Abnormal P300 in people with high risk of developing psychosis

Abstract

Background: Individuals with an "At Risk Mental State" (or "prodromal" symptoms) have a 20-40% chance of developing psychosis; however it is difficult to predict which of them will become ill on the basis of their clinical symptoms alone. We examined whether neurophysiological markers could help to identify those who are particularly vulnerable.Method: 35 cases meeting PACE criteria for the At Risk Mental State (ARMS) and 57 controls performed an auditory oddball task whilst their electroencephalogram was recorded. The latency and amplitude of the P300 and N100 waves were compared between groups using linear regression.Results: The P300 amplitude was significantly reduced in the ARMS group [8.6 ±6.4 microvolt] compared to controls [12.7 ±5.8 microvolt] (p<0.01). There were no group differences in P300 latency or in the amplitude and latency of the N100. Of the at-risk subjects that were followed up, seven (21%) developed psychosis. Please find attached a fully revised manuscript titled "Abnormal P300 in people with high risk of developing psychosis". We also enclose a letter with the comments from the reviewers and our detailed answers on how we have done all the changes requested. (t-test; p=0.93). Those making a transition to psychosis were marginally more educated but this was only at trend level with a 3 year average difference in the age at which they completed their studies (t-test; p=0.07).Similarly, logistic regression analyses showed that compared to those who remained at risk, the seven cases who made a transition to psychosis had no significant differences in P300 amplitude/latency or N100 amplitude/latency (p values ranging from 0.30 to 0.63 for all four analyses). We have reported these comparisons very concisely and cautiously because referee #2 said that these analyses with only 7 individual making a transition were preliminary and power is limited. Please see results section paragraph 2. RESPONSE TO REVIEWER #2:Thank you for your suggestions, which have improved the paper. Below are your comments in blue-italics and how we have amended the manuscript accordingly in black with cross-references to the revised manuscript.This paper addresses an important and timely topic, namely, whether auditory P300 is reduced in subjects with at risk mental states and whether the P300 predicts subsequent conversion to psychosis. The study finds a significant deficit in P300 in ARMS subjects, relative to controls, replicating a previously a previously published report. The study had the potential to incrementally * 2. Response to Reviews 2 contribute to the literature by examining the utility of baseline P300 deficits as a predictor of subsequent conversion to psychosis; however, the negative finding coupled with the lack of power for this analysis (only 7 converters) make this aspect of the study inconclusive. More detailed comments are provided below:We have added a paragraph in the discussion to acknowledge the limitation of our small group of converters and how we have low statistical power to compa...

White matter alterations related to P300 abnormalities in individuals at high risk for psychosis: an MRI–EEG study

“…[44][45][46] In support of these findings, previous diffusion tensor imaging (DTI) studies in patients with schizophrenia have confirmed reduced anisotropy in the frontal cortex, 47-50 the anterior cingulum 51,52 and the tempor al lobe. 20,53 The ARMS group also showed a reduced P300 amplitude compared with controls, in line with our previous results in a larger sample 14 and with other studies in patients at risk for psychosis. 15,54 Functionally, the P300 reflects the summation of multiple, simultaneously occurring cognitive and brain processes that are linked to attentional resource allocation and memory-updating operations in the brain.…”

“…12 Interestingly, 3 recent independent studies of individuals at enhanced risk for psychosis have confirmed that P300 ab normalities are already evident in the prepsychotic phases. [13][14][15] P300 can index a neuro biologic vulnerability to schizophrenia, in line with other studies showing P300 abnormalities in relatives of individuals with psychosis. 16,17 On the other hand, neuroimaging studies have indicated that patients at high risk for psychosis show alterations in white matter 18,19 volume in fronto-temporal regions.…”

“…The P300 results of a larger sample have been previously published. 14 We analyzed between-group differences in P300 amplitude with independent t tests (p < 0.05).…”

174.2 Psychosis Prediction: Stratification of Risk Estimation With Information-Processing and Premorbid Functioning Variables

“…[26][27][28] Several papers showed a reduced P300 amplitude in CHR subjects. [29][30][31][32][33][34] Yet, none of these reports included (enough) converted cases to enable a predictor analysis except for the DUPS study. 25 While all factors mentioned above contribute to the prediction of a first psychosis, their relative contribution is small.…”

EEG spectral power and negative symptoms in at-risk individuals predict transition to psychosis

“…This hypothesis originates from the observation that negative symptoms and quantitative EEG (qEEG) spectral power are correlated in different types of medicated and unmedicated schizophrenic patients. [19][20][21][22][23][24][25][26][27] Moreover, a recent study by our group 28 showed that negative symptoms are positively correlated with qEEG absolute power in delta (0.5-4 Hz), theta (4-8 Hz) and beta1 (12)(13)(14)(15) bands in the first episode (FE) of schizophrenia in neuroleptic-naïve patients. Presence of these correlations in neuroleptic naïve FE patients is a first requirement for the combination of negative symptoms with qEEG findings in ARMS patients to be a valid predictor for transition to psychosis.…”