Neural Anomalies during Vigilance in Schizophrenia: Diagnostic Specificity and Genetic Associations

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) , and first-degree biological relatives of schizophrenia patients ( N =55) and bipolar disorder patients ( N =28) and 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, possibly reflecting difficulties with contour perception. Larger early visual responses (i.e., N1) were associated with better task performance, while reduced N2 augmentation to target stimuli was specific to schizophrenia patients. Both schizophrenia patients and relatives of schizophrenia patients displayed reduced late cognitive responses (P3b) that predicted worse performance. Bipolar patients and their relatives exhibited performance deficits and some aberrant neural responses that were milder 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.