Negative Formal Thought Disorder Research Articles

Differences in the neural correlates of schizophrenia with positive and negative formal thought disorder in patients with schizophrenia in the ENIGMA dataset.

Formal thought disorder (FTD) is a clinical key factor in schizophrenia, but the neurobiological underpinnings remain unclear. In particular, the relationship between FTD symptom dimensions and patterns of regional brain volume loss in schizophrenia remains to be established in large cohorts. Even less is known about the cellular basis of FTD. Our study addresses these major obstacles by enrolling a large multi-site cohort acquired by the ENIGMA Schizophrenia Working Group (752 schizophrenia patients and 1256 controls), to unravel the neuroanatomy of FTD in schizophrenia and using virtual histology tools on implicated brain regions to investigate the cellular basis. Based on the findings of previous clinical and neuroimaging studies, we decided to separately explore positive, negative and total formal thought disorder. We used virtual histology tools to relate brain structural changes associated with FTD to cellular distributions in cortical regions. We identified distinct neural networks positive and negative FTD. Both networks encompassed fronto-occipito-amygdalar brain regions, but positive and negative FTD demonstrated a dissociation: negative FTD showed a relative sparing of orbitofrontal cortical thickness, while positive FTD also affected lateral temporal cortices. Virtual histology identified distinct transcriptomic fingerprints associated for both symptom dimensions. Negative FTD was linked to neuronal and astrocyte fingerprints, while positive FTD also showed associations with microglial cell types. These results provide an important step towards linking FTD to brain structural changes and their cellular underpinnings, providing an avenue for a better mechanistic understanding of this syndrome.

Formal thought disorder in patients with first-episode schizophrenia: Results of a one-year follow-up study

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.

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

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. 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. 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. 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.

Comparison of Formal Thought Disorder in the Acute Episode of Schizophrenia and Manic Episode of Bipolar Affective Disorder.

The aim of this study was to compare the formal thought disorder (FTD) in the acute episode of schizophrenia (SCHZ) and bipolar affective disorder (BPAD), and to determine the FTD dimensions associated with BPAD. The study included a total of 34 SCHZ patients not meeting the standardized remission criteria and 20 patients in BPAD manic episode. The patients completed the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression Scale (CGI), the Young Mania Rating Scale (YMRS), the Hamilton Depression Rating Scale (HAM-D) and the Thought and Language Disorder Scale (TALD) in order to assess FTD. The association of FTD with the diagnoses was analyzed by a logistic regression model including the TALD factors and the SCHZ and BPAD groups. Statistically significant differences were not determined between the demographic features, the CGI scores and the TALD objective positive factor scores of the SCHZ and BPAD groups. The objective negative and subjective negative factors (p<0.001 for all) were higher in SCHZ group and the subjective positive factor were significantly higher in BPAD group (p=0.028). In the logistic regression model, the TALD subjective positive factor was associated with BPAD diagnosis, and the objective negative factor was associated with SCHZ diagnosis. In the BPAD group, the TALD total score correlated positively with the manic episode severity, and the scores on the subjective negative and subjective positive factors correlated negatively with disease duration. The study results show that FTD is common to the acute episodes of both SCHZ and BPAD and that assessment of the subjective positive FTD symptoms and objective negative FTD symptoms may be useful to differentiate the acute episode of SCHZ from the BPAD manic episode.

M96. A NEW ASSESSMENT TOOL FOR FORMAL THOUGHT DISORDER IN SCHIZOPHRENIA: DOKUZ EYLUL THOUGHT DISORDER SCALE

BackgroundCurrent scales of formal thought disorder (FTD) in schizophrenia have been shown to hold considerable inadequacies: 1. The concept of FTD is usually limited to positive and negative symptoms of schizophrenia 2. There is no much consideration about pragmatic disturbances. 3. There are significant inconsistencies in measurements of posFTD and negFTD dimensions (eg, merely focusing on the positive dimension); 4. As to the comprehensive scales of posFTD and negFTD, administration or assessment is time-consuming for routine clinical use and they are not user friendly. Besides, some of the FTD scales include the utilization of materials such as pictures, figures, or extended structured interviews to be able to provide speech samples of the patient. Developing a new FTD assessment tool that can be practically applied in clinic might help clinicans in diagnosis, treatment and follow-up. The aim of our study was to develop a new scale for assessment of FTD and evaluate the reliability and validity of this scale. We named our new FTD scale as Dokuz Eylul Thought Disorder Scale (DETDS). The originality of this scale is based on the fact that it involves assessment of pragmatic comprehension as well as positive and negative FTD and it can be administered and scored practically in routine clinical examination.MethodsThis study included 130 patients with schizophrenia and 35 controls. For assessing the reliability of this new scale, internal consistency, test-retest and interrater reliability analyses were conducted. The validity of the scale was assessed with concurrent validity and factor analysis methods.ResultsIn the study, Cronbach’s was 0.86. The new scale has a good test-retest (r=0.83) and interrater (ICC=0.985) reliability. The posFTD subscale of the new scale showed high correlation with the posFTD subscale of the Scale for the Assessment of Positive Symptoms (SAPS) (r=0.95, p<0.001) and negFTD subscale of our scale showed high correlation with the alogia subscale of the Scale for the Assessment of Negative Symptoms (SANS) (r=0.95, p<0.001) and impoverishment of thought subscale of the Thought and Language Index (TLI) (r=0.66, p<0.001). The factor analysis revealed a 3-factor solution which explained 74.6% of the variance: 1. Positive Formal Thought Disorder, 2. Negative Formal Thought Disorder, 3. Pragmatic Comprehension Disorder.DiscussionOur findings showed that DETDS is a reliable and valid scale which can be used in assessing FTD in patients with schizophrenia in routine clinical use. Unlike most scales of FTD that are available in the literature, but similar to SANS, SAPS, and PANSS, it is practical to use because it is based on clinical interview. Another strength of DETDS is that it intensifies the posFTD and negFTD dimensions and scores them hierarchically in terms of severity. The fact that the new scale covers pragmatic comprehension disorders also presents an innovation to the literature.

The Complex Relationship Among Formal Thought Disorders, Neurocognition, and Functioning in Nonacutely Ill Schizophrenia Patients.

The aims of the present study were to 1) evaluate clinical differences between patients suffering from schizophrenia (SZ) with mild versus moderate/severe formal thought disorder (FTD); 2) explore relationships between dimensions of FTD, neuropsychological domains, and global functioning; and 3) compare clinical dimensions of FTD in early and late SZ. One hundred thirty-six individuals with schizophrenia were recruited and evaluated during a nonacute phase of illness. FTD was assessed with the Thought, Language, and Communication Scale. Partial correlations, t-tests, and stepwise regression were undertaken to address the study aims. Patients with moderate/severe FTD performed worse than those with mild FTD for processing speed, reasoning and problem solving, and social cognition, and demonstrated poorer global functioning. Early SZ did not differ from late SZ in terms of negative FTD and difficulty in abstract thinking (DAT). Negative FTD was correlated with reasoning and problem solving; DAT was correlated with social cognition. All clinical dimensions of FTD, regardless of neurocognitive impairment, accounted for a significant amount of variance in global functioning. FTD predicted global functioning, regardless of neurocognitive factors. Due to their stability in different phases of the course of the disease and their strong relationship with other core variables, Neg-FTD and DAT should be investigated as an intermediate phenotype of the illness.

Formal thought disorder is related to aberrations in language-related white matter tracts in patients with schizophrenia

This study examined the hypothesis that a fronto-temporal disconnection in the language network underpins formal thought disorder (FTD) in schizophrenia. Forty-nine patients with a schizophrenia spectrum disorder (27 with mild FTD, 22 with severe FTD) and 26 healthy controls (HC) were included. Overall psychopathology and FTD were assessed by the Positive and Negative Syndrome Scale and the Thought, Language, and Communication scale, respectively. White matter (WM) microstructure was analysed using Tract-Based Spatial Statistics. In patients, severity of overall FTD (TLC Sum Score) was predicted by decreased fractional anisotropy (FA) in the right superior longitudinal fasciculus (SLF), and severity of negative FTD (TLC Emptiness subscale) was predicted by increased FA in the left SLF and arcuate fasciculus (AF). Notably, these results were no longer significant after correction for multiple comparisons. Compared with HC, patients showed lower FA in all the investigated language-related WM tracts as well as across the whole WM skeleton. No difference in FA was found between patients with severe and patients with mild FTD. Our results are compatible with earlier studies reporting impairments in widely spread WM tracts including those related to language processing in patients with schizophrenia.

F146. S-KETAMINE-INDUCED NMDA RECEPTOR BLOCKADE DURING NATURAL SPEECH PRODUCTION AND ITS IMPLICATIONS FOR FORMAL THOUGHT DISORDER IN SCHIZOPHRENIA: A PHARMACO-FMRI STUDY

BackgroundFTD is a dimensional, phenomenologically defined construct, which can clinically be subdivided into positive (pFTD) versus negative (nFTD) as well as objective versus subjective symptom clusters. Structural and functional changes in the lateral temporal language areas have been related to formal thought disorder (FTD) in schizophrenia. Continuous, natural speech production activates the right lateral temporal lobe in schizophrenia, as opposed to the left in healthy subjects. Positive and negative FTD can be elicited in healthy subjects by glutamatergic NMDA blockade with ketamine. It is unclear, whether the glutamate system is related to the reversed hemispheric lateralization during speaking in patients.MethodsIn a double-blind, cross over, placebo-controlled study, 15 healthy, male, right-handed volunteers overtly described 7 pictures for 3 minutes each, while BOLD signal changes were acquired with fMRI. As a measure of linguistic demand, the number of words within 20-second epochs was correlated with BOLD responses.ResultsParticipants developed S-ketamine-induced psychotic symptoms, particularly positive FTD. Ketamine vs. placebo was associated with enhanced neural responses in the right middle and inferior temporal gyri.DiscussionSimilar to a previous fMRI study in schizophrenia patients vs. healthy controls applying the same design, S-ketamine reversed functional lateralization during speech production in healthy subjects. Results demonstrate an association between glutamatergic imbalance, dysactivations in lateral temporal brain areas, and FTD symptom formation. Left superior temporal gyrus (STG) cortical volume is decreased in schizophrenia patients (SZ) with pFTD in structural magnetic resonance imaging (sMRI) studies and shows reversed activation in functional MRI (fMRI) experiments during speech production. pFTDs are related to synaptic rarefication in the glutamate system of the superior and middle lateral temporal cortices.

S-Ketamine-Induced NMDA Receptor Blockade during Natural Speech Production and Its Implications for Formal Thought Disorder in Schizophrenia: A Pharmaco-fMRI Study

Structural and functional changes in the lateral temporal language areas have been related to formal thought disorder (FTD) in schizophrenia. Continuous, natural speech production activates the right lateral temporal lobe in schizophrenia, as opposed to the left in healthy subjects. Positive and negative FTD can be elicited in healthy subjects by glutamatergic NMDA blockade with ketamine. It is unclear whether the glutamate system is related to the reversed hemispheric lateralization during speaking in patients. In a double-blind, crossover, placebo-controlled study, 15 healthy, male, right-handed volunteers overtly described 7 pictures for 3 min each while BOLD signal changes were acquired with fMRI. As a measure of linguistic demand, the number of words within 20 s epochs was correlated with BOLD responses. Participants developed S-ketamine-induced psychotic symptoms, particularly positive FTD. Ketamine vs placebo was associated with enhanced neural responses in the right middle and inferior temporal gyri. Similar to a previous fMRI study in schizophrenia patients vs healthy controls applying the same design, S-ketamine reversed functional lateralization during speech production in healthy subjects. Results demonstrate an association between glutamatergic imbalance, dysactivations in lateral temporal brain areas, and FTD symptom formation.

Formal thought disorder in schizophrenia and bipolar disorder: A systematic review and meta-analysis

Historically, formal thought disorder has been considered as one of the distinctive symptoms of schizophrenia. However, research in last few decades suggested that there is a considerable clinical and neurobiological overlap between schizophrenia and bipolar disorder (BP). We conducted a meta-analysis of studies comparing positive (PTD) and negative formal thought disorder (NTD) in schizophrenia and BP. We included 19 studies comparing 715 schizophrenia and 474 BP patients. In the acute inpatient samples, there was no significant difference in the severity of PTD (d = –0.07, CI = –0.22–0.09) between schizophrenia and BP. In stable patients, schizophrenia was associated with increased PTD compared to BP (d = 1.02, CI = 0.35–1.70). NTD was significantly more severe (d = 0.80, CI = 0.52–0.1.08) in schizophrenia compared to BP. Our findings suggest that PTD is a shared feature of both schizophrenia and BP but persistent PTD or NTD can distinguish subgroups of schizophrenia from BP and schizophrenia patients with better clinical outcomes.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Distinct Neuropsychological Correlates in Positive and Negative Formal Thought Disorder Syndromes: The Thought and Language Disorder Scale in Endogenous Psychoses

The correlation of formal thought disorder (FTD) symptoms and subsyndromes with neuropsychological dimensions is as yet unclear. Evidence for a dysexecutive syndrome and semantic access impairments has been discussed in positive FTD, albeit focusing mostly on patients with schizophrenia. We investigated the correlation of the full range of positive and negative as well as subjective and objective FTD with neuropsychological domains in different patient groups. Patients with ICD-10 schizophrenia (n = 51), depression (n = 51), and bipolar mania (n = 18), as well as healthy subjects (n = 60), were interviewed with the Rating Scale for the Assessment of Objective and Subjective Formal Thought and Language Disorder (TALD) and assessed using a multidimensional neuropsychological test battery (executive function, semantic and lexical verbal fluency, attention, working memory, and abstract thinking). Partial correlation analysis, controlling for age and word knowledge, revealed significant results for the objective positive FTD dimension and executive dysfunctions. Objective negative FTD was associated with deficits in lexico-semantic retrieval, as well as attention and working memory dysfunctions. The results suggest that different neuropsychological substrates correlate with the multidimensional and phenomenologically different FTD syndromes. FTD is a complex, multidimensional syndrome with a variety of neuropsychological impairments, which should be accounted for in future studies investigating the pathogenesis of FTD.

Structural correlates of formal thought disorder in schizophrenia: An ultra-high field multivariate morphometry study

BackgroundPersistent formal thought disorder (FTD) is one of the most characteristic features of schizophrenia. Several neuroimaging studies report spatially distinct neuroanatomical changes in association with FTD. Given that most studies so far have employed a univariate localisation approach that obscures the study of covarying interregional relationships, the present study focussed on the multivariate systemic pattern of anatomical changes that contribute to FTD. MethodsSpeech samples from nineteen medicated clinically stable schizophrenia patients and 20 healthy controls were evaluated for subtle formal thought disorder. Ultra high-field (7T) anatomical Magnetic Resonance Imaging scans were obtained from all subjects. Multivariate morphometric patterns were identified using an independent component approach (source based morphometry). Using multiple regression analysis, the morphometric patterns predicting positive and negative FTD scores were identified. ResultsMorphometric variations in grey matter predicted a substantial portion of inter-individual variance in negative but not positive FTD. A pattern of concomitant striato-insular/precuneus reduction along with frontocingular grey matter increase had a significant association with negative FTD. ConclusionsThese results suggest that concomitant increase and decrease in grey matter occur in association with persistent negative thought disorder in clinically stable individuals with schizophrenia.

The German Translation and Validation of the Scale for the Assessment of Thought, Language and Communication: A Factor Analytic Study

The Scale for the Assessment of Thought, Language and Communication (TLC) represents an instrument for the assessment of formal thought disorder (FTD). The factorial dimensionality of the TLC has yielded ambiguous results for a distinction between positive (e.g. circumstantiality) and negative (e.g. poverty of speech) FTD. The purpose of the current study was to first translate and validate the TLC scale in German. Second, the internal structure was explored in order to identify different FTD dimensions. Two hundred and ten participants (146 patients with ICD-10 diagnoses: depression n = 63, schizophrenia n = 63, mania n = 20; 64 healthy subjects) were interviewed and FTD was rated with the TLC. The principal component analysis of the German TLC version revealed a 3-factor solution, reflecting a disorganized factor, an emptiness factor and a linguistic control factor. The current investigation yielded similar results to those originally reported for the TLC. Thus, a distinction between a positive disorganized, a negative and a semantic word level factor can be supported for the German translation.

Two new scales of formal thought disorder in schizophrenia

Information provided by patients and respective carers may help to understand formal thought disorder (FTD) in schizophrenia. Two scales, one for patients (FTD-patient) and one for carers (FTD-carer), were constructed to assess pragmatics, cognitive, paralinguistic, and non-verbal aspects of communication. In the first scale the patients themselves assess their verbal communication; in the second scale the carer assesses the speech of the respective patient. Both scales exhibited internal reliability and evidence of good test–retest reliability. Higher total scores on both scales (FTD-patient and FTD-carer) were significantly associated with positive FTD, but not with negative FTD. Principal component analysis of the scales yielded a multidimensional structure. It is suggested that FTD in schizophrenia may be associated with a range of deficits (e.g. pragmatics, lexical activation, working memory, sustained attention). These scales, in conjunction with the clinician's assessment, can provide a more comprehensive picture of FTD in schizophrenia, revealing its dimensions and making it possible to establish associations between symptoms of FTD and neuropsychological, neurophysiologic, and neuroimaging data. In addition, they provide service users' and carers' perspectives for the assessment of communication in schizophrenia.