2026 ECNP Congress

PS03-3036

Phenotyping thought disorder in treatment-resistant schizophrenia: a multidimensional analysis using the thought and language disorder scale and clinical correlates

Caterina Ceparano — F. Iannotta, C. Ricci, G. Pezzullo, A. Catino, W. Del Monaco, F. Iasevoli, A. de Bartolomeis · University of "Federico II" of Naples, Section of Psychiatry- Department of Neuroscience, Napoli, Italy

2026 ECNP Congress

Introduction

Formal thought disorder (TD) represents a core clinical marker of schizophrenia, significantly impacting global functioning and social integration [1]. Historically, psychiatric literature has distinguished between “fluent” and “non-fluent” thought disorders [2]. The Thought and Language Disorder (TALD) scale has emerged as a pivotal instrument, enabling clinicians to integrate the evaluation of objective signs with the patient’s own subjective experience of their cognitive and linguistic flow [3]. In the clinical landscape, treatment-resistant schizophrenia (TRS) poses unique diagnostic and therapeutic challenges.

Aims

The primary aim of this study was to characterize the specific profile of thought and language disorders in patients with TRS compared to treatment-responsive patients (SCZ). We aimed to analyse these differences across the various TALD subscales and investigate the role of potential clinical predictors.

Methods

This observational study involved 117 patients, clinically categorized into two groups: responders (SCZ = 61) and those meeting the Treatment Response and Resistance in Psychosis (TRRIP) criteria (TRS = 56) [4]. The TALD scale was utilised and subdivided into four distinct domains: Objective-Positive (OP), Objective-Negative (ON), Subjective-Positive (SP), and Subjective-Negative (SN). Clinical psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Statistical analyses were performed using R software. We employed Welch’s t-tests for group comparisons to account for unequal variances. Relationship between variables was assessed via Pearson correlations. A multiple linear regression model was constructed, controlling for age, sex, education, duration of illness, and chlorpromazine equivalents. Finally, a causal mediation analysis and a Receiver Operating Characteristic (ROC) curve analysis (using the Youden Index) were conducted to identify the optimal diagnostic cut-off for resistance.

Results

The TRS group exhibited significantly higher total TALD scores compared to the SCZ group (p = 0.032). Specifically, a marked impairment was found in the Objective-Positive domain (p = 0.025), reflecting greater observable disorganisation. Conversely, subjective dimensions showed no significant differences between groups (p > 0.30), resulting in a significantly larger “TALD Gap” (the discrepancy between objective signs and subjective awareness) in TRS patients (4.74 vs 2.55). Regression analysis revealed that education level significantly influences the detectability of thought disorders (p = 0.03), whereas duration of illness was not a significant predictor (p = 0.28). This supports the hypothesis that TD, as measured by the TALD, acts as a stable “trait” marker rather than a degenerative feature. A moderate correlation was confirmed between TALD scores and PANSS Negative symptoms (r = 0.40, p < 0.001). Causal mediation analysis demonstrated that negative symptoms act as a total mediator in the relationship between treatment resistance and communicative deficits. The ROC curve identified an optimal cut-off of 28.5 points (AUC 0.61), yielding a high specificity of 85.2% for the TRS profile.

Conclusions

Our findings suggest that treatment resistance in schizophrenia is characterised by objective linguistic disorganisation, primarily driven by the severity of the negative affective dimension. The TALD scale proves to be a sensitive tool for phenotyping these patients.These evidences highlight the importance of targeted linguistic assessments to optimise personalised therapeutic strategies in complex schizophrenia cases.

References

  1. Roche, E., et al., 2015. The clinical importance of formal thought disorder. Psychiatry Research 226(2-3), 432-440.
  2. Andreasen, N.C., 1979. Thought, language, and communication disorders. Archives of General Psychiatry 36(12), 1315-1321.
  3. Kircher, T., et al., 2014. TALD: The Thought and Language Disorder Scale. Schizophrenia Bulletin 40(6), 1178-1189.
  4. Howes, O.D., et al., 2017. Treatment-Resistant Schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology. American Journal of Psychiatry 174(3), 216-229.