Pharmacopsychiatry 2013; 46 - A85
DOI: 10.1055/s-0033-1353346

Prefrontal brain network connectivity indicates degree of both schizophrenia risk and cognitive dysfunction

PG Unschuld 1, AS Buchholz 2, M Varvaris 2, PCM van Zijl 3, CA Ross 2, JJ Pekar 3, C Hock 1, JA Sweeney 4, CA Tamminga 4, MS Keshavan 5, GD Pearlson 6, GK Thaker 7, DJ Schretlen 2
  • 1Division of Psychogeriatric Medicine, University of Zürich, Switzerland
  • 2Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
  • 3F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
  • 4Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA
  • 5Department of Psychiatry, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, MA, USA
  • 6Departments of Psychiatry and Neurobiology, Yale University School of Medicine, New Haven, CT, USA
  • 7Departments of Psychiatry, University of Maryland, School of Medicine, Baltimore, MD, USA

Cognitive dysfunction is a core feature of schizophrenia, and persons at risk for schizophrenia may show subtle deficits in attention and working memory. In this study we investigated the relationship between integrity of functional brain networks and performance in attention and working memory tasks as well as schizophrenia-risk. 235 adults representing three levels of risk (102 outpatients with schizophrenia, 70 unaffected first-degree relatives of persons with schizophrenia, and 63 unrelated healthy controls) completed resting-state functional magnetic resonance imaging and a battery of attention and working-memory tasks. Functional networks were defined based on coupling with seeds in the dACC, DLPFC, MPFC and BA17. Both patients with schizophrenia and their first-degree relatives showed cognitive-dysfunction compared to healthy controls. First canonicals indicated an inverse relationship between cognitive performance and connectivity within the DLPFC- and MPFC-networks. MANOVA revealed multivariate main effects of higher schizophrenia-risk status on increased connectivity within the DLPFC and MPFC networks. These data suggest that excessive connectivity within brain networks coupled to the DLPFC and MPFC, respectively, accompany cognitive deficits in persons at risk for schizophrenia. This might reflect compensatory reactions in neural systems required for cognitive processing of attention and working-memory tasks to brain changes associated with schizophrenia. This study was supported by NIH R01 MH077852, NIH-NIBIB P41-EB015909, NIH-T32MH015330.