Abstract
Many studies have examined either electroencephalogram (EEG) frequency activity or gray matter volumes (GMV) in various psychoses [including schizophrenia (SZ), schizoaffective (SZA), and psychotic bipolar disorder (PBP)]. Prior work demonstrated similar EEG and gray matter abnormalities in both SZ and PBP. Integrating EEG and GMV and jointly analyzing the combined data fully elucidates the linkage between the two and may provide better biomarker- or endophenotype-specificity for a particular illness. Joint exploratory investigations of EEG and GMV are scarce in the literature and the relationship between the two in psychosis is even less explored. We investigated a joint multivariate model to test whether the linear relationship or linkage between awake EEG (AEEG) frequency activity and GMV is abnormal across the psychosis dimension and if such effects are also present in first-degree relatives. We assessed 607 subjects comprising 264 probands [105 SZ, 72 SZA, and 87 PBP], 233 of their first degree relatives [82 SZ relatives (SZR), 71 SZA relatives (SZAR), and 80 PBP relatives (PBPR)], and 110 healthy comparison subjects (HC). All subjects underwent structural MRI (sMRI) and EEG scans. Frequency activity and voxel-based morphometric GMV were derived from EEG and sMRI data, respectively. Seven AEEG frequency and gray matter components were extracted using Joint independent component analysis (jICA). The loading coefficients (LC) were examined for group differences using analysis of covariance. Further, the LCs were correlated with psychopathology scores to identify relationship with clinical symptoms. Joint ICA revealed a single component differentiating SZ from HC (p < 0.006), comprising increased posterior alpha activity associated with decreased volume in inferior parietal lobe, supramarginal, parahippocampal gyrus, middle frontal, inferior temporal gyri, and increased volume of uncus and culmen. No components were aberrant in either PBP or SZA or any relative group. No significant association was identified with clinical symptom measures. Our data suggest that a joint EEG and GMV model yielded a biomarker specific to SZ, not abnormal in PBP or SZA. Alpha activity was related to both increased and decreased volume in different cortical structures. Additionally, the joint model failed to identify endophenotypes across psychotic disorders.
Highlights
Several independent electroencephalogram (EEG) and neuroimaging studies have been conducted in schizophrenia (SZ), schizoaffective (SZA), and psychotic bipolar disorder (PBP) [1, 2] with the aim of finding shared and specific biomarkers for these disorders
Of the seven components derived from these data by joint independent component analysis (jICA) (IC1-7 explaining ~88% of variance), only one component’s loading (IC5 with ~16% explained variance) showed significant main effect (F1,365 = 9.96, p < 0.0017) in the initial analysis contrasting psychosis (SZ + SZA + PBP) vs. healthy comparison (HC)
Post hoc tests revealed that the loading for IC5 was significantly higher in SZ probands compared to HC (p < 0.004 after Bonferroni correction for multiple group comparisons; see Figure 2), reflecting that strength of the coupling between EEG and gray matter volumes (GMV) was increased in SZ compared to HC
Summary
Several independent electroencephalogram (EEG) and neuroimaging (both functional and structural) studies have been conducted in schizophrenia (SZ), schizoaffective (SZA), and psychotic bipolar disorder (PBP) [1, 2] with the aim of finding shared and specific biomarkers for these disorders. A data-fusion type approach combines two data modalities by capitalizing complementary and unique modalityspecific information (for example, functional and structural) in an integrated model that can identify within-subject covarying patterns (linkage) across modalities [9]. Such a linkage serves in identifying disease-specific biomarkers or endophenotypic markers to advance gene discovery and provide improved and disease-specific treatment [10]. Many studies have examined either electroencephalogram (EEG) frequency activity or gray matter volumes (GMV) in various psychoses [including schizophrenia (SZ), schizoaffective (SZA), and psychotic bipolar disorder (PBP)]. We investigated a joint multivariate model to test whether the linear relationship or linkage between awake EEG (AEEG) frequency activity and GMV is abnormal across the psychosis dimension and if such effects are present in first-degree relatives
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