Dissecting the neurobiology of linguistic disorganisation and impoverishment in schizophrenia.

Schizophrenia provides a quintessential disease model of how disturbances in the molecular mechanisms of neurodevelopment lead to disruptions in the emergence of cognition. The central and often persistent feature of this illness is the disorganisation and impoverishment of language and related expressive behaviours. Though clinically more prominent, the periodic perceptual distortions characterised as psychosis are non-specific and often episodic. While several insights into psychosis have been gained based on study of the dopaminergic system, the mechanistic basis of linguistic disorganisation and impoverishment is still elusive. Key findings from cellular to systems-level studies highlight the role of ubiquitous, inhibitory processes in language production. Dysregulation of these processes at critical time periods, in key brain areas, provides a surprisingly parsimonious account of linguistic disorganisation and impoverishment in schizophrenia. This review links the notion of excitatory/inhibitory (E/I) imbalance at cortical microcircuits to the expression of language behaviour characteristic of schizophrenia, through the building blocks of neurochemistry, neurophysiology, and neurocognition.

Fully automated detection of formal thought disorder with Time-series Augmented Representations for Detection of Incoherent Speech (TARDIS).

Formal thought disorder (ThD) is a clinical sign of schizophrenia amongst other serious mental health conditions. ThD can be recognized by observing incoherent speech - speech in which it is difficult to perceive connections between successive utterances and lacks a clear global theme. Automated assessment of the coherence of speech in patients with schizophrenia has been an active area of research for over a decade, in an effort to develop an objective and reliable instrument through which to quantify ThD. However, this work has largely been conducted in controlled settings using structured interviews and depended upon manual transcription services to render audio recordings amenable to computational analysis. In this paper, we present an evaluation of such automated methods in the context of a fully automated system using Automated Speech Recognition (ASR) in place of a manual transcription service, with "audio diaries" collected in naturalistic settings from participants experiencing Auditory Verbal Hallucinations (AVH). We show that performance lost due to ASR errors can often be restored through the application of Time-Series Augmented Representations for Detection of Incoherent Speech (TARDIS), a novel approach that involves treating the sequence of coherence scores from a transcript as a time-series, providing features for machine learning. With ASR, TARDIS improves average AUC across coherence metrics for detection of severe ThD by 0.09; average correlation with human-labeled derailment scores by 0.10; and average correlation between coherence estimates from manual and ASR-derived transcripts by 0.29. In addition, TARDIS improves the agreement between coherence estimates from manual transcripts and human judgment and correlation with self-reported estimates of AVH symptom severity. As such, TARDIS eliminates a fundamental barrier to the deployment of automated methods to detect linguistic indicators of ThD to monitor and improve clinical care in serious mental illness.

The clinical relevance of formal thought disorder in the early stages of psychosis: results from the PRONIA study.

BACKGROUND: Formal thought disorder (FTD) has been associated with more severe illness courses and functional deficits in patients with psychotic disorders. However, it remains unclear whether the presence of FTD characterises a specific subgroup of patients showing more prominent illness severity, neurocognitive and functional impairments. This study aimed to identify stable and generalizable FTD-subgroups of patients with recent-onset psychosis (ROP) by applying a comprehensive data-driven clustering approach and to test the validity of these subgroups by assessing associations between this FTD-related stratification, social and occupational functioning, and neurocognition. METHODS: 279 patients with ROP were recruited as part of the multi-site European PRONIA study (Personalised Prognostic Tools for Early Psychosis Management; www.pronia.eu). Five FTD-related symptoms (conceptual disorganization, poverty of content of speech, difficulty in abstract thinking, increased latency of response and poverty of speech) were assessed with Positive and Negative Symptom Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS). RESULTS: The results with two patient subgroups showing different levels of FTD were the most stable and generalizable clustering solution (predicted clustering strength value = 0.86). FTD-High subgroup had lower scores in social (pfdr < 0.001) and role (pfdr < 0.001) functioning, as well as worse neurocognitive performance in semantic (pfdr < 0.001) and phonological verbal fluency (pfdr < 0.001), short-term verbal memory (pfdr = 0.002) and abstract thinking (pfdr = 0.010), in comparison to FTD-Low group. CONCLUSIONS: Clustering techniques allowed us to identify patients with more pronounced FTD showing more severe deficits in functioning and neurocognition, thus suggesting that FTD may be a relevant marker of illness severity in the early psychosis pathway.

Differences in single positive formal thought disorder symptoms between closely matched acute patients with schizophrenia and mania.

Formal thought disorders (FTD) are a hallmark diagnostic feature of schizophrenia (SZ) and (bipolar) mania (MA). FTD can be separated into positive (pFTD) and negative dimensions. It is unclear whether there are differences in pFTD on a single symptom level between acutely ill patients with SZ and MA, which cannot be attributed to cognitive impairment. We compared single pFTD symptoms in two groups of acutely ill patients with ICD-10 bipolar mania and schizophrenia, closely matched for age, sex, pFTD TALD score, verbal IQ and neuropsychological test performance (executive function, verbal fluency, attention, and working memory). SZ patients had higher severity of the TALD symptoms "perseverations" and "poverty of content of speech" than those with MA (Mann-Whitney U, significant, Bonferroni corrected). Speech in acute SZ patients differs from MA in that it conveys little information and adheres to previously mentioned ideas and topics. Matching for confounding variables, such as IQ and cognition, is important when comparing patients with different diagnoses.

Association between formal thought disorders, neurocognition and functioning in the early stages of psychosis: a systematic review of the last half-century studies.

Recent review articles provided an extensive collection of studies covering many aspects of format thought disorders (FTD) among their epidemiology and phenomenology, their neurobiological underpinnings, genetics as well as their transdiagnostic prevalence. However, less attention has been paid to the association of FTD with neurocognitive and functioning deficits in the early stages of evolving psychosis. Therefore, this systematic review aims to investigate the state of the art regarding the association between FTD, neurocognition and functioning in the early stages of evolving psychotic disorders in adolescents and young adults, by following the PRISMA flowchart. A total of 106 studies were screened. We included 8 studies due to their reports of associations between FTD measures and functioning outcomes measured with different scales and 7 studies due to their reports of associations between FTD measures and neurocognition. In summary, the main findings of the included studies for functioning outcomes showed that FTD severity predicted poor social functioning, unemployment, relapses, re-hospitalisations, whereas the main findings of the included studies for neurocognition showed correlations between attentional deficits, executive functions and FTD, and highlighted the predictive potential of executive dysfunctions for sustained FTD. Further studies in upcoming years taking advantage of the acceleration in computational psychiatry would allow researchers to re-investigate the clinical importance of FTD and their role in the transition from at-risk to full-blown psychosis conditions. Employing automated computer-assisted diagnostic tools in the early stages of psychosis might open new avenues to develop targeted neuropsychotherapeutics specific to FTD.

Brain functional correlates of formal thought disorder in schizophrenia: examining the frontal/dysexecutive hypothesis.

BACKGROUND: One hypothesis proposed to underlie formal thought disorder (FTD), the incoherent speech is seen in some patients with schizophrenia, is that it reflects impairment in frontal/executive function. While this proposal has received support in neuropsychological studies, it has been relatively little tested using functional imaging. This study aimed to examine brain activations associated with FTD, and its two main factor-analytically derived subsyndromes, during the performance of a working memory task. METHODS: Seventy patients with schizophrenia showing a full range of FTD scores and 70 matched healthy controls underwent fMRI during the performance of the 2-back version of the n-back task. Whole-brain corrected, voxel-based correlations with FTD scores were examined in the patient group. RESULTS: During 2-back performance the patients showed clusters of significant inverse correlation with FTD scores in the inferior frontal cortex and dorsolateral prefrontal cortex bilaterally, the left temporal cortex and subcortically in the basal ganglia and thalamus. Further analysis revealed that these correlations reflected an association only with 'alogia' (poverty of speech, poverty of content of speech and perseveration) and not with the 'fluent disorganization' component of FTD. CONCLUSIONS: This study provides functional imaging support for the view that FTD in schizophrenia may involve impaired executive/frontal function. However, the relationship appears to be exclusively with alogia and not with the variables contributing to fluent disorganization.

The cognitive aspect of formal thought disorder and its relationship with global social functioning and the quality of life in schizophrenia.

PURPOSE: It was expected that using a comprehensive scale like the Thought and Language Disorder Scale (TALD) for measurement of FTD would enable assessing its heterogeneity and its associations with cognitive impairment and functionality. This study has aimed to analyze the relationship between formal thought disorder (FTD) and cognitive functions, functionality, and quality of life in schizophrenia. METHODS: This cross-sectional exploratory study included 46 clinical participants meeting the DSM-5 diagnostic criteria for schizophrenia and 35 healthy individuals as the control groups. Data were acquired by means of the Turkish language version of the TALD, the Positive and Negative Syndrome Scale, the Clinical Global Impression Scale, the Functioning Assessment Short Test, the Social Functioning Scale, the World Health Organization Quality of Life Instrument-Short Form, and a neuropsychological test battery on executive functions, working memory, verbal fluency, abstract thinking, and response inhibition. Correlation analyses were conducted to detect significant relationships. RESULTS: The clinical group scored failures in all cognitive tests. The objective positive FTD was associated with deficits in executive functions and social functioning. The objective negative FTD was associated with poor performance in all cognitive domains, physical quality of life, and social and global functioning. The subjective negative FTD was negatively correlated with psychological quality of life. CONCLUSION: This study demonstrated that objective FTD factors reflect different underlying cognitive deficits and correlate with different functioning domains. Significant correlation was determined between subjective negative FTD and psychological quality of life. Given the close relationship of FTD with functioning and quality of life, the FTD-related cognitive deficits should be the key treatment goal in schizophrenia.

Questioning the status of aberrant speech patterns as psychiatric symptoms.

Speech disturbances manifest in various psychiatric conditions and demonstrate temporal variability in relation to acute and stable symptom periods. They can be externally assessed, which facilitates their potential use as an objective marker of illness stage. Continued research will have positive implications for diagnostics and long-term management in clinical settings.

Linguistic alignment and theory of mind impairments in schizophrenia patients' dialogic interactions.

BACKGROUND: Impairments of contextual processing and theory of mind (ToM) have both been offered as accounts of the deviant language characterising formal thought disorder (FTD) in schizophrenia. This study investigated these processes in patients' dialogue. We predicted that FTD patients would show a decrement in linguistic alignment, associated with impaired ToM in dialogue. METHODS: Speech samples were elicited via participation in an interactive computer-based task and a semi-structured interview to assess contextual processing abilities and ToM skills in dialogue, respectively, and from an interactive card-sorting task to measure syntactic alignment. Degree of alignment in dialogue and the syntactic task, and evidence of ToM in (i) dialogue and (ii) a traditional ToM task were compared across schizophrenia patients with FTD (n = 21), non-FTD patients (n = 22) and healthy controls (n = 21). RESULTS: FTD patients showed less alignment than the other two groups in dialogue, and than healthy controls on the syntactic task. FTD patients showed poorer performance on the ToM task than the other two groups, but only compared to the healthy controls in dialogue. The FTD group's degree of alignment in dialogue was correlated with ToM performance in dialogue but not with the traditional ToM task or with syntactic alignment. CONCLUSIONS: In dialogue, FTD patients demonstrate an impairment in employing available contextual information to facilitate their own subsequent production, which is associated with a ToM deficit. These findings indicate that a contextual processing deficit impacts on exploiting representations via the production system impoverishing the ability to make predictions about upcoming utterances in dialogue.

The characteristics of psychotic features in bipolar disorder.

BACKGROUND: In a large and comprehensively assessed sample of patients with bipolar disorder type I (BDI), we investigated the prevalence of psychotic features and their relationship with life course, demographic, clinical, and cognitive characteristics. We hypothesized that groups of psychotic symptoms (Schneiderian, mood incongruent, thought disorder, delusions, and hallucinations) have distinct relations to risk factors. METHODS: In a cross-sectional study of 1342 BDI patients, comprehensive demographical and clinical characteristics were assessed using the Structured Clinical Interview for DSM-IV (SCID-I) interview. In addition, levels of childhood maltreatment and intelligence quotient (IQ) were assessed. The relationships between these characteristics and psychotic symptoms were analyzed using multiple general linear models. RESULTS: A lifetime history of psychotic symptoms was present in 73.8% of BDI patients and included delusions in 68.9% of patients and hallucinations in 42.6%. Patients with psychotic symptoms showed a significant younger age of disease onset (ß = -0.09, t = -3.38, p = 0.001) and a higher number of hospitalizations for manic episodes (F11 338 = 56.53, p < 0.001). Total IQ was comparable between groups. Patients with hallucinations had significant higher levels of childhood maltreatment (ß = 0.09, t = 3.04, p = 0.002). CONCLUSIONS: In this large cohort of BDI patients, the vast majority of patients had experienced psychotic symptoms. Psychotic symptoms in BDI were associated with an earlier disease onset and more frequent hospitalizations particularly for manic episodes. The study emphasizes the strength of the relation between childhood maltreatment and hallucinations but did not identify distinct subgroups based on psychotic features and instead reported of a large heterogeneity of psychotic symptoms in BD.

Examination of formal thought disorder and its clinical correlates with the Turkish Version of the Thought and Language Disorder Scale (TALD-TR) in schizophrenia.

BACKGROUND: Formal thought disorder (FTD) is considered to be a fundamental feature of schizophrenia. This study aims to analyze psychometric properties of the Turkish version of "Thought and Language Disorder Scale (TALD)" and investigate the relationship between FTD and various clinical characteristics in patients with schizophrenia. METHODS: TALD was adapted into Turkish and applied to a total of 149 participants of which 114 had DSM-5 psychiatric diagnoses (schizophrenia N = 70, mania N = 20, depression N = 24) and 35 were healthy controls. Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale, Young Mania Rating Scale, and Clinical Global Impression were administered to detect illness severity. RESULTS: The principal component analyses revealed that the Turkish version of TALD (TALD-TR) consisted of four factors including the Objective Positive (OP), Subjective Negative (SN), Objective Negative (ON) and Subjective Positive (SP) symptom dimensions which were in line with the original TALD factorial structure. It was concluded that TALD-TR shows strong construct validity and high interrater reliability. The correlation analyses with TALD-TR and PANSS showed that there are positive correlations between the TALD-TR total score and the PANSS total and subscale scores. Each diagnostic group showed the distinct pattern of FTD. The mania group exhibited the highest mean total score in the OP, whereas the schizophrenia group exhibited the highest mean total score in the ON factor. In the schizophrenia group, the severity of FTD correlated positively with duration of illness and negatively with age at onset of illness. CONCLUSION: Adaptation of TALD into different languages seems to be possible, bringing in an international tool for research on FTD.

[Impairments of language and communication in schizophrenia]. / Beeinträchtigungen von Sprache und Kommunikation bei Schizophrenie.

Disorganized speech is one of the key symptoms of schizophrenia. This article provides an overview of those areas of speech and communication impaired in patients with schizophrenia. Moreover, the state of the art of behavioral interventions is summarized. In conclusion, more well-controlled speech-language therapy studies are required in order to improve participation and communication-related quality of life in schizophrenia.

Resting state perfusion in the language network is linked to formal thought disorder and poor functional outcome in schizophrenia.

OBJECTIVE: Formal thought disorder (FTD) is a core symptom in schizophrenia. Here, we focus on resting state cerebral blood flow (rCBF) linked to dimensions of FTD. METHODS: We included 47 schizophrenia spectrum patients and 30 age- and gender-matched healthy controls. We assessed FTD with the assessment of thought, language, and communication (TLC) and imaging on a 3T MRI scanner. Within patients, we tested the association of FTD dimensions and in a subgroup (n = 27) the association of functional outcome after 6 months with whole brain rCBF. RESULTS: Negative FTD was most prominently associated with perfusion within the superior temporal gyrus, while positive FTD was associated with perfusion within the supplementary motor area, and inferior frontal gyrus. Perfusion within the left supramarginal gyrus was associated with social functioning after 6 months. CONCLUSIONS: Distinguishable associations of rCBF with FTD dimensions point to distinct underlying pathophysiology. The location of aberrant perfusion patterns suggests that negative FTD might reflect defective access to semantic memory while positive FTD likely reflects defective suppression of irrelevant information during increased speech production. Finally, the neural correlates of thought block were also predictive of poor functional outcome. Thus, functional outcome and distinct FTD dimensions may share some pathophysiology.

Verbal Initiation, Suppression, and Strategy Use and the Relationship with Clinical Symptoms in Schizophrenia.

OBJECTIVES: Individuals with schizophrenia have difficulties on measures of executive functioning such as initiation and suppression of responses and strategy development and implementation. The current study thoroughly examines performance on the Hayling Sentence Completion Test (HSCT) in individuals with schizophrenia, introducing novel analyses based on initiation errors and strategy use, and association with lifetime clinical symptoms. METHODS: The HSCT was administered to individuals with schizophrenia (N=77) and age- and sex-matched healthy controls (N=45), along with background cognitive tests. The standard HSCT clinical measures (initiation response time, suppression response time, suppression errors), composite initiation and suppression error scores, and strategy-based responses were calculated. Lifetime clinical symptoms [formal thought disorder (FTD), positive, negative] were calculated using the Lifetime Dimensions of Psychosis Scale. RESULTS: After controlling for baseline cognitive differences, individuals with schizophrenia were significantly impaired on the suppression response time and suppression error scales. For the novel analyses, individuals with schizophrenia produced a greater number of initiation errors and subtly wrong errors, and produced fewer responses indicative of developing an appropriate strategy. Strategy use was negatively correlated with FTD symptoms in individuals with schizophrenia. CONCLUSIONS: The current study provides further evidence for deficits in the initiation and suppression of verbal responses in individuals with schizophrenia. Moreover, an inability to attain a strategy at least partly contributes to increased semantically connected errors when attempting to suppress responses. The association between strategy use and FTD points to the involvement of executive deficits in disorganized speech in schizophrenia. (JINS, 2016, 22, 735-743).

A new schizophrenia screening instrument based on evaluating the patient's writing.

Formal Thought Disorder (FTD) is a defining feature of schizophrenia, which is often assessed through patients' speech. Meanwhile, the written language is less studied. The aim of the present study is to establish and validate a comprehensive clinical screening scale, capturing the full variety of empirical characteristics of writing in patients with schizophrenia. The 16-item Screening Instrument for Schizophrenic Features in Writing (SISFiW) is derived from detailed literature review and a "brainstorming" discussion on 30 samples written by patients with schizophrenia. One hundred and fifty-seven participants (114 patients with an ICD-10 diagnoses of schizophrenia; 43 healthy control subjects) were interviewed and symptoms assessed with the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Thought, Language, and Communication (TLC). Article samples written by each participant were rated with the SISFiW. Results demonstrated significant difference of the SISFiW-total between the patient group and healthy controls [(3.61 ± 1.72) vs. (0.49 ± 0.63), t = 16.64, p<0.001]. The inter-rater reliability (weighted kappa = 0.72) and the internal consistency (Cronbach's alpha coefficient = 0.613) were acceptable, but correlations with the criterion (PANSS and TLC) were unremarkable. The ROC analysis indicated a cutoff point at 2 with the maximal sensitivity (93.0 %)/specificity (93.0 %). Discriminant analysis of the SISFiW items yielded 8 classifiers that discriminated between the diagnostic groups at a perfect overall performance (with 90.4 % of original and 88.5 % cross-validated grouped cases classified correctly). This instrument appears to be practicable and reliable, with relatively robust discriminatory power, and may serve as a complementary tool to existing FTD rating scales.

The Neurobiology of Formal Thought Disorder.

The concept of Formal Thought Disorder (FTD) is an ambiguous and disputed one, even though it has endured as a core psychopathological construct in clinical Psychiatry. FTD can be summarized as a multidimensional construct, reflecting difficulties or idiosyncrasies in thinking, language, and communication in general and is usually subdivided into positive versus negative. In this article, we aim to explore the putative neurobiology of FTD, ranging from changes in neurotransmitter systems to alterations in the functional anatomy of the brain. We also discuss recent critiques of the operationalist view of FTD and how they might fit in its biological underpinnings. We conclude that FTD might be the observable phenotype of many distinct underlying alterations in different proportions.

Mild vs. moderate: How behavioral speech measures predict metacognitive capacity across different levels of formal thought disorder.

Disorganized speech is a key component of formal thought disorder (FTD) in schizophrenia. Recent work has tied disorganized speech to deficits in metacognition, or one's ability to integrate experiences to form complex mental representations. The level of FTD at which differences in metacognitive capacity emerge remains unclear. Across two studies, using different cut scores to form FTD groups, we aimed to 1) explore the relationship between disorganized speech and metacognition and 2) compare trained rater and automated analysis methods. Clinical interviews were coded for disorganized speech and metacognition using the Communication Disturbances Index (CDI), Coh-Metrix multidimensional indices, and Metacognition Assessment Scale. In Study 1, we examined CDI and Coh-Metrix's ability to predict metacognition in FTD (n = 16) and non-FTD (n = 29) groups. We hypothesized the FTD group would have lower metacognition and that both CDI and Coh-Metrix would account for significant variance in metacognition. In Study 2, we conducted the same analyses with an independent sample using more stringent FTD cut scores (FTD: n = 23; non-FTD: n = 23). Analyses indicated that at a moderate but not mild cutoff: 1) automated methods differentiated FTD and non-FTD groups, 2) differences in metacognition emerged, and 3) behavioral measures accounted for significant variance (34%) in metacognition. Results emphasize the importance of setting the FTD cutoff at a moderate level and using samples that contain high levels of FTD. Findings extend research linking FTD and metacognition and demonstrate the benefit of pairing trained rater and automated speech measures.

Referential noun phrases distribute differently in Turkish speakers with schizophrenia.

In all human languages, noun phrases (NPs) (e.g., 'a field', 'the woman with a book') are used to identify entities in discourse. Previous evidence has shown that the spontaneous speech of patients with schizophrenia (Sz) shows differences in the distribution of grammatically different types of NPs, which are in part specific to patients with formal thought disorder (FTD). Here we sought to provide the first evidence of related grammatical effects in a non-Indo-European language. Results from a picture description task in a sample of 16 Turkish speakers with FTD (+FTD), 15 without FTD (-FTD), and 27 controls revealed that relative to controls, people with Sz over-produced NPs that are 'bare' (in the sense of lacking any grammatical items such as the or a in English). The +FTD group generally showed stronger effects than -FTD, and used more pronouns and less NPs co-referring with previously mentioned NPs. In addition, the dynamic distribution of NP types over narrative time showed an effect of increased mean distance between definite NPs in -FTD relative to controls. In +FTD but no other group there was an unexpected random distribution of indefinite DPs. Incidence rates of referential anomalies increased from controls to the -FTD and +FTD groups. These findings further confirm that Sz is manifest through specific linguistic effects in the referential structure of meaning as mediated by grammar. They provide a linguistic baseline for neurocognitive models of FTD and help to define appropriate targets for the automatic extraction of linguistic features to classify psychotic speech.

Structural and Functional Brain Patterns Predict Formal Thought Disorder's Severity and Its Persistence in Recent-Onset Psychosis: Results From the PRONIA Study.

BACKGROUND: Formal thought disorder (FThD) is a core feature of psychosis, and its severity and long-term persistence relates to poor clinical outcomes. However, advances in developing early recognition and management tools for FThD are hindered by a lack of insight into the brain-level predictors of FThD states and progression at the individual level. METHODS: Two hundred thirty-three individuals with recent-onset psychosis were drawn from the multisite European Prognostic Tools for Early Psychosis Management study. Support vector machine classifiers were trained within a cross-validation framework to separate two FThD symptom-based subgroups (high vs. low FThD severity), using cross-sectional whole-brain multiband fractional amplitude of low frequency fluctuations, gray matter volume and white matter volume data. Moreover, we trained machine learning models on these neuroimaging readouts to predict the persistence of high FThD subgroup membership from baseline to 1-year follow-up. RESULTS: Cross-sectionally, multivariate patterns of gray matter volume within the salience, dorsal attention, visual, and ventral attention networks separated the FThD severity subgroups (balanced accuracy [BAC] = 60.8%). Longitudinally, distributed activations/deactivations within all fractional amplitude of low frequency fluctuation sub-bands (BACslow-5 = 73.2%, BACslow-4 = 72.9%, BACslow-3 = 68.0%), gray matter volume patterns overlapping with the cross-sectional ones (BAC = 62.7%), and smaller frontal white matter volume (BAC = 73.1%) predicted the persistence of high FThD severity from baseline to follow-up, with a combined multimodal balanced accuracy of BAC = 77%. CONCLUSIONS: We report the first evidence of brain structural and functional patterns predictive of FThD severity and persistence in early psychosis. These findings open up avenues for the development of neuroimaging-based diagnostic, prognostic, and treatment options for the early recognition and management of FThD and associated poor outcomes.

Semantic Speech Networks Linked to Formal Thought Disorder in Early Psychosis.

BACKGROUND AND HYPOTHESIS: Mapping a patient's speech as a network has proved to be a useful way of understanding formal thought disorder in psychosis. However, to date, graph theory tools have not explicitly modelled the semantic content of speech, which is altered in psychosis. STUDY DESIGN: We developed an algorithm, "netts," to map the semantic content of speech as a network, then applied netts to construct semantic speech networks for a general population sample (N = 436), and a clinical sample comprising patients with first episode psychosis (FEP), people at clinical high risk of psychosis (CHR-P), and healthy controls (total N = 53). STUDY RESULTS: Semantic speech networks from the general population were more connected than size-matched randomized networks, with fewer and larger connected components, reflecting the nonrandom nature of speech. Networks from FEP patients were smaller than from healthy participants, for a picture description task but not a story recall task. For the former task, FEP networks were also more fragmented than those from controls; showing more connected components, which tended to include fewer nodes on average. CHR-P networks showed fragmentation values in-between FEP patients and controls. A clustering analysis suggested that semantic speech networks captured novel signals not already described by existing NLP measures. Network features were also related to negative symptom scores and scores on the Thought and Language Index, although these relationships did not survive correcting for multiple comparisons. CONCLUSIONS: Overall, these data suggest that semantic networks can enable deeper phenotyping of formal thought disorder in psychosis. Whilst here we focus on network fragmentation, the semantic speech networks created by Netts also contain other, rich information which could be extracted to shed further light on formal thought disorder. We are releasing Netts as an open Python package alongside this manuscript.