Intrinsic neural activity differences in psychosis biotypes: Findings from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium

Intro: The Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) proposed “Biotypes,” subgroups of psychosis cases with neuro-cognitive homology. Neural activity unbound to stimulus processing (nonspecific or intrinsic activity) was important for differentiating Biotypes, with Biotype-2 characterized by high nonspecific neural activity. A precise estimate of intrinsic activity (IA) was not included in the initial Biotypes characterization. This report hypothesizes intrinsic activity is a critical differentiating feature for psychosis Biotypes. Method: Participants were recruited at B-SNIP sites and included probands with psychosis (schizophrenia, schizoaffective disorder, bipolar I disorder), their first-degree biological relatives, and healthy persons (N = 1338). Probands were also sub-grouped by psychosis Biotype. 10-sec inter-stimulus intervals during an auditory paired-stimuli task were used to quantify intrinsic activity from 64 EEG sensors. Single-trial power and connectivity measures at empirically derived frequency bands were quantified. Multivariate discriminant and correlational analyses were used to summarize variables that efficiently and maximally differentiated groups by conventional diagnoses and Biotypes and to determine their relationship to clinical and social functioning. Results: Biotype-1 consistently exhibited low IA, and Biotype 2 exhibited high IA relative to healthy persons across power frequency bands (delta/theta, alpha, beta, gamma) and alpha band connectivity estimates. DSM groups did not differ from healthy persons on any IA measure. Discussion: Psychosis Biotypes, but not DSM syndromes, were differentiated by intrinsic activity; Biotype-2 was uniquely characterized by an accentuation of this measure. Neurobiologically defined psychosis subgroups may facilitate the use of intrinsic activity in translation models aimed at developing effective treatments for psychosis-relevant deviations in neural modulation.