Augmentation of Neuronal Network Plasticity in Schizophrenia

Study Overview
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Brief Summary
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Current pathophysiological models of schizophrenia focus on disconnectivity of distributed neuronal systems to explain the multitude of psychic symptoms. However, therapeutic strategies targeting this specific pathobiology are lacking. Our recent work provides strong evidence that complex video-game training interventions facilitate fronto-hippocampal structural and functional connectivity within 2 months in healthy subjects. The planned project transfers this knowledge into a training study in schizophrenic patients to counteract disease-related disconnectivity. Underlying mechanisms and behavioral effects are extensively parametrized by resting state functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), spectroscopy and clinical short- and long-term outcome.

Official Title
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Augmentation of Neuronal Network Plasticity in Schizophrenia

Conditions
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Schizophrenia, Healthy

Intervention / Treatment
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* Behavioral: 3D navigation video game intervention
* Behavioral: video game intervention without 3D navigation
* Behavioral: No 3D navigation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: clinically stabilized at least one schizophrenic episode in their lives International Classification of Diseases 10 (ICD-10) F20.x (and F25) Exclusion Criteria: clinically relevant anemia MRI contraindication earlier electroconvulsive shock treatment significant somatic or neurological disease significant alcohol or substance abuse in the year before more than 1h video games per day more than 6 months before study start simultaneous major psychiatric disease (if symptomatic in the foreground)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3D Super Mario Game Condition<br>3D navigation video game intervention | Behavioral: 3D navigation video game intervention<br>* Participants intensively train with a video game (Super Mario DS)<br>|
| Active Comparator: 2D Super Mario Game Condition<br>Video game intervention without 3D navigation | Behavioral: video game intervention without 3D navigation<br>* Participants train with a video game (Super Mario Bros)<br>|
| Active Comparator: Kindle Device<br>No 3D navigation | Behavioral: No 3D navigation<br>* Participants read on a kindle device (control group)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| T1 - MRI | The investigators look for structural volume changes in T1 images (MRI) specifically in the hippocampus and prefrontal areas due to training | 2 months (= training time and 2 months after training end) | 
| Cognition - Spatial Orientation | The investigators look for changes in cognition specifically regarding spatial orientation (MATRICS, computer tests measuring spatial orientation with and without external cue) due to training. | 2 months (= training time and 2 months after training end) | 
| Positive & Negative Symptoms in patients | The investigators look for changes in positive and negative symptoms (PANSS) due to training. | 2 months (= training time and 2 months after training end) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting State fMRI | The investigators look for blood oxygen level dependency (BOLD) changes in resting state fMRI specifically in the Hippocampus and Prefrontal Areas due to the training | 2 months (= training time and 2 months after training end) | 
| Spectroscopy - glutamate | The investigators look for glutamate concentration changes in the hippocampus due to the training | 2 month (= training time and 2 month after training end) | 
| Diffusion Tensor Imaging (DTI) | The investigators look for structural connectivity changes in DTI images due to the training | 2 month (= training time and 2 month after training end) | 
| Biomarkers (BDNF & interleukin 1 & 6) | The investigators look for plasticity induced changes in biomarkers (interleukin1 and 6 and BDNF [brain-derived neurotrophic factor]) due to training | 2 month (= training time and 2 month after training end) |