Magnetic resonance (MR) spectroscopic measurement of γ-aminobutyric acid (GABA) in major depression before and after electroconvulsive therapy

TY - JOUR

T1 - Magnetic resonance (MR) spectroscopic measurement of γ-aminobutyric acid (GABA) in major depression before and after electroconvulsive therapy

AU - Knudsen, Marie Krøll

AU - Near, Jamie

AU - Blicher, Anne Bastholm

AU - Videbech, Poul

AU - Blicher, Jakob Udby

PY - 2019/2/1

Y1 - 2019/2/1

N2 - OBJECTIVE: Prior studies suggest that a dysregulation of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) is involved in the pathophysiology of major depression. We aimed to elucidate changes in cortical GABA content in relation to depression and electroconvulsive therapy (ECT) using magnetic resonance spectroscopy (MRS).METHODS: In total, 11 patients with major depression or depressive episode of bipolar disorder (mean pre-ECT Ham-17 of 26) and 11 healthy subjects were recruited. GABA was quantified using short-TE MRS in prefrontal and occipital cortex. Other neurometabolites such as glutathione (GSH), N-acetylaspartate (NAA) and glutamate (Glu) were secondary outcome measures.RESULTS: No significant differences in GABA/Cr levels were observed between patients at baseline and healthy subjects in prefrontal cortex, t(20)=0.089, p=0.93 or occipital cortex t(21)=0.37, p=0.72. All patients improved on Ham-17 (mean post-ECT Ham-17 of 9). No significant difference was found in GABA, Glu, glutamine, choline or GSH between pre- and post-ECT values. However, we observed a significant decrease in NAA levels following ECT t(22)=3.89, p=0.0038, and a significant correlation between the NAA decline and the number of ECT sessions p=0.035.CONCLUSIONS: Our study does not support prior studies arguing for GABA as a key factor in the treatment effect of ECT on major depression. The reduction in NAA levels following ECT could be due to neuronal loss or a transient dysfunction in prefrontal cortex. As no long-term follow-up scan was performed, it is unknown whether NAA levels will normalise over time.

AB - OBJECTIVE: Prior studies suggest that a dysregulation of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) is involved in the pathophysiology of major depression. We aimed to elucidate changes in cortical GABA content in relation to depression and electroconvulsive therapy (ECT) using magnetic resonance spectroscopy (MRS).METHODS: In total, 11 patients with major depression or depressive episode of bipolar disorder (mean pre-ECT Ham-17 of 26) and 11 healthy subjects were recruited. GABA was quantified using short-TE MRS in prefrontal and occipital cortex. Other neurometabolites such as glutathione (GSH), N-acetylaspartate (NAA) and glutamate (Glu) were secondary outcome measures.RESULTS: No significant differences in GABA/Cr levels were observed between patients at baseline and healthy subjects in prefrontal cortex, t(20)=0.089, p=0.93 or occipital cortex t(21)=0.37, p=0.72. All patients improved on Ham-17 (mean post-ECT Ham-17 of 9). No significant difference was found in GABA, Glu, glutamine, choline or GSH between pre- and post-ECT values. However, we observed a significant decrease in NAA levels following ECT t(22)=3.89, p=0.0038, and a significant correlation between the NAA decline and the number of ECT sessions p=0.035.CONCLUSIONS: Our study does not support prior studies arguing for GABA as a key factor in the treatment effect of ECT on major depression. The reduction in NAA levels following ECT could be due to neuronal loss or a transient dysfunction in prefrontal cortex. As no long-term follow-up scan was performed, it is unknown whether NAA levels will normalise over time.

KW - Adult

KW - Aspartic Acid/analogs & derivatives

KW - Depressive Disorder, Major/diagnostic imaging

KW - Electroconvulsive Therapy/methods

KW - Female

KW - Humans

KW - Magnetic Resonance Spectroscopy/methods

KW - Male

KW - Middle Aged

KW - Occipital Lobe/diagnostic imaging

KW - Prefrontal Cortex/diagnostic imaging

KW - Treatment Outcome

KW - Young Adult

KW - gamma-Aminobutyric Acid/metabolism

U2 - 10.1017/neu.2018.22

DO - 10.1017/neu.2018.22

M3 - Journal article

C2 - 30079857

SN - 0924-2708

VL - 31

SP - 17

EP - 26

JO - Acta Neuropsychiatrica

JF - Acta Neuropsychiatrica

IS - 1

ER -