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

Abstract

IntroductionThe 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.MethodsData from four studies were combined using ComBat (to account for between-study differences) to analyse rCBF in 150 age- and sex-matched subjects (n = 30 healthy controls [HCs], n = 80 APS, n = 20 BLIPS and n = 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 p < 0.05.ResultsWhole-brain voxel-wise analyses and Bayesian ROI analyses were also conducted. No significant group differences were found in global [F(3,143) = 1,41, p = 0.24], bilateral frontal cortex [F(3,143) = 1.01, p = 0.39], hippocampus [F(3,143) = 0.63, p = 0.60] or striatum [F(3,143) = 0.52, p = 0.57] rCBF. Similar null findings were observed in lateralized ROIs (p > 0.05). All results were robust to addition of covariates (p > 0.05). No significant clusters were identified in whole-brain voxel-wise analyses (p > 0.05FWE). Weak-to-moderate evidence was found for an absence of rCBF differences between APS and BLIPS in Bayesian ROI analyses.ConclusionOn 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.

Physical exercise as an intervention in people at clinical high-risk for psychosis: A narrative review

“…Otros estudios han evidenciado una señalización dopaminérgica aumentada en mesencéfalo y estriado [4], mientras que diversas investigaciones han reportado alteraciones hipocampales. Entre estas alteraciones, se han citado modificaciones morfológicas en la sustancia gris [5] y aumento del flujo sanguíneo [6] y de su metabolismo, lo que conduciría a una disfunción dopaminérgica en el estriado [7,8], un hallazgo central en la psicosis.…”

Exploring causal mechanisms of psychosis risk

“…CHR-P individuals have altered brain structure ( Luna et al, 2022 , Merritt et al, 2021a ) and function ( Luna et al, 2022 ) compared to healthy controls. There is some evidence that these alterations in CHR-P represent an intermediate stage between healthy controls and FEP ( Kim et al, 2022 , Kindler et al, 2018 , Korda et al, 2022 ), but this evidence is inconsistent ( Oliver et al, 2023 , Schifani et al, 2017 , Zhao et al, 2022 ).…”