Cadenhead Kristin S, Duncan Erica, Addington Jean, Bearden Carrie, Cannon Tyrone D, Cornblatt Barbara A, Mathalon Dan, McGlashan Thomas H, Perkins Diana O, Seidman Larry J, Tsuang Ming, Walker Elaine F, Woods Scott W, Bauchman Peter, Belger Ayse, Carrión Ricardo E, Donkers Franc, Johannesen Jason, Light Gregory, Niznikiewicz Margaret, Nunag Jason, Roach Brian
Department of Psychiatry, University of California San Diego (UCSD), La Jolla, CA, United States.
Department of Psychiatry, Atlanta Veterans Affairs Healthcare System, Decatur, GA, United States.
Front Psychiatry. 2020 Aug 25;11:833. doi: 10.3389/fpsyt.2020.00833. eCollection 2020.
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.
Startle 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.
At 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).
This 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.
生物标志物在精神病前驱期研究中至关重要，因为它们有助于识别未来患精神病风险最高的个体，并深入了解神经发育异常背后的疾病机制。然后可针对生物标志物异常进行治疗，以预防或减轻疾病。人类惊吓范式已在包括精神病在内的精神病理学转化研究中用于评估前注意信息处理，已有五十多年历史。在迄今为止针对临床高危（CHR）精神病参与者的最大规模研究之一中，我们旨在评估惊吓指标作为风险生物标志物，以及年龄、性别、治疗和物质使用在这群高危个体中的作用。
对543名年龄在12至35岁之间的CHR参与者和218名正常对照（NC）参与者进行惊吓反应反应性、潜伏期和预脉冲抑制（PPI）评估。
在1年随访时，58名CHR参与者已转化为精神病。CHR组和NC组在任何惊吓测量指标上均无差异，但后来转化为精神病的CHR参与者的惊吓潜伏期明显比未转化为精神病的参与者慢，且这种效应在女性CHR参与者中更为明显。在CHR参与者中，PPI与年龄显著相关，但在NC参与者中并非如此，在后来转化为精神病的CHR参与者中年龄相关性最为显著，这与之前的报告一致。最后，由于大麻使用者的PPI更高，且使用者（CHR>NC）和非使用者（NC>CHR）的PPI组效应相反，因此存在显著的大麻使用与组间交互作用。
这是第一项在CHR人群中证明惊吓反应潜伏期与精神病转化之间关系的研究。PPI是一种重要的生物标志物，可能对被认为存在于易患精神病个体中的神经发育异常以及大麻的影响敏感。该样本中与年龄的显著相关性以及CHR大麻使用者中PPI更高的发现重复了另一大样本CHR参与者的研究结果。
