Dataset Information

Markers of glutamate synaptic transmission and plasticity are increased in the anterior cingulate cortex in bipolar disorder.

ABSTRACT:

Background

Cortical glutamate levels are elevated in bipolar disorder, but the interpretation of this increase is unclear because glutamate has metabolic as well as neurotransmitter roles. We investigated this by measuring vesicular glutamate transporter 1 (VGluT1) expression, which reflects activity at glutamate synapses. We also measured netrin-G1 and netrin-G2 messenger RNAs because these genes are involved in the formation and plasticity of glutamatergic connections.

Methods

Using quantitative polymerase chain reaction, we quantified transcripts for VGluT1, netrin-G1 (isoforms G1c, G1d, and G1f), and netrin-G2 in the anterior cingulate cortex from subjects with bipolar disorder (n = 34), schizophrenia (n = 35), and healthy control subjects (n = 35).

Results

Vesicular glutamate transporter 1, netrin-G2, and netrin-G1d and G1f were increased in bipolar disorder but not in schizophrenia. Netrin-G1c did not differ between groups. Netrin-G1c and netrin-G1f expression showed left-right asymmetries. Vesicular glutamate transporter 1 messenger RNA correlated with brain weight.

Conclusions

Increased VGluT1 expression is supportive of elevated glutamate neurotransmission in the anterior cingulate cortex in bipolar disorder. The netrin-G1 and netrin-G2 findings suggest there may be an underlying difference in the plasticity of the affected circuitry.

SUBMITTER: Eastwood SL

PROVIDER: S-EPMC2868790 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Publications

Markers of glutamate synaptic transmission and plasticity are increased in the anterior cingulate cortex in bipolar disorder.

Eastwood Sharon L SL Harrison Paul J PJ

Biological psychiatry 20100118 11

<h4>Background</h4>Cortical glutamate levels are elevated in bipolar disorder, but the interpretation of this increase is unclear because glutamate has metabolic as well as neurotransmitter roles. We investigated this by measuring vesicular glutamate transporter 1 (VGluT1) expression, which reflects activity at glutamate synapses. We also measured netrin-G1 and netrin-G2 messenger RNAs because these genes are involved in the formation and plasticity of glutamatergic connections.<h4>Methods</h4>U ...[more]

PMID: 20079890

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Project description:BackgroundThe subgenual Anterior Cingulate Cortex (sgACC), as a part of the Anterior Cingulate Cortex and the limbic system plays a crucial role in mood regulation. Previous structural and functional brain imaging studies of the sgACC have revealed alterations of Gray Matter (GM) volumes and Blood Oxygenation Level Dependent signals (BOLD) in patients with Major Depressive Disorder (MDD) and Bipolar Disorder (BD), suggesting potential biomarker traits for affective disorders.MethodIn this study we investigated the gray matter volume of the sgACC in 3 different patient groups: 40 MDD patients, of which 20 were medicated (MDDm) and 20 were unmedicated (MDDu), and 21 medicated BD patients, and compared them with 23 healthy volunteers. We examined GM volume alteration using high-resolution 7T Magnetic Resonance Imaging (MRI) which produced quantitative maps of the spin-lattice relaxation time (T1). T1 maps provide high contrast between gray and white matter, and at 7 Tesla voxels with submillimeter resolution can be acquired in a reasonable scan time. We developed a semi-automatic segmentation protocol based on refined landmarks derived from previous volumetric studies using quantitative T1 maps as raw input data for automatic tissue segmentation of GM, WM and CSF (cerebrospinal fluid) tissue. The sgACC ROI was then superimposed on these tissue probability maps and traced manually by two independent raters (F.B., M.M.) following our semi-automatic segmentation protocol. Interrater reliability was calculated on a subset of 10 brain scans for each hemisphere, showing an Intra-Class Correlation coefficient (ICC) r = 0.96 for left sgACC and r = 0.84 for right sgACC respectively. In summary, we have developed a reproducible and reliable semi-automatic segmentation protocol to measure gray matter volume in the sgACC. Based on previous findings from meta-analyses on morphometric studies of the sgACC, we hypothesized that patients with MDD would have lower gray matter sgACC volumes compared to healthy subjects.ResultsPost-hoc analysis revealed smaller subgenual volumes for the left hemisphere in both the medicated (MDDm) and non-medicated (MDDu) group versus healthy controls (p = .001, p = .008) respectively. For the right hemisphere, the (MDDu) and BD group exhibited significantly lower subgenual volumes than healthy controls (p < .001, p = .004) respectively.ConclusionTo our knowledge, this is the first morphometric MRI study using T1 maps obtained in high-resolution 7 Tesla MRI to compare MDD and BD patients with healthy controls.

Dataset Information

Markers of glutamate synaptic transmission and plasticity are increased in the anterior cingulate cortex in bipolar disorder.

Background

Methods

Results

Conclusions

Publications

Markers of glutamate synaptic transmission and plasticity are increased in the anterior cingulate cortex in bipolar disorder.

Similar Datasets

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