Relationship of prolonged acoustic startle latency to diagnosis and biotype in the bipolar-schizophrenia network on intermediate phenotypes (B–SNIP) cohort

Abstract

BackgroundLatency 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). Methods1143 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. ResultsLatency 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). ConclusionStartle 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.