PMID- 31492832 OWN - NLM STAT- MEDLINE DCOM- 20200309 LR - 20220315 IS - 2158-3188 (Electronic) IS - 2158-3188 (Linking) VI - 9 IP - 1 DP - 2019 Sep 6 TI - Bimodal distribution of tone-matching deficits indicates discrete pathophysiological entities within the syndrome of schizophrenia. PG - 221 LID - 10.1038/s41398-019-0557-8 [doi] LID - 221 AB - To date, no measures are available that permit differentiation of discrete, clinically distinct subtypes of schizophrenia (SZ) with potential differential underlying pathophysiologies. Over recent years, there has been increasing recognition that SZ is heterogeneously associated with deficits in early auditory processing (EAP), as demonstrated using clinically applicable tasks such as tone-matching task (TMT). Here, we pooled TMT performances across 310 SZ individuals and 219 healthy controls (HC), along with clinical, cognitive, and resting-state functional-connectivity MRI (rsFC-MRI) measures. In addition, TMT was measured in a group of 24 patients at symptomatic clinical high risk (CHR) for SZ and 24 age-matched HC (age range 7-27 years). We provide the first demonstration that the EAP deficits are bimodally distributed across SZ subjects (P < 0.0001 vs. unimodal distribution), with one group showing entirely unimpaired TMT performance (SZ-EAP+), and a second showing an extremely large TMT impairment (SZ-EAP-), relative to both controls (d = 2.1) and SZ-EAP+ patients (d = 3.4). The SZ-EAP- group predominated among samples drawn from inpatient sites, showed higher levels of cognitive symptoms (PANSS), worse social cognition and a differential deficit in neurocognition (MATRICS battery), and reduced functional capacity. rsFC-MRI analyses showed significant reduction in SZ-EAP- relative to controls between subcortical and cortical auditory regions. As opposed to SZ, CHR patients showed intact EAP function. In HC age-matched to CHR, EAP ability was shown to increase across the age range of vulnerability preceding SZ onset. These results indicate that EAP measure segregates between discrete SZ subgroups. As TMT can be readily implemented within routine clinical settings, its use may be critical to account for the heterogeneity of clinical outcomes currently observed across SZ patients, as well as for pre-clinical detection and efficacious treatment selection. FAU - Donde, Clement AU - Donde C AD - INSERM, U1028; CNRS, UMR5292; Lyon Neuroscience Research Center, Psychiatric Disorders: from Resistance to Response Team, Lyon, F-69000, France. clement.dondecoquelet@gmail.com. AD - University Lyon 1, Villeurbanne, F-69000, France. clement.dondecoquelet@gmail.com. AD - Centre Hospitalier Le Vinatier, Bron, France. clement.dondecoquelet@gmail.com. AD - Nathan Kline Institute, Orangeburg, NY, USA. clement.dondecoquelet@gmail.com. AD - Deppartment of Psychiatry, Columbia University Medical Center/New York State Psychiatric Institute, New York, NY, USA. clement.dondecoquelet@gmail.com. FAU - Martinez, Antigona AU - Martinez A AD - Nathan Kline Institute, Orangeburg, NY, USA. AD - Deppartment of Psychiatry, Columbia University Medical Center/New York State Psychiatric Institute, New York, NY, USA. FAU - Kantrowitz, Joshua T AU - Kantrowitz JT AD - Nathan Kline Institute, Orangeburg, NY, USA. AD - Deppartment of Psychiatry, Columbia University Medical Center/New York State Psychiatric Institute, New York, NY, USA. FAU - Silipo, Gail AU - Silipo G AD - Nathan Kline Institute, Orangeburg, NY, USA. FAU - Dias, Elisa C AU - Dias EC AD - Nathan Kline Institute, Orangeburg, NY, USA. FAU - Patel, Gaurav H AU - Patel GH AD - Deppartment of Psychiatry, Columbia University Medical Center/New York State Psychiatric Institute, New York, NY, USA. FAU - Sanchez-Pena, Juan AU - Sanchez-Pena J AD - Deppartment of Psychiatry, Columbia University Medical Center/New York State Psychiatric Institute, New York, NY, USA. FAU - Corcoran, Cheryl M AU - Corcoran CM AD - Deppartment of Psychiatry, Columbia University Medical Center/New York State Psychiatric Institute, New York, NY, USA. AD - Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA. FAU - Medalia, Alice AU - Medalia A AD - Deppartment of Psychiatry, Columbia University Medical Center/New York State Psychiatric Institute, New York, NY, USA. FAU - Saperstein, Alice AU - Saperstein A AD - Deppartment of Psychiatry, Columbia University Medical Center/New York State Psychiatric Institute, New York, NY, USA. FAU - Vail, Blair AU - Vail B AD - Deppartment of Psychiatry, Columbia University Medical Center/New York State Psychiatric Institute, New York, NY, USA. FAU - Javitt, Daniel C AU - Javitt DC AD - Nathan Kline Institute, Orangeburg, NY, USA. dcj2113@cumc.columbia.edu. AD - Deppartment of Psychiatry, Columbia University Medical Center/New York State Psychiatric Institute, New York, NY, USA. dcj2113@cumc.columbia.edu. LA - eng GR - R01 MH049334/MH/NIMH NIH HHS/United States GR - MH4933/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)/International GR - MH109289/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)/International GR - K23 MH108711/MH/NIMH NIH HHS/United States GR - MH99265/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)/International PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20190906 PL - United States TA - Transl Psychiatry JT - Translational psychiatry JID - 101562664 SB - IM MH - Adolescent MH - Adult MH - Attention/physiology MH - Auditory Perception/*physiology MH - Brain/*physiopathology MH - Child MH - Cognition/*physiology MH - Female MH - Hearing Tests MH - Humans MH - Learning/physiology MH - Male MH - Memory/physiology MH - Neuropsychological Tests MH - Problem Solving MH - Schizophrenia/*physiopathology MH - *Schizophrenic Psychology MH - *Social Perception MH - Young Adult PMC - PMC6731304 COIS- The authors declare that they have no conflict of interest. EDAT- 2019/09/08 06:00 MHDA- 2020/03/10 06:00 PMCR- 2019/09/06 CRDT- 2019/09/08 06:00 PHST- 2018/10/10 00:00 [received] PHST- 2019/06/20 00:00 [accepted] PHST- 2019/06/03 00:00 [revised] PHST- 2019/09/08 06:00 [entrez] PHST- 2019/09/08 06:00 [pubmed] PHST- 2020/03/10 06:00 [medline] PHST- 2019/09/06 00:00 [pmc-release] AID - 10.1038/s41398-019-0557-8 [pii] AID - 557 [pii] AID - 10.1038/s41398-019-0557-8 [doi] PST - epublish SO - Transl Psychiatry. 2019 Sep 6;9(1):221. doi: 10.1038/s41398-019-0557-8.