Deficits of entropy modulation of the EEG: A biomarker for altered function in schizophrenia and bipolar disorder?

Background: The synchronized activity of distributed neural assemblies ­ reflected in the electroencephalogram (EEG) ­ underpins mental function. In schizophrenia, modulation deficits of EEG spectral content during a P300 task have been replicated. The effects of treatment, chronicity and specificity in these deficits and their possible relationship with anatomic connectivity remain to be explored. Methods: We assessed spectral entropy modulation of the EEG during a P300 task in 79 patients with schizophrenia (of those, 31 werein their first episode), 29 patients with bipolar disorder and 48 healthy controls. Spectral entropy values summarize EEG characteristics by quantifying the irregularity of spectral content. In a subsample, we calculated the network architecture of structural connectivity using diffusion tensor imaging and graph-theory parameters. Results: We found significant spectral entropy modulation deficits with task performance in patients with chronic or first-episode schizophrenia and in patients with bipolar disorder, without significant pre-stimulus spectral entropy differences. The deficits were unrelated to treatment doses, and spectral entropy modulation did not differ between patients taking or not taking antipsychotics, lithium, benzodiazepines or antidepressants. Structural connectivity values were unrelated to spectral entropy modulation. In patients with schizophrenia, spectral entropy modulation was inversely related to negative symptoms and directly related to verbal memory. Limitations: All patients were taking medication. Patients with bipolar disorder were euthymic and chronic. The cross-sectional nature of this study prevented a more thorough analysis of state versus trait criteria for spectral entropy changes. Conclusion: Spectral entropy modulation with task performance is decreased in patients with schizophrenia and bipolar disorder. This deficit was not an effect of psychopharmacological treatment or structural connectivity and might reflect a deficit in the synchronization of the neural assemblies that underlie cognitive activity.

Association between electroencephalographic modulation, psychotic-like experiences and cognitive performance in the general population.

AIM: An association between deficit of electroencephalographic (EEG) modulation during an odd-ball task and psychotic symptoms has been described in clinical samples, in agreement with the proposed role for altered salience in psychosis. To discard the possible influence of medication, the relationship between psychotic-like experiences and EEG modulation in the general population was explored. METHODS: EEG and psychotic-like experiences were assessed in 194 healthy subjects during a P300 paradigm. EEG modulation was assessed as changes from pre-stimulus to response windows in spectral entropy (SE, a measurement of signal irregularity), median frequency (MF, a quantifier of the frequency distribution of oscillatory activity) and theta, alpha, beta-1, beta-2 and gamma relative power (RP, a summary of the distribution of spectral components). RESULTS: A significant widespread decrease in SE and MF from baseline to response was found, with a significant increase in RP for theta and a decrease for higher frequency bands, supporting an increase in EEG regularity and a slowing of brain oscillations during the response. Furthermore, a significant association was found between SE modulation and distress of negative psychotic-like experiences, as well as between verbal memory and RP modulation for beta-1. Performance in verbal fluency was associated with the increase in theta RP during the response. CONCLUSION: EEG irregularity of healthy subjects decreased at the expense of a larger contribution of theta RP and a decreased contribution of fast frequency bands. Subjects with smaller modulation showed poorer cognitive scores and greater distress of negative psychotic-like experiences.

Cannabis and first-episode psychosis: different long-term outcomes depending on continued or discontinued use.

OBJECTIVE: To examine the influence of cannabis use on long-term outcome in patients with a first psychotic episode, comparing patients who have never used cannabis with (a) those who used cannabis before the first episode but stopped using it during follow-up and (b) those who used cannabis both before the first episode and during follow-up. METHODS: Patients were studied following their first admission for psychosis. They were interviewed at years 1, 3, and 5. At follow-up after 8 years, functional outcome and alcohol and drug abuse were recorded. Patients were classified according to cannabis use: 25 had cannabis use before their first psychotic episode and continuous use during follow-up (CU), 27 had cannabis use before their first episode but stopped its use during follow-up (CUS), and 40 never used cannabis (NU). RESULTS: The 3 groups did not differ significantly in symptoms or functional outcome at baseline or during short-term follow-up. The CUS group exhibited better long-term functional outcome compared with the other 2 groups and had fewer negative symptoms than the CU group, after adjusting for potential confounders. For the CUS group, the effect size was 1.26 (95% confidence interval [CI]=0.65 to 1.86) for functional outcome and -0.72 (95% CI=-1.27 to -0.14) for negative symptoms. All patients experienced improvements in positive symptoms during long-term follow-up. CONCLUSION: Cannabis has a deleterious effect, but stopping use after the first psychotic episode contributes to a clear improvement in outcome. The positive effects of stopping cannabis use can be seen more clearly in the long term.

Poor long-term prognosis in mixed bipolar patients: 10-year outcomes in the Vitoria prospective naturalistic study in Spain.

OBJECTIVE: There have been few prospective long-term naturalistic studies of patients with mixed episodes of bipolar disorder. The aim of this study was to examine 10-year outcomes in patients with at least 1 mixed episode. METHOD: A naturalistic sample of bipolar I disorder patients (n = 120), representative of bipolar patients treated in a catchment area of Spain, was followed prospectively for up to 10 years. Outcomes including number (primary study outcome) and severity of episodes, hospitalizations, and suicide attempts were recorded at bimonthly visits. Bivariate and logistic regression models identified factors significantly associated with mixed episodes. The study was conducted from 1994 through 2004. RESULTS: 37% of patients had mixed episodes. Mixed-episode patients had younger mean age at onset compared with the nonmixed group (25.3 vs 30.8 years; P = .025). After adjusting for age at onset, mixed-episode patients had an increased risk of hospitalization compared with the nonmixed group (OR = 2.86; 95% CI, 1.09-7.52; P = .033) and more episodes (OR = 1.21; 95% CI, 1.10-1.31; P < .001). Other differences between mixed and nonmixed patients, such as alcohol abuse, psychotic symptoms, and suicidality, were partially mediated by age at onset and were not significantly different after controlling for this variable. Mixed-episode patients with previous suicide attempts had a significantly shorter time to first suicide attempt during follow-up than those without history of suicide attempts (P = .014). CONCLUSIONS: Although some factors associated with mixed episodes are mediated by a younger age at onset, the long-term prognosis of mixed-episode patients is worse than patients with nonmixed episodes.