Journal of the International Neuropsychological Society (2016), 22, 1026–1037. Copyright © INS. Published by Cambridge University Press, 2016. doi:10.1017/S1355617716000242 Auditory Vigilance and Working Memory in Youth at Familial Risk for Schizophrenia or Affective Psychosis in the Harvard Adolescent Family High Risk Study Larry J. Seidman, 1,2 Andrea Pousada-Casal, 1,3 Silvia Scala, 1,4 Eric C. Meyer, 5,6,7 William S. Stone, 1 Heidi W. Thermenos, 1,2 Elena Molokotos, 1 Jessica Agnew-Blais, 8 Ming T. Tsuang, 1,9 AND Stephen V. Faraone 10 1 Harvard Medical School, Department of Psychiatry, Massachusetts Mental Health Center Division of Public Psychiatry, Beth Israel Deaconess Medical Center, Boston, Massachusetts 2 Harvard Medical School, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 3 Saint Louis University, Madrid, Spain 4 Department of Public Health and Community Medicine, Section of Psychiatry and Clinical Psychology, University of Verona, P.le L.A. Scuro, Italy 5 VA VISN 17 Center of Excellence for Research on Returning War Veterans, Waco, Texas 6 Central Texas Veterans Healthcare System, Temple, Texas 7 Texas A&M Health Science Center, College of Medicine, College Station, Texas 8 MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience King’s College, London, United Kingdom 9 University of California, San Diego, Department of Psychiatry, Center for Behavior Genomics and Institute of Genomic Medicine, La Jolla, California 10 Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, New York, New York (RECEIVED August 25, 2015; FINAL REVISION February 25, 2016; ACCEPTED March 1, 2016) Abstract Background: The degree of overlap between schizophrenia (SCZ) and affective psychosis (AFF) has been a recurring question since Kraepelin’s subdivision of the major psychoses. Studying nonpsychotic relatives allows a comparison of disorder-associated phenotypes, without potential confounds that can obscure distinctive features of the disorder. Because attention and working memory have been proposed as potential endophenotypes for SCZ and AFF, we compared these cognitive features in individuals at familial high-risk (FHR) for the disorders. Methods: Young, unmedicated, first-degree relatives (ages, 13–25 years) at FHR-SCZ (n = 41) and FHR-AFF (n = 24) and community controls (CCs, n = 54) were tested using attention and working memory versions of the Auditory Continuous Performance Test. To determine if schizotypal traits or current psychopathology accounted for cognitive deficits, we evaluated psychosis proneness using three Chapman Scales, Revised Physical Anhedonia, Perceptual Aberration, and Magical Ideation, and assessed psychopathology using the Hopkins Symptom Checklist -90 Revised. Results: Compared to controls, the FHR-AFF sample was significantly impaired in auditory vigilance, while the FHR-SCZ sample was significantly worse in working memory. Both FHR groups showed significantly higher levels of physical anhedonia and some psychopathological dimensions than controls. Adjusting for physical anhedonia, phobic anxiety, depression, psychoticism, and obsessive-compulsive symptoms eliminated the FHR-AFF vigilance effects but not the working memory deficits in FHR-SCZ. Conclusions: The working memory deficit in FHR-SZ was the more robust of the cognitive impairments after accounting for psychopathological confounds and is supported as an endophenotype. Examination of larger samples of people at familial risk for different psychoses remains necessary to confirm these findings and to clarify the role of vigilance in FHR-AFF. (JINS, 2016, 22, 1026–1037) Keywords: Familial high-risk, Vigilance, Working memory, Psychopathology, Schizophrenia, Affective psychoses, Endophenotypes INTRODUCTION Kraepelin’s (1919) division of “dementia praecox” and “manic-depressive” disease (e.g., bipolar disorder) into separate neuropsychiatric disorders has been a fundamental nosological distinction for more than 100 years. However, there is growing evidence identifying common as well as distinct neurobiological features (Mayer, Zobel, & Wagner, 2007), including genetic liability (Berretini, 2000; Craddock, O’Donovan, & Owen, 2006; Cross-Disorder Group of the Psychiatric GWAS Consortium, 2013), brain structural INS is approved by the American Psychological Association to sponsor Continuing Education for psychologists. INS maintains responsibility for this program and its content. Correspondence and reprint requests to: Larry J. Seidman, Massachusetts Mental Health Center, Commonwealth Research Center, 5 th Floor, 75 Fenwood Road, Boston, MA 02115. E-mail: lseidman@bidmc.harvard.edu 1026 https://www.cambridge.org/core/terms. https://doi.org/10.1017/S1355617716000242 Downloaded from https://www.cambridge.org/core. IP address: 168.151.1.49, on 18 Sep 2017 at 12:30:22, subject to the Cambridge Core terms of use, available at