Reduced Density of Calbindin Immunoreactive GABAergic Neurons in the Occipital Cortex in Major Depression: Relevance to Neuroimaging Studies

Ketamine produces schizophrenia-like behavioral phenotypes in healthy people. Prolonged ketamine effects and exacerbation of symptoms were observed in schizophrenia patients after administration of ketamine. More recently, ketamine has been used as a potent antidepressant to treat patients with major depression. The genes and neurons that regulate behavioral responses to ketamine, however, remain poorly understood. Our previous studies found that Sp4 hypomorphic mice displayed several behavioral phenotypes relevant to psychiatric disorders, consistent with human SP4 gene associations with schizophrenia, bipolar, and major depression. Among those behavioral phenotypes, hypersensitivity to ketamine-induced hyperlocomotion has been observed in Sp4 hypomorphic mice. Here, we report differential genetic restoration of Sp4 expression in forebrain excitatory neurons or GABAergic neurons in Sp4 hypomorphic mice and the effects of these restorations on different behavioral phenotypes. Restoration of Sp4 in forebrain excitatory neurons did not rescue deficient sensorimotor gating, fear learning, or ketamine-induced hyperlocomotion. Restoration of Sp4 in forebrain GABAergic neurons, however, rescued ketamine-induced hyperlocomotion, but did not rescue deficient sensorimotor gating or fear learning. Our studies suggest that the Sp4 gene in forebrain GABAergic neurons plays an essential role in regulating some behavioral responses to ketamine.

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GABAergic neurons in nucleus accumbens are correlated to resilience and vulnerability to chronic stress for major depression

Oncotarget ◽

10.18632/oncotarget.16411 ◽

2017 ◽

Vol 8 (22) ◽

pp. 35933-35945 ◽

Cited By ~ 26

Author(s):

Zhaoming Zhu ◽

Guangyan Wang ◽

Ke Ma ◽

Shan Cui ◽

Jin-Hui Wang

Keyword(s):

Nucleus Accumbens ◽

Major Depression ◽

Chronic Stress ◽

Gabaergic Neurons

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

Acta Neuropsychiatrica ◽

10.1017/neu.2018.22 ◽

2018 ◽

Vol 31 (1) ◽

pp. 17-26 ◽

Cited By ~ 5

Author(s):

Marie Krøll Knudsen ◽

Jamie Near ◽

Anne Bastholm Blicher ◽

Poul Videbech ◽

Jakob Udby Blicher

Keyword(s):

Prefrontal Cortex ◽

Major Depression ◽

Magnetic Resonance ◽

Electroconvulsive Therapy ◽

Healthy Subjects ◽

Occipital Cortex ◽

Aminobutyric Acid ◽

Secondary Outcome ◽

Resonance Spectroscopy ◽

Significant Difference

AbstractObjectivePrior 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).MethodsIn 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.ResultsNo 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.ConclusionsOur 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.

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Common and distinct patterns of intrinsic brain activity alterations in major depression and bipolar disorder: voxel-based meta-analysis

Translational Psychiatry ◽

10.1038/s41398-020-01036-5 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Jiaying Gong ◽

Junjing Wang ◽

Shaojuan Qiu ◽

Pan Chen ◽

Zhenye Luo ◽

...

Keyword(s):

Bipolar Disorder ◽

Major Depression ◽

Brain Activity ◽

Meta Analysis ◽

Inferior Frontal Gyrus ◽

Superior Temporal Gyrus ◽

Occipital Cortex ◽

Anterior Cingulate ◽

The Right ◽

Intrinsic Brain Activity

Abstract Identification of intrinsic brain activity differences and similarities between major depression (MDD) and bipolar disorder (BD) is necessary. However, results have not yet yielded consistent conclusions. A meta-analysis of whole-brain resting-state functional MRI (rs-fMRI) studies that explored differences in the amplitude of low-frequency fluctuation (ALFF) between patients (including MDD and BD) and healthy controls (HCs) was conducted using seed-based d mapping software. Systematic literature search identified 50 studies comparing 1399 MDD patients and 1332 HCs, and 15 studies comparing 494 BD patients and 593 HCs. MDD patients displayed increased ALFF in the right superior frontal gyrus (SFG) (including the medial orbitofrontal cortex, medial prefrontal cortex [mPFC], anterior cingulate cortex [ACC]), bilateral insula extending into the striatum and left supramarginal gyrus and decreased ALFF in the bilateral cerebellum, bilateral precuneus, and left occipital cortex compared with HCs. BD showed increased ALFF in the bilateral inferior frontal gyrus, bilateral insula extending into the striatum, right SFG, and right superior temporal gyrus (STG) and decreased ALFF in the bilateral precuneus, left cerebellum (extending to the occipital cortex), left ACC, and left STG. In addition, MDD displayed increased ALFF in the left lingual gyrus, left ACC, bilateral precuneus/posterior cingulate gyrus, and left STG and decreased ALFF in the right insula, right mPFC, right fusiform gyrus, and bilateral striatum relative to BD patients. Conjunction analysis showed increased ALFF in the bilateral insula, mPFC, and decreased ALFF in the left cerebellum in both disorders. Our comprehensive meta-analysis suggests that MDD and BD show a common pattern of aberrant regional intrinsic brain activity which predominantly includes the insula, mPFC, and cerebellum, while the limbic system and occipital cortex may be associated with spatially distinct patterns of brain function, which provide useful insights for understanding the underlying pathophysiology of brain dysfunction in affective disorders, and developing more targeted and efficacious treatment and intervention strategies.

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Reduced density of glutamine synthetase immunoreactive astrocytes in different cortical areas in major depression but not in bipolar I disorder

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2015.00273 ◽

2015 ◽

Vol 9 ◽

Cited By ~ 19

Author(s):

Hans-Gert Bernstein ◽

Gabriela Meyer-Lotz ◽

Henrik Dobrowolny ◽

Jana Bannier ◽

Johann Steiner ◽

...

Keyword(s):

Major Depression ◽

Glutamine Synthetase ◽

Bipolar I Disorder ◽

Cortical Areas ◽

Reduced Density

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

Neuropsychopharmacology ◽

10.1038/sj.npp.1301234 ◽

2006 ◽

Vol 32 (2) ◽

pp. 471-482 ◽

Cited By ~ 238

Author(s):

Grazyna Rajkowska ◽

Gillian O'Dwyer ◽

Zsofia Teleki ◽

Craig A Stockmeier ◽

Jose Javier Miguel-Hidalgo

Keyword(s):

Prefrontal Cortex ◽

Major Depression ◽

Calcium Binding ◽

Binding Proteins ◽

Calcium Binding Proteins ◽

Gabaergic Neurons

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The structure of amorphous and polycrystalline materials using energy-filtered RDF analysis

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100130584 ◽

1992 ◽

Vol 50 (2) ◽

pp. 1190-1191

Author(s):

David Cockayne ◽

David McKenzie

Keyword(s):

Electron Diffraction ◽

Diffraction Pattern ◽

Density Function ◽

Electron Diffraction Pattern ◽

Polycrystalline Materials ◽

Nearest Neighbour ◽

X Ray ◽

Selected Area Electron Diffraction ◽

Reduced Density ◽

System F

The technique of Electron Reduced Density Function (RDF) analysis has ben developed into a rapid analytical tool for the analysis of small volumes of amorphous or polycrystalline materials. The energy filtered electron diffraction pattern is collected to high scattering angles (currendy to s = 2 sinθ/λ = 6.5 Å-1) by scanning the selected area electron diffraction pattern across the entrance aperture to a GATAN parallel energy loss spectrometer. The diffraction pattern is then converted to a reduced density function, G(r), using mathematical procedures equivalent to those used in X-ray and neutron diffraction studies.Nearest neighbour distances accurate to 0.01 Å are obtained routinely, and bond distortions of molecules can be determined from the ratio of first to second nearest neighbour distances. The accuracy of coordination number determinations from polycrystalline monatomic materials (eg Pt) is high (5%). In amorphous systems (eg carbon, silicon) it is reasonable (10%), but in multi-element systems there are a number of problems to be overcome; to reduce the diffraction pattern to G(r), the approximation must be made that for all elements i,j in the system, fj(s) = Kji fi,(s) where Kji is independent of s.

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