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- Title
Reduced parahippocampal and lateral temporal GABA<sub>A</sub>-[<sup>11</sup>C]flumazenil binding in major depression: preliminary results.
- Authors
Klumpers, Ursula M. H.; Veltman, Dick J.; Drent, Madeleine L.; Boellaard, Ronald; Comans, Emile F. I.; Meynen, Gerben; Lammertsma, Adriaan A.; Hoogendijk, Witte J. G.
- Abstract
Major depressive disorder (MDD) has been related to both a dysfunctional γ-amino butyric acid (GABA) system and to hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA). Although GABA has been suggested to inhibit HPA axis activity, their relationship has never been studied at the level of the central GABAA-benzodiazepine receptor in depressed patients or in relation to antidepressant treatment. Eleven depressed outpatients were compared, before and after treatment with citalopram, with nine age-matched healthy controls. The subjects were scanned using the positron emission tomography (PET) tracer [11C]flumazenil ([11C]FMZ). Parametric voxel-by-voxel Logan plots were compared with methods based on regions of interest (ROI), to provide volume of distribution (VT) and binding potential (BPND) values. Plasma GABA levels were determined and a dexamethasone-corticotropin releasing hormone (DEX-CRH) test was performed. In MDD, parametric voxel-by-voxel Logan plots showed bilateral reduced [11C]FMZ binding in the parahippocampal gyrus and right lateral superior temporal gyrus ( p uncorrected ≤0.001). In the temporal area, [11C]FMZ binding showed a strong inverse correlation with HPA axis activity. Plasma GABA did not discriminate MDD from controls, but correlated inversely with [11C]FMZ binding in the right insula. Following treatment with citalopram, voxel-based analysis revealed reduced binding in the right lateral temporal gyrus and dorsolateral prefrontal cortex. The bilateral reduction in limbic parahippocampal and right temporal [11C]FMZ binding found in MDD indicates decreased GABAA-benzodiazepine receptor complex affinity and/or number. The inverse relationship between GABAA binding in the temporal lobe and HPA axis activity, suggests that HPA axis hyperactivity is partly due to reduced GABA-ergic inhibition.
- Subjects
FLUMAZENIL; MENTAL depression; GABA; HYPOTHALAMIC-pituitary-adrenal axis; BENZODIAZEPINES; ANTIDEPRESSANTS
- Publication
European Journal of Nuclear Medicine & Molecular Imaging, 2010, Vol 37, Issue 3, p565
- ISSN
1619-7070
- Publication type
Article
- DOI
10.1007/s00259-009-1292-9