Event-Related Potential and Time-Frequency Endophenotypes for Schizophrenia and Psychotic Bipolar Disorder

Abstract

Background The investigators compared event related potential (ERP) amplitude measurements and event-related oscillations across a broad frequency range during an auditory oddball task using a comprehensive analysis approach to describe shared and unique neural auditory processing characteristics among healthy subjects (HP), schizophrenia probands (SZ) and their first-degree relatives (SZrel), and bipolar disorder I with psychosis probands (BDP) and their first-degree relatives (BDPrel). Methods This Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) sample consisted of clinically stable SZ (n=229) and BDP (n=188), healthy subjects (HP, n=284), SZrel (n=264) and BDPrel (n=239). They were administered an auditory oddball task in the electroencephalography (EEG) environment. Principal components analysis (PCA) derived data-driven frequency bands for measurement of evoked power. Spatial PCA reduced ERP and frequency data to component waveforms for each subject. Clusters of time-bins with significant group differences on magnitude of response were assessed for patterns of proband/relative differences from HP and familiality. Results Nine variables survived a linear discriminant analysis between HP, SZ, and BDP. Of those, two showed evidence (deficit in relatives and familiality) as genetic risk markers more specific to SZ (N1, P3b) while one was specific to BDP (P2) and one for psychosis in general (N2). Conclusions This study provides support for both shared and unique deficits in early sensory and late cognitive processing across psychotic diagnostic groups Additional ERP and time-frequency component alterations (frontal N2/P2, late high, early mid and low- frequency) may provide insight into deficits in underlying neural architecture and potential protective/compensatory mechanisms in unaffected relatives.

Clinical significance of auditory target P300 subcomponents in psychosis: Differential diagnosis, symptom profiles, and course

“…However, converging lines of evidence suggest that P3b reduction may be a relatively stable trait-like biological marker of vulnerability to disease rather than a consequence of disease state. For example, P3b amplitude reduction presents in high-risk cases (Bramon et al, 2007) and unaffected biological relatives of cases (Ethridge et al, 2014). Fourth, we assessed P300 subcomponents using an auditory oddball paradigm, but other kinds of tasks or stimuli may yield different results.…”

Alterations in hippocampal connectivity across the psychosis dimension

“…Individuals with these psychotic diagnoses share overlapping clinical manifestations and cognitive deficits in the domains of declarative and working memory, executive function, and attention (Seidman et al, 2002; Badner and Gershon, 2002; Thaker, 2008; Ivleva et al, 2010; Ivleva et al, 2012; Hill et al, 2013; Tamminga et al, 2013). Moreover, the diagnoses share similar patterns of aberrant resting state- and event related potential-based EEG activity, oculomotor abnormalities, and shared genetic susceptibility markers, albeit of varying severity (Bramon and Sham, 2001; Badner and Gershon, 2002; Harris et al, 2009; Ivleva et al, 2010; Narayanan et al, 2013; Ethridge et al, 2014). In addition, they share similar pathological characteristics of whole brain fMRI resting-state networks across SZ and BD-P (Karbasforoushan and Woodward, 2012; Khadka et al, 2013).…”

Electrophysiological Endophenotypes for Schizophrenia

“…Although seemingly contradictory results have been published, (e.g., 173,228 ), the most recent study -consisting of a large sample of schizophrenia and bipolar patients and their relatives - showed that gamma abnormalities are a feature of psychosis, regardless of diagnosis, and are heritable. 171 …”