Healthy Volunteers
Conditions
Brief summary
Alterations of functional brain networks have been frequently demonstrated in schizophrenia, although the exact underlying molecular mechanisms remain unrevealed. Ketamine is known to exert its schizophrenia-like effects through modulation of the glutamatergic system, thus facilitating the investigation of the impact of this specific transmitter system on resting state functional brain networks. The aim of the study is therefore to use pharmacological functional Magnetic Resonance Imaging (phMRI) to examine changes in brain networks involved in schizophrenia in response to ketamine application compared to placebo. 30 healthy subjects (15 females) will be examined twice using a double-blind, placebo-controlled, randomized, crossover, counterbalanced-order design. Resting state fMRI will be investigated before, during and after either placebo or ketamine intravenous infusion for 20 minutes. Prior to the main trial 10 additional participants will be included in an open pilot trial. Hypothesis: Ketamine application will induce changes in resting state networks previously associated with schizophrenia and in the connectivity of relevant brain regions such as the striatum, thalamus, caudate, hippocampus and amygdala. Furthermore, the application of ketamine will provoke changes in the BOLD-activation in three fMRI paradigms each performed before and after ketamine infusion.
Interventions
Bolus: 15 mg/kg over 1 minute, followed by a maintenance infusion of 0.25 mg/kg/h for 19 minutes.
Sponsors
Medical University of Vienna
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* general health based on history, physical examination, ECG, laboratory screening and structured clinical interview for DSM-IV(SCID) * willingness and competence to sign the informed consent form * aged 18 to 55 years
Exclusion criteria
* any medical, psychiatric or neurological illness * current or former substance abuse * any implant or stainless steel graft and any other contraindications for MRI * pregnancy * first degree relatives with a history of psychiatric illness or substance abuse * failures to comply with the study protocol or to follow the instructions of the investigating team * lifetime use of antipsychotic drugs * treatment with psychotropic agents such as SSRIs within the last 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ketamine-induced changes in BOLD-activity over time | 1 year | participants will be measured twice and all participants are expected to be recruited and measured within 1 year |
Secondary
| Measure | Time frame |
|---|---|
| Change of task-induced BOLD-activity by ketamine application | 60 minutes (before and after ketamine infusion) at each MRI session (interval between MRI scans: 1 week) |
Countries
Austria
Outcome results
None listed