Dimensions of Formal Thought Disorder and Their Relation to Gray- and White Matter Brain Structure in Affective and Psychotic Disorders

Abstract

Factorial dimensions and neurobiological underpinnings of formal thought disorders (FTD) have been extensively investigated in schizophrenia spectrum disorders (SSD). However, FTD are also highly prevalent in other disorders. Still, there is a lack of knowledge about transdiagnostic, structural brain correlates of FTD. In N = 1071 patients suffering from DSM-IV major depressive disorder, bipolar disorder, or SSD, we calculated a psychopathological factor model of FTD based on the SAPS and SANS scales. We tested the association of FTD dimensions with 3 T MRI measured gray matter volume (GMV) and white matter fractional anisotropy (FA) using regression and interaction models in SPM12. We performed post hoc confirmatory analyses in diagnostically equally distributed, age- and sex-matched sub-samples to test whether results were driven by diagnostic categories. Cross-validation (explorative and confirmatory) factor analyses revealed three psychopathological FTD factors: disorganization, emptiness, and incoherence. Disorganization was negatively correlated with a GMV cluster comprising parts of the middle occipital and angular gyri and positively with FA in the right posterior cingulum bundle and inferior longitudinal fascicle. Emptiness was negatively associated with left hippocampus and thalamus GMV. Incoherence was negatively associated with FA in bilateral anterior thalamic radiation, and positively with the hippocampal part of the right cingulum bundle. None of the gray or white matter associations interacted with diagnosis. Our results provide a refined mapping of cross-disorder FTD phenotype dimensions. For the first time, we demonstrated that their neuroanatomical signatures are associated with language-related gray and white matter structures independent of diagnosis.

Voice patterns as markers of schizophrenia: building a cumulative generalizable approach via a cross-linguistic and meta-analysis based investigation

“…This multilingual corpus may represent an ideal benchmark dataset for testing the reliability and generalizability (e.g., out of sample predictability) of voice analysis results in schizophrenia 73 , and the necessary ground for assessing its clinical applicability 74 . Not least, future studies should focus more on cross-diagnostic comparisons aimed at capturing symptom dimensions which extend over a single disorder 75,76 , and implement longitudinal designs able to test more complex hypothesis on the interaction between antipsychotic medication type and dosage, clinical (e.g., illness severity and duration) and sociodemographic (e.g., sex differences 77 ) characteristics, and speech production.…”

Latent Factors of Language Disturbance and Relationships to Quantitative Speech Features

“…37 Overall, our model is very similar to the 3-factor model for formal thought disorder reported by Stein et al in their crossdiagnostic sample of N=1,071. 25 They describe an emptiness factor (poverty of speech and content, increased latency, and blocking), a disorganization factor (tangentiality, circumstantiality, derailment, pressure of speech), and an incoherence factor (incoherence, distractibility). The principal differences are that we include decreased vocal inflection in our impaired expressivity factor (since we are looking at speech as a whole, and not specifically thought disorder), and that we prefer the term "inefficiency" over "disorganization" because "disorganization" is an overly broad term than can The 3-factor model proposed here can be understood in the context of linguistic theories on pragmatics.…”

“…We need to define cross-diagnostically diagnoses. 25 Speech graph features have been shown to be a good marker of thought disorder in mania and SSD, 15 and to be related to cross-diagnostic psychopathological dimensions. 26 referential: echolalia and self-reference).…”

“…Notably, in a large sample (N=1,071), Stein et al found three factors of speech disturbance (emptiness, disorganization, and incoherence) which were linked to changes in distinct brain regions and valid across diagnoses. 25 Speech graph features have been shown to be a good marker of thought disorder in mania and SSD, 15 and to be related to cross-diagnostic psychopathological dimensions. 26 However, there are few studies examining whether quantitative speech features are consistently related to cross-diagnostic dimensions of speech disturbance.…”

Language Network Dysfunction and Formal Thought Disorder in schizophrenia

“…Two large transdiagnostic symptom mapping studies of FTD have been reported in recent times, drawing on the same FOR2107 cohort of n=1071 patients [49]. In whole-brain exploratory analyses relating gray matter volume and white matter integrity to positive FTD (derived from a multi-scale factor analysis) and FTD-scale specific positive (disorganisation, incoherence) and negative FTD factors (emptiness), Stein and colleagues report associations outside of the core LN (right middle frontal gyrus, left middle occipital gyrus, anterior thalamic radiation and right posterior cingulum) [50,51]. Conventional language regions do not appear prominent in these transdiagnostic analyses even when a focussed ROI analysis is attempted [51].…”