PMID- 32227226 OWN - NLM STAT- MEDLINE DCOM- 20210514 LR - 20220129 IS - 1745-1701 (Electronic) IS - 0586-7614 (Print) IS - 0586-7614 (Linking) VI - 46 IP - 3 DP - 2020 Apr 10 TI - Neural Circuitry of Novelty Salience Processing in Psychosis Risk: Association With Clinical Outcome. PG - 670-679 LID - 10.1093/schbul/sbz089 [doi] AB - Psychosis has been proposed to develop from dysfunction in a hippocampal-striatal-midbrain circuit, leading to aberrant salience processing. Here, we used functional magnetic resonance imaging (fMRI) during novelty salience processing to investigate this model in people at clinical high risk (CHR) for psychosis according to their subsequent clinical outcomes. Seventy-six CHR participants as defined using the Comprehensive Assessment of At-Risk Mental States (CAARMS) and 31 healthy controls (HC) were studied while performing a novelty salience fMRI task that engaged an a priori hippocampal-striatal-midbrain circuit of interest. The CHR sample was then followed clinically for a mean of 59.7 months (~5 y), when clinical outcomes were assessed in terms of transition (CHR-T) or non-transition (CHR-NT) to psychosis (CAARMS criteria): during this period, 13 individuals (17%) developed a psychotic disorder (CHR-T) and 63 did not. Functional activation and effective connectivity within a hippocampal-striatal-midbrain circuit were compared between groups. In CHR individuals compared to HC, hippocampal response to novel stimuli was significantly attenuated (P = .041 family-wise error corrected). Dynamic Causal Modelling revealed that stimulus novelty modulated effective connectivity from the hippocampus to the striatum, and from the midbrain to the hippocampus, significantly more in CHR participants than in HC. Conversely, stimulus novelty modulated connectivity from the midbrain to the striatum significantly less in CHR participants than in HC, and less in CHR participants who subsequently developed psychosis than in CHR individuals who did not become psychotic. Our findings are consistent with preclinical evidence implicating hippocampal-striatal-midbrain circuit dysfunction in altered salience processing and the onset of psychosis. CI - (c) The Author(s) 2019. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com. FAU - Modinos, Gemma AU - Modinos G AD - Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. AD - Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. FAU - Allen, Paul AU - Allen P AD - Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. AD - Department of Psychology, University of Roehampton, London, UK. FAU - Zugman, Andre AU - Zugman A AD - Departamento de Psiquiatria, Universidade Federal de Sao Paulo, Sao Paulo, Brazil. FAU - Dima, Danai AU - Dima D AD - Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. AD - Department of Psychology, School of Arts and Social Sciences, City, University of London, London, UK. FAU - Azis, Matilda AU - Azis M AD - Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. FAU - Samson, Carly AU - Samson C AD - Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. FAU - Bonoldi, Ilaria AU - Bonoldi I AD - Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. FAU - Quinn, Beverly AU - Quinn B AD - CAMEO Early Intervention in Psychosis Service, Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK. FAU - Gifford, George W G AU - Gifford GWG AD - Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. FAU - Smart, Sophie E AU - Smart SE AD - Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. FAU - Antoniades, Mathilde AU - Antoniades M AD - Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. FAU - Bossong, Matthijs G AU - Bossong MG AD - Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands. FAU - Broome, Matthew R AU - Broome MR AD - School of Psychology, University of Birmingham, Birmingham UK. FAU - Perez, Jesus AU - Perez J AD - CAMEO Early Intervention in Psychosis Service, Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK. AD - Department of Psychiatry, University of Cambridge, Cambridge, UK. AD - Department of Neuroscience, Instituto de Investigacion Biomedica de Salamanca (IBSAL), University of Salamanca, Salamanca, Spain. FAU - Howes, Oliver D AU - Howes OD AD - Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. FAU - Stone, James M AU - Stone JM AD - Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. FAU - Grace, Anthony A AU - Grace AA AD - Departments of Neuroscience, Psychiatry and Psychology, University of Pittsburgh, Pittsburgh, PA. FAU - McGuire, Philip AU - McGuire P AD - Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. LA - eng GR - MC_U120097115/MRC_/Medical Research Council/United Kingdom GR - 202397/Wellcome Trust/United Kingdom GR - MR/N026063/1/MRC_/Medical Research Council/United Kingdom GR - 091667/Wellcome Trust/United Kingdom GR - Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Schizophr Bull JT - Schizophrenia bulletin JID - 0236760 SB - IM MH - Adult MH - Attention/*physiology MH - *Connectome MH - Corpus Striatum/diagnostic imaging/*physiopathology MH - Female MH - Follow-Up Studies MH - Hippocampus/diagnostic imaging/*physiopathology MH - Humans MH - Magnetic Resonance Imaging MH - Male MH - Mesencephalon/diagnostic imaging/*physiopathology MH - Nerve Net/diagnostic imaging/*physiopathology MH - Pattern Recognition, Visual/*physiology MH - Prodromal Symptoms MH - Psychomotor Performance/physiology MH - Psychotic Disorders/diagnostic imaging/*physiopathology MH - Schizophrenia/diagnostic imaging/*physiopathology MH - Young Adult PMC - PMC7147595 MID - EMS84625 OTO - NOTNLM OT - fMRI OT - hippocampus OT - prodrome OT - psychosis OT - salience OT - schizophrenia EDAT- 2020/04/01 06:00 MHDA- 2021/05/15 06:00 PMCR- 2021/04/10 CRDT- 2020/04/01 06:00 PHST- 2020/04/01 06:00 [pubmed] PHST- 2021/05/15 06:00 [medline] PHST- 2020/04/01 06:00 [entrez] PHST- 2021/04/10 00:00 [pmc-release] AID - 5571189 [pii] AID - sbz089 [pii] AID - 10.1093/schbul/sbz089 [doi] PST - ppublish SO - Schizophr Bull. 2020 Apr 10;46(3):670-679. doi: 10.1093/schbul/sbz089.