PMID- 33005152 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220417 IS - 1664-0640 (Print) IS - 1664-0640 (Electronic) IS - 1664-0640 (Linking) VI - 11 DP - 2020 TI - Evidence of Slow Neural Processing, Developmental Differences and Sensitivity to Cannabis Effects in a Sample at Clinical High Risk for Psychosis From the NAPLS Consortium Assessed With the Human Startle Paradigm. PG - 833 LID - 10.3389/fpsyt.2020.00833 [doi] LID - 833 AB - 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. METHODS: 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. RESULTS: 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). DISCUSSION: 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. CI - Copyright (c) 2020 Cadenhead, Duncan, Addington, Bearden, Cannon, Cornblatt, Mathalon, McGlashan, Perkins, Seidman, Tsuang, Walker, Woods, Bauchman, Belger, Carrion, Donkers, Johannesen, Light, Niznikiewicz, Nunag and Roach. FAU - Cadenhead, Kristin S AU - Cadenhead KS AD - Department of Psychiatry, University of California San Diego (UCSD), La Jolla, CA, United States. FAU - Duncan, Erica AU - Duncan E AD - Department of Psychiatry, Atlanta Veterans Affairs Healthcare System, Decatur, GA, United States. AD - Department of Psychiatry, Emory University School of Medicine, Atlanta, GA, United States. FAU - Addington, Jean AU - Addington J AD - Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada. FAU - Bearden, Carrie AU - Bearden C AD - Department of Psychiatry and Psychology, University of California Los Angeles (UCLA), Los Angeles, CA, United States. FAU - Cannon, Tyrone D AU - Cannon TD AD - Department of Psychiatry and Psychology, Yale University, New Haven, CT, United States. FAU - Cornblatt, Barbara A AU - Cornblatt BA AD - Department of Psychiatry and Psychology, The Feinstein Institute for Medical Research, Manhasset, NY, United States. AD - Department of Psychology, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY, United States. AD - The Zucker Hillside Hospital, New York, NY, United States. FAU - Mathalon, Dan AU - Mathalon D AD - University of California, San Francisco, San Francisco, CA, United States. AD - San Francisco VA Medical Center, San Francisco, VA, United States. FAU - McGlashan, Thomas H AU - McGlashan TH AD - Department of Psychiatry and Psychology, Yale University, New Haven, CT, United States. FAU - Perkins, Diana O AU - Perkins DO AD - Department of Psychology, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY, United States. AD - University of North Carolina (UNC), Chapel Hill, NC, United States. FAU - Seidman, Larry J AU - Seidman LJ AD - Department of Psychiatry, Harvard University, Boston, MA, United States. FAU - Tsuang, Ming AU - Tsuang M AD - Department of Psychiatry, University of California San Diego (UCSD), La Jolla, CA, United States. FAU - Walker, Elaine F AU - Walker EF AD - Department of Psychiatry, Atlanta Veterans Affairs Healthcare System, Decatur, GA, United States. FAU - Woods, Scott W AU - Woods SW AD - Department of Psychiatry and Psychology, Yale University, New Haven, CT, United States. FAU - Bauchman, Peter AU - Bauchman P AD - San Francisco VA Medical Center, San Francisco, VA, United States. FAU - Belger, Ayse AU - Belger A AD - University of North Carolina (UNC), Chapel Hill, NC, United States. FAU - Carrion, Ricardo E AU - Carrion RE AD - Department of Psychiatry and Psychology, The Feinstein Institute for Medical Research, Manhasset, NY, United States. AD - Department of Psychology, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY, United States. AD - The Zucker Hillside Hospital, New York, NY, United States. FAU - Donkers, Franc AU - Donkers F AD - University of North Carolina (UNC), Chapel Hill, NC, United States. FAU - Johannesen, Jason AU - Johannesen J AD - Department of Psychiatry and Psychology, Yale University, New Haven, CT, United States. FAU - Light, Gregory AU - Light G AD - Department of Psychiatry, University of California San Diego (UCSD), La Jolla, CA, United States. FAU - Niznikiewicz, Margaret AU - Niznikiewicz M AD - Department of Psychiatry, Harvard University, Boston, MA, United States. FAU - Nunag, Jason AU - Nunag J AD - Department of Psychiatry, University of California San Diego (UCSD), La Jolla, CA, United States. FAU - Roach, Brian AU - Roach B AD - University of California, San Francisco, San Francisco, CA, United States. AD - San Francisco VA Medical Center, San Francisco, VA, United States. LA - eng GR - P50 HD103573/HD/NICHD NIH HHS/United States GR - U01 MH082022/MH/NIMH NIH HHS/United States PT - Journal Article DEP - 20200825 PL - Switzerland TA - Front Psychiatry JT - Frontiers in psychiatry JID - 101545006 PMC - PMC7479820 OTO - NOTNLM OT - age OT - cannabis OT - latency OT - neurodevelopment OT - prepulse inhibition OT - prodrome OT - schizophrenia OT - startle EDAT- 2020/10/03 06:00 MHDA- 2020/10/03 06:01 PMCR- 2020/08/25 CRDT- 2020/10/02 05:43 PHST- 2020/05/17 00:00 [received] PHST- 2020/07/31 00:00 [accepted] PHST- 2020/10/02 05:43 [entrez] PHST- 2020/10/03 06:00 [pubmed] PHST- 2020/10/03 06:01 [medline] PHST- 2020/08/25 00:00 [pmc-release] AID - 10.3389/fpsyt.2020.00833 [doi] PST - epublish SO - Front Psychiatry. 2020 Aug 25;11:833. doi: 10.3389/fpsyt.2020.00833. eCollection 2020.