Abstract
Biomarkers are important in the study of the prodromal period of psychosis because they can help to identify individuals at greatest risk for future psychotic illness and provide insights into disease mechanism underlying neurodevelopmental abnormalities. The biomarker abnormalities can then be targeted with treatment, with an aim toward prevention or mitigation of disease. The human startle paradigm has been used in translational studies of psychopathology including psychotic illness to assess preattentive information processing for over 50 years. In one of the largest studies to date in clinical high risk (CHR) for psychosis participants, we aimed to evaluate startle indices as biomarkers of risk along with the role of age, sex, treatment, and substance use in this population of high risk individuals.MethodsStartle response reactivity, latency, and prepulse inhibition (PPI) were assessed in 543 CHR and 218 Normal Comparison (NC) participants between the ages of 12 and 35.ResultsAt 1 year follow-up, 58 CHR participants had converted to psychosis. CHR and NC groups did not differ across any of the startle measures but those CHR participants who later converted to psychosis had significantly slower startle latency than did those who did not convert to psychosis, and this effect was driven by female CHR participants. PPI was significantly associated with age in the CHR, but not the NC, participants with the greatest positive age correlations present in those CHR participants who later converted to psychosis, consistent with a prior report. Finally, there was a significant group by cannabis use interaction due to greater PPI in cannabis users and opposite PPI group effects in users (CHR>NC) and non-users (NC>CHR).DiscussionThis is the first study to demonstrate a relationship of startle response latency to psychotic conversion in a CHR population. PPI is an important biomarker that may be sensitive to the neurodevelopmental abnormalities thought to be present in psychosis prone individuals and the effects of cannabis. The significant correlations with age in this sample as well as the finding of greater PPI in CHR cannabis users replicate findings from another large sample of CHR participants.
Highlights
A better understanding of the early stages of psychosis along with biomarkers linked to psychosis risk can lead to better treatments that target the mechanism of disease and perhaps alter the course of illness
clinical high risk (CHR) and normal comparison (NC) groups did not differ across any of the startle measures but those CHR participants who later converted to psychosis had significantly slower startle latency than did those who did not convert to psychosis, and this effect was driven by female CHR participants
prepulse inhibition (PPI) was significantly associated with age in the CHR, but not the NC, participants with the greatest positive age correlations present in those CHR participants who later converted to psychosis, consistent with a prior report
Summary
A better understanding of the early stages of psychosis along with biomarkers linked to psychosis risk can lead to better treatments that target the mechanism of disease and perhaps alter the course of illness. Few studies have reported on startle reactivity or prepulse inhibition (PPI) in participants at clinical high risk (CHR) for psychosis (1–5). Togay et al (2) reported that (N = 29) CHR participants had reduced PPI deficits relative to NC and familial high-risk participants. Cadenhead (3) did not find PPI deficits in CHR (N = 89) compared to NC but did find significant sex, medication, cannabis and tobacco effects on startle measures. A small sample of CHR participants (N = 6) who later converted to psychosis in the Cadenhead study had greater PPI than both NC and CHR participants who did not convert to psychosis by 2 year follow-up. A significant positive correlation between PPI and age was found in CHR participants in the Cadenhead study that was not present in NC, revealing possible neurodevelopmental differences in the early psychosis population (3)
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