EEG-Based Measures in At-Risk Mental State and Early Stages of Schizophrenia: A Systematic Review

Abstract

Introduction: Electrophysiological (EEG) abnormalities in subjects with schizophrenia have been largely reported. In the last decades, research has shifted to the identification of electrophysiological alterations in the prodromal and early phases of the disorder, focusing on the prediction of clinical and functional outcome. The identification of neuronal aberrations in subjects with a first episode of psychosis (FEP) and in those at ultra high-risk (UHR) or clinical high-risk (CHR) to develop a psychosis is crucial to implement adequate interventions, reduce the rate of transition to psychosis, as well as the risk of irreversible functioning impairment. The aim of the review is to provide an up-to-date synthesis of the electrophysiological findings in the at-risk mental state and early stages of schizophrenia.Methods: A systematic review of English articles using Pubmed, Scopus, and PsychINFO was undertaken in July 2020. Additional studies were identified by hand-search. Electrophysiological studies that included at least one group of FEP or subjects at risk to develop psychosis, compared to healthy controls (HCs), were considered. The heterogeneity of the studies prevented a quantitative synthesis.Results: Out of 319 records screened, 133 studies were included in a final qualitative synthesis. Included studies were mainly carried out using frequency analysis, microstates and event-related potentials. The most common findings included an increase in delta and gamma power, an impairment in sensory gating assessed through P50 and N100 and a reduction of Mismatch Negativity and P300 amplitude in at-risk mental state and early stages of schizophrenia. Progressive changes in some of these electrophysiological measures were associated with transition to psychosis and disease course. Heterogeneous data have been reported for indices evaluating synchrony, connectivity, and evoked-responses in different frequency bands.Conclusions: Multiple EEG-indices were altered during at-risk mental state and early stages of schizophrenia, supporting the hypothesis that cerebral network dysfunctions appear already before the onset of the disorder. Some of these alterations demonstrated association with transition to psychosis or poor functional outcome. However, heterogeneity in subjects' inclusion criteria, clinical measures and electrophysiological methods prevents drawing solid conclusions. Large prospective studies are needed to consolidate findings concerning electrophysiological markers of clinical and functional outcome.

Duration Mismatch Negativity Predicts Remission in First-Episode Schizophrenia Patients

“…These results expanded a previous finding in chronic schizophrenia with a short clinical follow-up (6 months) ( 11 ) and further supported a clinical utility of dMMN at earlier illness stages as a predictive marker of treatment response and recovery. Given that CHR individuals likely have reduced dMMN amplitudes, which may underpin their psychosis risk ( 12 , 13 ) and functional and symptomatic improvement at follow-up period ( 22 , 27 ), dMMN abnormalities may be a rather stable biomarker during the course of psychosis that could not be explained only by the effect of antipsychotic medication and/or illness chronicity after the onset. It is considered that MMN is generated by a fronto-temporal network associated with pre-attentive sensory processing ( 16 ) and that MMN reduction in schizophrenia may reflect N-methyl-D-aspartate (NMDA) receptor hypofunction ( 17 , 18 ).…”

“…The fMMN amplitude at baseline was mildly decreased in the FES group compared to the H group, but there was no difference between the R and NR groups. This result may be partly explained by the notion that fMMN has less stability and replicability than dMMN ( 50 ), but it is also possible that fMMN abnormalities in schizophrenia emerge more robustly only during the chronic stages ( 12 ). Indeed, several fMMN studies in schizophrenia have demonstrated that its amplitude is associated with illness duration ( 51 ) and longitudinally declines during early illness stages ( 30 , 52 ).…”

“…However, current evidence supports that clinical and neurobiological factors associated with early neurodevelopmental pathology e.g., premorbid intelligence ( 6 ), obstetric complications ( 7 ), and gross brain morphology ( 8 , 9 ) as well as genetic factors ( 10 ) may also contribute to worse functional outcomes and symptom severity in later stages of schizophrenia. In recent years, as described below, event-related potential (ERP) abnormalities are considered to be suitable biomarkers of functional recovery for schizophrenia ( 11 ) and clinical high risk (CHR) patients ( 12 , 13 ). To our knowledge, however, very few studies to date have attempted a detailed examination of a potential link between ERP at early stages after onset and clinical remission (i.e., symptom remission and improvements in cognitive and social functions) in schizophrenia.…”

“…Based on the literature, we hypothesized that preserved baseline dMMN amplitude would be associated with symptomatic remission and better cognitive and social functions at follow-up in patients with FES. We also examined the relationship between frequency MMN (fMMN), which may be a less sensitive marker of schizophrenia than dMMN ( 12 ) but likely reflects cognitive functioning at later stages in CHR individuals ( 22 ), and remission in FES patients given that this has yet to be reported. Moreover, we explored potential differences in longitudinal MMN changes between the FES patients with and without symptomatic remission.…”

Investigating the Relationships of P3b with Negative Symptoms and Neurocognition in Subjects with Chronic Schizophrenia

“…In psychiatric research, P300 started to gain attention due to the consistent alterations recorded in subjects with schizophrenia. In fact, numerous studies have reported a reduction in P300 amplitude and delayed latency of its peak both in subjects with chronic schizophrenia [ 95 , 96 , 97 ] and in subjects at prodromal and early stages of the illness [ 98 ].…”