Reduced Anterior Cingulate Glutamate in Pediatric Major Depression: A Magnetic Resonance Spectroscopy Study

Rosenberg, David; MacMaster, Frank P.; Mirza, Yousha; Smith, Janet; Easter, Phillip C.; Banerjee, Sube; Bhandari, Rashmi; Boyd, Courtney; Lynch, Michelle; Rose, Michelle; Ivey, Jennifer; Villafuerte, Rosemond A.; Moore, Gregory J.; Renshaw, Perry F.

doi:10.1016/j.biopsych.2005.05.007

Cited by 130 publications

(81 citation statements)

References 41 publications

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“…To our knowledge, this is the first study to show such changes in subcortical regions. Most of the previous reports in the literature have shown these changes in cortical regions, particularly in the anterior cingulate (Auer et al, 2000;Rosenberg et al, 2005). We also demonstrated that myo-inositol levels were increased in the frontal white matter in diabetic patients with and without major depression.…”

Section: Discussionsupporting

confidence: 74%

“…Use of MRS to study the biochemical changes associated with major depression has shown a number of findings over the past few years. These include increases in choline, myo-inositol, and decreases in n-acetyl aspartate and glutamate associated with major depression Vythilingam et al, 2003;Auer et al, 2000;Rosenberg et al, 2005). These metabolic changes associated with major depression have been shown to correlate with electroconvulsive and antidepressant treatment as well.…”

Section: Introductionmentioning

confidence: 99%

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Measurement of Brain Metabolites in Patients with type 2 Diabetes and Major Depression Using Proton Magnetic Resonance Spectroscopy

Ajilore¹,

Haroon²,

Kumaran³

et al. 2006

Neuropsychopharmacol

109

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Type 2 diabetes and major depression are disorders that are mutual risk factors and may share similar pathophysiological mechanisms. To further understand these shared mechanisms, the purpose of our study was to examine the biochemical basis of depression in patients with type 2 diabetes using proton MRS. Patients with type 2 diabetes and major depression (n ¼ 20) were scanned along with patients with diabetes alone (n ¼ 24) and healthy controls (n ¼ 21) on a 1.5 T MRI/MRS scanner. Voxels were placed bilaterally in dorsolateral white matter and the subcortical nuclei region, both areas important in the circuitry of late-life depression. Absolute values of myoinositol, creatine, N-acetyl aspartate, glutamate, glutamine, and choline corrected for CSF were measured using the LC-Model algorithm. Glutamine and glutamate concentrations in depressed diabetic patients were significantly lower (po0.001) in the subcortical regions as compared to healthy and diabetic control subjects. Myo-inositol concentrations were significantly increased (po0.05) in diabetic control subjects and depressed diabetic patients in frontal white matter as compared to healthy controls. These findings have broad implications and suggest that alterations in glutamate and glutamine levels in subcortical regions along with white matter changes in myo-inositol provide important neurobiological substrates of mood disorders.

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Section: Discussionsupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Measurement of Brain Metabolites in Patients with type 2 Diabetes and Major Depression Using Proton Magnetic Resonance Spectroscopy

Ajilore¹,

Haroon²,

Kumaran³

et al. 2006

Neuropsychopharmacol

109

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“…In this study, acceptably reliable peaks, as defined by LCModel quality control criteria, were recorded consistently for each of these. Thereby, the Gln resonance was smaller and relatively more variable than Glx and Glu, as has been seen by others (Auer et al, 2000;Rosenberg et al, 2005). Higher field strength may better quantify Gln and separate it from Glu as evidenced by a 4-T study of left anterior cingulate finding reductions in both Glu and Gln in schizophrenia (Theberge et al, 2003).…”

Section: Discussionmentioning

confidence: 56%

“…Frontal cortex and basal ganglia Glx elevations have also been reported in pediatric bipolar disorder; the acute mood state and Cr levels were not reported (Castillo et al, 2000). In contrast, below-normal anterior cingulate [Glx] has been reported in unipolar depression with (Rosenberg et al, 2005;Mirza et al, 2004) or without (Auer et al, 2000;Pfleiderer et al, 2003) below-normal [Cr]. Despite phenomenologic similarities between bipolar and unipolar depression, the epidemiology, course of illness (age of onset, associated comorbidities), and potential liability of antidepressant treatment suggest that these are in fact, two different disease states (Bowden, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…It is unclear if the potential for 1 HMRS anterior cingulate glutamate to distinguish bipolar from unipolar depression is related to the different disease state (bipolar glutamate increase/unipolar glutamate decrease) or to the current phenomenologic presentation (atypical glutamate increase/melancholic glutamate decrease). The unipolar studies that reported reduced anterior cingulate [Glx] (Rosenberg et al, 2005;Mirza et al, 2004;Auer et al, 2000;Pfleiderer et al, 2003) did not report glutamate levels based on subtype or pattern of depression.…”

Section: Discussionmentioning

confidence: 99%

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Increased Anterior Cingulate/Medial Prefrontal Cortical Glutamate and Creatine in Bipolar Depression

Frye

Watzl

Banakar

et al. 2007

Neuropsychopharmacol

202

127

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Proton magnetic resonance spectroscopy ( 1 HMRS) is an in vivo brain imaging method that can be used to investigate psychotropic drug mechanism of action. This study evaluated baseline 1 HMRS spectra of bipolar depressed patients and whether the level of cerebral metabolites changed after an open trial of lamotrigine, an anti-glutamatergic mood stabilizer. Twenty-three bipolar depressed and 12 control subjects underwent a MRS scan of the anterior cingulate/medial prefrontal cortex. The scan was performed on a GE whole-body 1.5 T MRI scanner using single-voxel PRESS (TE/TR ¼ 30/3000 ms, 3 Â 3 Â 3 cm 3 and post-processed offline with LCModel. Baseline CSF-corrected absolute concentrations of glutamate + glutamine ([Glx]), glutamate ([Glu]), and creatine + phosphocreatine ([Cr]) were significantly higher in bipolar depressed subjects vs healthy controls. The non-melancholic subtype had significantly higher baseline [Glx] and [Glu] levels than the melancholic subtype. Remission with lamotrigine was associated with significantly lower post-treatment glutamine ([Gln]) in comparison to non-remission. These data suggest that non-melancholic bipolar depression is characterized by increased glutamate coupled with increased energy expenditure. Lamotrigine appears to reduce glutamine levels associated with treatment remission. Further study is encouraged to determine if these MR spectroscopic markers can delineate drug mechanism of action and subsequent treatment response.

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Evidence for Increased Glutamatergic Cortical Facilitation in Children and Adolescents With Major Depressive Disorder

et al. 2013

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Reduced Anterior Cingulate Glutamate in Pediatric Major Depression: A Magnetic Resonance Spectroscopy Study

Cited by 130 publications

References 41 publications

Measurement of Brain Metabolites in Patients with type 2 Diabetes and Major Depression Using Proton Magnetic Resonance Spectroscopy

Measurement of Brain Metabolites in Patients with type 2 Diabetes and Major Depression Using Proton Magnetic Resonance Spectroscopy

Increased Anterior Cingulate/Medial Prefrontal Cortical Glutamate and Creatine in Bipolar Depression

Evidence for Increased Glutamatergic Cortical Facilitation in Children and Adolescents With Major Depressive Disorder

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