Effective electroconvulsive therapy reverses glutamate/glutamine deficit in the left anterior cingulum of unipolar depressed patients

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199

115

Negatively balanced neurotrophic factors may be important in precipitating clinical depression. Recently, it has been reported that antidepressant therapy may exert positive neurotrophic effects. The aim of this study was to detect probable neurotrophic changes during electroconvulsive therapy (ECT). For this purpose, N-acetylaspartate (NAA), an amino acid exclusively located in neurons, and other brain metabolites such as glutamine/glutamate (Glx), choline (Cho), and creatine (Cr) were measured in patients by localized proton magnetic resonance spectroscopy. A total of 28 severely depressed patients (DSM-IV) were enrolled, and the left amygdalar region was investigated by proton STEAM spectroscopy before and after unilateral ECT. The results were compared with 28 age-and gender-matched controls using nonparametric paired and unpaired tests. A significant increase in NAA was observed only in ECT responders (n ¼ 14; p ¼ 0.019). Five out of 14 nonresponders to ECT monotherapy were remeasured following a clinical improvement after continued ECT combined with antidepressants and were then found also to present a significant increase in NAA. In all successfully treated patients, parallel observations, that is, increased levels, were made for Glx, whereas Cho and Cr were unchanged. In conclusion, our preliminary finding of increased NAA concentrations after successful ECT may indicate a probable neurotrophic effect of ECT. Neuropsychopharmacology (2003) 28, 720-725.

Section: Discussionsupporting

confidence: 69%

Neurotrophic Effects of Electroconvulsive Therapy: A Proton Magnetic Resonance Study of the Left Amygdalar Region in Patients with Treatment-Resistant Depression

Michael

Erfurth

Ohrmann

et al. 2002

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199

115

“…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%

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

Frye

Watzl

Banakar

et al. 2007

202

127

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.

“…To assure high intraindividual reproducibility, scans were referenced to readily identifiable anatomic landmarks within the brain; the base of the voxel was aligned perpendicular to the tip of the genu corporis callosi (Pfleiderer et al, 2003).…”

Section: Magnetic Resonance Spectroscopy ( 1 H-mrs)mentioning

confidence: 99%

Acute Shift in Glutamate Concentrations Following Experimentally Induced Panic with Cholecystokinin Tetrapeptide—A 3T-MRS Study in Healthy Subjects

Zwanzger

Zavorotnyy

Gencheva

et al. 2013

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According to preclinical studies, glutamate has been implicated in the pathogenesis of anxiety. In order to elucidate the role of glutamate in anxiety and panic in humans, brain glutamate þ glutamine (Glx) levels were measured during cholecystokinin-tetrapeptide (CCK-4)-induced panic using magnetic resonance spectroscopy (MRS). Eighteen healthy subjects underwent a CCK-4 challenge. MR spectra were obtained from the anterior cingulate cortex (ACC) using a single voxel point-resolved spectroscopy method and analyzed using LCModel. A combined fitting of Glx was performed. Panic was assessed using the Acute Panic Inventory (API) and Panic Symptom Scale (PSS) scores. Moreover, hypothalamic-pituitary-adrenal axis stimulation was monitored throughout the challenge. There was a significant panic response following CCK-4 as revealed by a marked increase in both the panic scores (API: F(1,17) ¼ 149.41; po0.0001; PSS: F(1,17) ¼ 88.03; po0.0001) and heart rate (HR: F(1,17) ¼ 72.79; po0.0001). MRS measures showed a significant increase of brain Glx/creatine (Glx/Cr) levels peaking at 2-10 min after challenge (F(1,17) ¼ 15.94; p ¼ 0.001). There was also a significant increase in CCK-4-related cortisol release (F(6,11) ¼ 8.68; p ¼ 0.002). Finally, significant positive correlations were found between baseline Glx/Cr and both API max (r ¼ 0.598; p ¼ 0.009) and maximum heart rate (HR max ) during challenge (r ¼ 0.519; p ¼ 0.027). Our results suggest that CCK-4-induced panic is accompanied by a significant glutamate increase in the bilateral ACC. The results add to the hypothesis of a disturbance of the inhibitory-excitatory equilibrium and suggest that apart from static alterations rapid and dynamic neurochemical changes might also be relevant for the neural control of panic attacks.