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Therapeutic response and neurobiological prediction markers in auditory verbal hallucinations

Titel Englisch Therapeutic response and neurobiological prediction markers in auditory verbal hallucinations
Gesuchsteller/in Dierks Thomas
Nummer 146789
Förderungsinstrument Projektförderung (Abt. I-III)
Forschungseinrichtung Abteilung Psychiatrische Neurophysiologie Universitätsklinik und Poliklinik für Psychiatrie
Hochschule Universität Bern - BE
Hauptdisziplin Nervenheilkunde, Psychiatrie
Beginn/Ende 01.07.2014 - 30.06.2018
Bewilligter Betrag 499'375.00
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Alle Disziplinen (3)

Disziplin
Nervenheilkunde, Psychiatrie
Neurophysiologie und Hirnforschung
Pathophysiologie

Keywords (10)

neurophysiology; MRI; EEG; tDCS; therapy; prediction; hallucinations; schizophrenia; NIRS; TMS

Lay Summary (Deutsch)

Lead
Neurobiologische Mechanismen und Vorhersage von therapeutischem Erfolg bei akustischen Halluzinationen.
Lay summary

Schizophrenie ist verbunden mit Störungen in der Kommunikation, Kognition und Gefühlswelt und führt aus diesem Grund zu einem grossen persönlichen Leiden sowie einer erheblichen Belastung für die Angehörigen und unsere Gesellschaft. Bis 80% der Patienten leiden an sprachlich-akustischen Halluzinationen, welche somit eines der häufigsten Symptome der Krankheit sind. Halluzinationen können extrem emotional belastend sein für die Patienten, nicht selten verbunden mit sowohl Selbst- wie auch Fremdgefährdung. Aus diesem Grund ist eine möglichst effektive Therapie notwendig, um das Leiden wie auch die Kosten zu minimieren. Leider waren die therapeutischen Möglichkeiten bisher ziemlich beschränkt und die häufigste Behandlungsmethode ist die Psychopharmakatherapie. Jedoch bei 20-30% der Patienten wirken die Medikamente nicht sehr gut gegen die Halluzinationen. Somit ist es dringend notwendig, neue innovative therapeutische Optionen zu entwickeln. Basierend auf neurobiologischen Erkenntnissen zur Entstehung von Halluzinationen wurden nicht-pharmakologische Behandlungsmöglichkeiten wie transkranielle Magnetstimulation entwickelt. Kürzlich haben wir zudem die transkranielle Gleichstrombehandlung eingeführt mit ersten guten Ergebnissen bei minimalen Nebenwirkungen. Vor Kurzem haben Studien gezeigt, dass Patienten sehr unterschiedlich auf die verschiedenen therapeutischen Methoden reagieren. Aus diesem Grund ist es das Ziel dieser Studie die biologischen Mechanismen, die zu einem positiven Behandlungserfolg führen, besser zu verstehen und somit rechtzeitig diejenigen Patienten zu erkennen, welche auf eine Therapie mit Erfolg reagieren. Damit verbunden ist das Ziel, das persönliche Leiden der Patienten und deren Angehörigen sowie die Belastung unserer Gesellschaft zu vermindern.

Direktlink auf Lay Summary Letzte Aktualisierung: 24.10.2013

Lay Summary (Englisch)

Lead
Therapeutic response and neurobiological prediction markers in auditory verbal hallucinations
Lay summary

Schizophrenia is a disorder of communication, cognition and emotion and thus leads to a high degree of personal and familiar suffering as well as burden on the society. Up till 80% of the patients suffer from auditory verbal hallucinations (AVH) being one of the most common symptoms of this disorder with diagnostic value. AVH can be extremely emotional distressing to the patients, often endangering themselves as well as others. Thus an efficient therapeutic regime is indispensable to lower suffering and costs. Unfortunately the therapeutic options are rather limited and the most conventional therapeutic strategy is the use of antipsychotic drugs, however, in about 20-30 % of the patients even extended antipsychotic medication does not ameliorate AVH. Thus new therapeutic options and/or regimens are needed. Based upon neurobiological research regarding the generation of AVH non-pharmacological treatments like transcranial magnetic stimulation (TMS) were developed. Recently we additionally introduced transcranial direct current stimulation (tDCS) for AVH treatment and initial experience and results indicate a positive effect in patients. Recent studies has indicated that patients with AVH respond differently to various therapeutic approaches. Thus the aims of the project are to identify treatment responders based upon a better understanding of the neurobiological mechanisms responsible for responsiveness and to investigate if TMS/tDCS are effective treatment alternatives to conventional antipsychotic treatment in patients with schizophrenia and as a result to reduce both the individual suffering in patients and their relatives as well as the burden upon the society.

Direktlink auf Lay Summary Letzte Aktualisierung: 24.10.2013

Verantw. Gesuchsteller/in und weitere Gesuchstellende

Mitarbeitende

Projektpartner

Publikationen

Publikation
Am I hallucinating or is my fusiform cortex activated? Functional activation differences in schizophrenia patients with and without hallucinations
Kunzelmann Katharina, Grieder Matthias, van Swam Claudia, Homan Philipp, Winkelbeiner Stephanie, Hubl Daniela, Dierks Thomas (2018), Am I hallucinating or is my fusiform cortex activated? Functional activation differences in schizophrenia patients with and without hallucinations, in The European Journal of Psychiatry.
Formal thought disorder is related to aberrations in language-related white matter tracts in patients with schizophrenia
Cavelti Marialuisa, Winkelbeiner Stephanie, Federspiel Andrea, Walther Sebastian, Stegmayer Katharina, Giezendanner Stéphanie, Laimböck Karin, Dierks Thomas, Strik Werner, Horn Helge, Homan Philipp (2018), Formal thought disorder is related to aberrations in language-related white matter tracts in patients with schizophrenia, in Psychiatry Research: Neuroimaging, 279, 40-50.
Decreased blood flow in the right insula and middle temporal gyrus predicts negative formal thought disorder in schizophrenia
Winkelbeiner Stephanie, Cavelti Marialuisa, Federspiel Andrea, Kunzelmann Katharina, Dierks Thomas, Strik Werner, Horn Helge, Homan Philipp (2018), Decreased blood flow in the right insula and middle temporal gyrus predicts negative formal thought disorder in schizophrenia, in Schizophrenia Research.
Targeting Obsessive-Compulsive Symptoms With rTMS and Perfusion Imaging
Winkelbeiner Stephanie, Suker Samir, Bachofner Hanta, Eisenhardt Sarah, Steinau Sarah, Walther Sebastian, Federspiel Andrea, Dierks Thomas, Strik Werner, Homan Philipp (2018), Targeting Obsessive-Compulsive Symptoms With rTMS and Perfusion Imaging, in American Journal of Psychiatry, 175(1), 81-83.
Targeting Obsessive-Compulsive Symptoms With rTMS and Perfusion Imaging
Winkelbeiner Stephanie, Suker Samir, Bachofner Hanta, Eisenhardt Sarah, Steinau Sarah, Walther Sebastian, Federspiel Andrea, Dierks Thomas, Strik Werner, Homan Philipp (2018), Targeting Obsessive-Compulsive Symptoms With rTMS and Perfusion Imaging, in American Journal of Psychiatry, 175(1), 81-83.

Zusammenarbeit

Gruppe / Person Land
Formen der Zusammenarbeit
Center of Cognition for Learning and Memory, Univ. of Bern Schweiz (Europa)
- vertiefter/weiterführender Austausch von Ansätzen, Methoden oder Resultaten
- Publikation
Inst. of Neuroradiology, Univ. of Bern Schweiz (Europa)
- vertiefter/weiterführender Austausch von Ansätzen, Methoden oder Resultaten
- Publikation
- Forschungsinfrastrukturen
Ahmanson-Lovelace Brain Mapping Center, UCLA Vereinigte Staaten von Amerika (Nordamerika)
- vertiefter/weiterführender Austausch von Ansätzen, Methoden oder Resultaten
Clinical Neuroscience Network Univ. of Bern Schweiz (Europa)
- vertiefter/weiterführender Austausch von Ansätzen, Methoden oder Resultaten
- Publikation
- Forschungsinfrastrukturen
Dept of Psychiatry, Vanderbilt University Vereinigte Staaten von Amerika (Nordamerika)
- vertiefter/weiterführender Austausch von Ansätzen, Methoden oder Resultaten
The Feinstein Institute for Medical Research Hofstra Northwell School of Medicine Vereinigte Staaten von Amerika (Nordamerika)
- vertiefter/weiterführender Austausch von Ansätzen, Methoden oder Resultaten
- Publikation
- Austausch von Mitarbeitern

Wissenschaftliche Veranstaltungen

Aktiver Beitrag

Titel Art des Beitrags Titel des Artikels oder Beitrages Datum Ort Beteiligte Personen
Joint Meeting of the Electroencephalography and Clinical Neuroscience Society Vortrag im Rahmen einer Tagung Muting the voices with brain stimulation 04.09.2018 Pittsburgh, Vereinigte Staaten von Amerika Dierks Thomas; Hubl Daniela; Winkelbeiner Stephanie;
4th Burghölzli Psychiatry Meeting 2017 Poster No effect of transcranial direct current stimulation over the auditory cortex on auditory-evoked potentials. 30.11.2017 Zurich, Schweiz Kunzelmann Katharina; Dierks Thomas;
4th International Consortium Meeting on Hallucination Research Poster Altered Functional Activation in Verbal Fluency Linked to Auditory Verbal Hallucinations. 06.11.2017 Lille, Frankreich Dierks Thomas; Hubl Daniela; Kunzelmann Katharina;
2nd European Conference on Brain Stimulation in Psychiatry Vortrag im Rahmen einer Tagung Individualized Treatment of Positive Symptoms in Schizophrenia: Potentials & Pitfalls 12.10.2017 Munich, Deutschland Winkelbeiner Stephanie;
17th World Psychiatry Congress Vortrag im Rahmen einer Tagung Affected Speech in Schizophrenia - From Emptiness & Disorganization to Hallucinations 08.10.2017 Berlin, Deutschland Winkelbeiner Stephanie;
International Conference on Basic and Clinical Multimodal Imaging: BACI 2017 Poster Sigma as a potential predictor for schizotypal personality 11.09.2017 Bern, Schweiz Winkelbeiner Stephanie;
12th Annual Meeting Clinical Neuroscience Bern Poster Formal thought disorder in schizophrenia and white matter abnormalities. 08.09.2017 Bern, Schweiz Winkelbeiner Stephanie;
15th European Neurology Congress 2017 London Poster Altered Functional Activation in Verbal Fluency Linked to Auditory Verbal Hallucinations. 29.08.2017 London, Grossbritannien und Nordirland Kunzelmann Katharina; Dierks Thomas; Hubl Daniela;
Human Brain Mapping conference Poster Bilateral temporal tDCS enhances sleep-dependent episodic memory consolidation 25.06.2017 Vancouver, Vereinigte Staaten von Amerika Dierks Thomas; Winkelbeiner Stephanie;
10th Annual Meeting Clinical Neuroscience Bern Poster Therapeutic Response and Neurobiological Prediction Markers in Auditory Verbal Hallucinations 22.01.2015 Bern, Schweiz Winkelbeiner Stephanie; Kunzelmann Katharina; Dierks Thomas;
GHS symposium 2014 Münchenwiler Poster Neurobiological Prediction Markers for Therapeutic Response in Auditory Verbal Hallucinations (AVH) 26.11.2014 Münchenwiler, Schweiz Hubl Daniela; Winkelbeiner Stephanie; Kunzelmann Katharina; Dierks Thomas;
Clinical Neuroscience Bern Poster Therapeutic Response and Neurobiological Prediction Markers in Auditory Verbal Hallucinations. 01.09.2014 Bern, Schweiz Winkelbeiner Stephanie; Kunzelmann Katharina; Dierks Thomas;


Veranstaltungen zum Wissenstransfer

Aktiver Beitrag

Titel Art des Beitrags Titel des Artikels oder Beitrages Datum Ort Beteiligte Personen
Collegium Generale Bern: Visionen: Erscheinungen und andere Halluzinationen Vortrag 08.03.2017 Bern, Schweiz


Auszeichnungen

Titel Jahr
Travel award from StanCon 2018, Bayesian statistics conference, Helsinki, Finland. 2018

Verbundene Projekte

Nummer Titel Start Förderungsinstrument
124114 Impact of qualitative MR perfusion imaging on the management of patients with carotid artery disease 01.10.2009 SPUM
112578 Neurobiological mechanisms of auditory verbal hallucinations 01.06.2006 Projektförderung (Abt. I-III)
136249 Resting states of the brain and state dependent information processing in health and disease 01.01.2012 Sinergia
142743 Cerebral Functional Connectivity in Arterial Spin Labeling data 01.02.2013 Advanced Postdoc.Mobility

Abstract

Schizophrenia is a disorder of communication, cognition and emotion and thus leads to a high degree of personal and familiar suffering as well as burden on the society. The prevalence rate for schizophrenia is approximately 1.1% of the population, thus about 50 Million people worldwide suffer from schizophrenia and the financial cost is estimated to be about 60 billion CHF. Up till 80% of the patients suffer from auditory verbal hallucinations (AVH) being one of the most common symptoms of this disorder with diagnostic value. AVH can be extremely emotional distressing to the patients, often endangering themselves as well as others. Thus an efficient therapeutic regime is indispensable to lower suffering and costs. Unfortunately the therapeutic options are rather limited and the most conventional therapeutic strategy is the use of antipsychotic drugs, however, in about 20-30 % of the patients even extended antipsychotic medication does not ameliorate AVH. Unfortunately, especially after exacerbation of symptoms many patients refuse conventional anti-psychotic therapy or a necessary increase of the dosage. Besides antipsychotic medication alternative therapeutic regimens like psychotherapy, psychoeducation, psychosocial interventions offer some improvement with electroconvulsive treatment as a last resort. Thus new therapeutic options and/or regimens are needed. Based upon neurobiological research regarding the generation of AVH non-pharmacological treatments like transcranial magnetic stimulation (TMS) were developed in non-responders to conventional drug therapy. Recently we additionally introduced transcranial direct current stimulation (tDCS) for AVH treatment and initial experience and results indicate a positive effect in patients. Presently still more important, several studies have demonstrated TMS to be an efficient therapeutic option with effect sizes from about 0.5 to 1.4, indicating a medium to large therapeutic effect. However, recently in larger cohorts of patients this statement has been challenged. In our own TMS studies we have observed response rates of about 40-60%, differentiated in patients exhibiting full remissions and patients with nearly no response. Obviously patients with AVH respond differently to various therapeutic approaches. In this context it is important to realize that all TMS studies have been performed on non-responders to conventional drug therapy. Considering that it may take longer than 2 to 4 months to establish if patients AVH respond to conventional therapy and that some patients neither respond to pharmacological nor TMS therapy it seems urgently necessary to understand the reason for these differential responsiveness. Furthermore it is urgently needed to investigate if TMS/tDCS are therapeutic alternatives to conventional antipsychotic treatment. Thus the aims of the following proposed project are to identify treatment responders based upon a better understanding of the neurobiological mechanisms responsible for responsiveness and to investigate if TMS/tDCS are effective treatment alternatives to conventional antipsychotic treatment. Regarding the identification of responders we in our own studies demonstrated an involvement of the language and auditory system in the generation of AVH comprising structural and functional cerebral alterations. Especially the superior temporal lobe (STL), including primary auditory cortex (PAC) and its connections, was identified as a key region involved in the generation, modulation and therapy of AVH. Based thereupon we aim to identify markers for the responsiveness to various therapeutic approaches, comprising conventional pharmacological antipsychotic therapy, TMS and tDCS of AVH in 100 patients suffering from schizophrenia (partly non-adherent to conventional therapy). We postulate that depending on which therapy a patient responds to the activity in the STL and its involvement in language networks will be different. Resting state networks of the language system, structural and functional connectivity as well as task related activity of the STL will be investigated. The study and the technology will be based upon knowledge and equipment previously sponsored by various SNF grants (single projects, SPUM and R´Equip). In conclusion we aim to identify neurobiological markers of responsiveness to various therapeutic regimes in AVH. Besides an improved understanding of the neurobiology of schizophrenia and AVH our goal is to improve the therapeutic alternatives in patients with AVH and thus to reduce both the individual suffering in patients and their relatives as well as the burden upon the society.
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