Plasma acetyl-l-carnitine and l-carnitine in major depressive episodes: a case–control study before and after treatment

2021 ◽  
pp. 1-10
Author(s):  
Abd El Kader Ait Tayeb ◽  
Romain Colle ◽  
Khalil El-Asmar ◽  
Kenneth Chappell ◽  
Cécile Acquaviva-Bourdain ◽  
...  
Keyword(s):  
Antidepressant Treatment ◽  
Mitochondrial Metabolism ◽  
Major Depressive ◽  
Depressed Patients ◽  
Before And After ◽  
Underlying Mechanisms ◽  
Major Depressive Episodes ◽  
Depressive Episodes ◽  
Control Study ◽  
New Strategies

Abstract Background Major depressive disorder (MDD) is the main cause of disability worldwide, its outcome is poor, and its underlying mechanisms deserve a better understanding. Recently, peripheral acetyl-l-carnitine (ALC) has been shown to be lower in patients with major depressive episodes (MDEs) than in controls. l-Carnitine is involved in mitochondrial function and ALC is its short-chain acetyl-ester. Our first aim was to compare the plasma levels of l-carnitine and ALC, and the l-carnitine/ALC ratio in patients with a current MDE and healthy controls (HCs). Our second aim was to assess their changes after antidepressant treatment. Methods l-Carnitine and ALC levels and the carnitine/ALC ratio were measured in 460 patients with an MDE in a context of MDD and in 893 HCs. Depressed patients were re-assessed after 3 and 6 months of antidepressant treatment for biology and clinical outcome. Results As compared to HC, depressed patients had lower ALC levels (p < 0.00001), higher l-carnitine levels (p < 0.00001) and higher l-carnitine/ALC ratios (p < 0.00001). ALC levels increased [coefficient: 0.18; 95% confidence interval (CI) 0.12–0.24; p < 0.00001], and l-carnitine levels (coefficient: −0.58; 95% CI −0.75 to −0.41; p < 0.00001) and l-carnitine/ALC ratios (coefficient: −0.41; 95% CI −0.47 to −0.34; p < 0.00001), decreased after treatment. These parameters were completely restored after 6 months of antidepressant. Moreover, the baseline l-carnitine/ALC ratio predicted remission after 3 months of treatment (odds ratio = 1.14; 95% CI 1.03–1.27; p = 0.015). Conclusions Our data suggest a decreased mitochondrial metabolism of l-carnitine into ALC during MDE. This decreased mitochondrial metabolism is restored after a 6-month antidepressant treatment. Moreover, the magnitude of mitochondrial dysfunction may predict remission after 3 months of antidepressant treatment. New strategies targeting mitochondria should be explored to improve treatments of MDD.

The olfactory deficits of depressed patients are restored after remission with venlafaxine treatment

2020 ◽  
pp. 1-9
Author(s):  
Romain Colle ◽  
Khalil El Asmar ◽  
Céline Verstuyft ◽  
Pierre-Marie Lledo ◽  
Françoise Lazarini ◽  
...  
Keyword(s):  
Antidepressant Treatment ◽  
Depression Severity ◽  
Major Depressive ◽  
Depressed Patients ◽  
Before And After ◽  
Major Depressive Episodes ◽  
Depressive Episodes ◽  
Drug Free ◽  
A Current ◽  
Psychophysical Test

Abstract Background It is unclear whether olfactory deficits improve after remission in depressed patients. Therefore, we aimed to assess in drug-free patients the olfactory performance of patients with major depressive episodes (MDE) and its change after antidepressant treatment. Methods In the DEP-ARREST-CLIN study, 69 drug-free patients with a current MDE in the context of major depressive disorder (MDD) were assessed for their olfactory performances and depression severity, before and after 1 (M1) and 3 (M3) months of venlafaxine antidepressant treatment. They were compared to 32 age- and sex-matched healthy controls (HCs). Olfaction was assessed with a psychophysical test, the Sniffin’ Sticks test (Threshold: T score; Discrimination: D score; Identification: I score; total score: T + D + I = TDI score) and Pleasantness (pleasantness score: p score; neutral score: N score; unpleasantness score: U score). Results As compared to HCs, depressed patients had lower TDI olfactory scores [mean (s.d.) 30.0(4.5) v. 33.3(4.2), p < 0.001], T scores [5.6(2.6) v. 7.4(2.6), p < 0.01], p scores [7.5(3.0) v. 9.8(2.8), p < 0.001)] and higher N scores [3.5(2.6) v. 2.1(1.8), p < 0.01]. T, p and N scores at baseline were independent from depression and anhedonia severity. After venlafaxine treatment, significant increases of T scores [M1: 7.0(2.6) and M3: 6.8(3.1), p < 0.01] and p scores [M1: 8.1(3.0) and M3: 8.4(3.3), p < 0.05] were evidenced, in remitters only (T: p < 0.01; P: p < 0.01). Olfaction improvement was mediated by depression improvement. Conclusions The olfactory signature of MDE is restored after venlafaxine treatment. This olfaction improvement is mediated by depression improvement.

Nitric Oxide Synthase activity in major depressive episodes before and after antidepressant treatment: Results of a large case-control treatment study

2020 ◽  
pp. 1-10 ◽  
Author(s):  
E. Loeb ◽  
K. El Asmar ◽  
S. Trabado ◽  
F. Gressier ◽  
R. Colle ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Antidepressant Treatment ◽  
Control Treatment ◽  
Major Depressive ◽  
Chromatography Method ◽  
Depressed Patients ◽  
Oxide Synthase ◽  
Major Depressive Episodes ◽  
Depressive Episodes

Abstract Background Nitric oxide synthase (NOS) activity, an enzyme potentially involved in the major depressive episodes (MDE), could be indirectly measured by the L-Citrulline/L-Arginine ratio (L-Cit/L-Arg). The aim of this study was: (1) to compare the NOS activity of patients with a MDE to that of healthy controls (HC); (2) to assess its change after antidepressant treatment. Methods A total of 460 patients with a current MDE in a context of major depressive disorder (MDD) were compared to 895 HC for NOS activity (L-Cit/L-Arg plasma ratio). L-Arg and L-Cit plasma levels were measured using a MS-based liquid chromatography method. Depressed patients were assessed at baseline, and after 3 and 6 months of antidepressant treatment for depression severity and clinical response. Results Depressed patients had a lower NOS activity than HC at baseline [0.31 ± 0.09 v. 0.38 ± 0.12; 95% confidence interval (CI) −0.084 to −0.062, p < 0.0001]. Lower NOS activity at baseline predicted a higher response rate [odds ratio (OR) = 29.20; 95% CI 1.58–536.37; p = 0.023]. NOS activity in depressed patients increased significantly up to 0.34 ± 0.08 after antidepressant treatment (Est = 0.0034; 95% CI 0.0002–0.0067; p = 0.03). Conclusions Depressed patients have a decreased NOS activity that improves after antidepressant treatment and predicts drug response. NOS activity may be a promising biomarker for MDE in a context of MDD.

scholarly journals Blood microbiota and metabolomic signature of major depression before and after antidepressant treatment: a prospective case–control study

2021 ◽  
Vol 46 (3) ◽  
pp. E358-E368
Author(s):  
Dragos Ciocan ◽  
Anne-Marie Cassard ◽  
Laurent Becquemont ◽  
Céline Verstuyft ◽  
Cosmin Sebastian Voican ◽  
...  
Keyword(s):  
Depressive Episode ◽  
Major Depressive Episode ◽  
Antidepressant Treatment ◽  
Case Control ◽  
Healthy Controls ◽  
Major Depressive ◽  
Rdna Sequencing ◽  
Before And After ◽  
Major Depressive Episodes ◽  
Depressive Episodes

Background: The microbiota interacts with the brain through the gut–brain axis, and a distinct dysbiosis may lead to major depressive episodes. Bacteria can pass through the gut barrier and be found in the blood. Using a multiomic approach, we investigated whether a distinct blood microbiome and metabolome was associated with major depressive episodes, and how it was modulated by treatment. Methods: In this case–control multiomic study, we analyzed the blood microbiome composition, inferred bacterial functions and metabolomic profile of 56 patients experiencing a current major depressive episode and 56 matched healthy controls, before and after treatment, using 16S rDNA sequencing and liquid chromatography coupled to tandem mass spectrometry. Results: The baseline blood microbiome in patients with a major depressive episode was distinct from that of healthy controls (patients with a major depressive episode had a higher proportion of Janthinobacterium and lower levels of Neisseria) and changed after antidepressant treatment. Predicted microbiome functions confirmed by metabolomic profiling showed that patients who were experiencing a major depressive episode had alterations in the cyanoamino acid pathway at baseline. High baseline levels of Firmicutes and low proportions of Bosea and Tetrasphaera were associated with response to antidepressant treatment. Based on inferred baseline metagenomic profiles, bacterial pathways that were significantly associated with treatment response were related to xenobiotics, amino acids, and lipid and carbohydrate metabolism, including tryptophan and drug metabolism. Metabolomic analyses showed that plasma tryptophan levels are independently associated with response to antidepressant treatment. Limitations: Our study has some limitations, including a lack of information on blood microbiome origin and the lack of a validation cohort to confirm our results. Conclusion: Patients with depression have a distinct blood microbiome and metabolomic signature that changes after treatment. Dysbiosis could be a new therapeutic target and prognostic tool for the treatment of patients who are experiencing a major depressive episode.

Poster 46: Major Depressive Episodes Before and After Spinal Cord Injury

2009 ◽  
Vol 90 (10) ◽  
pp. e25
Author(s):  
Claire Kalpakjian ◽  
Robin Hanks ◽  
Tamara Bushnik ◽  
Charles Bombardier
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Major Depressive ◽  
Cord Injury ◽  
Before And After ◽  
Major Depressive Episodes ◽  
Depressive Episodes

scholarly journals Maintenance Pharmacotherapy for Recurrent Major Depressive Disorder in Primary Care: A 5-year Follow-up Study

2017 ◽  
Vol 41 (1) ◽  
pp. 111-114 ◽  
Author(s):  
K. Riihimäki ◽  
M. Vuorilehto ◽  
E. Isometsä
Keyword(s):  
Primary Care ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Maintenance Treatment ◽  
Antidepressant Treatment ◽  
Major Depressive ◽  
Recurrent Major Depressive Disorder ◽  
Major Depressive Episodes ◽  
Depressive Episodes

AbstractBackgroundMost practice guidelines recommend maintenance antidepressant treatment for recurrent major depressive disorder. However, the degree to which such guidance is actually followed in primary health care has remained obscure. We investigated the provision of maintenance antidepressant treatment within a representative primary care five-year cohort study.MethodsIn the Vantaa Primary Care Depression Study, a stratified random sample of 1119 adult patients was screened for depression using the Prime-MD. Depressive and comorbid psychiatric disorders were diagnosed using SCID-I/P and SCID-II interviews. Of the 137 patients with depressive disorders, 82% completed the prospective five-year follow-up. A graphic life chart enabling evaluation of the longitudinal course of episodes plus duration of pharmacotherapies was used. In accordance with national guidelines, an indication for maintenance treatment was defined to exist after three or more lifetime major depressive episodes (MDEs); maintenance treatment was to commence four months after onset of full remission.ResultsOf the cohort patients, 34% (46/137) had three or more lifetime MDEs, thus indicating the requirement for maintenance pharmacotherapy. Of these, half (54%, 25/46) received maintenance treatment, for only 29% (489/1670) of the months indicated.ConclusionsIn this cohort of depressed primary care patients, half of patients with indications for maintenance treatment actually received it, and only for a fraction of the time indicated. Antidepressant maintenance treatment for the prevention of recurrences is unlikely to be subject to large-scale actualization as recommended, which may significantly undermine the potential public health benefits of treatment.

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