Network Dysfunction, Schizophrenia and Pharmacological Magnetic Resonance Imaging (phMRI)

Brain Network Dysfunction as a Model for Schizophrenia: Connectivity Alterations Using Ketamine and Pharmacological Magnetic Resonance Imaging

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.

participants will be measured twice and all participants are expected to be recruited and measured within 1 year

60 minutes (before and after ketamine infusion) at each MRI session (interval between MRI scans: 1 week)

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

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