Abstract
Network-level dysconnectivity has been studied in positive and negative symptoms of schizophrenia. Conceptual disorganization (CD) is a symptom subtype that predicts impaired real-world functioning in psychosis. Systematic reviews have reported aberrant connectivity in formal thought disorder, a construct related to CD. However, no studies have investigated whole-brain functional correlates of CD in psychosis. We sought to investigate brain regions explaining the severity of CD in patients with first-episode psychosis (FEPs) compared with healthy controls (HCs). We computed whole-brain binarized degree centrality maps of 31 FEPs, 25 HCs, and characterized the patterns of network connectivity in the 2 groups. In FEPs, we related these findings to the severity of CD. We also studied the effect of positive and negative symptoms on altered network connectivity. Compared to HCs, reduced centrality of a right superior temporal gyrus (rSTG) cluster was observed in the FEPs. In patients exhibiting high CD, increased centrality of a medial superior parietal (mSPL) cluster was observed, compared to patients exhibiting low CD. This cluster was strongly correlated with CD scores but not with other symptom scores. Our observations are congruent with previous findings of reduced but not increased centrality. We observed increased centrality of mSPL suggesting that cortical reorganization occurs to provide alternate routes for information transfer. These findings provide insight into the underlying neural processes mediating the presentation of symptoms in untreated FEP. Longitudinal tracking of the symptom course will be useful to assess the mechanisms underlying these compensatory changes.
Highlights
Disorganization is one of the three distinct syndromes of schizophrenia[1,2,3,4], defined collectively as the impairment of the form of thought processes (conceptual disorganization (CD)) and bizarre actions
In patients with high P2 compared to low P2, we observed a significant increase in binarized degree centrality (bDC) of a medial superior parietal cluster, comprising of paracentral lobule and precuneus regions
The low P2 group did not differ from the healthy controls in the bDC of this cluster (t[55] = 1.6, p = 0.11) while the high P2 group had significantly higher bDC than healthy controls (t[36] = 4.94, p < 0.001) (mean (SD) in controls = 0.35 (0.33); low P2 = 0.22 (0.23); high P2 = 0.68 (0.33); see Supplementary Result 2 for more details)
Summary
Disorganization is one of the three distinct syndromes of schizophrenia[1,2,3,4], defined collectively as the impairment of the form of thought processes (conceptual disorganization (CD)) and bizarre actions (behavioral disorganization). CD is referred to as “formal thought disorder (FTD)”, though the latter is often measured using specific instruments that focus on testing aspects of speech rather than the clinical interpretation of disorganization. While the construct of FTD encompasses both positive (e.g., illogical, tangential, and loosened speech) as well as negative (e.g., poverty of speech and reduced content of speech). The acute CD resolves in many patients over time[11,12,13,14], and often covaries with the severity of positive symptoms such as delusions and hallucinations, while the CD seen in chronic stages often emerges as a distinct subtype, with more negative features of FTD being noted[15]. The persistence of CD despite treatment in longitudinal cohorts has led to the suggestion that existing treatments are not fully effective in alleviating the degree of disorganization in patients with psychosis[12,16,17]
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