Increased Cortical GABA Concentrations in Depressed Patients Receiving ECT

Sanacora, Gerard; Mason, Graeme F.; Rothman, Douglas L.; Hyder, Fahmeed; Ciarcia, James; Ostroff, Robert; Berman, R.; Krystal, John H.

doi:10.1176/appi.ajp.160.3.577

Cited by 435 publications

(241 citation statements)

References 12 publications

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“…A proton magnetic resonance spectroscopy study in live patients shows a highly significant 52% reduction in GABA levels in the occipital cortex of 14 medication-free depressed subjects (Sanacora et al, 1999). Later studies by the same group demonstrate that low levels of GABA in the occipital cortex can be reversed by treatment with SSRIs or ECT (Sanacora et al, 2002(Sanacora et al, , 2003a. The ability of an SSRI to normalize GABA levels in depression and even increase it in healthy subjects (Bhagwagar et al, 2004b) suggests close interactions between these systems.…”

Section: Discussionmentioning

confidence: 99%

“…A proton magnetic resonance spectroscopy study revealed a large, 52% reduction in GABA levels in the occipital cortex of 14 medication-free depressed subjects as compared to 18 healthy control subjects (Sanacora et al, 1999). Later studies by the same investigators demonstrated that low levels of GABA in the occipital cortex in depressed patients can be reversed by treatment with selective serotonin reuptake inhibitors (SSRIs) or ECT (Sanacora et al, 2002(Sanacora et al, , 2003a. Interestingly, in the occipital cortex of healthy controls, SSRI treatment also results in the acute elevation of GABA (Bhagwagar et al, 2004b).…”

Section: Introductionmentioning

confidence: 99%

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GABAergic Neurons Immunoreactive for Calcium Binding Proteins are Reduced in the Prefrontal Cortex in Major Depression

Rajkowska

O'Dwyer

Teleki

et al. 2006

Neuropsychopharmacol

366

234

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Post-mortem morphometric studies report reductions in the average density and size of cortical neurons in the dorsolateral prefrontal cortex (dlPFC) and orbitofrontal cortex (ORB) in major depressive disorder (MDD). The contribution of specific neuronal phenotypes to this general pathology in depression is still unclear. Post-mortem sections from the dlPFC and ORB regions of 14 subjects with MDD and 11 controls were immunostained to visualize calbindin-immunoreactive (CB-IR) and parvalbumin-immunoreactive (PV-IR) presumptive GABAergic neurons. A three-dimensional cell counting probe was used to assess the cell packing density and size of CB-IR neurons in layers II + IIIa and PV-IR neurons in layers III-VI. The density of CB-IR neurons was significantly reduced by 50% in depression in the dlPFC and there was a trend toward reduction in the ORB. The size of CB-IR somata was significantly decreased (18%) in depression in the dlPFC with a trend toward reduction in the ORB. In contrast, there was no difference in the density of PV-IR neurons between the depressed and control groups in the dlPFC. The size of PV-IR neuronal soma was unchanged in depressed compared to control subjects in either dlPFC or ORB. In depression, subpopulations of GABAergic neurons may be affected differently in dlPFC and ORB. A significant reduction in the density and size of GABAergic interneurons immunoreactive for calcium binding proteins was found predominantly in the dlPFC region. These cellular changes are consistent with recent neuroimaging studies revealing a reduction in the cortical levels of GABA in depression.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

GABAergic Neurons Immunoreactive for Calcium Binding Proteins are Reduced in the Prefrontal Cortex in Major Depression

Rajkowska

O'Dwyer

Teleki

et al. 2006

Neuropsychopharmacol

366

234

View full text Add to dashboard Cite

show abstract

“…Studies using proton magnetic resonance spectroscopy (MRS) have shown lowered GABA levels in occipital cortex in acutely depressed patients, particularly those with a melancholic syndrome (Sanacora et al 2004). Both SSRI treatment (Sanacora et al 2002) and electroconvulsive therapy (ECT) (Sanacora et al 2003) increase GABA levels in depressed patients ; however, this effect is not seen with cognitive behaviour therapy despite clinical improvement (Sanacora et al 2006).…”

Section: Gamma-aminobutyric Acid (Gaba)mentioning

confidence: 99%

‘It's not over when it's over’: persistent neurobiological abnormalities in recovered depressed patients

2007

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The tendency of major depression to recur is a leading problem in clinical management and is responsible for much of the illness burden. Until recently, biological studies of depression have focused on the mechanisms involved in acute illness but there are now many data to suggest that neurobiological abnormalities persist when depressed patients are clinically recovered and withdrawn from medication. These abnormalities encompass a number of neurochemical and neuropsychological mechanisms that could be relevant to recurrence, including changes in the availability of serotonin (5-hydroxytryptamine, 5-HT) receptor subtypes, decreases in cortical c-aminobutyric acid (GABA), increases in cortisol secretion and negative biases in the processing of emotional information. Studies of groups at high risk of depression before illness onset will help to clarify which biological abnormalities precede the development of depression and which are the product of recurrent illness. Ultimately this work should lead to a better understanding of the neurobiology of vulnerability to depression and more innovative approaches to primary and secondary prevention.

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“…GABA concentrations measured with proton magnetic resonance spectroscopy were significantly elevated in the occipital cortex of depressed patients following ECT. [26] The increased levels of GABA in association with ECT may explain its antidepressant actions. In addition, increased GABA concentrations in the occipital cortex were also found during treatment of MDD with serotonergic antidepressants.…”

Section: Gaba In Mdsmentioning

confidence: 99%

The role of anti-glutamic acid decarboxylase autoantibodies in mood disorders

Liguori¹,

Manchia²,

Tondo³

2015

Neuroimmunol Neuroinflammation

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Increased Cortical GABA Concentrations in Depressed Patients Receiving ECT

Abstract: Occipital cortex GABA concentrations increase two-fold following ECT. This suggests possible GABAergic involvement in ECT's mechanism of anticonvulsant and antidepressant actions.

Cited by 435 publications

References 12 publications

GABAergic Neurons Immunoreactive for Calcium Binding Proteins are Reduced in the Prefrontal Cortex in Major Depression

GABAergic Neurons Immunoreactive for Calcium Binding Proteins are Reduced in the Prefrontal Cortex in Major Depression

‘It's not over when it's over’: persistent neurobiological abnormalities in recovered depressed patients

The role of anti-glutamic acid decarboxylase autoantibodies in mood disorders

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