Resting state electroencephalogram oscillatory abnormalities in schizophrenia and psychotic bipolar patients and their relatives from the bipolar and schizophrenia network on intermediate phenotypes study

Abstract

Background: Abnormal resting state electroencephalogram (EEG) oscillations are reported in schizophrenia (SZ) and bipolar disorder, illnesses with overlapping symptoms and genetic risk. However, less evidence exists on whether similar EEG spectral abnormalities are present in individuals with both disorders or whether these abnormalities are present in first-degree relatives, possibly representing genetic predisposition for these disorders.

Methods: Investigators examined 64-channel resting state EEGs of 225 SZ probands and 201 first-degree relatives (SZR), 234 psychotic bipolar (PBP) probands and 231 first-degree relatives (PBPR), and 200 healthy control subjects. Eight independent resting state EEG spectral components and associated spatial weights were derived using group independent component analysis. Analysis of covariance was conducted on spatial weights to evaluate group differences. Relative risk estimates and familiality were evaluated on abnormal spectral profiles in probands and relatives.

Results: Both SZ and PBP probands exhibited increased delta, theta, and slow and fast alpha activity. Post-hoc pair-wise comparison revealed increased frontocentral slow beta activity in SZ and PBP probands as well as SZR and PBPR. Augmented frontal delta activity was exhibited by SZ probands and SZR, whereas PBP probands and PBPR showed augmented fast alpha activity.

Conclusions: Both SZ and PBP probands demonstrated aberrant low-frequency activity. Slow beta activity was abnormal in SZ and PBP probands as well as SZR and PBPR perhaps indicating a common endophenotype for both disorders. Delta and fast alpha activity were unique endophenotypes for SZ and PBP probands, respectively. The EEG spectral activity exhibited moderate relative risk and heritability estimates, serving as intermediate phenotypes in future genetic studies for examining biological mechanisms underlying the pathogenesis of the two disorders.

Keywords: Bipolar disorder; EEG; intermediate phenotypes; psychosis; resting state; schizophrenia.

Figure 1

Mean frequency component over epochs across all subjects (n=1271) and associated scalp topography from group independent component analysis (GICA). The spectral components are randomly ordered in GICA but for ease we have reordered the eight spectral components from low to high frequency (1.5–50 Hz). The spatial weights of each frequency component are dimensionless measure indicating the strength of the connection or association with that component. The spatial weights were transformed to Z-scores for visualization.

Figure 2

F-maps and significance levels from the omnibus analysis of covariance test comparing spatial weights from GICA across three groups. The three groups comprised schizophrenia and psychotic bipolar disorder probands (n=459) their relatives (n=432) and healthy controls (n=200). ‘X’ indicates significant after Bonferroni correction for 64 leads (p=0.05/64).

Figure 3

Mean spatial weights in schizophrenia (SZ) probands, their relatives (SZR) and healthy controls (HC) and significance levels from pairwise post-hoc t-test. The topographic weights are dimensionless quantity. ‘X’ indicates significant after multiple comparison correction for 5 comparisons (p=0.05/5). Activity and P maps are shown at all leads for continuity, but only leads significant in the analysis of covariance and significantly different in probands and relatives vs HC are highlighted in relatives.

Figure 4

Mean spatial weights in psychotic bipolar disorder (PBP) probands, their relatives (PBPR) and healthy controls (HC) and significance levels from pairwise post-hoc t-test. The topographic weights are dimensionless quantity. ‘X’ indicates significant after multiple comparison correction for 5 comparisons (p=0.05/5). Activity and P maps are shown at all leads for continuity, but only leads significant in the analysis of covariance and significantly different in probands and relatives vs HC are highlighted in relatives.

Figure 5

Mean spatial weights of clinically relevant leads significantly differing between healthy controls and both probands and relatives. (A) Increased delta (N8) activity in schizophrenia (SZ) probands (n=225) and their relatives (SZR) (n=201) compared to healthy controls (HC) (n=200), (B) augmented fast alpha (N2) activity in psychotic bipolar disorder (PBP) probands (n=234) and their relatives (PBPR) (n=231) vs HC (n=200), (C) increased slow beta (N4) in SZ and SZR compared to HC and (D) increased slow beta (N4) in PBP and PBPR compared to HC. All the displayed leads were significantly different between HC and both probands and relatives after Bonferroni correction for pairwise comparison (p=0.05/5). Error bars represent SEM.