Parsing neurobiological heterogeneity of the clinical high-risk state for psychosis: A pseudo-continuous arterial spin labelling study

Dominic Oliver; Cathy Davies; Fernando Zelaya; Pierluigi Selvaggi; Andrea De Micheli; Ana Catalan; Helen Baldwin; Maite Arribas; Gemma Modinos; Nicolas A. Crossley; Paul Allen; Alice Egerton; Sameer Jauhar; Oliver D. Howes; Philip McGuire; Paolo Fusar-Poli

doi:10.3389/fpsyt.2023.1092213

Parsing neurobiological heterogeneity of the clinical high-risk state for psychosis: A pseudo-continuous arterial spin labelling study

Dominic Oliver, Cathy Davies, Fernando Zelaya, Pierluigi Selvaggi, Andrea De Micheli, Ana Catalan, Helen Baldwin, Maite Arribas, Gemma Modinos, Nicolas A. Crossley, Paul Allen, Alice Egerton, Sameer Jauhar, Oliver D. Howes, Philip McGuire, Paolo Fusar-Poli

Research output: Contribution to journal › Article › peer-review

35 Downloads (Pure)

Abstract

The impact of the clinical high-risk for psychosis (CHR-P) construct is dependent on accurately predicting outcomes. Individuals with brief limited intermittent psychotic symptoms (BLIPS) have higher risk of developing a first episode of psychosis (FEP) compared to individuals with attenuated psychotic symptoms (APS). Supplementing subgroup stratification with information from candidate biomarkers based on neurobiological parameters, such as resting-state, regional cerebral blood flow (rCBF), may help refine risk estimates. Based on previous evidence, we hypothesized that individuals with BLIPS would exhibit increased rCBF compared to APS in key regions linked to dopaminergic pathways. Data from four studies were combined using ComBat (to account for between-study differences) to analyse rCBF in 150 age- and sex-matched subjects ( = 30 healthy controls [HCs], = 80 APS, = 20 BLIPS and = 20 FEP). Global gray matter (GM) rCBF was examined in addition to region-of-interest (ROI) analyses in bilateral/left/right frontal cortex, hippocampus and striatum. Group differences were assessed using general linear models: (i) alone; (ii) with global GM rCBF as a covariate; (iii) with global GM rCBF and smoking status as covariates. Significance was set at 0.05). All results were robust to addition of covariates ( > 0.05). No significant clusters were identified in whole-brain voxel-wise analyses ( > 0.05 ). Weak-to-moderate evidence was found for an absence of rCBF differences between APS and BLIPS in Bayesian ROI analyses. On this evidence, APS and BLIPS are unlikely to be neurobiologically distinct. Due to this and the weak-to-moderate evidence for the null hypothesis, future research should investigate larger samples of APS and BLIPS through collaboration across large-scale international consortia. [Abstract copyright: Copyright © 2023 Oliver, Davies, Zelaya, Selvaggi, De Micheli, Catalan, Baldwin, Arribas, Modinos, Crossley, Allen, Egerton, Jauhar, Howes, McGuire and Fusar-Poli.]

Original language	English
Pages (from-to)	1092213
Journal	FRONTIERS IN PSYCHIATRY
Volume	14
Early online date	8 Mar 2023
DOIs	https://doi.org/10.3389/fpsyt.2023.1092213
Publication status	E-pub ahead of print - 8 Mar 2023

Keywords

Psychiatry
clinical high risk for psychosis
brief limited intermittent psychotic symptoms
attenuated psychosis syndrome
arterial spin labelling
neuroimaging

Access to Document

10.3389/fpsyt.2023.1092213

fpsyt-14-1092213.pdfFinal published version, 871 KBLicence: CC BY

https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1092213/fullLicence: CC BY

Cite this

Oliver, D., Davies, C., Zelaya, F., Selvaggi, P., De Micheli, A., Catalan, A., Baldwin, H., Arribas, M., Modinos, G., Crossley, N. A., Allen, P., Egerton, A., Jauhar, S., Howes, O. D., McGuire, P., & Fusar-Poli, P. (2023). Parsing neurobiological heterogeneity of the clinical high-risk state for psychosis: A pseudo-continuous arterial spin labelling study. FRONTIERS IN PSYCHIATRY, 14, 1092213. Advance online publication. https://doi.org/10.3389/fpsyt.2023.1092213

@article{a80a2c0088634b489296d0080d72a33c,

title = "Parsing neurobiological heterogeneity of the clinical high-risk state for psychosis: A pseudo-continuous arterial spin labelling study",

abstract = "The impact of the clinical high-risk for psychosis (CHR-P) construct is dependent on accurately predicting outcomes. Individuals with brief limited intermittent psychotic symptoms (BLIPS) have higher risk of developing a first episode of psychosis (FEP) compared to individuals with attenuated psychotic symptoms (APS). Supplementing subgroup stratification with information from candidate biomarkers based on neurobiological parameters, such as resting-state, regional cerebral blood flow (rCBF), may help refine risk estimates. Based on previous evidence, we hypothesized that individuals with BLIPS would exhibit increased rCBF compared to APS in key regions linked to dopaminergic pathways. Data from four studies were combined using ComBat (to account for between-study differences) to analyse rCBF in 150 age- and sex-matched subjects ( = 30 healthy controls [HCs], = 80 APS, = 20 BLIPS and = 20 FEP). Global gray matter (GM) rCBF was examined in addition to region-of-interest (ROI) analyses in bilateral/left/right frontal cortex, hippocampus and striatum. Group differences were assessed using general linear models: (i) alone; (ii) with global GM rCBF as a covariate; (iii) with global GM rCBF and smoking status as covariates. Significance was set at 0.05). All results were robust to addition of covariates ( > 0.05). No significant clusters were identified in whole-brain voxel-wise analyses ( > 0.05 ). Weak-to-moderate evidence was found for an absence of rCBF differences between APS and BLIPS in Bayesian ROI analyses. On this evidence, APS and BLIPS are unlikely to be neurobiologically distinct. Due to this and the weak-to-moderate evidence for the null hypothesis, future research should investigate larger samples of APS and BLIPS through collaboration across large-scale international consortia. [Abstract copyright: Copyright {\textcopyright} 2023 Oliver, Davies, Zelaya, Selvaggi, De Micheli, Catalan, Baldwin, Arribas, Modinos, Crossley, Allen, Egerton, Jauhar, Howes, McGuire and Fusar-Poli.]",

keywords = "Psychiatry, clinical high risk for psychosis, brief limited intermittent psychotic symptoms, attenuated psychosis syndrome, arterial spin labelling, neuroimaging",

author = "Dominic Oliver and Cathy Davies and Fernando Zelaya and Pierluigi Selvaggi and {De Micheli}, Andrea and Ana Catalan and Helen Baldwin and Maite Arribas and Gemma Modinos and Crossley, {Nicolas A.} and Paul Allen and Alice Egerton and Sameer Jauhar and Howes, {Oliver D.} and Philip McGuire and Paolo Fusar-Poli",

year = "2023",

month = mar,

day = "8",

doi = "10.3389/fpsyt.2023.1092213",

language = "English",

volume = "14",

pages = "1092213",

journal = "FRONTIERS IN PSYCHIATRY",

issn = "1664-0640",

publisher = "Frontiers Media",

}

Oliver, D, Davies, C, Zelaya, F, Selvaggi, P, De Micheli, A, Catalan, A, Baldwin, H, Arribas, M, Modinos, G, Crossley, NA, Allen, P, Egerton, A, Jauhar, S, Howes, OD, McGuire, P & Fusar-Poli, P 2023, 'Parsing neurobiological heterogeneity of the clinical high-risk state for psychosis: A pseudo-continuous arterial spin labelling study', FRONTIERS IN PSYCHIATRY, vol. 14, pp. 1092213. https://doi.org/10.3389/fpsyt.2023.1092213

TY - JOUR

T1 - Parsing neurobiological heterogeneity of the clinical high-risk state for psychosis: A pseudo-continuous arterial spin labelling study

AU - Oliver, Dominic

AU - Davies, Cathy

AU - Zelaya, Fernando

AU - Selvaggi, Pierluigi

AU - De Micheli, Andrea

AU - Catalan, Ana

AU - Baldwin, Helen

AU - Arribas, Maite

AU - Modinos, Gemma

AU - Crossley, Nicolas A.

AU - Allen, Paul

AU - Egerton, Alice

AU - Jauhar, Sameer

AU - Howes, Oliver D.

AU - McGuire, Philip

AU - Fusar-Poli, Paolo

PY - 2023/3/8

Y1 - 2023/3/8

N2 - The impact of the clinical high-risk for psychosis (CHR-P) construct is dependent on accurately predicting outcomes. Individuals with brief limited intermittent psychotic symptoms (BLIPS) have higher risk of developing a first episode of psychosis (FEP) compared to individuals with attenuated psychotic symptoms (APS). Supplementing subgroup stratification with information from candidate biomarkers based on neurobiological parameters, such as resting-state, regional cerebral blood flow (rCBF), may help refine risk estimates. Based on previous evidence, we hypothesized that individuals with BLIPS would exhibit increased rCBF compared to APS in key regions linked to dopaminergic pathways. Data from four studies were combined using ComBat (to account for between-study differences) to analyse rCBF in 150 age- and sex-matched subjects ( = 30 healthy controls [HCs], = 80 APS, = 20 BLIPS and = 20 FEP). Global gray matter (GM) rCBF was examined in addition to region-of-interest (ROI) analyses in bilateral/left/right frontal cortex, hippocampus and striatum. Group differences were assessed using general linear models: (i) alone; (ii) with global GM rCBF as a covariate; (iii) with global GM rCBF and smoking status as covariates. Significance was set at 0.05). All results were robust to addition of covariates ( > 0.05). No significant clusters were identified in whole-brain voxel-wise analyses ( > 0.05 ). Weak-to-moderate evidence was found for an absence of rCBF differences between APS and BLIPS in Bayesian ROI analyses. On this evidence, APS and BLIPS are unlikely to be neurobiologically distinct. Due to this and the weak-to-moderate evidence for the null hypothesis, future research should investigate larger samples of APS and BLIPS through collaboration across large-scale international consortia. [Abstract copyright: Copyright © 2023 Oliver, Davies, Zelaya, Selvaggi, De Micheli, Catalan, Baldwin, Arribas, Modinos, Crossley, Allen, Egerton, Jauhar, Howes, McGuire and Fusar-Poli.]

AB - The impact of the clinical high-risk for psychosis (CHR-P) construct is dependent on accurately predicting outcomes. Individuals with brief limited intermittent psychotic symptoms (BLIPS) have higher risk of developing a first episode of psychosis (FEP) compared to individuals with attenuated psychotic symptoms (APS). Supplementing subgroup stratification with information from candidate biomarkers based on neurobiological parameters, such as resting-state, regional cerebral blood flow (rCBF), may help refine risk estimates. Based on previous evidence, we hypothesized that individuals with BLIPS would exhibit increased rCBF compared to APS in key regions linked to dopaminergic pathways. Data from four studies were combined using ComBat (to account for between-study differences) to analyse rCBF in 150 age- and sex-matched subjects ( = 30 healthy controls [HCs], = 80 APS, = 20 BLIPS and = 20 FEP). Global gray matter (GM) rCBF was examined in addition to region-of-interest (ROI) analyses in bilateral/left/right frontal cortex, hippocampus and striatum. Group differences were assessed using general linear models: (i) alone; (ii) with global GM rCBF as a covariate; (iii) with global GM rCBF and smoking status as covariates. Significance was set at 0.05). All results were robust to addition of covariates ( > 0.05). No significant clusters were identified in whole-brain voxel-wise analyses ( > 0.05 ). Weak-to-moderate evidence was found for an absence of rCBF differences between APS and BLIPS in Bayesian ROI analyses. On this evidence, APS and BLIPS are unlikely to be neurobiologically distinct. Due to this and the weak-to-moderate evidence for the null hypothesis, future research should investigate larger samples of APS and BLIPS through collaboration across large-scale international consortia. [Abstract copyright: Copyright © 2023 Oliver, Davies, Zelaya, Selvaggi, De Micheli, Catalan, Baldwin, Arribas, Modinos, Crossley, Allen, Egerton, Jauhar, Howes, McGuire and Fusar-Poli.]

KW - Psychiatry

KW - clinical high risk for psychosis

KW - brief limited intermittent psychotic symptoms

KW - attenuated psychosis syndrome

KW - arterial spin labelling

KW - neuroimaging

U2 - 10.3389/fpsyt.2023.1092213

DO - 10.3389/fpsyt.2023.1092213

M3 - Article

SN - 1664-0640

VL - 14

SP - 1092213

JO - FRONTIERS IN PSYCHIATRY

JF - FRONTIERS IN PSYCHIATRY

ER -