Insight Into Hippocampal Neuroplasticity in Schizophrenia by Investigating Molecular Pathways During Physical Training

Study Overview
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Brief Summary
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Aerobic endurance training has shown positive effects on symptoms, cognition, daily functioning, and the structure of the hippocampus in patients with schizophrenia. The study investigates genetic and epigenetic influences on neuroplastic changes following three months of endurance training. A control group performs flexibility, strength, and balance training. The main objective is to examine the association between a genetic risk score for schizophrenia and volume increase in the CA4/DG region of the hippocampus. Additional goals include examining changes in synapses, brain structure, function, and metabolism, as well as clinical symptoms and cognitive performance.

Official Title
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Insight Into Hippocampal Neuroplasticity in Schizophrenia by Investigating Molecular Pathways During Physical Training

Conditions
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Schizophrenia, Neuronal Plasticity, Exercise

Intervention / Treatment
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* Procedure: Aerobic Endurance Training
* Procedure: Flexibility, strengthening and balance training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent for voluntary study participation. Patients with schizophrenia: diagnosis of schizophrenic psychosis according to ICD10 and DSM V, Positive And Negative Syndrome Scale (PANSS) total score ≤ 75 before the start of the intervention Reliable contraception in women of childbearing age Patients must have been treated with individualized medication according to valid treatment guidelines. All antipsychotic substances are allowed, also as depot medication. Treatment with one as well as with two antipsychotic substances is possible. The additional administration of low- and medium-potency antipsychotic substances as on-demand medication for the treatment of agitation and sleep disorders is possible, provided that the daily dosage of 150 CPZ units is not exceeded. The active substance and dose of the individualized antipsychotic medication used to achieve the inclusion criterion of psychopathological symptom remission must be constant for at least 2 weeks before inclusion in the study. Exclusion Criteria: Lack of reliability and sanity (examined by an independent psychiatrist) Positive urine drug screen for illicit drugs (except benzodiazepines) Acute suicide risk Other relevant psychiatric axis-I disorders according to the diagnostic testing procedure (Mini International Neuropsychiatric Interview, MINI) Other relevant neurological or other disorders Pregnancy or lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention Group<br>Aerobic endurance training on a bicycle ergometer | Procedure: Aerobic Endurance Training<br>* Aerobic endurance training on a bicycle ergometer (week 1 to 6: three units per week á 40 minutes, week 7 to 12: three units á 45 minutes, in groups of up to three patients over 13 weeks)<br>|
| Active Comparator: Control Group<br>Flexibility, strengthening and balance training | Procedure: Flexibility, strengthening and balance training<br>* Flexibility, strengthening and balance training (exercises from the areas of stretching, strength, balance and relaxation, 3x40 min from week 1-2, 3x45 min from week 3-4 and 3x50 min from week 5-13, in groups of up to three patients over 13 weeks)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hippocampal volume | Change in hippocampal subregion cornu ammonis (CA) 4 volume (∆CA4/DG) and its correlation with polygenetic risk factor (PRS) | 13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive functions | verbal memory, working memory, motor speed, verbal fluency, attention and speed of information processing assessed by BACS | 13 weeks | 
| Executive functions | visual attention and task switching (TMT-A, B), episodic memory with the What-Where-When Test and visuo-spatial short- and long-term memory with the Brief Visuospatial Memory Test-Revised (BVMT-R) | 13 weeks | 
| Symptoms severity | change over study duration assessed by PANSS, BNSS, CDSS | 13 weeks | 
| Functioning in daily life | Assessed by SOFAS, GAF, FROGS | 13 weeks | 
| Cardiovascular risk factors | Aerobic fitness levels (W/kg), body weight, waist circumference, body fat, lipid panel, HbA1c, physical activity as assessed with the IPAQ will be evaluated. | 13 weeks |