Background: Disturbances in the expression of thought is a core feature of schizophrenia but assessment of disordered thinking is challenging, relying on clinical intuition which may contribute to the paucity of mechanistic understanding of disorganization seen in early stages of psychosis. We studied the use of linguistic connectives in relation to clinically quantified dimensions of thought disorder using automated speech analysis in untreated, first episode psychosis (FEPs) and healthy controls (HCs)Methods: Data were collected from 39 treatment-naïve, actively psychotic first episode patients (FEPs) recruited on first contact and 23 group matched healthy controls. Three one-minute speech samples were induced in response to photographs from the Thematic Apperception Test and speech was analyzed using COH-METRIX software. Five connectives variables from the Coh-Metrix software were reduced using principle component analysis, resulting in two linguistic connectives factors. Thought disorder was assessed using the Thought Language Index (TLI) and the PANSS-8. Results: linguistic connective factors predicted disorganized thought, but not impoverishment suggesting aberrant use of connectives is specific to positive thought disorder. Factor 2 (increased temporal, reduced logical connectives), showed statistically significant main effects (F[2,56]=5.58, p=0.006) on ANOVA among HCs, low- and high-disorganization FEPs. Post-hoc differences were noted between High- and Low- disorganization FEPs (p=0.004). Factor 2 was not correlated with measures of disease severity or cognition suggesting connective use is a specific index of disorganized thinking rather than overall illness status.Conclusions: Disorganization in psychosis, assessed on the basis of clinical judgement, is likely linked to the excessive or inappropriate use of linguistic connectives leading to an intuitive sense of incoherence to the observer. In the early stages of untreated psychosis, thought disorder may be quantifiable more reliably using automated syntax analysis.
Background:Network level dysconnectivity has been studied in positive and negative symptoms of schizophrenia. Conceptual disorganization (CD) is a symptom subtype which 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).Methods:We computed whole-brain binarized degree centrality maps of 31 FEPs, 25 HCs and characterized the patterns of network connectivity in the two 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.Results:Compared to HCs, reduced hubness of a right superior temporal gyrus (rSTG) cluster was observed in the FEPs. In patients exhibiting high CD, increased hubness of a medial superior parietal (mSPL) cluster was observed, compared to patients exhibiting low CD. These two regions were strongly correlated with CD scores but not with other symptom scores.Discussion:Our observations are congruent with previous findings of reduced but not increased hubness. We observed increased hubness of mSPL suggesting that cortical reorganization occurs to provide alternate routes for information transfer.Conclusion:These findings provide insight into the underlying neural processes mediating the presentation of symptoms in untreated FEP. A longitudinal tracking of the symptom course will be useful to assess the mechanisms underlying these compensatory changes.
Background: Although approximately 1/3 of individuals with schizophrenia are Treatment Resistant (TR), identifying these subjects prospectively for early intervention remains challenging. The Treatment Response and Resistance in Psychosis (TRIPP; Howes et al, 2017) working group recently published consensus guidelines defining lack of response as a <20% improvement in symptoms. However, it is unclear whether these criteria are sensitive in First Episode Schizophrenia (FES). Method: Patients experiencing a first episode of psychosis referred to the Prevention and Early Intervention Program for Psychosis (PEPP) in London, Canada were followed-up with longitudinal symptom assessments. We evaluated two improvement thresholds for ‘probable TR’ classifications; <20% (as per TRIPP) and <50% to identify subjects satisfying ‘probable TR’ based on positive, negative, and total symptom domains.Results: Using the criterion of <50% total, or <20% negative symptom improvement,resulted in ‘probable TR’ rates of 37% and 33% respectively, with notable overlap between the 2criteria (77% satisfying both). Using a 20% cut-off for positive and total symptomsresulted in very low rates of ‘probable TR’. Logistic regression analyses demonstrated that poorpremorbid functioning, longer duration of untreated illness, and limited treatment response atmonths one and two were significantly associated with probable TR (<50% totalsymptom improvement).Conclusions: Our results suggest that probable TR may be identified at 6 months after FESusing a time-based approach only by including negative symptoms (either alone, with a 20%improvement threshold, or in addition to positive symptoms, with a total 50%threshold) in the definition.
Background: Disorganized thinking is a core feature of acute psychotic episodes that is linked to social and vocational functioning. Based on the close association between cingulum and disorganized thinking, we examine three candidate mechanistic markers in relation to acute conceptual disorganization (CD) in first episode psychosis: glutamate excess; cortical antioxidant (glutathione) status and the integrity of the cingulum bundle. Methods: We used fractional anisotropy (FA) maps from 7T diffusion-weighted imaging to investigate bilateral cingulum based on a probabilistic white-matter atlas. We compared the high-CD, low-CD and healthy control groups and performed probabilistic fiber tracking from the identified clusters (ROI within cingulum) to the rest of the brain. We quantified glutamate and glutathione with magnetic-resonance-spectroscopy (MRS) in the dorsal anterior cingulate cortex.Results: There was a significant FA reduction (F=9.04; p=0.036) in a cluster in left cingulum in high-CD compared to low-CD (Cohen’s d=1.39; p=0.003) and controls (Cohen’s d=0.86; p=0.009). Glutamate levels did not vary among the groups, but glutathione levels were higher in high-CD compared to the low-CD group. Higher glutathione related to lower FA in the high-CD group in the cingulum cluster.Discussion: Acute CD relates to indicators of oxidative stress as well as reduced white matter integrity of the cingulum but not to MRI-based glutamatergic excess. We propose that both oxidative imbalance and structural dysconnectivity underlie acute disorganization.Limitation: MRS measures of glutamine were highly uncertain and MRs was acquired from a single voxel only.
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