Abstract
BackgroundIndividuals with attenuated or sub-threshold psychotic symptoms (STPS) are considered at-risk for psychosis. The notion that STPS represent “early psychosis” holds promise as it suggests the possibility of charting the developmental course of psychotic illness with neuroimaging. However, recent evidence suggests that a significant minority of patients in a first episode of psychosis (FEP) do not recall pre-onset STPS, suggesting diversity in early positive symptom course. This diversity may be reflected at the level of neurodevelopment. While imaging studies of at-risk youth and FEP patients reveal progressive trends in cortical thinning across stages of illness, none have considered the STPS history of FEP patients. To better understand neurobiological trends across illness stages, we investigate the relationships between STPS history and cortical thickness in FEP patients using a whole-brain approach.MethodsPatients (N=93) were recruited from a specialized early intervention clinic for FEP at the Douglas Mental Health University Institute. The Circumstances of Onset and Relapse Schedule was administered to identify youth who recalled at least one of nine expert-selected STPS prior to their FEP (STPS+, N=67) compared to those who did not (STPS-, N=26). These STPS include: Suspiciousness or odd ideas of reference, odd or bizarre ideas that are not delusional, unusual or eccentric behavior, unusual perceptual experiences that are not clearly psychotic, disorganized or odd speech, inappropriate affect, hallucinations or delusions (sub-threshold), and passivity experiences. Age and sex-matched healthy controls were recruited (N=83) for comparison. Participants were scanned on a 1.5T MRI scanner between 1 and 3 times at baseline, at 1-year follow-up, and at 2-year follow-up. Structural T1-weighted images were processed through the CIVET 2.1 pipeline. Cortical thickness values of 320 scans (143 HC, 123 STPS+, 54 STPS-) that passed quality control were extracted for group analysis. Linear mixed effects models controlling for effects of age, sex, education, and mean whole-brain thickness were applied to obtain vertex-wise F-test maps comparing groups.ResultsPost-hoc vertex-wise t-test maps were thresholded with Random Field Theory (p-cluster=0.001) and revealed that compared to controls, only STPS- patients exhibited significantly thinner cortical thickness in the right inferior frontal gyrus (peak t(162.3)=4.13, p<0.001). Examination of mean cortical thickness within this cluster, comparing patient groups only, revealed that compared to STPS+ patients, STPS- patients exhibited significantly thinner cortical thickness (t(172)=-2.55, p=0.01). This difference was most pronounced at baseline.DiscussionThese results indicate that within the right prefrontal cortex, STPS+/- patients may undergo different cortical maturation trajectories leading up to and through a first episode of psychosis. These differences may explain differential vulnerability to sub-threshold psychotic symptomology before a full-blown episode. In addition to suggesting differential underlying neurobiology related to STPS, these results suggest the importance of considering STPS history in mapping the trajectories of cortical thickness among FEP patients.
Highlights
Hand gestures are an integral part of social interactions and are involved in nonverbal and verbal communication
Our findings showed an association of gesture production with network attributes and specific connections within the praxis network
The results revealed an association of impaired gesture performance with structural alterations of the praxis network, including global and local efficiency and many connections of interest
Summary
Volumetric brain differences between persons meeting criteria for a clinical high-risk state for psychosis (CHR) and healthy controls (HC) have been previously reported, yet little is known about potential abnormalities in surface-based morphological measures. A multi-site analysis conducted in 104 CHR persons found global increases in cortical gyrification compared to HC (Sasabayashi et al 2017). Gyrification abnormalities in CHR could potentially serve as early neuromarkers of elevated risk, and could eventually be used to identify objectively and efficiently the CHR state. Local gyrification was quantified automatically across the whole brain as absolute mean curvature for each vertex of the brain surface mesh consisting of thousands of individual measurement points. Vertex-wise differences of curvature values were calculated applying a General Linear Model, corrected for age, gender and site effects.
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