Positive 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.

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.

Neurobiological substrates of the positive formal thought disorder in schizophrenia revealed by seed connectome-based predictive modeling

Formal thought disorder (FTD) is a core symptom cluster of schizophrenia, but its neurobiological substrates remain poorly understood. Here we collected resting-state fMRI data from 276 subjects at seven sites and employed machine-learning to investigate the neurobiological correlates of FTD along positive and negative symptom dimensions in schizophrenia. Three a priori, meta-analytically defined FTD-related brain regions were used as seeds to generate whole-brain resting-state functional connectivity (rsFC) maps, which were then compared between schizophrenia patients and controls. A repeated cross-validation procedure was realized within the patient group to identify clusters whose rsFC patterns to the seeds were repeatedly observed as significantly associated with specific FTD dimensions. These repeatedly identified clusters (i.e., robust clusters) were functionally characterized and the rsFC patterns were used for predictive modeling to investigate predictive capacities for individual FTD dimensional-scores. Compared with controls, differential rsFC was found in patients in fronto-temporo-thalamic regions. Our cross-validation procedure revealed significant clusters only when assessing the seed-to-whole-brain rsFC patterns associated with positive-FTD. RsFC patterns of three fronto-temporal clusters, associated with higher-order cognitive processes (e.g., executive functions), specifically predicted individual positive-FTD scores (p = 0.005), but not other positive symptoms, and the PANSS general psychopathology subscale (p > 0.05). The prediction of positive-FTD was moreover generalized to an independent dataset (p = 0.013). Our study has identified neurobiological correlates of positive FTD in schizophrenia in a network associated with higher-order cognitive functions, suggesting a dysexecutive contribution to FTD in schizophrenia. We regard our findings as robust, as they allow a prediction of individual-level symptom severity.

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.

Cortical thickness and formal thought disorder in schizophrenia: An ultra high-field network-based morphometry study

BackgroundPersistent 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. MethodsWe 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. ResultsPatients 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. ConclusionsThese 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.

Evidence for gesture-speech mismatch detection impairments in schizophrenia

Patients with schizophrenia suffer from impairments in the perception and production of gestures. The extent to which patients can access the semantic association between speech and co-verbal gestures in concrete or abstract/metaphorical meaning contexts is unknown. We investigated 1) how patients differ from controls in gesture matching performance, 2) how performance differs in the context of abstract versus concrete meaning, and 3) whether formal thought disorder (FTD) symptom severity predicts task impairment. Forty-five patients with schizophrenia spectrum disorders (two subgroups, “mild” and “severe”) took part in this study. Participants were presented with video clips, each showing an actor saying a sentence while producing a gesture. Sentences contained either concrete or abstract/metaphorical information, and the accompanying gesture was either semantically related or unrelated to the sentence. Participants indicated via button press whether the gesture matched the content of the verbal utterance. Both patient subgroups demonstrated reduced performance in all comparisons. A significant interaction was found between patient subgroup and sentence abstractness. Task performance was worst for patients with severe positive FTD symptomatology in the abstract condition, while there were no patient subgroup differences in the concrete condition. These data shed new light on gesture-speech mismatch detection impairments in schizophrenia.

Language comprehension and neurocognition independently and concurrently contribute to formal thought disorder severity in schizophrenia

Formal thought disorder (FTD) in schizophrenia is a prevalent symptom that has a significant impact on patients but low remediation options. This is largely due to a still unclear aetiology, where both neurocognitive and language dysfunction have been shown to contribute. Given established relationships between neurocognition and language themselves, this study aimed to examine if language comprehension impairments have a significant effect on FTD severity independent of neurocognition. 54 schizophrenia/schizoaffective disorder patients (M = 43.35, SD = 10.74) completed three measures of language comprehension along with the MATRICS Consensus Cognitive Battery and the D-KEFS Colour Word Interference Test. Symptomatology was assessed using the Positive and Negative Symptom Scale and the Scale for the Assessment of Thought, Language and Communication. Hierarchical linear regression analyses revealed syntactic sentence processing had a significant, and independent, contribution to positive FTD severity above neurocognition, while semantic sentence processing and single word semantic processing did not. The findings support the existence of a specific relationship between language comprehension dysfunction and FTD; however the question of generalisation to all aspects of language processing or FTD types needs further investigation. The establishment of a specific language-related impairment in schizophrenia which contributes independently to FTD severity supports the benefit of language-based remediation approaches for alleviating FTD symptoms and their effects. Clinical, aetiological and nosological implications of the results are discussed.

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.

Affective systems induce formal thought disorder in early-stage psychosis.

Although formal thought disorder (FTD) has been described since early conceptualizations of psychosis, its underlying mechanisms are unclear. Evidence suggests FTD may be influenced by affective and cognitive systems; however, few have examined these relationships-with none focusing on early-stage psychosis (EP). In this study, positive FTD and speech production were measured in sex- and race-matched EP (n = 19) and healthy control (n = 19) groups by assessing "reactivity"-a change in experimental compared with baseline conditions-across baseline, affective, and cognitive conditions. Relationships with functioning were also examined within each group. Three key findings emerged: (a) the EP group displayed large differences in positive FTD and speech production, (b) those with EP exhibited affective reactivity for positive FTD, and (c) positive FTD and affective reactivity were linked with poor real-world functioning in EP and these relationships did not considerably change when controlling for positive symptom (e.g., delusions, hallucinations) severity. Our findings provide preliminary evidence that affective, but not cognitive, systems play a critical role in positive FTD. Affective reactivity, in particular, may aid in predicting those with EP who go on to develop serious social impairments. Future work should focus on whether affective systems differentially influence those at separate points on the psychosis-spectrum in an effort to establish evidence-based treatments for FTD. (PsycINFO Database Record

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.

Formal thought disorder in non-clinical individuals with auditory verbal hallucinations

BackgroundAuditory verbal hallucinations (AVH) and formal thought disorder (FTD) may originate from the same aberration in the language system. The hypothesis of a shared neurobiological basis would be strengthened by the presence of FTD in individuals who frequently experience AVH, but do not meet DSM-IV criteria for a psychotic disorder. MethodsIn this study, FTD was quantified in 40 non-clinical subjects with AVH, in 50 healthy subjects without AVH and in 40 schizophrenia patients with AVH. Recorded speech samples were analysed by one rater who was blind to the presence/absence of AVH and to diagnosis, using the Thought and Language Index. ResultsNegative FTD was barely present in non-clinical subjects with AVH and in healthy controls without AVH. Positive FTD, however, was significantly higher in both groups experiencing AVH than in controls without AVH. Severity of positive FTD did not differ significantly between non-clinical subjects with AVH and schizophrenia patients with AVH. ConclusionNegative FTD (alogia) appears not to be associated with AVH. However, the fact that positive FTD (disorganised speech) in schizophrenia patients with AVH is equally high in non-clinical subjects with AVH indicates that these two symptoms tend to co-occur, which may be suggestive of a shared neurobiological substrate.

Formal Thought Disorder, Neuropsychology and Insight in Schizophrenia

Background: Information provided by patients with schizophrenia and their respective carers is used to study the descriptive psychopathology and neuropsychology of formal thought disorder (FTD). Sampling and Methods: Relatively intellectually preserved schizophrenia patients (n = 31) exhibiting from no to severe positive FTD completed a self-report scale of FTD, a scale of insight as well as several tests of executive and semantic function. The patients’ carers completed another scale of FTD to assess the patients’ speech. Results: FTD as self-reported by patients was significantly associated with the synonyms test performance and severity of the reality distortion dimension. FTD as assessed by a clinician and by the patients’ carers was significantly associated with executive test performance and performance in a test of associative semantics. Overall insight was significantly associated with severity of the reality distortion dimension and graded naming test performance, but was not associated with self-reported FTD or severity of FTD as assessed by the clinician or carers. Conclusions: The self-reported experience of FTD has different clinical and neuropsychological correlates from those of FTD as assessed by clinicians and carers. The assessment of FTD by patients and carers used along with the clinician’s assessment may further the study of this group of symptoms.

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.

Neural correlates of formal thought disorder in schizophrenia: preliminary findings from a functional magnetic resonance imaging study.

Formal thought disorder (FTD) is a core symptom of schizophrenia, but its pathophysiology is little understood. We examined the neural correlates of FTD using functional magnetic resonance imaging. Blood oxygenation level-dependent contrast was measured using functional magnetic resonance imaging while 6 patients with schizophrenia and 6 control subjects spoke about 7 Rorschach inkblots for 3 minutes each. In patients, varying degrees of thought-disordered speech were elicited during each "run." In a within-subject design, the severity of positive FTD was correlated with the level of blood oxygenation level-dependent contrast in the 2 runs that showed the highest variance of FTD in each patient. The severity of positive FTD in patients was negatively correlated (P<.001) with signal changes in the left superior and middle temporal gyri. Positive correlations were evident in the cerebellar vermis, the right caudate body, and the precentral gyrus. The severity of positive FTD was inversely correlated with the level of activity in the Wernicke area, a region implicated in the production of coherent speech. Reduced activity in this area might contribute to the articulation of incoherent speech. Because of the small sample size, these findings should be considered preliminary.

Neuropsychological deficit and symptomatology: Evidence for the heterogeneity of positive symptoms

The positive-negative symptom dichotomy has strongly influenced recent conceptualizations of the nature of schizophrenia. Several studies have now shown that negative symptoms are significantly associated with one another but that intercorrelations among positive symptoms are less strong. A recent factor analytic study by our group on the SANS/SAPS found three factors rather than the two suggested by the positive-negative distinction (Arndt, Alliger & Andreasen, Br J Psychiatry, in press). Negative global scores made up one clear factor but positive globals split, with hallucinations and delusions making up one factor and positive formal thought disorder (PFTD) and bizarre behavior forming another. The present study explores the possibility that positive symptoms may be differentially related to cognitive performance. Data will be reported from three independent samples of schizophrenics (DSM-III criteria) studied at the University of Iowa Psychiatric Hospital. All patients received a comprehensive neuropsychological battery. Severity of negative symptoms was found to be related to a wide range of cognitive deficits including lower IQ scores and poorer performance on measures of attention and memory. Severity of hallucinations and delusions, in contrast, was not significantly related to deficiencies on any measure in the battery. Patients with high ratings on PFTD and bizarre behavior showed a pattern of cognitive disorganization that was less consistent across the three studies than the generalized deficit associated with negative symptoms. The results support previous findings that negative symptoms are associated with cognitive deficit that may reflect underlying brain pathology. Florid positive symptoms show no evidence of association with cognitive impairment. We will discuss the possibility that the cognitive disorganization associated with PFTD and bizarre behavior reflects a neuropathological process independent of that associated with negative symptoms.