoms, and cognitive deficits
We studied whether glutamate concentrations in prefrontal brain regions would mediate this relationship between early-life stress (ELS) experience and psychotic symptom severity
One of the main findings was that patients with PSY experienced significantly higher occurrences of ELS than healthy controls (HC), which is consistent with previous research (Bailey et al, 2018; Varese et al, 2012)
Summary
Psychotic disorders are debilitating conditions that are primarily characterized by positive symptoms (including delusions, hallucinations, and disorganized thoughts), negative symptoms (such as avolition, alogia, or apathy), and cognitive deficits (such as social cognition and working memory impairments). Proton magnetic resonance spectroscopy (1H-MRS) studies examined both the glutamate hypothesis of schizophrenia and the NMDA-r hypofunction model by measuring resting-state glutamate levels in prefrontal brain regions in individuals with SZ and BP. Such studies reported inconsistent findings of glutamate levels in the dorsolateral prefrontal cortex (DLPFC) in patients with SZ (Poels et al, 2014) with studies reporting (a) increased glutamate levels (Olbrich et al, 2008; Rüsch et al, 2008), (b) decreased glutamate levels, (Ćurčić-Blake et al, 2017) or (c) no difference in glutamate levels (Yoo et al, 2009) in the DLPFC compared to healthy controls (HC). To date no study has examined the association between ELS experience and severity of psychotic symptoms in individuals with PSY when considering glutamate concentrations as a potential neurobiological mechanism, including working memory function (Aas et al, 2012; Janssen et al, 2004)
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