الوصف: |
BACKGROUND: Of the various symptom complexes of established psychosis, network level dysconnectivity has been widely studied in association with positive and negative symptoms. Very few studies have focused on studying the dysconnectivity patterns associated with disorganization, specifically conceptual disorganization (CD), which explains the impairments in both the goal-directed sequencing of thought processes and real-world functioning. Systematic reviews have revealed aberrant connectivity patterns in formal thought disorder (a construct related to CD) at all stages of the illness, suggesting the underlying persistence of CD. However, these studies investigate connectivity patterns between specific regions of interest or resting state networks. No studies have investigated the whole-brain functional correlates of CD in psychosis. We thus sought to investigate the brain regions explaining the severity of CD in patients with first-episode psychosis (FEPs) in comparison with healthy controls (HCs). METHODS: Participants were recruited as part of a longitudinal neuroimaging project that follows changes in early psychosis during the course of treatment. 31 HC and 38 antipsychotic-naive FEP subjects were included in the study sample. Subjects were assessed using DSM-5 criteria and the 8 item Positive and Negative Syndrome Scale (PANSS-8) and underwent 2 magnetic resonance imaging (MRI) scans at 7T (one T2*-weighted resting-state functional MRI (rs-fMRI) scan, one T1-weighted structural MRI). After preprocessing, whole-brain binarized degree centrality (bDC) maps were computed to characterize the patterns of network connectivity in the two study samples. Statistical analyses included the following: 1) A two-sample t-test comparing connectivity patterns in the HC and FEP groups with bDC maps as the dependent variable, examining the effect of diagnosis accounting for gender as the covariate, 2) Similarly, a two-sample t-test comparing connectivity patterns in the two patient groups (low CD or Low P2, high CD or High P2) with bDC maps as the dependent variable, examining the effect of the severity of symptoms accounting for gender as the covariate. RESULTS: Compared to HCs, the FEPs showed a reduction in hubness of a cluster located in the superior temporal gyrus (rSTG) (right: t = 5.00, p < 0.001). This cluster was functionally connected with clusters in the middle frontal gyrus (left: t = 8.41, p < 0.001; right: t = 7.59, p < 0.001), cerebellum (left: t = 8.02, p < 0.001) and thalamus (left: t = 9.72, p < 0.001). In patients exhibiting high CD severity, increased hubness of a medial superior parietal (mSPL) cluster (left: t = 4.93, p = 0.001) was observed, compared to patients exhibiting low CD severity. This cluster was functionally connected with clusters in the superior temporal (right: t = 8.39, p < 0.001) and middle temporal (right: t = 7.07, p < 0.001) gyri. The summary measure (first eigenvariate) of the mSPL cluster’s centrality showed strong correlation with the severity of CD but no other symptoms. DISCUSSION: Our observations extend the previous findings of reduced hubness in the superior temporal and insular regions in established schizophrenia to early-stage untreated, active phase of illness. Nevertheless, the increase in peripheral hubness in this first-episode sample was limited to conceptually disorganized patients, indicating the possible role of functional cortical reorganization and re-routing of information transfer in early stages of thought disorder. |