Cognitive, Clinical Features Related to Auditory Oddball Responses Along the Schizophrenia-Bipolar Spectrum

Investigators assessed the relationship between clinical and cognitive features and oddball neural deviations across the schizophrenia-bipolar spectrum.

Variation in the neural processing of auditory stimulation was found to be related to psychosis and bipolar disorder, according to findings of a study published in The American Journal of Psychiatry.

Study participants (N=1078) were recruited at 5 Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium sites and 3 Psychosis and Affective Research Domains and Intermediate Phenotypes (PARDIP) sites. Individuals had been diagnosed with bipolar disorder-I without psychosis (n=66), bipolar disorder-I with psychosis (n=171), schizoaffective disorder (n=201), or schizophrenia (n=225), or were healthy first-degree relatives of patients (n=415). Participants were assessed by electroencephalogram (EEG) while undergoing an auditory oddball response test in 20-ms segments using 64 sensors, by the Montgomery-Åsberg Depression Rating Scale (MADRS), and by the Positive and Negative Syndrome Scale (PANSS).

Study cohorts ranged in average age from 37.20 to 40.39 years, between 29% and 62% were men, and between 30% and 68% were White.

A total of 3 of the 26 EEG variables tested best captured the group differences.

The first significant variate discriminated healthy participants from patients along psychopathology severity. The specific neural variables corresponding with these differences were parietal N200 (r, -0.50) and mid low-frequency (r, 0.48) responses during the target trial and N100 (r, -0.45) and early/mid low-frequency (r, 0.44) responses during the standard trial. In addition, these same features strongly correlated with cognitive function (r, 0.91).

The second significant variate discriminated between bipolar disorder with and without psychosis. The specific neural variables were event-related potential P50 (r, 0.31), beta (r, 0.34), and early gamma (r, 0.46) responses during the standard trial.

The third significant variate discriminated between healthy or nonaffective psychosis groups from bipolar disorder cohorts. The neural variables most associated with this variate were standard trial P200 (r, 0.57) and frontal P3a (r, 0.45) responses and event-related potential responses during the target trial (r, 0.40).

Correlates were identified between the clinical latent component and higher MADRS score (r, 0.48), social functioning (r, 0.36), lower PANSS positive symptom score (r, -0.34), and lower PANSS negative symptom score (r, -0.34). Similarly, the neural latent component correlated with standard rising P200 (r, -0.46) and target frontal late trials (r, -0.51).

This study was limited by the imbalanced numbers of participants across cohorts and the fact that most patients were on medication during assessment.

These data suggest that there is variation in the neural processing of auditory stimulation. The study authors concluded that better understanding of the neurobiology of the psychosis-bipolar spectrum may identify viable biomarkers for therapeutic targets.

Disclosure: An author declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Parker DA, Trotti RL, McDowell JE, et al. Auditory oddball responses across the schizophrenia-bipolar spectrum and their relationship to cognitive and clinical features. Am J Psychiatry. 2021;178(10):952-964. doi:10.1176/appi.ajp.2021.20071043