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Schizophr Bull. 2020 Feb 11. pii: sbaa001. doi: 10.1093/schbul/sbaa001. [Epub ahead of print]

Cognitive Impairment and Diminished Neural Responses Constitute a Biomarker Signature of Negative Symptoms in Psychosis.

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Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX.
Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens, GA.
Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
Departments of Psychiatry and Neurobiology, Yale University School of Medicine, New Haven, CT.
Institute of Living, Hartford Hospital, Hartford, CT.
Department of Psychiatry, University of Chicago, Chicago, IL.
Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH.
Institut Recherche Pierre-Fabre, Toulouse, France.
McArthur and Associates GmBH, Basel, Switzerland.


The treatment of negative symptoms (NS) in psychosis represents an urgent unmet medical need given the significant functional impairment it contributes to psychosis syndromes. The lack of progress in treating NS is impacted by the lack of known pathophysiology or associated quantitative biomarkers, which could provide tools for research. This current analysis investigated potential associations between NS and an extensive battery of behavioral and brain-based biomarkers in 932 psychosis probands from the B-SNIP database. The current analyses examined associations between PANSS-defined NS and (1) cognition, (2) pro-/anti-saccades, (3) evoked and resting-state electroencephalography (EEG), (4) resting-state fMRI, and (5) tractography. Canonical correlation analyses yielded symptom-biomarker constructs separately for each biomarker modality. Biomarker modalities were integrated using canonical discriminant analysis to summarize the symptom-biomarker relationships into a "biomarker signature" for NS. Finally, distinct biomarker profiles for 2 NS domains ("diminished expression" vs "avolition/apathy") were computed using step-wise linear regression. NS were associated with cognitive impairment, diminished EEG response amplitudes, deviant resting-state activity, and oculomotor abnormalities. While a connection between NS and poor cognition has been established, association to neurophysiology is novel, suggesting directions for future mechanistic studies. Each biomarker modality was related to NS in distinct and complex ways, giving NS a rich, interconnected fingerprint and suggesting that any one biomarker modality may not adequately capture the full spectrum of symptomology.


bipolar disorder; multivariate statistics/EEG; oculomotor/biotype; schizophrenia


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