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Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis.

ABSTRACT: Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P individuals compared with healthy controls (HC), and in relation to subsequent transition to a first episode of psychosis. The ENIGMA CHR-P consortium applied a harmonised analysis to neuroimaging data across 29 international sites, including 1579 CHR-P individuals and 1243 HC, offering the largest pooled CHR-P neuroimaging dataset to date. Regional heterogeneity was indexed with the Variability Ratio (VR) and Coefficient of Variation (CV) ratio applied at the group level. Personalised estimates of heterogeneity of SA, CT and SV brain profiles were indexed with the novel Person-Based Similarity Index (PBSI), with two complementary applications. First, to assess the extent of within-diagnosis similarity or divergence of neuroanatomical profiles between individuals. Second, using a normative modelling approach, to assess the 'normativeness' of neuroanatomical profiles in individuals at CHR-P. CHR-P individuals demonstrated no greater regional heterogeneity after applying FDR corrections. However, PBSI scores indicated significantly greater neuroanatomical divergence in global SA, CT and SV profiles in CHR-P individuals compared with HC. Normative PBSI analysis identified 11 CHR-P individuals (0.70%) with marked deviation (>1.5 SD) in SA, 118 (7.47%) in CT and 161 (10.20%) in SV. Psychosis transition was not significantly associated with any measure of heterogeneity. Overall, our examination of neuroanatomical heterogeneity within the CHR-P state indicated greater divergence in neuroanatomical profiles at an individual level, irrespective of psychosis conversion. Further large-scale investigations are required of those who demonstrate marked deviation.

SUBMITTER: Baldwin H

PROVIDER: S-EPMC9325730 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis.

Baldwin Helen H Radua Joaquim J Antoniades Mathilde M Haas Shalaila S SS Frangou Sophia S Agartz Ingrid I Allen Paul P Andreassen Ole A OA Atkinson Kimberley K Bachman Peter P Baeza Inmaculada I Bartholomeusz Cali F CF Chee Michael W L MWL Colibazzi Tiziano T Cooper Rebecca E RE Corcoran Cheryl M CM Cropley Vanessa L VL Ebdrup Bjørn H BH Fortea Adriana A Glenthøj Louise Birkedal LB Hamilton Holly K HK Haut Kristen M KM Hayes Rebecca A RA He Ying Y Heekeren Karsten K Kaess Michael M Kasai Kiyoto K Katagiri Naoyuki N Kim Minah M Kindler Jochen J Klaunig Mallory J MJ Koike Shinsuke S Koppel Alex A Kristensen Tina D TD Bin Kwak Yoo Y Kwon Jun Soo JS Lawrie Stephen M SM Lebedeva Irina I Lee Jimmy J Lin Ashleigh A Loewy Rachel L RL Mathalon Daniel H DH Michel Chantal C Mizrahi Romina R Møller Paul P Nelson Barnaby B Nemoto Takahiro T Nordholm Dorte D Omelchenko Maria A MA Pantelis Christos C Raghava Jayachandra M JM Røssberg Jan I JI Rössler Wulf W Salisbury Dean F DF Sasabayashi Daiki D Schall Ulrich U Smigielski Lukasz L Sugranyes Gisela G Suzuki Michio M Takahashi Tsutomu T Tamnes Christian K CK Tang Jinsong J Theodoridou Anastasia A Thomopoulos Sophia I SI Tomyshev Alexander S AS Uhlhaas Peter J PJ Værnes Tor G TG van Amelsvoort Therese A M J TAMJ Van Erp Theo G M TGM Waltz James A JA Westlye Lars T LT Wood Stephen J SJ Zhou Juan H JH McGuire Philip P Thompson Paul M PM Jalbrzikowski Maria M Hernaus Dennis D Fusar-Poli Paolo P

Translational psychiatry 20220726 1

Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P individuals compared with healthy controls (HC), and ...[more]

PMID: 35882855

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Project description:Serum neuronal autoantibodies, such as those to the NMDA receptor (NMDAR), are detectable in a subgroup of patients with psychotic disorders. It is not known if they are present before the onset of psychosis or whether they are associated with particular clinical features or outcomes. In a case-control study, sera from 254 subjects at clinical high risk (CHR) for psychosis and 116 healthy volunteers were tested for antibodies against multiple neuronal antigens implicated in CNS autoimmune disorders, using fixed and live cell-based assays (CBAs). Within the CHR group, the relationship between NMDAR antibodies and symptoms, cognitive function and clinical outcomes over 24 month follow-up was examined. CHR subjects were not more frequently seropositive for neuronal autoantibodies than controls (8.3% vs. 5.2%; OR = 1.50; 95% CI: 0.58-3.90). The NMDAR was the most common target antigen and NMDAR IgGs were more sensitively detected with live versus fixed CBAs (p < 0.001). Preliminary phenotypic analyses revealed that within the CHR sample, the NMDAR antibody seropositive subjects had higher levels of current depression, performed worse on the Rey Auditory Verbal Learning Task (p < 0.05), and had a markedly lower IQ (p < 0.01). NMDAR IgGs were not more frequent in subjects who later became psychotic than those who did not. NMDAR antibody serostatus and titre was associated with poorer levels of functioning at follow-up (p < 0.05) and the presence of a neuronal autoantibody was associated with larger amygdala volumes (p < 0.05). Altogether, these findings demonstrate that NMDAR autoantibodies are detectable in a subgroup of CHR subjects at equal rates to controls. In the CHR group, they are associated with affective psychopathology, impairments in verbal memory, and overall cognitive function: these findings are qualitatively and individually similar to core features of autoimmune encephalitis and/or animal models of NMDAR antibody-mediated CNS disease. Overall the current work supports further evaluation of NMDAR autoantibodies as a possible prognostic biomarker and aetiological factor in a subset of people already meeting CHR criteria.

Dataset Information

Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis.

Publications

Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis.

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