Neuroimaging alterations and relapse in early-stage psychosis

Abstract

Background: Recent reports have indicated that symptom exacerbation after a period of improvement, referred to as relapse, in early-stage psychosis could result in brain changes and poor disease outcomes. We hypothesized that substantial neuroimaging alterations may exist among patients who experience relapse in early-stage psychosis.

Methods: We studied patients with psychosis within 2 years after the first psychotic event and healthy controls. We divided patients into 2 groups, namely those who did not experience relapse between disease onset and the magnetic resonance imaging (MRI) scan (no-relapse group) and those who did experience relapse between these 2 timings (relapse group). We analyzed 3003 functional connectivity estimates between 78 regions of interest (ROIs) derived from resting-state functional MRI data by adjusting for demographic and clinical confounding factors.

Results: We studied 85 patients, incuding 54 in the relapse group and 31 in the no-relapse group, along with 94 healthy controls. We observed significant differences in 47 functional connectivity estimates between the relapse and control groups after multiple comparison corrections, whereas no differences were found between the no-relapse and control groups. Most of these pathological signatures (64%) involved the thalamus. The Jonckheere-Terpstra test indicated that all 47 functional connectivity changes had a significant cross-group progression from controls to patients in the no-relapse group to patients in the relapse group.

Limitations: Longitudinal studies are needed to further validate the involvement and pathological importance of the thalamus in relapse.

Conclusion: We observed pathological differences in neuronal connectivity associated with relapse in early-stage psychosis, which are more specifically associated with the thalamus. Our study implies the importance of considering neurobiological mechanisms associated with relapse in the trajectory of psychotic disorders.

Figure 1

Altered functional connectivity in the relapse group, compared with the control group. (A) Visualization of 47 significant functional connectivity estimates. Orange and green semicircles represent the left and right brain hemispheres, respectively. Numbers on the semicircles denote regions of interest (ROIs). The thalamus, number 24, is highlighted in red. Lines between numbers represent functional connectivity. Estimates with q-values smaller than 0.01, 0.01–0.03, or 0.03–0.05 are in red, blue, or green, respectively. (B) Number of significant functional connectivity estimates of each ROI. Most estimates (30 of 47) involved the thalamus (highlighted with a dark bar). Note: ACC = anterior cingulate cortex; AG = angular gyrus; Caud = caudate nucleus; CerebellumGM = cerebellum grey matter; Cu = cuneus; FuG = fusiform gyrus; GP = globus pallidus; IFG = inferior frontal gyrus; IOG = inferior occipital gyrus; ITG = inferior temporal gyrus; LFOG = lateral fronto-orbital gyrus; LG = lingual gyrus; MFG = middle frontal gyrus; DPFC = dorsolateral prefrontal cortex; MFOG = middle fronto-orbital gyrus; MOG = middle occipital gyrus; MTG = middle temporal gyrus; PCC = posterior cingulate cortex; PFC = prefrontal cortex; PoCG = postcentral gyrus; PrCG = precentral gyrus; PrCu = precuneus; Put = putamen; RG = gyrus rectus; SMG = supramarginal gyrus; SOG = superior occipital gyrus; SPG = superior frontal gyrus; STG = superior temporal gyrus.

Figure 2

Top 6 significant functional connectivity estimates (ranked based on p values) altered between the relapse and healthy control groups. Note: IOG = inferior occipital gyrus; L = left; MOG = middle occipital gyrus; R = right; SOG = superior occipital gyrus; SPG = superior frontal gyrus.