RP7 Clinical Research of Mental Disorders – Running Grants and Projects

NATIONAL PROJECTS EXCEPT OPERATIONAL PROGRAMMES

The Czech Science Foundation

Cognitive Superaging (18-06199S)
Investigator: MUDr. Miloslav Kopeček, Ph.D.
Principle investigator: NIMH
Duration: 1.1.2018–31.12.2020
Total budget NIMH: 5 208 000 CZK
Abstract: Results from neuropsychological studies indicate a general age-related decline in cognition. Despite this fact, there is a group of oldest-old individuals with better cognitive functioning than the mean of sexagenarians. This group is called superagers. Most superaging studies have been focused primarily on memory and did not deal with other cognitive domains. Cross-sectional superaging studies are not able to evaluate directly the role of cognitive maintenance and disentangle its role from cognitive reserve. Our study is an extension of a longitudinal study (n = 540) realized in 2012–2015. We will assess 100 adults older than 79 years with the same neuropsychological tests and questionnaires as in 2012 and 2015. We will test the hypothesis that cognitive maintenance (based on six years change of cognition) is a better predictor of cognitive aging (cognitive performance in 2018) than the cognitive reserve (cognitive performance in 2012).

The Stranger as a Symbol of Otherness – How Personality Influences Our Attitudes (19-10057S)
Investigator: doc. PhDr. Marek Preiss, Ph.D.
Principle investigator: NIMH
Duration: 1.1.2019–31.12.2021
Total budget NIMH: 4 282 000 CZK
Abstract: This project is concerned with the attitude toward otherness, while taking into account the personality functioning and the attitudes toward foreigners, minorities, and migrants. It enhances the sociological and anthropological concept of otherness by examining the psychodynamic interpretation of various differences, while putting the emphasis on the unfamiliarity of our own differentness/otherness. Furthermore, it accentuates the explanation of the attitudes toward otherness in terms of fear of losing the center core of one´s identity – the psychic home. Likewise, it builds upon the previous work and enhances the knowledge of otherness by an in-depth recognition of the personality and by measuring the variability of one´s daily attitudes “here and now.” In the first part of the project, participant´s personality is subjected to an in-depth assessment of personality functioning. The second part of the project monitors 5 different groups of participants (xenophobic, xenophilic, personality disorders, high levels of neuroticism, and general population) using experience sampling.

The role of Inferior Parietal Lobe in Self-Agency (20-24782S)
Investigator: prof. MUDr. Pavel Mohr, Ph.D.
Principle investigator: NIMH
Duration: 1.1.2020–31.12.2022
Total budget NIMH: 7 731 000 CZK
Abstract: The ability of identifying and distinguishing one's own actions from the external processes (Self / Other Agency) is a key prerequisite for one's orientation in the world and society. Proposed project builds upon results of our previous fMRI experiments both on healthy participants and schizophrenia patients. Here, using the combination of dynamical causal modeling (DCM) and noninvasive brain neuromodulation (tACS), we aim for confirming the causal role of inferior parietal lobe (IPL) in Self / Other Agency discrimination. Project is divided into five steps, starting with identifying the candidate subregion within IPL based on contrast analysis and DCM on the MRI data obtained in experiments realized earlier. Following will be an explorative and confirmatory neuromodulation experiments, aiming for confirming the causal role of identified region by targeted external neuromodulation. Comparison of pre- and post-neuromodulation resting state MRI will verify the effective locus of neuromodulation protocol.

Psychoplastogenicity of Psilocybin – the Interplay of Serotonergic Mechanisms, Sleep-wake Cycle and Neuroplasticity on Memory Consolidation (20-25349S)
Investigator: doc. RNDr. Zdeňka Bendová, Ph.D.
Principle investigator: NIMH
Duration: 1.1.2020–31.12.2022
Total budget NIMH: 12 029 000 CZK
Abstract: Serotonergic psychedelic psilocybin is currently extensively studied as a so-called fast-acting antidepressant in the indication of pharmacoresistant depression. One of the most likely mechanisms leading to an antidepressant effect is the induction of synaptic plasticity. In depression cognitive deficits are a common symptom. Previously we have found that psilocin improves spatial memory consolidation in the rat. The aim of the project is therefore to evaluate the effect of 5-HT2A/C and 5-HT1A agonist psilocybin on the hippocampus-dependent memory consolidation in Morris water maze and novel object and place recognition tasks in relation to synaptic plasticity in the rat. In order to evaluate the effect of sleep and sleep deprivation, EEG / EMG and behavioural activity will be continuously recorded in animals via wireless implantable telemetry. Synaptic plasticity will be evaluated in 3D brain organoids derived from animals from cognitive experiments. The role of 5-HT2A/C and 5-HT1A receptors will be assessed using selective antagonists in both in vivo models and organoids.

 

 

Czech Health Research Council 

Transcranial Magnetic Stimulation in the Treatment of Bipolar Depression (16-31380A)
Investigator: MUDr. Tomáš Novák, Ph.D.
Principle investigator: NIMH
Duration: 1.4.2016–31.12.2020
Total budget NIMH: 6 119 000 Kč
Abstract: Four-week, randomized, sham-controlled, double-blind, parallel study to evaluate the efficacy of high-frequency MRI-guided repetetive transcranial magnetic stimulation (rTMS) targeted to two different brain areas in bipolar depression with the consequent four-week open-label extension will be carried out. Sixty patients will be randomized to the three groups: 1) active rTMS over the left dorsolateral prefrontal cortex, 2) active rTMS over the right ventrolateral prefrontal cortex, 3) sham rTMS. Site of application will be navigated by T1-weighted MRI images. Patients will continue on stable dose of mood stabilizers during the study.  Primary outcome is the change in MADRS scale among groups, secondary are the rate of MADRS responders, change in self-evaluation scales for depression, and the rate of sustained response over the follow-up. EEG before and after study will be analyzed by low-resolution electromagnetic tomography (LOTERA) to find out the change in brain electric activity related to response to rTMS.

Developmental Dynamics of Clinical and Neurophysiological Features in Children and Adolescents at Genetic Risk of Bipolar Affective Disorder (17-32478A)
Investigator: MUDr. Tomáš Novák, Ph.D.
Principal investigator: Motol University Hospital (MUDr. Michal Goetz, Ph.D.)
Co-investigator/Partner: NIMH
Duration: 1.4.2017–31.12.2020
Total budget: 8 157 000 CZK
Total budget NIMH: 3 501 000 CZK
Abstract: Prospective, cohort, observational study, of children and adolescents at risk of bipolar disorder ( high-risk offspring, HRO). The objective is to identify clinical and laboratory markers of the risk of mood disorder. Sixty HRO and sixty age and sex matched offspring of parents without psychiatric illness as
controls will be assessed annually. Frequency of the of psychiatric diagnosis, scores of anxiety and affective symptoms, self reported QoL, executive and attention functions, memory and emotion recognition will be assessed. Sleep quality and quantity by the use of subjective and objective methods as well as electroencephalographic indicators of fronto-limbic-connectivity will be evaluated. The differences between HRO and controls, between symptomatic and asymptomatic HRO and between follow-up evaluations will be compared.

Causes of Assaultive Behavior among Patients with Psychosis (17-32445A)
Investigator: Tereza Příhodová, MA
Principle investigator: Charles University Prague, 1st Medical (doc. MUDr. jan Vevera, Ph.D.)
Co-investigator/Partner: NIMH
Doba řešení: 1.4.2017–51.12.2020
Total budget: 7 847 000 CZK
Total budget NIMH: 2 123 000 NIMH
Abstract: The proposed project is aimed to study the causes, predictors and motivations of violent behavior of inpatients with psychosis. Origins of violence in patients with schizophrenia are heterogeneous, with different pathways leading to the same phenotype of violent behavior. The study will include the patients with the diagnosis of schizophrenia and acute psychotic disorder that will be admitted to the Psychiatric Department of Charles University, 1st Medical Faculty, Prague (N 80) and Psychiatric hospital in Bohnice (N 420) at any time between 1 /4/2017 and 31/12/ 2019, and who will exhibit violence during the present hospitalization. Based on our Pilot studies I and III we expect to find 500 violent patients (250 females, 250 males). Nature of violent behavior and its predictors will be analyzed by interview, scales and behavioral task. Better understanding of factors underlying violent behavior will help us address appropriate therapeutic interventions and improve validity of commonly used violence risk prediction instruments.

Sleep and Brain Changes Related to Memory Decline in Mild Cognitive Impairment (NV18-07-00272)
Investigator: doc. MUDr. Aleš Bartoš, Ph.D.
Principle investigator: NIMH
Duration: 1.1.2018–31.12.2021
Total budget NIMH: 9 433 000 CZK
Abstract: The expected aging of the population will increase people with memory disease and dementia, especially Alzheimer's disease. Mild cognitive impairment (MCI) is a risk syndrome in which intervention can delay the development of Alzheimer's disease. Sleep disorders and changes in magnetic resonance imaging of the brain occur along with memory impairment in MCI. The aim of the project is to find the connection between slow-wave sleep and sleep spindles, corresponding brain structures and memory consolidation during sleep using polysomnography, magnetic resonance imaging of the brain and paired associative learning test. Then we will investigate whether it is possible to enhance memory consolidation during sleep in MCI by manipulating sleep rhythms using acoustic stimulation. Based on the results, we will illuminate mechanisms between sleep, brain structure, and memory impairment in MCI. This comprehensive sleep approach can bring new insights into early interventions and other clinical strategies at the stage of MCI.

Overlap of Neurodegenerative Dementias and Their Clinic-pathological Correlations: A Prospectiveretrospective Multicentric Study (NV19-04-00090)
Investigator: doc. MUDr. Aleš Bartoš, Ph.D.
Principle investigator: Thomayer Hospital (doc. MUDr. Radoslav Matěj, Ph.D.)
Co-investigator-Partner: NIMH; University Hospital Olomouc (doc. MUDr. Kateřina Menšíková, Ph.D.); Hospital
 Na Homolce (MUDr. Jiří Keller, Ph.D.); General University Hospital in Prague (prof. MUDr. Jan Roth, CSc.)
Duration: 1.5.2019–31.12.2022
Total budget: 15 127 000 CZK
Total budget NIMH: 1 580 000 CZK
Abstract: Neurodegenerative diseases are serious fatal disorders caused by progressive loss of specific neuronal populations.Correct recognition of neurodegenerative dementias during the patients’ life is still very difficult.Combinations of two or more neurodegenerative diseases are far more common than previously admitted, even though more precise epidemiological data is still missing. Overlap of neurodegenerative diseases may be involved into a more rapid progression or very atypical presentation in many patients.Moreover, newly described neuropathological entities related to the aging-Aging-related tau astrogliopathy(ARTAG) or Primary age-related tauopathy(PART)-are more frequent than previously expected and till this time a precise definition of the clinical picture of these impairments is missing.The principal objective is to estimate the proportion of comorbid neurodegenerative dementias in a single centre and in a neuropathological reference laboratory based on retrospective and prospective clinic-pathological correlations in order to improve the clinical diagnosis of different diseases.

Psychoplastogenicity of Psilocybin – the Interplay of Serotonergic Mechanisms, Sleep-wake Cycle and Neuroplasticity on Memory Consolidation (20-25349S)
Investigator: doc. RNDr. Zdeňka Bendová, Ph.D.
Principle investigator: NIMH
Duration: 1.1.2020–31.12.2022
Total budget NIMH: 12 029 000 CZK
Abstract: Serotonergic psychedelic psilocybin is currently extensively studied as a so-called fast-acting antidepressant in the indication of pharmacoresistant depression. One of the most likely mechanisms leading to an antidepressant effect is the induction of synaptic plasticity. In depression cognitive deficits are a common symptom. Previously we have found that psilocin improves spatial memory consolidation in the rat. The aim of the project is therefore to evaluate the effect of 5-HT2A/C and 5-HT1A agonist psilocybin on the hippocampus-dependent memory consolidation in Morris water maze and novel object and place recognition tasks in relation to synaptic plasticity in the rat. In order to evaluate the effect of sleep and sleep deprivation, EEG / EMG and behavioural activity will be continuously recorded in animals via wireless implantable telemetry. Synaptic plasticity will be evaluated in 3D brain organoids derived from animals from cognitive experiments. The role of 5-HT2A/C and 5-HT1A receptors will be assessed using selective antagonists in both in vivo models and organoids.

Gut Microbiome and Autoimmune Mechanisms in Patients with Central Hypersomnia
(NU20-04-00088)
Investigator: MUDr. Jitka Bušková, Ph.D.
Principle investigator: Všeobecná fakultní nemocnice v Praze
Project partners: NIMH, Mikrobiologický ústav AV ČR
Duration: 1.5.2020–31.12.2023
Total budget: 13 999 000 Kč
Total budget NIMH: 1 807 000 Kč
Abstract: Narcolepsy type 1 (NT1), narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH)
have as a main symptom central hypersomnia (CH). The etiopathophysiology of NT1 is related to the hypocretin deficiency of autoimmune origin. The etiopathophysiology of NT2 and IH is unknown. There are doubts on the independence of NT2 and IH and their long-term course. The gut microbiota has an impact on brain functions and behavior either directly by mediators’ production or indirectly via autoantibodies against selected neurons. This evokes the hypothesis that microbiota has a role in
etiopathophysiology of diseases with CH and may modify actual intensity of hypersomnia itself. Patients with CH and healthy controls will be clinically examined (including the long-term evolution of NT2 and IH). Their stools will be genetically analyzed in attempt to define the microbiome of the gut microbiota. The autoantibodies will be searched in their blood. The results will be mutually correlated. This research may elucidate the pathophysiology of CH disorders as well as may help to counselling
the patients and fina
Primary scientific aims: 1. To analyze the composition of the intestinal microbiome in patients with central hypersomnia and to compare it to healthy individuals. 2. To compare the composition of the gut microbiome in NT1, NT2, IH, and healthy controls. 3. To detect potential changes in intestinal barrier functions in patients with central hypersomnia. 4. To determine levels of autoantibodies against hypocretin in the serum of patients with central hypersomnia and in healthy subjects and to detect other possible autoantibodies against neuronal antigens in the serum of patients with central hypersomnia. 5. To correlate the changes found in gut microbiome composition, gut barrier function and autoantibody levels with clinical findings in patients (day-time sleep parameters, night sleep quality, co-morbidity such as depression, REM sleep muscle atonia disturbances, restless leg syndrome, sleep apnea, treatment etc.), and with parameters of biological samples obtained earlier in the diagnosis of disease (blood, HLA DQB1*0602 positivity and cerebrospinal fluid hypocretin level).
Secondary scientific aims: 1. To describe retrospectively the long-term evolution of NT2 and IH and to describe the clinical status of NT2 and IH in the elderly. 2. To analyze the influence of microbiota and eating habits on efficacy of standard pharmacological treatments. 3. Validation of Narcolepsy severity scale and Idiopathic hypersomnia severity scale in the Czech language. 4. Further participation of both
clinical departments in EU-NN scientific program (http://eu-nn.com/) (database etc.).

 

 

The Technology Agency of The Czech Republic

 

Alivio mobile game reducing OCD symptoms (TL03000637)
Investigator: MUDr. Pavla Stopková, Ph.D.
Principle investigator: Pixelfield s.r.o. (Filip Háša)
Project partner: NIMH Duration: 1.4.2020–31.3.2022
Total budget: 6 481 426 CZK
Total budget NIMH: 2 585 919 CZK
Abstract: The main objective of the proposed project is to create a therapeutic tool in the form of a mobile game Alivio that would help people with subsyndromal, mild to moderate obsessive-compulsive (OC) symptoms to alleviate symptoms (obsessions and compulsions) by using cognitive-behavioral therapy (KBT). The secondary objective of Alivio is to reach the general public and in an innovative way, through one's own experience, to familiarize with the typical symptoms of OCD disease and its subtypes. Alivio, together with a promotional campaign, could contribute to raising awareness of OCD disease that affects a significant part of the population and is not adequately addressed.

 

OPERATIONAL PROGRAMMES

OP Prague – Growth Pole of The Czech Republic

PoC of commercialization concepts formulated by Innovation Agency ILA II (CZ.07.1.02/0.0/0.0/16_040/0000369)
Investigator: doc. MUDr. Aleš Bartoš, Ph.D.
Principle investigator: ILA s.r.o. 
Co-investigator/Partner: NIMH
Duration: 1.1.2018–30.6.2020
Total budget: 13 207 789 CZK
Total budget NIMH: 3 725 053 CZK
Abstract: The project of the National Institute of Mental Health focuses on developing the capacities, knowledge and skills of the applicant's managerial, research and other personnel in the field of strategic R&D management, as well as setting up and implementing strategic management within the research organization in accordance with the European Charter for Researchers and the Code of Conduct for the Recruitment of Researchers and to Achieve the HR Award.

 

INTERNATIONAL PROJECTS

Interreg DANUBE

Innovation for Dementia in the Danube Region, INDEED (INDEED is DTP2-087-1.2)
Investigator: doc. MUDr. Aleš Bartoš, Ph.D.
Principle investigator: Klinikum rechts der Isar der Technischen Universität München
Co-investigator: NIMH
Partners: The Brain Company Austria, Wirtschaftsuniversitat Wien, Bulgarian Society of Dementia, Social Cluster Association HU, Romanian Alzheimer Society, Memory Centre Bratislava, University of Ljubljana, Alzheimer Association Bosna Hercegovina, Federal Ministry of Health- Federation of Bosnia and Herzegovina, Medical University of Sofia, City of Zagreb, Ministry of Health of the Republic of Croatia, University of Zagreb, MEDIWARE corp.CZ, Bavarian Research Alliance GmbH, Bavarian State Ministry of Health and Care, German Alzheimer Association, Slovak Medical Association
Duration: 1.7.2018–30.6.2021
Total budget: 1 726 514 Euro
Total budget NIMH: 52 074 Euro
https://www.nudz.cz/files/pdf/indeed-final4.pdf

 

 

 


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