Heritability of acoustic startle magnitude, prepulse inhibition, and startle latency in schizophrenia and control families

Abstract

Prepulse inhibition (PPI) is an acoustic startle paradigm that has been used as an operational measure of sensorimotor gating. Many patients with schizophrenia have impaired PPI, and several lines of evidence suggest that PPI may represent a heritable endophenotype in this disease. We examined startle magnitude and latencies in 40 schizophrenia patients, 58 first-degree relatives of these patients and 100 healthy controls. After removing low-startlers, we investigated PPI and startle habituation in 34 schizophrenia patients, 43 relatives and 86 control subjects. Heritability analyses were conducted using a variance-component approach. We found significant heritability of 45% for PPI at the 60-ms interval and 67% for startle magnitude. Onset latency heritability estimates ranged between 39% and 90% across trial types, and those for peak latency ranged from 29% to 68%. Heritability of startle habituation trended toward significance at 31%. We did not detect differences between controls and either schizophrenia patients or their family members for PPI, startle magnitude or habituation. Startle latencies were generally longer in schizophrenia patients than controls. The heritability findings give impetus to applying genetic analyses to PPI variables, and suggest that startle latency may also be a useful measure in the study of potential endophenotypes for schizophrenia.

Asians demonstrate reduced sensitivity to unpredictable threat: A preliminary startle investigation using genetic ancestry in a multiethnic sample.

“…In other words, across all racial (and consequently ethnic) identifications, European and Asian genetic ancestry was associated with individual differences in baseline startle. Previous research has indicated that startle magnitude is highly heritable (Anokhin, Heath, Myers, Ralano, & Wood, 2003; Hasenkamp et al, 2010), and results from the present study support the notion that racial differences may be at least partially genetically influenced. Interestingly, neither European nor Asian genetic ancestry was associated with startle potentiation during the NPU-threat task.…”

Gating Deficit Heritability and Correlation With Increased Clinical Severity in Schizophrenia Patients With Positive Family History

“…The heritability of PPI in the entire COGS-1 sample was lower at 29% (26), which is likely due to the combined influence of the stronger genetic transmission of genes underlying PPI in the multiply affected families and the apparent lack of genetic transmission in the singleton families on the heritability of this endophenotype. Prior heritability estimates for pulse-alone startle magnitude range from 67% to 70% in schizophrenia families and healthy twins, respectively (29, 30), and show reasonable consistency with the estimates obtained for the entire COGS-1 sample (62%), as well as across the subsets stratified by family history (54–60%). Taken together, these data suggest that variation in startle magnitude may be generally, and highly, heritable in humans, and that the inhibition observed in the prepulse paradigm is of particular relevance to schizophrenia, with a substantial genetic component.…”

The impact of sex and menstrual cycle on the acoustic startle response

“…Regarding ASR, inter-individual differences appear to be due to other factors than sex such as, for instance, environmental or genetic variation. For example, ASR heritability has been reported to be in the range of 59-61% [55] and 67% [56]. Nevertheless, previous studies reported conflicting results on the impact of sex on ASR: while some found no difference between men and women [32,[35][36][37] others reported larger startle magnitudes in women at least in some ASR parameters [27,38,39].…”