Effects of Quetiapine on Ultrastructural Hippocampal and Neurochemical Changes in Patients With Bipolar Disorder: Searching for Antidepressant and Mood Stabilising Neurophysiology

RWTH Aachen University33 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Bipolar Disorder

Interventions

SeroquelDRUG

for 4 weeks, 300 - 800 mg per day in 2 doses

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * age ranging 18 - 55 years old * intelligence coefficient (IQ) of minimum 85 as estimated by MWT-B * MRI compatibility * for healthy volunteers - no DSM-IV diagnosis * patients should have had a diagnosis of bipolar disorder in accordance with DSM-IV. Exclusion Criteria: * substances or alcohol abuse or dependence (except caffeine and nicotine) at enrollment; * medical conditions that would affect absorption, distribution, metabolism or excretion of study treatment; * unstable or inadequately treated medical illness (diabetes, angina, pectoris, hypertension); * diabetes mellitus * patients who in the opinion of the investigator pose a risk of suicide or danger to self or others, * patients who known intolerance or lack of response to Quetiapine fumarate, * patients who use of any of the cytochrome P450 3A4 inhibitors (ketoconazole, itraconazole, nelfinavir, ritonavir, fluvoxamine and saquinavir) in the 14 days preceding enrollment, * patients who use of any of the cytochrome P450 inducers (phenytoin, carbamazepine, barbiturates, rifampin, St. John's Wort and glucocorticoids) in the 14 days preceding enrollment, * current treatment of Quetiapine or use of mood stabilizer or antidepressant as co-medication throughout the study. * lack of inform consent

Locations (1)

Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital Aachen

Aachen, Germany

Outcomes

Primary Outcomes

Anisotropy in hippocampal formation detected with Diffusion Tensor Imaging (DTI)

Detection of pharmacologically induced equivalents of neurogenesis and synaptic sprouting in the hippocampal region.

Time frame: after 6 weeks

Secondary Outcomes

safety and tolerability of medical treatment

Observation of adverse events and tolerability assessed by vital signs and clinical chemistry

Time frame: every time during the study

Detection of pharmacologically induced localised volume changes

Measurement with 3D MPRAGE (structural scan)

Time frame: after 6 weeks

Detection of pharmacologically induced localised changes in water content

differentiation between neurogenesis/sprouting and mere water intake

Time frame: after 6 weeks

Detection of pharmacologically induced neurochemical changes in the medial temporal regions (Glx and NAA, choline)

Measurement of glutamate and N-acetylaspartate in the medial temporal lobe with MRS

Time frame: after 6 weeks

Detection of pharmacologically induced differential activation during an episodic memory task measured with fMRI.

Measurement of BOLD response using fMRI during an episodic memory test

Time frame: after 6 weeks

Data from ClinicalTrials.gov

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