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Alarabi M, Burton L, Powell V, Isinger T, Agarwal SM, Remington G. Formal Thought Disorders and Neurocognition in Treatment-Resistant Schizophrenia: Trouble du cours de la pensée et neurocognition dans la schizophrénie réfractaire. CANADIAN JOURNAL OF PSYCHIATRY. REVUE CANADIENNE DE PSYCHIATRIE 2025; 70:229-239. [PMID: 39497431 PMCID: PMC11562935 DOI: 10.1177/07067437241293985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2024]
Abstract
OBJECTIVE Formal thought disorders (FTDs), a core feature of schizophrenia, have been subdivided into positive and negative types, and are clinically assessed by examining speech (objective) or patient introspection (subjective). Despite being associated with poorer treatment response and worse outcomes, FTDs have been understudied in patients with schizophrenia, in particular treatment-resistant schizophrenia (TRS) or schizoaffective disorder. We aimed to explore the relationship between the severity of positive and negative FTDs and neurocognition as well as social/occupational functioning in this clinical subgroup. METHOD This was a retrospective chart review conducted at the Clozapine Clinic at the Centre for Addiction and Mental Health, Toronto, Canada. We reviewed charted standardized assessment of FTDs using the Thought and Language Disorder (TALD) scale, neurocognition using the Brief Cognitive Assessment Tool for Schizophrenia (B-CATS), and functioning using the Social and Occupational Functioning Assessment Scale (SOFAS) between October 2022 and June 2023. Following the original factor structure of the TALD, we computed 4- factor scores that combined positive or negative and objective or subjective FTDs. We then explored the correlation between the scores from each TALD factor and the neurocognition and functioning scores. RESULTS We analysed data for 23 outpatients on clozapine. After the Bonferroni adjustment, total TALD scores, indicating overall severity of FTDs, were strongly and inversely correlated with SOFAS scores (p < 0.001). A strong inverse correlation was found between the objective positive TALD factor and Letter-Number Span verbal working memory scores, r(21) = -0.63, p < 0.001. CONCLUSIONS Our results demonstrate the strong relationship between FTDs, neurocognition, and social/occupational functioning in a sample of TRS outpatients. Within the cognitive domains assessed, verbal working memory impairment had the strongest correlation with positive FTDs, such as derailment or tangentiality. These findings highlight the value of employing standardized psychopathological scales for FTDs in clinical practice.
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Affiliation(s)
- Mohammed Alarabi
- Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Canada
- Department of Psychiatry, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Leah Burton
- Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Canada
| | - Valerie Powell
- Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Canada
| | - Tanner Isinger
- Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Canada
| | - Sri Mahavir Agarwal
- Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Canada
- Institute of Medical Sciences, University of Toronto, Toronto, Canada
- Department of Psychiatry, University of Toronto, Toronto, Canada
| | - Gary Remington
- Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Canada
- Institute of Medical Sciences, University of Toronto, Toronto, Canada
- Department of Psychiatry, University of Toronto, Toronto, Canada
- Department of Psychological Clinical Science, University of Toronto Scarborough, Toronto, Canada
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Alonso-Sanchez MF, Z-Rivera L, Otero M, Portal J, Cavieres Á, Alfaro-Faccio P. Aberrant brain language network in schizophrenia spectrum disorder: a systematic review of its relation to language signs beyond symptoms. Front Psychiatry 2024; 15:1244694. [PMID: 39026525 PMCID: PMC11254709 DOI: 10.3389/fpsyt.2024.1244694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 06/07/2024] [Indexed: 07/20/2024] Open
Abstract
Background Language disturbances are a core feature of schizophrenia, often studied as a formal thought disorder. The neurobiology of language in schizophrenia has been addressed within the same framework, that language and thought are equivalents considering symptoms and not signs. This review aims to systematically examine published peer-reviewed studies that employed neuroimaging techniques to investigate aberrant brain-language networks in individuals with schizophrenia in relation to linguistic signs. Methods We employed a language model for automatic data extraction. We selected our studies according to the PRISMA recommendations, and we conducted the quality assessment of the selected studies according to the STROBE guidance. Results We analyzed the findings from 37 studies, categorizing them based on patient characteristics, brain measures, and language task types. The inferior frontal gyrus (IFG) and superior temporal gyrus (STG) exhibited the most significant differences among these studies and paradigms. Conclusions We propose guidelines for future research in this field based on our analysis. It is crucial to investigate larger networks involved in language processing, and language models with brain metrics must be integrated to enhance our understanding of the relationship between language and brain abnormalities in schizophrenia.
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Affiliation(s)
- María F. Alonso-Sanchez
- Escuela de Fonoaudiología, Centro de Investigación del Desarrollo en Cognición y Lenguaje (CIDCL), Facultad de Medicina, Universidad de Valparaíso, Viña del Mar, Chile
| | - Lucía Z-Rivera
- Advanced Center for Electrical and Electronic Engineering (AC3E), Universidad Técnica Federico Santa María, Valparaíso, Chile
| | - Mónica Otero
- Facultad de Ingeniería, Arquitectura y Diseño, Universidad San Sebastián, Santiago de Chile, Chile
- Centro BASAL Ciencia & Vida, Universidad San Sebastián, Santiago de Chile, Chile
| | - Jorge Portal
- Advanced Center for Electrical and Electronic Engineering (AC3E), Universidad Técnica Federico Santa María, Valparaíso, Chile
- Departamento de Electrónica, Univeridad Técnica Federico Santa María (USM), Valparaíso, Chile
| | - Álvaro Cavieres
- Departamento de Psiquiatría, Escuela de Medicina, Universidad de Valparaíso, Valparaíso, Chile
| | - Pedro Alfaro-Faccio
- Instituto de Literatura y Ciencias del Lenguaje, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile
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Rogers B. Evaluating frontoparietal network topography for diagnostic markers of Alzheimer's disease. Sci Rep 2024; 14:14135. [PMID: 38898075 PMCID: PMC11187222 DOI: 10.1038/s41598-024-64699-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Accepted: 06/12/2024] [Indexed: 06/21/2024] Open
Abstract
Numerous prospective biomarkers are being studied for their ability to diagnose various stages of Alzheimer's disease (AD). High-density electroencephalogram (EEG) methods show promise as an accurate, economical, non-invasive approach to measuring the electrical potentials of brains associated with AD. Event-related potentials (ERPs) may serve as clinically useful biomarkers of AD. Through analysis of secondary data, the present study examined the performance and distribution of N4/P6 ERPs across the frontoparietal network (FPN) using EEG topographic mapping. ERP measures and memory as a function of reaction time (RT) were compared between a group of (n = 63) mild untreated AD patients and a control group of (n = 73) healthy age-matched adults. Based on the literature presented, it was expected that healthy controls would outperform patients in peak amplitude and mean component latency across three parameters of memory when measured at optimal N4 (frontal) and P6 (parietal) locations. It was also predicted that the control group would exhibit neural cohesion through FPN integration during cross-modal tasks, thus demonstrating healthy cognitive functioning consistent with older healthy adults. By targeting select frontal and parietal EEG reference channels based on N4/P6 component time windows and positivity, our findings demonstrated statistically significant group variations between controls and patients in N4/P6 peak amplitudes and latencies during cross-modal testing. Our results also support that the N4 ERP might be stronger than its P6 counterpart as a possible candidate biomarker. We conclude through topographic mapping that FPN integration occurs in healthy controls but is absent in AD patients during cross-modal memory tasks.
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Affiliation(s)
- Bayard Rogers
- Department of Psychology, University of Glasgow, School of Psychology and Neuroscience, Glasgow, Scotland, UK.
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Dornelles E, Correia DT. The Neurobiology of Formal Thought Disorder. Curr Top Med Chem 2024; 24:1773-1783. [PMID: 38243933 DOI: 10.2174/0115680266272521240108102354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2023] [Revised: 11/01/2023] [Accepted: 11/02/2023] [Indexed: 01/22/2024]
Abstract
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.
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Affiliation(s)
- Erik Dornelles
- Clínica Universitária de Psicologia e Psiquiatria, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
- Departamento de Psiquiatria, Centro Hospitalar Universitário Lisboa Norte, Lisboa, Portugal
| | - Diogo Telles Correia
- Clínica Universitária de Psicologia e Psiquiatria, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
- Departamento de Psiquiatria, Centro Hospitalar Universitário Lisboa Norte, Lisboa, Portugal
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Stoyanov D, Paunova R, Dichev J, Kandilarova S, Khorev V, Kurkin S. Functional magnetic resonance imaging study of group independent components underpinning item responses to paranoid-depressive scale. World J Clin Cases 2023; 11:8458-8474. [PMID: 38188204 PMCID: PMC10768520 DOI: 10.12998/wjcc.v11.i36.8458] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 11/10/2023] [Accepted: 12/05/2023] [Indexed: 12/22/2023] Open
Abstract
BACKGROUND Our study expand upon a large body of evidence in the field of neuropsychiatric imaging with cognitive, affective and behavioral tasks, adapted for the functional magnetic resonance imaging (MRI) (fMRI) experimental environment. There is sufficient evidence that common networks underpin activations in task-based fMRI across different mental disorders. AIM To investigate whether there exist specific neural circuits which underpin differential item responses to depressive, paranoid and neutral items (DN) in patients respectively with schizophrenia (SCZ) and major depressive disorder (MDD). METHODS 60 patients were recruited with SCZ and MDD. All patients have been scanned on 3T magnetic resonance tomography platform with functional MRI paradigm, comprised of block design, including blocks with items from diagnostic paranoid (DP), depression specific (DS) and DN from general interest scale. We performed a two-sample t-test between the two groups-SCZ patients and depressive patients. Our purpose was to observe different brain networks which were activated during a specific condition of the task, respectively DS, DP, DN. RESULTS Several significant results are demonstrated in the comparison between SCZ and depressive groups while performing this task. We identified one component that is task-related and independent of condition (shared between all three conditions), composed by regions within the temporal (right superior and middle temporal gyri), frontal (left middle and inferior frontal gyri) and limbic/salience system (right anterior insula). Another component is related to both diagnostic specific conditions (DS and DP) e.g. It is shared between DEP and SCZ, and includes frontal motor/language and parietal areas. One specific component is modulated preferentially by to the DP condition, and is related mainly to prefrontal regions, whereas other two components are significantly modulated with the DS condition and include clusters within the default mode network such as posterior cingulate and precuneus, several occipital areas, including lingual and fusiform gyrus, as well as parahippocampal gyrus. Finally, component 12 appeared to be unique for the neutral condition. In addition, there have been determined circuits across components, which are either common, or distinct in the preferential processing of the sub-scales of the task. CONCLUSION This study has delivers further evidence in support of the model of trans-disciplinary cross-validation in psychiatry.
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Affiliation(s)
- Drozdstoy Stoyanov
- Department of Psychiatry, Medical University Plovdiv, Plovdiv 4000, Bulgaria
| | - Rositsa Paunova
- Research Institute, Medical University, Plovdiv 4002, Bulgaria
| | - Julian Dichev
- Faculty of Medicine, Medical University, Plovdiv 4002, Bulgaria
| | - Sevdalina Kandilarova
- Department of Psychiatry and Medical Psychology, Medical University, Plovdiv 4002, Bulgaria
| | - Vladimir Khorev
- Baltic Center for Artificial Intelligence and Neurotechnology, Immanuel Kant Baltic Federal University, Kaliningrad 236041, Russia
| | - Semen Kurkin
- Baltic Center for Artificial Intelligence and Neurotechnology, Immanuel Kant Baltic Federal University, Kaliningrad 236041, Russia
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Buciuman MO, Oeztuerk OF, Popovic D, Enrico P, Ruef A, Bieler N, Sarisik E, Weiske J, Dong MS, Dwyer DB, Kambeitz-Ilankovic L, Haas SS, Stainton A, Ruhrmann S, Chisholm K, Kambeitz J, Riecher-Rössler A, Upthegrove R, Schultze-Lutter F, Salokangas RKR, Hietala J, Pantelis C, Lencer R, Meisenzahl E, Wood SJ, Brambilla P, Borgwardt S, Falkai P, Antonucci LA, Bertolino A, Liddle P, Koutsouleris N. Structural and Functional Brain Patterns Predict Formal Thought Disorder's Severity and Its Persistence in Recent-Onset Psychosis: Results From the PRONIA Study. BIOLOGICAL PSYCHIATRY. COGNITIVE NEUROSCIENCE AND NEUROIMAGING 2023; 8:1207-1217. [PMID: 37343661 DOI: 10.1016/j.bpsc.2023.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Revised: 06/01/2023] [Accepted: 06/03/2023] [Indexed: 06/23/2023]
Abstract
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.
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Affiliation(s)
- Madalina-Octavia Buciuman
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany; International Max Planck Research School for Translational Psychiatry, Munich, Germany; Max Planck Institute for Psychiatry, Munich, Germany
| | - Oemer Faruk Oeztuerk
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany; International Max Planck Research School for Translational Psychiatry, Munich, Germany; Max Planck Institute for Psychiatry, Munich, Germany
| | - David Popovic
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany; International Max Planck Research School for Translational Psychiatry, Munich, Germany; Max Planck Institute for Psychiatry, Munich, Germany
| | - Paolo Enrico
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Anne Ruef
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany
| | - Nadia Bieler
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany
| | - Elif Sarisik
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany; International Max Planck Research School for Translational Psychiatry, Munich, Germany; Max Planck Institute for Psychiatry, Munich, Germany
| | - Johanna Weiske
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany
| | - Mark Sen Dong
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany
| | - Dominic B Dwyer
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany; Orygen, the National Centre of Excellence for Youth Mental Health, Melbourne, Victoria, Australia
| | - Lana Kambeitz-Ilankovic
- Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany
| | - Shalaila S Haas
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Alexandra Stainton
- Centre for Youth Mental Health, University of Melbourne, Melbourne, Victoria, Australia
| | - Stephan Ruhrmann
- Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany
| | | | - Joseph Kambeitz
- Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany
| | | | - Rachel Upthegrove
- Institute for Mental Health, University of Birmingham, Birmingham, United Kingdom
| | - Frauke Schultze-Lutter
- Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-Universität, Düsseldorf, Germany; Department of Psychology, Faculty of Psychology, Airlangga University, Surabaya, Indonesia; University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland
| | | | - Jarmo Hietala
- Department of Psychiatry, University of Turku, Turku, Finland
| | - Christos Pantelis
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Carlton South, Melbourne, Victoria, Australia; NorthWestern Mental Health, Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia
| | - Rebekka Lencer
- Department of Psychiatry and Psychotherapy, University of Münster, Münster, Germany
| | - Eva Meisenzahl
- Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-Universität, Düsseldorf, Germany
| | - Stephen J Wood
- Orygen, the National Centre of Excellence for Youth Mental Health, Melbourne, Victoria, Australia; Centre for Youth Mental Health, University of Melbourne, Melbourne, Victoria, Australia; School of Psychology, University of Birmingham, Birmingham, United Kingdom
| | - Paolo Brambilla
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy; Department of Neurosciences and Mental Health, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Stefan Borgwardt
- Department of Psychiatry and Psychotherapy, University of Lübeck, Lüebeck, Germany
| | - Peter Falkai
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany; Max Planck Institute for Psychiatry, Munich, Germany
| | - Linda A Antonucci
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany; Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro", Bari, Italy
| | - Alessandro Bertolino
- Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro", Bari, Italy; Department of Translational Biomedicine and Neuroscience (DiBraiN) - University of Bari "Aldo Moro," Bari, Italy
| | - Peter Liddle
- Division of Mental Health and Clinical Neuroscience, Institute of Mental Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom
| | - Nikolaos Koutsouleris
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany; Max Planck Institute for Psychiatry, Munich, Germany; Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
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Barattieri di San Pietro C, Barbieri E, Marelli M, de Girolamo G, Luzzatti C. Processing Argument Structure and Syntactic Complexity in People with Schizophrenia Spectrum Disorders. JOURNAL OF COMMUNICATION DISORDERS 2022; 96:106182. [PMID: 35065337 DOI: 10.1016/j.jcomdis.2022.106182] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 12/14/2021] [Accepted: 01/05/2022] [Indexed: 06/14/2023]
Abstract
INTRODUCTION Deficits in language comprehension and production have been repeatedly observed in Schizophrenia Spectrum Disorders (SSD). However, the characterization of the language profile of this population is far from complete, and the relationship between language deficits, impaired thinking and cognitive functions is widely debated. OBJECTIVE The aims of the present study were to assess production and comprehension of verbs with different argument structures, as well as production and comprehension of sentences with canonical and non-canonical word order in people with SSD. In addition, the study investigated the relationship between language deficits and cognitive functions. METHODS Thirty-four participants with a diagnosis of SSD and a group of healthy control participants (HC) were recruited and evaluated using the Italian version of the Northwestern Assessment of Verbs and Sentences (NAVS, Cho-Reyes & Thompson, 2012; Barbieri et al., 2019). RESULTS Results showed that participants with SSD were impaired - compared to HC - on both verb and sentence production, as well as on comprehension of syntactically complex (but not simple) sentences. While verb production was equally affected by verb-argument structure complexity in both SSD and HC, sentence comprehension was disproportionately more affected by syntactic complexity in SSD than in HC. In addition, in the SSD group, verb production deficits were predicted by performance on a measure of visual attention, while sentence production and comprehension deficits were explained by performance on measures of executive functions and working memory, respectively. DISCUSSION Our findings support the hypothesis that language deficits in SSD may be one aspect of a more generalized, multi-domain, cognitive impairment, and are consistent with previous findings pointing to reduced inter- and intra-hemispheric connectivity as a possible substrate for such deficits. The study provides a systematic characterization of lexical and syntactic deficits in SSD and demonstrates that psycholinguistically-based assessment tools may be able to capture language deficits in this population.
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Affiliation(s)
| | - Elena Barbieri
- Department of Communication Sciences and Disorders, Northwestern University, Evanston, IL, USA
| | - Marco Marelli
- Department of Psychology, University of Milano-Bicocca, Milan, Italy; Milan Center for Neuroscience, NeuroMI
| | - Giovanni de Girolamo
- Psychiatric Epidemiology and Evaluation Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
| | - Claudio Luzzatti
- Department of Psychology, University of Milano-Bicocca, Milan, Italy; Milan Center for Neuroscience, NeuroMI
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Application of Mass Multivariate Analysis on Neuroimaging Data Sets for Precision Diagnostics of Depression. Diagnostics (Basel) 2022; 12:diagnostics12020469. [PMID: 35204560 PMCID: PMC8871050 DOI: 10.3390/diagnostics12020469] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 01/18/2022] [Accepted: 02/08/2022] [Indexed: 01/29/2023] Open
Abstract
We used the Mass Multivariate Method on structural, resting-state, and task-related fMRI data from two groups of patients with schizophrenia and depression in order to define several regions of significant relevance to the differential diagnosis of those conditions. The regions included the left planum polare (PP), the left opercular part of the inferior frontal gyrus (OpIFG), the medial orbital gyrus (MOrG), the posterior insula (PIns), and the parahippocampal gyrus (PHG). This study delivered evidence that a multimodal neuroimaging approach can potentially enhance the validity of psychiatric diagnoses. Structural, resting-state, or task-related functional MRI modalities cannot provide independent biomarkers. Further studies need to consider and implement a model of incremental validity combining clinical measures with different neuroimaging modalities to discriminate depressive disorders from schizophrenia. Biological signatures of disease on the level of neuroimaging are more likely to underpin broader nosological entities in psychiatry.
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Stein F, Buckenmayer E, Brosch K, Meller T, Schmitt S, Ringwald KG, Pfarr JK, Steinsträter O, Enneking V, Grotegerd D, Heindel W, Meinert S, Leehr EJ, Lemke H, Thiel K, Waltemate L, Winter A, Hahn T, Dannlowski U, Jansen A, Nenadić I, Krug A, Kircher T. Dimensions of Formal Thought Disorder and Their Relation to Gray- and White Matter Brain Structure in Affective and Psychotic Disorders. Schizophr Bull 2022; 48:902-911. [PMID: 35064667 PMCID: PMC9212109 DOI: 10.1093/schbul/sbac002] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
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.
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Affiliation(s)
- Frederike Stein
- To whom correspondence should be addressed; Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany; tel: +49-6421-58 63831, fax: +49-6421-58 65197, e-mail:
| | - Elena Buckenmayer
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
| | - Katharina Brosch
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany,Center for Mind, Brain and Behavior, University of Marburg, Marburg, Germany
| | - Tina Meller
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany,Center for Mind, Brain and Behavior, University of Marburg, Marburg, Germany
| | - Simon Schmitt
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany,Center for Mind, Brain and Behavior, University of Marburg, Marburg, Germany,Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany
| | - Kai Gustav Ringwald
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany,Center for Mind, Brain and Behavior, University of Marburg, Marburg, Germany
| | - Julia Katharina Pfarr
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany,Center for Mind, Brain and Behavior, University of Marburg, Marburg, Germany
| | - Olaf Steinsträter
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany,Center for Mind, Brain and Behavior, University of Marburg, Marburg, Germany,Core-Facility Brainimaging, Faculty of Medicine, Philipps-University Marburg, Marburg, Germany
| | - Verena Enneking
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
| | - Dominik Grotegerd
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
| | - Walter Heindel
- Department of Radiology, University of Münster, Münster, Germany
| | - Susanne Meinert
- Institute for Translational Psychiatry, University of Münster, Münster, Germany,Institute for Translational Neuroscience, University of Münster, Münster, Germany
| | - Elisabeth J Leehr
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
| | - Hannah Lemke
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
| | - Katharina Thiel
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
| | - Lena Waltemate
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
| | - Alexandra Winter
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
| | - Tim Hahn
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
| | - Udo Dannlowski
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
| | - Andreas Jansen
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany,Center for Mind, Brain and Behavior, University of Marburg, Marburg, Germany,Core-Facility Brainimaging, Faculty of Medicine, Philipps-University Marburg, Marburg, Germany
| | - Igor Nenadić
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany,Center for Mind, Brain and Behavior, University of Marburg, Marburg, Germany
| | - Axel Krug
- Department of Psychiatry und Psychotherapy, University of Bonn, Bonn, Germany
| | - Tilo Kircher
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany,Center for Mind, Brain and Behavior, University of Marburg, Marburg, Germany
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10
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Chen S, Tang Y, Fan X, Qiao Y, Wang J, Wen H, Wang W, Wang H, Yang F, Sheng J. The role of white matter abnormality in the left anterior corona radiata: In relation to formal thought disorder in patients with schizophrenia. Psychiatry Res 2022; 307:114302. [PMID: 34890908 DOI: 10.1016/j.psychres.2021.114302] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Revised: 11/17/2021] [Accepted: 11/19/2021] [Indexed: 12/27/2022]
Abstract
White matter abnormality has been widely reported in patients with schizophrenia (Sz). However, few studies have focused on the relationship between the white matter deficit and formal thought disorder (FTD). Moreover, the role of genetic high risk in FTD-related white matter deficit remains unclear. The present study recruited 46 Sz patients, 18 unaffected first-degree relatives of Sz patients, and 29 healthy controls. There was a widespread fractional anisotropy (FA) reduction in Sz. In addition, reduced FA in the left anterior corona radiata was related to more severe FTD symptoms in Sz. However, the genetic high-risk group only showed lower mean FA in the left anterior limb of the internal capsule than healthy controls. Our findings suggest that abnormality in the left anterior corona radiata may only occur in Sz but not in the genetic high-risk group. Such an abnormality might be associated with the severity of FTD symptoms. Meanwhile, genetic vulnerability may contribute to the abnormality in the left anterior limb of the internal capsule. Better analytical methods are needed to validate our results.
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Affiliation(s)
- Shan Chen
- Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China
| | - Yingying Tang
- Shanghai Key Laboratory of Psychotic Disorders,Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; Department of EEG and Imaging, Shanghai Mental Health Center, Shanghai JiaoTong University School of Medicine, Shanghai 200030, China
| | - Xiaoduo Fan
- UMass Memorial Health Care & University of Massachusetts Medical School, Worcester, MA 01605, United States
| | - Yi Qiao
- Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China
| | - Jijun Wang
- Shanghai Key Laboratory of Psychotic Disorders,Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; Department of EEG and Imaging, Shanghai Mental Health Center, Shanghai JiaoTong University School of Medicine, Shanghai 200030, China
| | - Hun Wen
- Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China
| | - Wenzheng Wang
- Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China
| | - Hongyan Wang
- Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China
| | - Fuzhong Yang
- Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China.
| | - Jianhua Sheng
- Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China.
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11
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Palaniyappan L. Dissecting the neurobiology of linguistic disorganisation and impoverishment in schizophrenia. Semin Cell Dev Biol 2021; 129:47-60. [PMID: 34507903 DOI: 10.1016/j.semcdb.2021.08.015] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 08/13/2021] [Accepted: 05/06/2021] [Indexed: 12/16/2022]
Abstract
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.
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Affiliation(s)
- Lena Palaniyappan
- Department of Psychiatry,University of Western Ontario, London, Ontario, Canada; Robarts Research Institute,University of Western Ontario, London, Ontario, Canada; Lawson Health Research Institute, London, Ontario, Canada.
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12
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Schultze-Lutter F, Schimmelmann BG, Flückiger R, Michel C. Effects of age and sex on clinical high-risk for psychosis in the community. World J Psychiatry 2020; 10:101-124. [PMID: 32477906 PMCID: PMC7243619 DOI: 10.5498/wjp.v10.i5.101] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Revised: 03/23/2020] [Accepted: 03/30/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Recent reports of both heightened prevalence rates and limited clinical relevance of clinical high-risk (CHR) criteria and their relevant symptoms in children and adolescents indicate an important role of neurodevelopment in the early detection of psychoses. Furthermore, sex effects in CHR symptoms have been reported, though studies were inconclusive. As sex also impacts on neurodevelopment, we expected that sex might have an additional contribution to age in the prevalence and clinical relevance of CHR symptoms and criteria.
AIM To investigate age and sex effects on CHR criteria and symptoms and their association with psychosocial impairment and mental disorder.
METHODS In this cross-sectional cohort study, n = 2916 8- to 40-year-olds, randomly drawn from the population register of the Swiss canton Bern, were assessed in semi-structured interviews by phone or face-to-face for CHR symptoms and criteria using the Structured Interview for Psychosis-Risk Syndromes and the Schizophrenia Proneness Instrument in its child and youth, and adult version, respectively. Furthermore, social and occupational functioning and DSM-IV axis I disorders were assessed. Simple and interaction effects of age and sex on CHR symptoms and criteria, and interaction effects of age, sex, and CHR symptoms and criteria on presentation of functional impairment and of non-psychotic disorder were investigated using logistic regression analyses.
RESULTS Altogether, 542 (18.6%) participants reported any CHR symptom; of these, 261 (9.0%) participants reported any one of the 11 criteria relevant cognitive and perceptual basic symptoms, and 381 (13.1%) any one of the five attenuated or transient psychotic symptoms (attenuated psychotic symptoms/brief intermittent psychotic symptoms). Fewer participants met any one of the CHR criteria (n = 82, 2.8%) or any one of the three recently recommended CHR criteria (n = 38, 1.3%). Both age and sex were significantly (P < 0.05) associated with CHR symptoms and criteria, mostly by younger age and female sex. Though slightly differing between symptom groups, age thresholds were detected around the turn from adolescence to adulthood; they were highest for cognitive basic symptoms and CHR criteria. With the exception of the infrequent speech disorganization attenuated psychotic symptom, the interaction of age with CHR symptoms and criteria predicted functional impairment; whereas, independent of each other, sex and CHR symptoms mostly predicted mental disorders.
CONCLUSION Age and sex differentially impact on CHR symptoms and criteria; these differences may support better understanding of causal pathways. Thus, future CHR studies should consider effects of sex and age.
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Affiliation(s)
- Frauke Schultze-Lutter
- Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine University, Düsseldorf 40692, Germany
| | - Benno G Schimmelmann
- University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern 3000, Switzerland
- University Hospital of Child and Adolescent Psychiatry, University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Rahel Flückiger
- University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern 3000, Switzerland
| | - Chantal Michel
- University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern 3000, Switzerland
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13
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Schoretsanitis G, Stegmayer K, Razavi N, Federspiel A, Müller TJ, Horn H, Wiest R, Strik W, Walther S. Inferior frontal gyrus gray matter volume is associated with aggressive behavior in schizophrenia spectrum disorders. Psychiatry Res Neuroimaging 2019; 290:14-21. [PMID: 31254799 DOI: 10.1016/j.pscychresns.2019.06.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2018] [Revised: 06/19/2019] [Accepted: 06/21/2019] [Indexed: 12/19/2022]
Abstract
We aimed to assess potential gray matter (GM) alterations for aggressive patterns of behavior in a sample of in- and outpatients with schizophrenia spectrum disorders. Eighty-four patients previously participating in brain volumetric studies were included. Aggression was assessed using the Modified Overt Aggression Scales (MOAS) based upon review of clinical records of the hospital register. Multiple regression analyses for total MOAS and each MOAS subscale separately were conducted correcting for age, sex, history of addiction, chlorpromazine equivalents, illness duration, and total intracranial volume. Significant effects were reported in two cases; the total MOAS scores and MOAS verbal aggression scores were associated with GM volume in left inferior frontal gyrus. From the demographic/clinical characteristics, only the number of episodes correlated with the subscales and the total MOAS scores. Our results highlight the role of GM volume in left inferior frontal gyri in patients with history of aggression. This evidence ties in well with previous data reporting involvement of these regions in response control and semantic networks.
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Affiliation(s)
- Georgios Schoretsanitis
- University of Bern, University Hospital of Psychiatry, Bern, Switzerland; Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA; Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA.
| | | | - Nadja Razavi
- University of Bern, University Hospital of Psychiatry, Bern, Switzerland
| | - Andrea Federspiel
- University of Bern, University Hospital of Psychiatry, Bern, Switzerland
| | - Thomas J Müller
- University of Bern, University Hospital of Psychiatry, Bern, Switzerland; Privatklinik Meiringen, Meiringen, Switzerland
| | - Helge Horn
- Institute of Psychiatry and Psychotherapy Bern, Switzerland; University of Bern, University Hospital of Psychiatry, Bern, Switzerland
| | - Roland Wiest
- Institute of Neuroradiology, Inselspital, Bern, Switzerland
| | - Werner Strik
- University of Bern, University Hospital of Psychiatry, Bern, Switzerland
| | - Sebastian Walther
- University of Bern, University Hospital of Psychiatry, Bern, Switzerland
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14
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Cavelti M, Winkelbeiner S, Federspiel A, Walther S, Stegmayer K, Giezendanner S, Laimböck K, Dierks T, Strik W, Horn H, Homan P. Formal thought disorder is related to aberrations in language-related white matter tracts in patients with schizophrenia. Psychiatry Res Neuroimaging 2018; 279:40-50. [PMID: 29861197 DOI: 10.1016/j.pscychresns.2018.05.011] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Revised: 04/20/2018] [Accepted: 05/21/2018] [Indexed: 12/14/2022]
Abstract
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.
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Affiliation(s)
- Marialuisa Cavelti
- Translational Research Center, University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern 60 3000 Switzerland; Orygen, The National Centre of Excellence in Youth Mental Health & Centre for Youth Mental Health, University of Melbourne, Parkville, VIC 3052, Australia.
| | - Stephanie Winkelbeiner
- Translational Research Center, University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern 60 3000 Switzerland
| | - Andrea Federspiel
- Translational Research Center, University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern 60 3000 Switzerland
| | - Sebastian Walther
- Translational Research Center, University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern 60 3000 Switzerland
| | - Katharina Stegmayer
- Translational Research Center, University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern 60 3000 Switzerland
| | | | - Karin Laimböck
- Translational Research Center, University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern 60 3000 Switzerland
| | - Thomas Dierks
- Translational Research Center, University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern 60 3000 Switzerland
| | - Werner Strik
- Translational Research Center, University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern 60 3000 Switzerland
| | - Helge Horn
- Translational Research Center, University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern 60 3000 Switzerland; Institute for Psychiatry and Psychotherapy Bern, Waisenhausplatz 25, Bern 3011, Switzerland
| | - Philipp Homan
- Translational Research Center, University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern 60 3000 Switzerland; Center for Psychiatric Neuroscience, The Feinstein Institute for Medical Research, Hofstra Northwell School of Medicine, New York, NY, USA
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15
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Cavelti M, Kircher T, Nagels A, Strik W, Homan P. Is formal thought disorder in schizophrenia related to structural and functional aberrations in the language network? A systematic review of neuroimaging findings. Schizophr Res 2018; 199:2-16. [PMID: 29510928 DOI: 10.1016/j.schres.2018.02.051] [Citation(s) in RCA: 73] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2017] [Revised: 12/20/2017] [Accepted: 02/25/2018] [Indexed: 12/29/2022]
Abstract
Formal thought disorder (FTD) is a core feature of schizophrenia, a marker of illness severity and a predictor of outcome. The underlying neural mechanisms are still a matter of debate. This study aimed at 1) reviewing the literature on the neural correlates of FTD in schizophrenia, and 2) testing the hypothesis that FTD correlates with structural and functional aberrations in the language network. Medline, PsychInfo, and Embase were searched for neuroimaging studies, which applied a clinical measure to assess FTD in adults with schizophrenia and were published in English or German in peer-reviewed journals until December 2016. Of 412 articles identified, 61 studies were included in the review. Volumetric studies reported bilateral grey matter deficits (L > R) to be associated with FTD in the inferior frontal gyrus, the superior temporal gyrus and the inferior parietal lobe. The same regions showed hyperactivity in resting state functional magnetic resonance imaging (fMRI) studies and both hyper- and hypoactivity in fMRI studies that employed semantic processing or free speech production tasks. Diffusion tensor imaging studies demonstrated white matter aberrations in fibre tracts that connect the frontal and temporo-parietal regions. FTD in schizophrenia was found to be associated with structural and functional aberrations in the language network. However, there are studies that did not find an association between FTD and neural aberrations of the language network and regions not included in the language network have been associated with FTD. Thus, future research is needed to clarify the specificity of the language network for FTD in schizophrenia.
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Affiliation(s)
- Marialuisa Cavelti
- Translational Research Center, University Hospital of Psychiatry and Psychotherapy, University of Bern, 3000 Bern 60, Switzerland; Orygen, The National Centre of Excellence in Youth Mental Health & Centre for Youth Mental Health, University of Melbourne, Parkville, Victoria 3052, Australia
| | - Tilo Kircher
- Department of Psychiatry and Psychotherapy, University of Marburg, Rudolf-Bultmann-Strasse 8, 35039 Marburg, Germany
| | - Arne Nagels
- Johannes Gutenberg University, General Linguistics, 55099 Mainz, Germany
| | - Werner Strik
- Translational Research Center, University Hospital of Psychiatry and Psychotherapy, University of Bern, 3000 Bern 60, Switzerland
| | - Philipp Homan
- Translational Research Center, University Hospital of Psychiatry and Psychotherapy, University of Bern, 3000 Bern 60, Switzerland; Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Hofstra Northwell School of Medicine, 350 Community Drive, Manhasset, NY 11030, USA.
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16
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Sumner PJ, Bell IH, Rossell SL. A systematic review of task-based functional neuroimaging studies investigating language, semantic and executive processes in thought disorder. Neurosci Biobehav Rev 2018; 94:59-75. [PMID: 30142368 DOI: 10.1016/j.neubiorev.2018.08.005] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Revised: 05/16/2018] [Accepted: 08/09/2018] [Indexed: 01/30/2023]
Abstract
The aim of the current systematic review was to synthesise the research that has investigated thought disorder (TD) using task-based functional neuroimaging techniques to target executive, language, or semantic functions. Thirty-five pertinent studies were identified from January 1990 to August 2016. Functional correlates of TD included the superior and middle temporal, fusiform, and inferior frontal gyri bilaterally, as well as the left and right cingulate cortex, the right caudate nucleus, and the cerebellum. TD-related increases and decreases in activation were both evident in most of these regions. However, the specificity of these correlates from general clinical and cognitive influences is unknown. The cortical regions implicated overlap with those thought to contribute to language and semantic systems. Cortico-striatal circuitry may also play a role in some aspects of TD through aberrant salience representation and inappropriate attentional prioritisation. To advance the field further, greater integration across structural, functional, and behavioural measures is required, in addition to non-unitary considerations of TD.
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Affiliation(s)
- Philip J Sumner
- Centre for Mental Health, Faculty of Health, Arts and Design, Swinburne University of Technology, Melbourne, VIC, Australia; Monash Alfred Psychiatry Research Centre (MAPrc), Central Clinical School, Monash University and The Alfred Hospital, Melbourne, VIC, Australia.
| | - Imogen H Bell
- Centre for Mental Health, Faculty of Health, Arts and Design, Swinburne University of Technology, Melbourne, VIC, Australia; Monash Alfred Psychiatry Research Centre (MAPrc), Central Clinical School, Monash University and The Alfred Hospital, Melbourne, VIC, Australia
| | - Susan L Rossell
- Centre for Mental Health, Faculty of Health, Arts and Design, Swinburne University of Technology, Melbourne, VIC, Australia; Monash Alfred Psychiatry Research Centre (MAPrc), Central Clinical School, Monash University and The Alfred Hospital, Melbourne, VIC, Australia; Psychiatry, St Vincent's Hospital, Melbourne, VIC, Australia
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17
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Strik W, Stegmayer K, Walther S, Dierks T. Systems Neuroscience of Psychosis: Mapping Schizophrenia Symptoms onto Brain Systems. Neuropsychobiology 2018; 75:100-116. [PMID: 29258073 DOI: 10.1159/000485221] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Schizophrenia research has been in a deadlock for many decades. Despite important advances in clinical treatment, there are still major concerns regarding long-term psychosocial reintegration and disease management, biological heterogeneity, unsatisfactory predictors of individual course and treatment strategies, and a confusing variety of controversial theories about its etiology and pathophysiological mechanisms. In the present perspective on schizophrenia research, we first discuss a methodological pitfall in contemporary schizophrenia research inherent in the attempt to link mental phenomena with the brain: we claim that the time-honored phenomenological method of defining mental symptoms should not be contaminated with the naturalistic approach of modern neuroscience. We then describe our Systems Neuroscience of Psychosis (SyNoPsis) project, which aims to overcome this intrinsic problem of psychiatric research. Considering schizophrenia primarily as a disorder of interindividual communication, we developed a neurobiologically informed semiotics of psychotic disorders, as well as an operational clinical rating scale. The novel psychopathology allows disentangling the clinical manifestations of schizophrenia into behavioral domains matching the functions of three well-described higher-order corticobasal brain systems involved in interindividual human communication, namely, the limbic, associative, and motor loops, including their corticocortical sensorimotor connections. The results of several empirical studies support the hypothesis that the proposed three-dimensional symptom structure, segregated into the affective, the language, and the motor domain, can be specifically mapped onto structural and functional abnormalities of the respective brain systems. New pathophysiological hypotheses derived from this brain system-oriented approach have helped to develop and improve novel treatment strategies with noninvasive brain stimulation and practicable clinical parameters. In clinical practice, the novel psychopathology allows confining the communication deficits of the individual patient, shifting attention from the symptoms to the intact resources. We have studied this approach and observed important advantages for therapeutic alliances, personalized treatment, and de-escalation strategies. Future studies will further conjoin clinical definitions of psychotic symptoms with brain structures and functions, and disentangle structural and functional deficit patterns within these systems to identify neurobiologically distinct subsyndromes. Neurobiologically homogeneous patient groups may provide new momentum for treatment research. Finally, lessons learned from schizophrenia research may contribute to developing a comprehensive perspective on human experience and behavior that integrates methodologically distinct, but internally consistent, insights from humanities and neuroscience.
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18
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Kircher T, Bröhl H, Meier F, Engelen J. Formal thought disorders: from phenomenology to neurobiology. Lancet Psychiatry 2018; 5:515-526. [PMID: 29678679 DOI: 10.1016/s2215-0366(18)30059-2] [Citation(s) in RCA: 92] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Revised: 11/27/2017] [Accepted: 12/07/2017] [Indexed: 01/15/2023]
Abstract
Formal thought disorder (FTD) is present in most psychiatric disorders and in some healthy individuals. In this Review, we present a comprehensive, integrative, and multilevel account of what is known about FTD, covering genetic, cellular, and neurotransmitter effects, environmental influences, experimental psychology and neuropsychology, brain imaging, phenomenology, linguistics, and treatment. FTD is a dimensional, phenomenologically defined construct, which can be clinically subdivided into positive versus negative and objective versus subjective symptom clusters. Because FTDs have been traditionally linked to schizophrenia, studies in other diagnoses are scarce. Aetiologically, FTD is the only symptom under genetic influence in schizophrenia as shown in linkage studies, but familial communication patterns (allusive thinking) have also been associated with the condition. Positive FTDs are related to synaptic rarefication in the glutamate system of the superior and middle lateral temporal cortices. Cortical volume of the left superior temporal gyrus is decreased in patients with schizophrenia who have positive FTD in structural MRI studies and shows reversed hemispheric (right more than left) activation in functional MRI experiments during speech production. Semantic network dysfunction in positive FTD has been demonstrated in experiments of indirect semantic hyperpriming (reaction time). In acute positive FTD, antipsychotics are effective, but a subgroup of patients have treatment-resistant, chronic, positive or negative FTD. Specific psychotherapy as treatment for FTD has not yet been developed. With this solid data on the pathogenesis of FTD, we can now implement clinical studies to treat this condition.
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Affiliation(s)
- Tilo Kircher
- Department of Psychiatry and Psychotherapy, Marburg University, Marburg, Germany.
| | - Henrike Bröhl
- Department of Psychiatry and Psychotherapy, Marburg University, Marburg, Germany
| | - Felicitas Meier
- Department of Psychiatry and Psychotherapy, Marburg University, Marburg, Germany
| | - Jennifer Engelen
- Department of Psychiatry and Psychotherapy, Marburg University, Marburg, Germany
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19
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Nagels A, Cabanis M, Oppel A, Kirner-Veselinovic A, Schales C, Kircher T. S-Ketamine-Induced NMDA Receptor Blockade during Natural Speech Production and Its Implications for Formal Thought Disorder in Schizophrenia: A Pharmaco-fMRI Study. Neuropsychopharmacology 2018; 43:1324-1333. [PMID: 29105665 PMCID: PMC5916352 DOI: 10.1038/npp.2017.270] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2017] [Revised: 09/14/2017] [Accepted: 10/16/2017] [Indexed: 02/04/2023]
Abstract
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.
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Affiliation(s)
- Arne Nagels
- Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany
- Department of English and Linguistics, Johannes Gutenberg University, Mainz, Germany
| | - Maurice Cabanis
- Department of Psychiatry and Psychotherapy, Social Neuroscience Lab, University of Lübeck, Lübeck, Germany
- Clinic for Addiction Medicine and Addictive Behaviour, Centre for Mental Health, Stuttgart, Germany
| | - Andrea Oppel
- Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany
| | | | - Christian Schales
- Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany
| | - Tilo Kircher
- Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany
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White matter correlates of the disorganized speech dimension in schizophrenia. Eur Arch Psychiatry Clin Neurosci 2018; 268:99-104. [PMID: 28032254 DOI: 10.1007/s00406-016-0753-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2016] [Accepted: 12/13/2016] [Indexed: 01/15/2023]
Abstract
Disorganized speech is related to functional abnormalities in schizophrenia. To test the association between formal thought disorders (FTDs) and white matter microstructure, we applied a behavioral rating and diffusion tensor imaging in 61 patients with schizophrenia spectrum disorders. The Bern Psychopathology Scale was used to rate the dimension of language abnormalities ranging from negative FTDs, basically unaltered speech, to positive FTDs. Tract-based spatial statistics indicated increased fractional anisotropy in left hemispheric pathways of the language system in patients with negative FTDs. Thus, altered white matter properties in relevant fiber tracts may represent vulnerability to specific formal thought disorders.
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21
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Wigand ME, Lang FU, Reichhardt L, Schulze TG, Walther S, Becker T, Jäger M. Severe clinical events in 100 patients with schizophrenia: a retrospective clinical description using a system-specific psychopathological approach. Nord J Psychiatry 2018; 72:1-8. [PMID: 28846054 DOI: 10.1080/08039488.2017.1368701] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Catatonic states and numerous other severe clinical events can complicate the course of schizophrenia. Whether these severe courses are associated with particular system-specific symptom dimensions remain unclear. Aim is to assess the frequency of severe clinical events in a clinical population and to investigate the association of these events with sociodemographic data and system-specific psychopathology, combining qualitative and quantitative data. We performed a comprehensive retrospective description of a well-described and geographically stable sample of 100 patients with schizophrenia or schizoaffective disorder and linked severe clinical events with sociodemographic data at inclusion into the study (as indicators of social functioning) and symptoms at first admission, classified with the Bern Psychopathology Scale (BPS). We found 12 mentions of catatonic stupor or excitement, 45 of suicide attempts, 26 of suicidality, 18 of deliberate self-harm, 18 of self-threatening behaviour other than deliberate self-harm, 34 of violence against other persons, 18 of violence against objects and six of sexual harassment. Disinhibited language on first admission seemed to be a protective factor against suicidality and disinhibited motor behaviour seemed to predict self-threatening and violent behaviour. Catatonia and violence in particular seemed to be socially disabling. This exploratory study showed that the BPS is a promising instrument and might represent a system-specific approach in identifying patients at risk for severe sequelae of schizophrenia. This will have to be tested in future prospective studies.
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Affiliation(s)
- Moritz E Wigand
- a Department of Psychiatry and Psychotherapy II , Ulm University , Günzburg , Germany
| | - Fabian U Lang
- a Department of Psychiatry and Psychotherapy II , Ulm University , Günzburg , Germany.,b Medical Practice for Psychiatry and Psychotherapy Lang , Gersthofen , Germany
| | - Lea Reichhardt
- a Department of Psychiatry and Psychotherapy II , Ulm University , Günzburg , Germany
| | - Thomas G Schulze
- c Institute of Psychiatric Phenomics and Genomics , LMU München , Munich , Germany
| | - Sebastian Walther
- d Translational Research Center , University Hospital of Psychiatry , Bern , Switzerland
| | - Thomas Becker
- a Department of Psychiatry and Psychotherapy II , Ulm University , Günzburg , Germany
| | - Markus Jäger
- a Department of Psychiatry and Psychotherapy II , Ulm University , Günzburg , Germany.,e Department of Psychiatry, Psychosomatic and Psychotherapy , Bezirkskrankenhaus Kempten , Kempten , Germany
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22
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Egeland J, Holmen TL, Bang-Kittilsen G, Bigseth TT, Engh JA. Category fluency in schizophrenia: opposing effects of negative and positive symptoms? Cogn Neuropsychiatry 2018; 23:28-42. [PMID: 29279010 DOI: 10.1080/13546805.2017.1418306] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
INTRODUCTION Category fluency is associated with speed-, executive- and semantic impairments in schizphrenia. It has traditionally been linked to negative symptoms, whereas the relation to positive symptoms is mixed. Associations to the consensus negative, positive and disorganisation factors have not been analysed before. METHODS Animal fluency was administered to 81 patients with schizophrenia. Measures of overall performance and applied strategies were analysed in relation to the Wallwork five-factor PANSS-model. RESULTS Negative and disorganisation symptoms were negatively related to overall fluency performance. Positive symptoms were positively related to overall performance when controlling for disorganisation symptoms. Negative symptoms were related to fewer switches, less repetitions, less single animals intrusions, and both less rare and common animals. Positive symptoms were related to more effective retrieval of sub-category exemplars following a sub-category title, whereas there were no relation between symptoms and exemplars when the title was not retrieved. The Beta values of negative and positive symptoms were opposite. CONCLUSION This is the first study showing that positive symptoms are related to increased fluency performance when disorganisation is controlled for. Like previous studies, negative symptoms were found to depress fluency. Strategy measures indicated that negative symptoms predispose for rigidity, whereas positive symptoms facilitate more efficient associative pathways.
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Affiliation(s)
- Jens Egeland
- a Research Unit, Division of Mental Health & Addiction , Vestfold Hospital Trust , Tønsberg , Norway.,b Department of Psychology , University of Oslo , Oslo , Norway
| | - Tom Langerud Holmen
- a Research Unit, Division of Mental Health & Addiction , Vestfold Hospital Trust , Tønsberg , Norway
| | - Gry Bang-Kittilsen
- a Research Unit, Division of Mental Health & Addiction , Vestfold Hospital Trust , Tønsberg , Norway
| | - Therese Torgersen Bigseth
- a Research Unit, Division of Mental Health & Addiction , Vestfold Hospital Trust , Tønsberg , Norway
| | - John Abel Engh
- a Research Unit, Division of Mental Health & Addiction , Vestfold Hospital Trust , Tønsberg , Norway
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Wigand ME, Lang FU, Müller-Stierlin AS, Reichhardt L, Trif S, Schulze TG, Strik W, Becker T, Jäger M. Psychosis Is Mutable over Time: A Longitudinal Psychopathology Study. Psychopathology 2018. [PMID: 29539617 DOI: 10.1159/000486897] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND A neurobiologically informed, system-specific psychopathological approach has been suggested for use in schizophrenia. However, to our knowledge, such an approach has not been used to prospectively describe the course of schizophrenia. SAMPLING AND METHODS We assessed psychopathology in a well-described sample of 100 patients with schizophrenia or schizoaffective disorder with the Bern Psychopathology Scale (BPS) at 6-month intervals for up to 18 months. The BPS groups symptoms into the 3 domains language, affectivity and motor behaviour; each domain is rated as being normal, inhibited or disinhibited. In addition, we collected qualitative psychopathological data in the form of case reports. RESULTS Forty-eight patients completed at least 2 assessments over the course of at least 1 year. Of these, 16 patients (33.3%) showed a bipolar course pattern (i.e., a switch from inhibited to disinhibited or vice versa) in 1 domain and 6 patients (12.5%) in more than 1 domain. Shifts from 1 dominant domain to another were seen frequently (n = 20, 41.7%), but shifts between 1 dominant domain and a combination of dominant domains were more common (n = 33, 68.8%). CONCLUSIONS The course of schizophrenia is heterogeneous and shows frequent changes in psychopathology. This should be taken into account in the communication with patients and in the research on underlying illness mechanisms and treatment. A major limitation of this study is the small sample size.
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Affiliation(s)
- Moritz E Wigand
- Department of Psychiatry II, Ulm University, Günzburg, Germany
| | - Fabian U Lang
- Department of Psychiatry II, Ulm University, Günzburg, Germany.,Medical Practice for Psychiatry and Psychotherapy Lang, Gersthofen, Germany
| | | | - Lea Reichhardt
- Department of Psychiatry II, Ulm University, Günzburg, Germany
| | - Silvana Trif
- Department of Psychiatry II, Ulm University, Günzburg, Germany
| | - Thomas G Schulze
- Institute of Psychiatric Phenomics and Genomics, LMU München, München, Germany
| | - Werner Strik
- Translational Research Center, University Hospital of Psychiatry, Bern, Switzerland
| | - Thomas Becker
- Department of Psychiatry II, Ulm University, Günzburg, Germany
| | - Markus Jäger
- Department of Psychiatry II, Ulm University, Günzburg, Germany.,Department of Psychiatry, Psychosomatics and Psychotherapy, Bezirkskrankenhaus Kempten, Kempten, Germany
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24
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Stegmayer K, Strik W, Federspiel A, Wiest R, Bohlhalter S, Walther S. Specific cerebral perfusion patterns in three schizophrenia symptom dimensions. Schizophr Res 2017; 190:96-101. [PMID: 28320578 DOI: 10.1016/j.schres.2017.03.018] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2016] [Revised: 03/02/2017] [Accepted: 03/05/2017] [Indexed: 12/18/2022]
Abstract
Dimensional concepts such as the Research Domain Criteria initiative have been proposed to disentangle the heterogeneity of schizophrenia. One model introduced three neurobiologically informed behavioral dimensions: language, affectivity and motor behavior. To study the brain-behavior associations of these three dimensions, we investigated whether current behavioral alterations were linked to resting state perfusion in distinct brain circuits in schizophrenia. In total, 47 patients with schizophrenia spectrum disorders and 44 healthy controls were included. Psychopathology was assessed with the Positive And Negative Syndrome Scale and the Bern Psychopathology scale (BPS). The BPS provides severity ratings of three behavioral dimensions (language, affectivity and motor). Patients were classified according to the severity of alterations (severe, mild, no) in each dimension. Whole brain resting state cerebral blood flow (CBF) was compared between patient subgroups and controls. Two symptom dimensions were associated with distinct CBF changes. Behavioral alterations in the language dimension were linked to increased CBF in Heschl's gyrus. Altered affectivity was related to increased CBF in amygdala. The ratings of motor behavior instead were not specifically associated with CBF. Investigating behavioral alterations in three schizophrenia symptom dimensions identified distinct regional CBF changes in the language and limbic brain circuits. The results demonstrate a hitherto unknown segregation of pathophysiological pathways underlying a limited number of specific symptom dimensions in schizophrenia.
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Affiliation(s)
- Katharina Stegmayer
- Translational Research Center, University Hospital of Psychiatry, Bern, Switzerland.
| | - Werner Strik
- Translational Research Center, University Hospital of Psychiatry, Bern, Switzerland
| | - Andrea Federspiel
- Translational Research Center, University Hospital of Psychiatry, Bern, Switzerland
| | - Roland Wiest
- Support Center of Advanced Neuroimaging (SCAN), University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern, Switzerland
| | - Stephan Bohlhalter
- Neurology and Neurorehabilitation Center, Kantonsspital Luzern, Lucerne, Switzerland
| | - Sebastian Walther
- Translational Research Center, University Hospital of Psychiatry, Bern, Switzerland
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25
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Stegmayer K, Stettler M, Strik W, Federspiel A, Wiest R, Bohlhalter S, Walther S. Resting state perfusion in the language network is linked to formal thought disorder and poor functional outcome in schizophrenia. Acta Psychiatr Scand 2017; 136:506-516. [PMID: 28865406 PMCID: PMC5656821 DOI: 10.1111/acps.12790] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/25/2017] [Indexed: 01/31/2023]
Abstract
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.
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Affiliation(s)
- K. Stegmayer
- Translational Research CenterUniversity Hospital of PsychiatryUniversity of BernBernSwitzerland
| | - M. Stettler
- Translational Research CenterUniversity Hospital of PsychiatryUniversity of BernBernSwitzerland
| | - W. Strik
- Translational Research CenterUniversity Hospital of PsychiatryUniversity of BernBernSwitzerland
| | - A. Federspiel
- Translational Research CenterUniversity Hospital of PsychiatryUniversity of BernBernSwitzerland
| | - R. Wiest
- Support Center of Advanced Neuroimaging (SCAN)University Institute of Diagnostic and Interventional NeuroradiologyInselspitalBernSwitzerland
| | - S. Bohlhalter
- Neurology and Neurorehabilitation CenterKantonsspital LuzernLucerneSwitzerland
| | - S. Walther
- Translational Research CenterUniversity Hospital of PsychiatryUniversity of BernBernSwitzerland
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26
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Park CH, Lee S, Kim T, Won WY, Lee KU. Different alterations in brain functional networks according to direct and indirect topological connections in patients with schizophrenia. Schizophr Res 2017; 188:82-88. [PMID: 28109669 DOI: 10.1016/j.schres.2017.01.025] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2016] [Revised: 01/13/2017] [Accepted: 01/13/2017] [Indexed: 12/11/2022]
Abstract
Schizophrenia displays connectivity deficits in the brain, but the literature has shown inconsistent findings about alterations in global efficiency of brain functional networks. We supposed that such inconsistency at the whole brain level may be due to a mixture of different portions of global efficiency at sub-brain levels. Accordingly, we considered measuring portions of global efficiency in two aspects: spatial portions by considering sub-brain networks and topological portions by considering contributions to global efficiency according to direct and indirect topological connections. We proposed adjacency and indirect adjacency as new network parameters attributable to direct and indirect topological connections, respectively, and applied them to graph-theoretical analysis of brain functional networks constructed from resting state fMRI data of 22 patients with schizophrenia and 22 healthy controls. Group differences in the network parameters were observed not for whole brain and hemispheric networks, but for regional networks. Alterations in adjacency and indirect adjacency were in opposite directions, such that adjacency increased, but indirect adjacency decreased in patients with schizophrenia. Furthermore, over connections in frontal and parietal regions, increased adjacency was associated with more severe negative symptoms, while decreased adjacency was associated with more severe positive symptoms of schizophrenia. This finding indicates that connectivity deficits associated with positive and negative symptoms of schizophrenia may involve topologically different paths in the brain. In patients with schizophrenia, although changes in global efficiency may not be clearly shown, different alterations in brain functional networks according to direct and indirect topological connections could be revealed at the regional level.
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Affiliation(s)
- Chang-Hyun Park
- Ewha Brain Institute, Ewha Womans University, Seoul, Republic of Korea
| | - Seungyup Lee
- Department of Psychiatry, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Taewon Kim
- Department of Psychiatry, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Republic of Korea
| | - Wang Yeon Won
- Department of Psychiatry, St. Paul's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Kyoung-Uk Lee
- Department of Psychiatry, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
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27
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Wensing T, Cieslik EC, Müller VI, Hoffstaedter F, Eickhoff SB, Nickl-Jockschat T. Neural correlates of formal thought disorder: An activation likelihood estimation meta-analysis. Hum Brain Mapp 2017; 38:4946-4965. [PMID: 28653797 DOI: 10.1002/hbm.23706] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Revised: 05/24/2017] [Accepted: 06/16/2017] [Indexed: 11/10/2022] Open
Abstract
Formal thought disorder (FTD) refers to a psychopathological dimension characterized by disorganized and incoherent speech. Whether symptoms of FTD arise from aberrant processing in language-related regions or more general cognitive networks, however, remains debated. Here, we addressed this question by a quantitative meta-analysis of published functional neuroimaging studies on FTD. The revised Activation Likelihood Estimation (ALE) algorithm was used to test for convergent aberrant activation changes in 18 studies (30 experiments) investigating FTD, of which 17 studies comprised schizophrenia patients and one study healthy subjects administered to S-ketamine. Additionally, we analyzed task-dependent and task-independent (resting-state) functional connectivity (FC) of brain regions showing convergence in activation changes. Subsequent functional characterization was performed for the initial clusters and the delineated connectivity networks by reference to the BrainMap database. Consistent activation changes were found in the left superior temporal gyrus (STG) and two regions within the left posterior middle temporal gyrus (p-MTG), ventrally (vp-MTG) and dorsally (dp-MTG). Functional characterization revealed a prominent functional association of ensuing clusters from our ALE meta-analysis with language and speech processing, as well as auditory perception in STG and with social cognition in dp-MTG. FC analysis identified task-dependent and task-independent networks for all three seed regions, which were mainly related to language and speech processing, but showed additional involvement in higher order cognitive functions. Our findings suggest that FTD is mainly characterized by abnormal activation in brain regions of the left hemisphere that are associated with language and speech processing, but also extend to higher order cognitive functions. Hum Brain Mapp 38:4946-4965, 2017. © 2017 Wiley Periodicals, Inc.
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Affiliation(s)
- Tobias Wensing
- Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen, Germany.,Institute of Neuroscience and Medicine, Brain & Behaviour (INM-7), Research Centre Jülich, Germany.,JARA Translational Brain Medicine, Aachen, Germany
| | - Edna C Cieslik
- Institute of Neuroscience and Medicine, Brain & Behaviour (INM-7), Research Centre Jülich, Germany.,Institute for Systems Neuroscience, Medical Faculty, Heinrich-Heine University Düsseldorf, Germany
| | - Veronika I Müller
- Institute of Neuroscience and Medicine, Brain & Behaviour (INM-7), Research Centre Jülich, Germany.,Institute for Systems Neuroscience, Medical Faculty, Heinrich-Heine University Düsseldorf, Germany
| | - Felix Hoffstaedter
- Institute of Neuroscience and Medicine, Brain & Behaviour (INM-7), Research Centre Jülich, Germany.,Institute for Systems Neuroscience, Medical Faculty, Heinrich-Heine University Düsseldorf, Germany
| | - Simon B Eickhoff
- Institute of Neuroscience and Medicine, Brain & Behaviour (INM-7), Research Centre Jülich, Germany.,Institute for Systems Neuroscience, Medical Faculty, Heinrich-Heine University Düsseldorf, Germany
| | - Thomas Nickl-Jockschat
- Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen, Germany.,JARA Translational Brain Medicine, Aachen, Germany
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28
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Murphy E, Benítez-Burraco A. Bridging the Gap between Genes and Language Deficits in Schizophrenia: An Oscillopathic Approach. Front Hum Neurosci 2016; 10:422. [PMID: 27601987 PMCID: PMC4993770 DOI: 10.3389/fnhum.2016.00422] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2016] [Accepted: 08/08/2016] [Indexed: 12/11/2022] Open
Abstract
Schizophrenia is characterized by marked language deficits, but it is not clear how these deficits arise from the alteration of genes related to the disease. The goal of this paper is to aid the bridging of the gap between genes and schizophrenia and, ultimately, give support to the view that the abnormal presentation of language in this condition is heavily rooted in the evolutionary processes that brought about modern language. To that end we will focus on how the schizophrenic brain processes language and, particularly, on its distinctive oscillatory profile during language processing. Additionally, we will show that candidate genes for schizophrenia are overrepresented among the set of genes that are believed to be important for the evolution of the human faculty of language. These genes crucially include (and are related to) genes involved in brain rhythmicity. We will claim that this translational effort and the links we uncover may help develop an understanding of language evolution, along with the etiology of schizophrenia, its clinical/linguistic profile, and its high prevalence among modern populations.
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Affiliation(s)
- Elliot Murphy
- Division of Psychology and Language Sciences, University College London London, UK
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29
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Cavelti M, Homan P, Vauth R. The impact of thought disorder on therapeutic alliance and personal recovery in schizophrenia and schizoaffective disorder: An exploratory study. Psychiatry Res 2016; 239:92-8. [PMID: 27137967 DOI: 10.1016/j.psychres.2016.02.070] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2015] [Revised: 10/15/2015] [Accepted: 02/03/2016] [Indexed: 01/27/2023]
Abstract
Thought and language disorders are a main feature of schizophrenia. The aim of the study is to explore the impact of thought disorder on therapeutic alliance and personal recovery because of its interference with verbal communication. Thought disorder, positive and negative symptoms (Positive and Negative Syndrome Scale), functioning (Modified Global Assessment of Functioning scale), insight (Scale to Assess Unawareness of Mental Disorder), attachment insecurity (Psychosis Attachment Measure), therapeutic alliance (Scale to Assess the Therapeutic Relationship), and personal recovery (Recovery Assessment Scale, Integration Sealing-Over Scale) were assessed in 133 outpatients with schizophrenia or schizoaffective disorder at baseline and twelve months later. The data were analyzed by hierarchical multiple linear regression. Higher levels of thought disorder were significantly associated with lower clinicians' ratings, but not with patients' ratings of therapeutic alliance. In addition, lower clinicians' ratings of therapeutic alliance were significantly linked to a more sealing over and less integrative recovery style. In fact, the lower therapeutic alliance ratings mediated the association between thought disorder and a sealing over recovery style. The results highlight the importance of considering thought disorder in treatment of schizophrenia and schizoaffective disorder which may interfere with therapeutic alliance and treatment efforts towards recovery.
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Affiliation(s)
- Marialuisa Cavelti
- Translational Research Center, University Hospital of Psychiatry and Psychotherapy, University of Bern, Bolligenstrasse 111, CH-3000 Bern 60, Switzerland.
| | - Philipp Homan
- Translational Research Center, University Hospital of Psychiatry and Psychotherapy, University of Bern, Bolligenstrasse 111, CH-3000 Bern 60, Switzerland
| | - Roland Vauth
- Psychiatric University Clinics Basel, Center for Psychotic Disorders, Kornhausgasse 7, CH-4501 Basel, Switzerland
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30
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Petcu EB, Sherwood K, Popa-Wagner A, Buga AM, Aceti L, Miroiu RI. Artistic Skills Recovery and Compensation in Visual Artists after Stroke. Front Neurol 2016; 7:76. [PMID: 27242659 PMCID: PMC4865522 DOI: 10.3389/fneur.2016.00076] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2015] [Accepted: 04/29/2016] [Indexed: 12/05/2022] Open
Abstract
Background Art is a characteristic of mankind, which requires superior central nervous processing and integration of motor functions with visual information. At the present time, a significant amount of information related to neurobiological basis of artistic creation has been derived from neuro-radiological cognitive studies, which have revealed that subsequent to tissue destruction, the artists continue to create art. The current study aims to review the most important cases of visual artists with stroke and to discuss artistic skills recovery and compensation as well as artistic style after stroke. Methods The role of various central nervous system regions in artistic creation was reviewed on the basis of previously published functional studies. Our PubMed search (1995–2015) has identified 10 famous artists with right cerebral stroke as well as 5 with left cerebral stroke who survived and continued to create art after stroke. As the artists included in this review lived at various times during the twentieth century and in different countries, clinical information related to their case was limited. However, it appears that artistic skills recovery and compensation appear within days after stroke. Some of the artists would subsequently change their artistic style. All these elements have been evaluated within the context of specific clinical cases. Conclusion The poststroke artistic skills recovery and compensation with development of a new style or the opposite, regaining the previous prestroke style, represents a significant element of clinical importance in medical rehabilitation as well as neuroesthetics, which requires further evaluation. At the present time, the molecular mechanisms of artistic creation are poorly understood, and more standardized clinical and experimental studies are needed.
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Affiliation(s)
- Eugen Bogdan Petcu
- Griffith University School of Medicine, Gold Coast Campus, QLD, USA; Queensland Eye Institute, Brisbane, QLD, Australia
| | - Katherine Sherwood
- Art Department and Disability Studies Program, University of California Berkeley , Berkeley, CA , USA
| | - Aurel Popa-Wagner
- Department of Psychiatry, University of Medicine Rostock , Rostock , Germany
| | - Ana Maria Buga
- Center of Clinical and Experimental Research, University of Medicine and Pharmacy Craiova , Craiova , Romania
| | | | - Rodica Ileana Miroiu
- Griffith University School of Dentistry and Oral Health , Gold Coast Campus, QLD , Australia
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31
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Nishida K, Razavi N, Jann K, Yoshimura M, Dierks T, Kinoshita T, Koenig T. Integrating Different Aspects of Resting Brain Activity: A Review of Electroencephalographic Signatures in Resting State Networks Derived from Functional Magnetic Resonance Imaging. Neuropsychobiology 2015; 71:6-16. [PMID: 25766483 DOI: 10.1159/000363342] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2014] [Accepted: 04/28/2014] [Indexed: 11/19/2022]
Abstract
Electroencephalography (EEG) is an established measure in the field of brain resting state with a range of quantitative methods (qEEG) that yield unique information about neuronal activation and synchronization. Meanwhile, in the last decade, functional magnetic resonance imaging (fMRI) studies have revealed the existence of more than a dozen resting state networks (RSNs), and combined qEEG and fMRI have allowed us to gain understanding about the relationship of qEEG and fMRI-RSNs. However, the overall picture is less clear because there is no a priori hypothesis about which EEG features correspond well to fMRI-RSNs. We reviewed the associations of several types of qEEG features to four RSNs considered as neurocognitive systems central for higher brain processes: the default mode network, dorsal and ventral frontoparietal networks, and the salience network. We could identify 12 papers correlating qEEG and RSNs in adult human subjects and employing a simultaneous design under a no-task resting state condition. A systematic overview investigates which qEEG features replicably relate to the chosen RSNs. This review article leads to the conclusion that spatially delimited θ and whole/local α may be the most promising measures, but the time domain methods add important additional information. © 2015 S. Karger AG, Basel.
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32
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Kircher T, Krug A, Stratmann M, Ghazi S, Schales C, Frauenheim M, Turner L, Fährmann P, Hornig T, Katzev M, Grosvald M, Müller-Isberner R, Nagels A. A rating scale for the assessment of objective and subjective formal Thought and Language Disorder (TALD). Schizophr Res 2014; 160:216-21. [PMID: 25458572 DOI: 10.1016/j.schres.2014.10.024] [Citation(s) in RCA: 82] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Revised: 10/13/2014] [Accepted: 10/19/2014] [Indexed: 11/26/2022]
Abstract
Formal thought disorder (FTD) is a core syndrome of schizophrenia. However, patients with other diagnoses, such as mania and depression amongst others, also present with FTD. We introduce a novel, comprehensive clinical rating scale, capturing the full variety of FTD phenomenology including subjective experiences. The 30-item Thought and Language Disorder (TALD) scale is based on a detailed review of the literature, encompassing all formal thought disorder symptoms reported from the early 20th century onwards. Objectively observable symptoms as well as subjective phenomena were included. Two hundred and ten participants (146 patients ICD-10 diagnoses: depression n=63, schizophrenia n=63, mania n=20; 64 healthy control subjects) were interviewed and symptoms rated with the TALD, TLC, HAMD, YMRS and SAPS/SANS. A principal component analyses was performed for the TALD to differentiate sub-syndromes. The principal component analysis revealed four FTD factors; objective and subjective as well as positive and negative factor dimensions. The correlation analyses with the TLC and the SAPS/SANS FTD sub-scores demonstrated the factor validity for the objective factors. The different diagnoses showed a distinct pattern of symptom severity in each of the factors, with mania patients exhibiting the highest value in the positive, objective dimension. The scale showed good psychometric results, which makes it a practicable, nosologically-open instrument for the detailed assessment of all FTD dimensions. The results strengthen the importance of subjective symptom assessment reported by the patient.
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Affiliation(s)
- Tilo Kircher
- Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany.
| | - Axel Krug
- Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany
| | - Mirjam Stratmann
- Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany
| | - Sayed Ghazi
- Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany
| | - Christian Schales
- Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany
| | - Michael Frauenheim
- Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany
| | - Lena Turner
- Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany
| | - Paul Fährmann
- Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany
| | - Tobias Hornig
- Department of Neurology, University of Freiburg, Hauptstr. 5, 79104 Freiburg, Germany
| | - Michael Katzev
- Department of Neurology, University of Freiburg, Hauptstr. 5, 79104 Freiburg, Germany
| | - Michael Grosvald
- Department of English Literature & Linguistics, College of Arts & Sciences, Qatar University, PO Box 2713, Doha, Qatar
| | | | - Arne Nagels
- Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany
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Shifted coupling of EEG driving frequencies and fMRI resting state networks in schizophrenia spectrum disorders. PLoS One 2013; 8:e76604. [PMID: 24124576 PMCID: PMC3790692 DOI: 10.1371/journal.pone.0076604] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2013] [Accepted: 08/26/2013] [Indexed: 01/05/2023] Open
Abstract
Introduction The cerebral resting state in schizophrenia is altered, as has been demonstrated separately by electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) resting state networks (RSNs). Previous simultaneous EEG/fMRI findings in healthy controls suggest that a consistent spatiotemporal coupling between neural oscillations (EEG frequency correlates) and RSN activity is necessary to organize cognitive processes optimally. We hypothesized that this coupling is disorganized in schizophrenia and related psychotic disorders, in particular regarding higher cognitive RSNs such as the default-mode (DMN) and left-working-memory network (LWMN). Methods Resting state was investigated in eleven patients with a schizophrenia spectrum disorder (n = 11) and matched healthy controls (n = 11) using simultaneous EEG/fMRI. The temporal association of each RSN to topographic spectral changes in the EEG was assessed by creating Covariance Maps. Group differences within, and group similarities across frequencies were estimated for the Covariance Maps. Results The coupling of EEG frequency bands to the DMN and the LWMN respectively, displayed significant similarities that were shifted towards lower EEG frequencies in patients compared to healthy controls. Conclusions By combining EEG and fMRI, each measuring different properties of the same pathophysiology, an aberrant relationship between EEG frequencies and altered RSNs was observed in patients. RSNs of patients were related to lower EEG frequencies, indicating functional alterations of the spatiotemporal coupling. Significance The finding of a deviant and shifted coupling between RSNs and related EEG frequencies in patients with a schizophrenia spectrum disorder is significant, as it might indicate how failures in the processing of internal and external stimuli, as commonly seen during this symptomatology (i.e. thought disorders, hallucinations), arise.
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Rapp AM, Steinhäuser AE. Functional MRI of sentence-level language comprehension in schizophrenia: a coordinate-based analysis. Schizophr Res 2013; 150:107-13. [PMID: 23911258 DOI: 10.1016/j.schres.2013.07.019] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2012] [Revised: 06/18/2013] [Accepted: 07/06/2013] [Indexed: 11/18/2022]
Abstract
Numerous authors have hypothesised that abnormal pathways for language play a key role in the pathophysiology of schizophrenia, a notion that is supported by structural imaging and post-mortem findings especially in patients with thought disorder and auditory verbal hallucinations. Recently, an increasing number of functional magnetic resonance imaging (fMRI) investigations addressed language comprehension schizophrenia. We present a systematic review of the fMRI-studies on sentence- and text-level language comprehension in schizophrenia. 13 studies met the inclusion criteria. Additional studies specifically addressed language lateralization. Coordinates for differential contrasts for healthy controls>patients reported in these studies indicate that the left fronto-temporal language network is altered in schizophrenia. 33 out of the 51 reported coordinates are located in the left hemisphere. Overactivation in schizophrenia extends into premotor areas and is about equally divided among the left and right hemispheres. Several negative studies indicate heterogeneity within schizophrenia, which could possibly be related to the severity of thought disorder or auditory verbal hallucinations of patients. Activation changes related to thought disorder within schizophrenia (n=4 studies) include the inferior frontal and superior temporal gyri and are moderately lateralized to the left hemisphere. Although current fMRI literature is still insufficient to draw decisive conclusions, results point towards functionally altered pathways for language in schizophrenia. This notion is also plausible from the viewpoint of psychopathology especially since hallmark symptoms of the disease, thought disorder, auditory verbal hallucinations and alogia, are expressed in terms of language or represent abnormalities of language function.
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Affiliation(s)
- Alexander M Rapp
- Department of Psychiatry, University of Tübingen, Calwerstrasse 14, 72076 Tübingen, Germany.
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Sans-Sansa B, McKenna PJ, Canales-Rodríguez EJ, Ortiz-Gil J, López-Araquistain L, Sarró S, Dueñas RM, Blanch J, Salvador R, Pomarol-Clotet E. Association of formal thought disorder in schizophrenia with structural brain abnormalities in language-related cortical regions. Schizophr Res 2013; 146:308-13. [PMID: 23522907 DOI: 10.1016/j.schres.2013.02.032] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2012] [Revised: 02/11/2013] [Accepted: 02/24/2013] [Indexed: 01/29/2023]
Abstract
BACKGROUND Formal thought disorder (FTD) in schizophrenia has been found to be associated with volume reductions in the left superior temporal cortex. However, there have been negative findings and some studies have also found associations in other cortical regions. METHOD Fifty-one schizophrenic patients were evaluated for presence of FTD with the Thought, Language and Communication (TLC) scale and underwent whole-brain structural MRI using optimized voxel-based morphometry (VBM). Fifty-nine matched healthy controls were also scanned. RESULTS Compared to 31 patients without FTD (global TLC rating 0 or 1), 20 patients with FTD (global TLC rating 2-5) showed clusters of volume reduction in the medial frontal and orbitofrontal cortex bilaterally, and in two left-sided areas approximating to Broca's and Wernicke's areas. The pattern of FTD-associated volume reductions was largely different from that found in a comparison between the healthy controls and the patients without FTD. Analysis of correlations within regions-of-interest based on the above clusters indicated that the 'fluent disorganization' component of FTD was correlated with volume reductions in both Broca's and Wernicke's areas, whereas poverty of content of speech was correlated with reductions in the medial frontal/orbitofrontal cortex. CONCLUSIONS The findings point to a relationship between FTD in schizophrenia and structural brain pathology in brain areas involved in language and executive function.
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Jann K, Orosz A, Dierks T, Wang DJJ, Wiest R, Federspiel A. Quantification of network perfusion in ASL cerebral blood flow data with seed based and ICA approaches. Brain Topogr 2013; 26:569-80. [PMID: 23508714 DOI: 10.1007/s10548-013-0280-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2012] [Accepted: 03/07/2013] [Indexed: 10/27/2022]
Abstract
Independent component analysis (ICA) or seed based approaches (SBA) in functional magnetic resonance imaging blood oxygenation level dependent (BOLD) data became widely applied tools to identify functionally connected, large scale brain networks. Differences between task conditions as well as specific alterations of the networks in patients as compared to healthy controls were reported. However, BOLD lacks the possibility of quantifying absolute network metabolic activity, which is of particular interest in the case of pathological alterations. In contrast, arterial spin labeling (ASL) techniques allow quantifying absolute cerebral blood flow (CBF) in rest and in task-related conditions. In this study, we explored the ability of identifying networks in ASL data using ICA and to quantify network activity in terms of absolute CBF values. Moreover, we compared the results to SBA and performed a test-retest analysis. Twelve healthy young subjects performed a fingertapping block-design experiment. During the task pseudo-continuous ASL was measured. After CBF quantification the individual datasets were concatenated and subjected to the ICA algorithm. ICA proved capable to identify the somato-motor and the default mode network. Moreover, absolute network CBF within the separate networks during either condition could be quantified. We could demonstrate that using ICA and SBA functional connectivity analysis is feasible and robust in ASL-CBF data. CBF functional connectivity is a novel approach that opens a new strategy to evaluate differences of network activity in terms of absolute network CBF and thus allows quantifying inter-individual differences in the resting state and task-related activations and deactivations.
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Affiliation(s)
- Kay Jann
- Department of Psychiatric Neurophysiology, University Hospital of Psychiatry, University of Bern, Bolligenstrasse 111, 3000, Bern 60, Switzerland,
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Redpath HL, Cooper D, Lawrie SM. Imaging symptoms and syndromes: similarities and differences between schizophrenia and bipolar disorder. Biol Psychiatry 2013; 73:495-6. [PMID: 23438631 DOI: 10.1016/j.biopsych.2013.01.015] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2013] [Accepted: 01/11/2013] [Indexed: 11/28/2022]
Affiliation(s)
- Holly L Redpath
- Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, United Kingdom.
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Current world literature. Curr Opin Psychiatry 2013; 26:231-6. [PMID: 23364282 DOI: 10.1097/yco.0b013e32835dd9de] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Orosz A, Jann K, Federspiel A, Horn H, Höfle O, Dierks T, Wiest R, Strik W, Müller T, Walther S. Reduced Cerebral Blood Flow Within the Default-Mode Network and Within Total Gray Matter in Major Depression. Brain Connect 2012; 2:303-10. [DOI: 10.1089/brain.2012.0101] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022] Open
Affiliation(s)
- Ariane Orosz
- Department of Psychiatric Neurophysiology, University Hospital of Psychiatry, Bern, Switzerland
| | - Kay Jann
- Department of Psychiatric Neurophysiology, University Hospital of Psychiatry, Bern, Switzerland
| | - Andrea Federspiel
- Department of Psychiatric Neurophysiology, University Hospital of Psychiatry, Bern, Switzerland
| | - Helge Horn
- University Hospital of Psychiatry, Bern, Switzerland
| | - Oliver Höfle
- University Hospital of Psychiatry, Bern, Switzerland
| | - Thomas Dierks
- Department of Psychiatric Neurophysiology, University Hospital of Psychiatry, Bern, Switzerland
| | - Roland Wiest
- Institute of Diagnostic and Interventional Neuroradiology, University of Bern, Bern, Switzerland
| | - Werner Strik
- University Hospital of Psychiatry, Bern, Switzerland
| | - Thomas Müller
- University Hospital of Psychiatry, Bern, Switzerland
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