Letter to the Editor

Formal thought disorder and neurocognition in schizophrenia: The question of individual mechanisms

Disorganised speech, or, formal thought disorder (FTD), is considered one of the core features of psychosis, yet its factor structure remains debated. This systematic review aimed to identify the core dimensions of FTD. In line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA), a systematic review was conducted on the FTD factor analytic literature. Sixteen studies were identified from PsycINFO, PubMed and Web of Science between October 1971 and January 2023. Across the 39 factor analyses investigated, findings demonstrated the prominence of a three-factor structure. Broad agreement was found for two factors within the three-factor model, which were typically referred to as disorganisation and negative, with the exact nature of the third dimension requiring further clarification. The quality assessment revealed some methodological challenges relating to the assessment of FTD and conducted factor analyses. Future research should clarify the exact nature of the third dimension across different patient groups and methodologies to determine whether a consistent transdiagnostic concept of FTD can be elucidated.

Different dimensions of formal thought disorder (FTD) are distinguished by different patterns of cognitive dysfunction in patients with schizophrenia; however, inconsistent findings may relate to patient-related confounds. To avoid these confounds, we examined relationships between FTD dimensions and cognitive domains in a non-clinical sample with attenuated schizophrenia-like traits, or schizotypal traits, on the Schizotypal Personality Questionnaire (N = 91). To our knowledge, no study has done this. FTD dimension scores were derived following principal component analysis of the Scale for the Assessment of Thought, Language and Communication (TLC dimensions: Disorganisation, Verbosity, Emptiness) and the Thought and Language Index (TLI dimensions: Negative, Idiosyncratic). The sample completed a comprehensive neuropsychological battery. Findings indicate that higher-order reasoning, executive function (set shift and generative ability) and language/semantic functioning are the primary drivers of FTD in our non-clinical sample with elevated schizotypal traits, in line with schizophrenia research. FTD may have shared aetiology along the schizophrenia spectrum.

Formal thought disorder (FTD) refers to abnormal speech patterns that can be characterized by deficiencies in thought organization and direction. The present study aimed to assess the factor structure of FTD and to examine its relationship with cognition and clinical features at first admission in patients with first-episode schizophrenia. We also examined the course of FTD during the twelve months after first admission. We assessed FTD using the alogia items of the Scale for the Assessment of Negative Symptoms and FTD items of the Scale for the Assessment of Positive Symptoms in 160 drug-naïve patients. A three-factor structure as a disorganization factor, poverty factor, and verbosity factor were found in principal component analysis. The poverty factor was correlated negatively with executive functions, attention, and global cognition. The poverty factor was also correlated with global functioning. Admission FTD factor scores were not related to global functioning and work/study status at one year. The positive-FTD score decreased from admission to the third month, but no change occurred from the third to the twelfth month. The negative-FTD score did not differ throughout the follow-up. Our findings showed that FTD had three factors. Each factor had a different relationship with cognition and functioning.

Cognitive impairment is characteristic of schizophrenia but the nature and severity often differ between patients and the relationship with subjective quality of life (sQOL) is inconsistent. This study sought to better characterise the cognition-sQOL relationship in schizophrenia by 1) examining associations between factor analysis-derived cognitive domains and sQOL, 2) investigating if these domains independently predicted sQOL, and 3) exploring if clinical, demographic and functional variables moderated any significant relationships. 47 schizophrenia/schizoaffective disorder patients and 48 healthy controls were assessed. QOL was measured using the Lehman’s QOL Interview. Composite scores were created to represent objective QOL and sQOL, and factor analysis was used to determine cognitive domains from 14 cognitive tasks. Three cognitive domains were derived: visuospatial planning, verbal linguistic and inhibition switching. Tasks comprising the verbal linguistic cognitive domain were significantly associated with and predicted sQOL. Moderation analyses revealed that the direction of this relationship differed between patients and healthy controls, and may be moderated by positive symptom severity in patients. In conclusion, meaning-based (e.g. verbal-linguistic) cognitive abilities may be most closely related to sQOL in schizophrenia. Symptomatology may also impact this relationship, with worsening sQOL among those with more intact verbal-linguistic processing and persistent positive symptoms. These patients may therefore be at greater risk for poor sQOL, but may be more motivated and capable of engaging in and benefiting from offered psychosocial interventions.

Persistent formal thought disorder (FTD) is a core feature of schizophrenia. Recent cognitive and neuroimaging studies indicate a distinct mechanistic pathway underlying the persistent positive FTD (pFTD or disorganized thinking), though its structural determinants are still elusive. Using network-based cortical thickness estimates from ultra-high field 7-Tesla Magnetic Resonance Imaging (7T MRI), we investigated the structural correlates of pFTD.

We obtained speech samples and 7T MRI anatomical scans from medicated clinically stable patients with schizophrenia (n = 19) and healthy controls (n = 20). Network-based morphometry was used to estimate the mean cortical thickness of 17 functional networks covering the entire cortical surface from each subject. We also quantified the vertexwise variability of thickness within each network to quantify the spatial coherence of the 17 networks, estimated patients vs. controls differences, and related the thickness of the affected networks to the severity of pFTD.

Patients had reduced thickness of the frontoparietal and default mode networks, and reduced spatial coherence affecting the salience and the frontoparietal control network. A higher burden of positive FTD related to reduced frontoparietal thickness and reduced spatial coherence of the salience network. The presence of positive FTD, but not its severity, related to the reduced thickness of the language network comprising of the superior temporal cortex.

These results suggest that cortical thickness of both cognitive control and language networks underlie the positive FTD in schizophrenia. The structural integrity of cognitive control networks is a critical determinant of the expressed severity of persistent FTD in schizophrenia.