Effects of Quetiapine on Ultrastructural Hippocampal and Neurochemical Changes in Patients With Bipolar Disorder: Searching for Antidepressant and Mood Stabilising Neurophysiology
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Effects of Quetiapine on Ultrastructural Hippocampal and Neurochemical Changes in Patients With Bipolar Disorder: Searching for Antidepressant and Mood Stabilising Neurophysiology|
- Anisotropy in hippocampal formation detected with Diffusion Tensor Imaging (DTI) [ Time Frame: after 6 weeks ]Detection of pharmacologically induced equivalents of neurogenesis and synaptic sprouting in the hippocampal region.
- safety and tolerability of medical treatment [ Time Frame: every time during the study ]Observation of adverse events and tolerability assessed by vital signs and clinical chemistry
- Detection of pharmacologically induced localised volume changes [ Time Frame: after 6 weeks ]Measurement with 3D MPRAGE (structural scan)
- Detection of pharmacologically induced localised changes in water content [ Time Frame: after 6 weeks ]differentiation between neurogenesis/sprouting and mere water intake
- Detection of pharmacologically induced neurochemical changes in the medial temporal regions (Glx and NAA, choline) [ Time Frame: after 6 weeks ]Measurement of glutamate and N-acetylaspartate in the medial temporal lobe with MRS
- Detection of pharmacologically induced differential activation during an episodic memory task measured with fMRI. [ Time Frame: after 6 weeks ]Measurement of BOLD response using fMRI during an episodic memory test
|Study Start Date:||December 2007|
|Study Completion Date:||December 2010|
|Primary Completion Date:||February 2010 (Final data collection date for primary outcome measure)|
No Intervention: Healthy volunteers
MRI compatible, no present or past DSM-IV diagnosis
Active Comparator: patients with Bipolar Disorder
MRI compatible, presence of DSM-IV diagnosis for Bipolar Disorder
for 4 weeks, 300 - 800 mg per day in 2 doses
Quetiapine is an antipsychotic that has mood stabilizing and antidepressant effects (Vieta, 2005). Animal studies showed that the expression of neurotrophins and the subsequent modulation of the neuroplastic processes, including neurogenesis in the hippocampus, play a key role in the mechanism of mood stabilizing (Kim et al., 2004) and antidepressant (Santarelli et al., 2003). Since atypical antipsychotics also have antidepressant and mood stabilizing effect, it is hypothesized that the common mechanism of action in all three pharmacological classes is neurogenesis and synaptic sprouting in the hippocampal region. Thus, the aim of this study was to test this hypothesis.
Quetiapine was associated with antidepressant and mood stabilizing effects in patients with bipolar disorder (Vieta, 2005). The evidence based on animal studies shows that administration of quetiapine attenuates the decrease in levels of brain-derived neurotrophic factor in the hippocampi. This may explain the improved cognitive symptoms in patients with schizophrenia and depression (Luo et al., 2005, Park et al, 2006).
The aim of the study was to determine the pharmacological induced equivalents of neurogenesis and synaptic sprouting in the hippocampus, localized volume changes, changes in water content and neurochemical changes in the medial temporal regions.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01552837
|Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital Aachen|
|Aachen, Germany, 52074|
|Study Director:||Klaus Mathiak, Prof MD||Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital Aachen|