Nicholas Massa1, Andrew V Owens2, Wesley Harmon3, Arpita Bhattacharya4, Elena I Ivleva5, Sarah Keedy6, John A Sweeney7, Godfrey D Pearlson8, Matcheri S Keshavan9, Carol A Tamminga5, Brett A Clementz10, Erica Duncan11. 1. Atlanta Veterans Affairs Medical Center, Decatur, GA, 30033, USA; Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA. 2. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, 30329, USA. 3. Emory University, Atlanta, GA, 30322, USA. 4. University of Washington, Seattle, WA, 98195, USA. 5. University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA. 6. University of Chicago, Chicago, IL, 60637, USA. 7. Department of Psychiatry, University of Cincinnati, Cincinnati, OH, 45219, USA. 8. Yale University and Institute of Living, New Haven, CT, 06520, USA. 9. Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, 02115, USA. 10. Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens, GA, 30602, USA. 11. Atlanta Veterans Affairs Medical Center, Decatur, GA, 30033, USA; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, 30329, USA. Electronic address: erica.duncan@va.gov.
Abstract
BACKGROUND: Latency of the acoustic startle reflex is the time from presentation of the startling stimulus until the response and provides an index of neural processing speed. Latency is prolonged in schizophrenia, is 90% heritable, and predicts conversion to schizophrenia in a high-risk population. The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) consortium investigates neurobiological features found in psychotic disorders spanning diagnostic criteria for schizophrenia (SCZ), schizoaffective disorder (SAD), and psychotic bipolar disorder (BP). We investigated whether differences in startle latency and prepulse inhibition (PPI) occur in probands, their first-degree relatives, and neurobiologically defined subgroups of the probands (Biotypes). METHODS: 1143 subjects were included from the B-SNIP cohort: 143 with SCZ, 178 SCZ relatives (SCZ-Fam), 123 with SAD, 152 SAD relatives (SAD-Fam), 138 BP, 183 BP relatives (BP-Fam), and 226 controls (CON). A Biopac system recorded the eyeblink component of the startle reflex during startle testing. RESULTS: Latency differed by diagnosis (F(3,620) = 5.10, p = 0.002): SCZ, SAD, and BP probands had slower latency than CON, with relatives intermediate. Biotypes 1 and 2 had slower latency than CON (p < 0.031) but Biotype 3 did not differ from CON. PPI did not separate CON from other subjects when analyzed by diagnoses nor when analyzed by biotype. Biotype 1 relatives had slower latency (F(3,663) = 3.49, p = 0.016) and more impaired PPI than Biotype 2 and 3 relatives (F(3,663) = 2.77, p = 0.041). CONCLUSION: Startle latency is prolonged in psychotic disorders that cross traditional diagnostic categories. These data suggest a genetic difference between biotypes that span across clinically defined diagnoses. Published by Elsevier B.V.
BACKGROUND: Latency of the acoustic startle reflex is the time from presentation of the startling stimulus until the response and provides an index of neural processing speed. Latency is prolonged in schizophrenia, is 90% heritable, and predicts conversion to schizophrenia in a high-risk population. The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) consortium investigates neurobiological features found in psychotic disorders spanning diagnostic criteria for schizophrenia (SCZ), schizoaffective disorder (SAD), and psychotic bipolar disorder (BP). We investigated whether differences in startle latency and prepulse inhibition (PPI) occur in probands, their first-degree relatives, and neurobiologically defined subgroups of the probands (Biotypes). METHODS: 1143 subjects were included from the B-SNIP cohort: 143 with SCZ, 178 SCZ relatives (SCZ-Fam), 123 with SAD, 152 SAD relatives (SAD-Fam), 138 BP, 183 BP relatives (BP-Fam), and 226 controls (CON). A Biopac system recorded the eyeblink component of the startle reflex during startle testing. RESULTS: Latency differed by diagnosis (F(3,620) = 5.10, p = 0.002): SCZ, SAD, and BP probands had slower latency than CON, with relatives intermediate. Biotypes 1 and 2 had slower latency than CON (p < 0.031) but Biotype 3 did not differ from CON. PPI did not separate CON from other subjects when analyzed by diagnoses nor when analyzed by biotype. Biotype 1 relatives had slower latency (F(3,663) = 3.49, p = 0.016) and more impaired PPI than Biotype 2 and 3 relatives (F(3,663) = 2.77, p = 0.041). CONCLUSION:Startle latency is prolonged in psychotic disorders that cross traditional diagnostic categories. These data suggest a genetic difference between biotypes that span across clinically defined diagnoses. Published by Elsevier B.V.
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