Neural anomalies during vigilance in schizophrenia: Diagnostic specificity and genetic associations

Samuel D. Klein, Laurie L. Shekels, Kathryn A. McGuire, Scott R. Sponheim

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Impaired vigilance is a core cognitive deficit in schizophrenia and may serve as an endophenotype (i.e., mark genetic liability). We used a continuous performance task with perceptually degraded stimuli in schizophrenia patients (N = 48), bipolar disorder patients (N = 26), first-degree biological relatives of schizophrenia patients (N = 55) and bipolar disorder patients (N = 28), as well as healthy controls (N = 68) to clarify whether previously reported vigilance deficits and abnormal neural functions were indicative of genetic liability for schizophrenia as opposed to a generalized liability for severe psychopathology. We also examined variation in the Catechol-O-methyltransferase gene to evaluate whether brain responses were related to genetic variation associated with higher-order cognition. Relatives of schizophrenia patients had an increased rate of misidentification of nontarget stimuli as targets when they were perceptually similar, suggestive of difficulties with contour perception. Larger early visual responses (i.e., N1) were associated with better task performance in patients with schizophrenia consistent with enhanced N1 responses reflecting beneficial neural compensation. Additionally, reduced N2 augmentation to target stimuli was specific to schizophrenia. Both patients with schizophrenia and first-degree relatives displayed reduced late cognitive responses (P3b) that predicted worse performance. First-degree relatives of bipolar patients exhibited performance deficits, and displayed aberrant neural responses that were milder than individuals with liability for schizophrenia and dependent on sex. Variation in the Catechol-O-methyltransferase gene was differentially associated with P3b in schizophrenia and bipolar groups. Poor vigilance in schizophrenia is specifically predicted by a failure to enhance early visual responses, weak augmentation of mid-latency brain responses to targets, and limited engagement of late cognitive responses that may be tied to genetic variation associated with prefrontal dopaminergic availability. Experimental results illustrate specific neural functions that distinguish schizophrenia from bipolar disorder and provides evidence for a putative endophenotype that differentiates genetic liability for schizophrenia from severe mental illness more broadly.

Original languageEnglish (US)
Article number102414
JournalNeuroImage: Clinical
Volume28
DOIs
StatePublished - 2020

Bibliographical note

Funding Information:
This work was supported by grants from the Department of Veterans Affairs Clinical Science Research and Development Service ( I01CX001843 to SRS), the National Institutes of Mental Health ( R01MH112583 to SRS), and the Minnesota Medical Foundation ( SMF - 2075-99 to SRS); and by the Mental Health Patient Service Line at the Veterans Affairs Medical Center, Minneapolis Minnesota. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs or the Minnesota Medical Foundation . These funding sources played no role in study design, data collection, analysis, and interpretation, writing this report, or the decision to submit this article for publication.

Funding Information:
This work was supported by grants from the Department of Veterans Affairs Clinical Science Research and Development Service (I01CX001843 to SRS), the National Institutes of Mental Health (R01MH112583 to SRS), and the Minnesota Medical Foundation (SMF-2075-99 to SRS); and by the Mental Health Patient Service Line at the Veterans Affairs Medical Center, Minneapolis Minnesota. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs or the Minnesota Medical Foundation. These funding sources played no role in study design, data collection, analysis, and interpretation, writing this report, or the decision to submit this article for publication. We thank the EEG research assistants, clinical assessors and diagnosticians for their contributions to data collection and consultation during data analyses. The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.

Publisher Copyright:
© 2020

Keywords

  • Bipolar disorder
  • Electrophysiology
  • Endophenotype
  • Evoked potential
  • Genetic liability
  • Schizophrenia
  • Vigilance

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