Neuroimaging data published in Schizophrenia Bulletin identified a novel association between negative symptoms (NS) in psychosis and diminished resting state and evoked electroencephalography (EEG) amplitudes. Together with cognitive impairment and eye movement abnormalities, diminished EEG response appears to form a neurobiological “fingerprint” for NS in psychosis.

The Bipolar-Schizophrenia Network for Intermediate Phenotypes-1 (B-SNIP1) study involves a 5-site phenotyping cohort of patients with psychosis syndrome, including those with schizophrenia (n=397), schizoaffective disorder (n=223), or bipolar I disorder with psychosis (n=312). The researchers captured NS with the Positive and Negative Syndrome Scale (PANSS) and provided a range of measures, including the Montgomery-Asberg Depression Rating Scales (MADRS) and Global Assessment of Functioning (GAF). They also performed phenotyping tests to examine associations between NS and the following biomarker modalities: 1) cognition, assessed per the Brief Assessment of Cognition in Schizophrenia (BACS); 2) rapid eye movement abnormalities, including anti- and pro-saccade performance; 3) resting-state and evoked EEG; 4) resting-state functional magnetic resonance imaging (fMRI); and 5) structural tractography MRI.

All biomarker measures were adjusted for age and sex using models derived from the B-SNIP1 healthy control cohort (n=459). Canonical correlation analyses were performed separately for each biomarker modality, allowing for interpretation of the strength of polarity of each association. Stepwise multivariable analyses integrating all biomarkers were used to identify which modalities had the highest discriminatory capacity for NS. Separate biomarker analyses were also performed for the 2 proposed subdomains of NS: “diminished expression” and “avolition/apathy.”

All B-SNIP1 participants (49.7% women) were 15 to 65 years of age and 92.7% were on at least 1 psychotropic medication. Compared to those without NS, patients with NS displayed more severe clinical symptoms on the PANSS positive and general symptom subscales (P <.001). NS were more common in patients with schizophrenia (48.8%) and schizoaffective disorder (42.1%) vs bipolar disorder (21.8%).

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Canonical discriminant analysis identified a set of 11 biomarkers with maximum discriminatory capacity between NS and non-NS, including poor or slow saccades, poor emotion recognition, low BACS, low evoked-EEG amplitudes, and decreased frontoparietal resting state fMRI activity. Regarding NS domains, “diminished expression” was predicted by low BACS (P <.001), low evoked-EEG amplitude (P <.001), poor antisaccade performance (P =.01), and poor emotion recognition (P =.04). Avolition/apathy severity was associated with low evoked-EEG amplitude (P =.002), suggesting that NS domains have distinct neurobiological mechanisms.

In analyses of specific NS items, low BACS score predicted blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, lack of spontaneity, motor retardation, and active social withdrawal, though associations were typically of nominal significance. Inclusion of first-generation antipsychotics in statistical models did not appear to attenuate any biomarker associations.  

Several biomarker modalities have utility as predictors of NS, including cognition, evoked and resting-state EEG, fMRI, and pro-/anti-saccades. Analyses stratified by NS domain supported distinct neurobiological mechanisms for “diminished expression” and “avolition/apathy.” The cross-sectional study design prevented in-depth analysis of certain covariates, including antipsychotic medication use, white matter tracts, and depression symptoms.

The study authors concluded that the results “highlight the potential value of extensive biomarker batteries and integration across multiple levels of analysis for characterizing a neurobiologically complex clinical construct.” However, they warned that “any one biomarker modality may not adequately capture the full spectrum of symptomology.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry.

Please see the original reference for a full list of authors’ disclosures.


Hudgens-Haney ME, Clementz BA, Ivleva EI, et al. Cognitive impairment and diminished neural responses constitute a biomarker signature of negative symptoms in psychosis [published online February 11, 2020]. Schizophr Bull. doi: 10.1093/schbul/sbaa001