MK4MDD

Genetic/Epigenetic Locus Search Cross Data Search

Study Report

Reference

Citation	Klumpers, 2010 PubMed
Full Info	Klumpers, U.M., Veltman, D.J., Drent, M.L., Boellaard, R., Comans, E.F., Meynen, G., Lammertsma, A.A. and Hoogendijk, W.J. (2010) Reduced parahippocampal and lateral temporal GABAA-[11C]flumazenil binding in major depression: preliminary results. Eur J Nucl Med Mol Imaging, 37, 565-574.

Study

Hypothesis or Background	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.
Sample Information	Eleven depressed outpatients were compared, before and after treatment with citalopram, with nine age-matched healthy controls.
Method Detail	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.
Method Keywords	positron emission tomography (PET); dose administration
Result	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.
Conclusions	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.

Relationships reported by Klumpers, 2010

Component A Approved Name (Name in Paper)	Component A Type	Component B Approved Name (Name in Paper)	Component B Type	Statistical Result	Relationship Description	Result Category (Positive/Negative))
MDD	syndrome	Hypothalamic-pituitary-adrenal axis (hypothalamic-pituitary-adrenal axis (HPA))	neurobiological system		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).	Positive
right insula (right insula)	brain morphology and function	gamma-Aminobutyric Acid receptor (GABA(A)-benzodiazepine receptor)	molecule		Plasma GABA did not discriminate MDD from controls, but correlated inversely with [(11)C]FMZ binding in the right insula.	Positive
Temporal Lobe (temporal area)	brain morphology and function	gamma-Aminobutyric Acid receptor (GABA(A)-benzodiazepine receptor)	molecule		In the temporal area, [(11)C]FMZ binding showed a strong inverse correlation with HPA axis activity.	Positive
Hypothalamic-pituitary-adrenal axis (hypothalamic-pituitary-adrenal axis (HPA))	neurobiological system	gamma-Aminobutyric Acid receptor (GABA(A)-benzodiazepine receptor)	molecule		In the temporal area, [(11)C]FMZ binding showed a strong inverse correlation with HPA axis activity. 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.	Positive
MDD	syndrome	Parahippocampal gyrus (parahippocampal gyrus)	brain morphology and function	P-value uncorrected < or =0.001	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). 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.	Positive
MDD	syndrome	right superior temporal gyrus (right lateral superior temporal gyrus)	brain morphology and function	P-value uncorrected < or =0.001	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). 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.	Positive
Hypothalamic-pituitary-adrenal axis (hypothalamic-pituitary-adrenal axis (HPA))	neurobiological system	Gamma-aminobutyric acid (GABA)ergic system (gamma-aminobutyric acid (GABA)ergic system)	neurobiological system		In the temporal area, [(11)C]FMZ binding showed a strong inverse correlation with HPA axis activity. 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.	Positive
MDD	syndrome	Gamma-aminobutyric acid (GABA)ergic system (gamma-aminobutyric acid (GABA)ergic system)	neurobiological system		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).	Positive