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Clinical Trial
. 2010 Mar;37(3):565-74.
doi: 10.1007/s00259-009-1292-9. Epub 2009 Nov 5.

Reduced parahippocampal and lateral temporal GABAA-[11C]flumazenil binding in major depression: preliminary results

Ursula M H Klumpers  1 , Dick J Veltman, Madeleine L Drent, Ronald Boellaard, Emile F I Comans, Gerben Meynen, Adriaan A Lammertsma, Witte J G Hoogendijk
Affiliations
Clinical Trial

Reduced parahippocampal and lateral temporal GABAA-[11C]flumazenil binding in major depression: preliminary results

Ursula M H Klumpers et al. Eur J Nucl Med Mol Imaging. 2010 Mar.

Abstract

Purpose: Major depressive disorder (MDD) has been related to both a dysfunctional gamma-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 GABA(A)-benzodiazepine receptor in depressed patients or in relation to antidepressant treatment.

Methods: 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 [(11)C]flumazenil ([(11)C]FMZ). Parametric voxel-by-voxel Logan plots were compared with methods based on regions of interest (ROI), to provide volume of distribution (V(T)) and binding potential (BP(ND)) values. Plasma GABA levels were determined and a dexamethasone-corticotropin releasing hormone (DEX-CRH) test was performed.

Results: In MDD, parametric voxel-by-voxel Logan plots showed bilateral reduced [(11)C]FMZ binding in the parahippocampal gyrus and right lateral superior temporal gyrus (p uncorrected < or =0.001). In the temporal area, [(11)C]FMZ binding showed a strong inverse correlation with HPA axis activity. Plasma GABA did not discriminate MDD from controls, but correlated inversely with [(11)C]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.

Conclusion: The bilateral reduction in limbic parahippocampal and right temporal [(11)C]FMZ binding found in MDD indicates decreased GABA(A)-benzodiazepine receptor complex affinity and/or number. The inverse relationship between GABA(A) binding in the temporal lobe and HPA axis activity, suggests that HPA axis hyperactivity is partly due to reduced GABA-ergic inhibition.

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References

    1. Pharmacopsychiatry. 2003 Nov;36 Suppl 3:S207-14 - PubMed
    1. J Comput Assist Tomogr. 1997 Jul-Aug;21(4):554-66 - PubMed
    1. Arch Gen Psychiatry. 2007 Feb;64(2):193-200 - PubMed
    1. Biol Psychiatry. 2006 Feb 1;59(3):284-6 - PubMed
    1. Depress Anxiety. 2007;24(7):495-517 - PubMed

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