Reduced mitochondrial respiration in T cells of patients with major depressive disorder

Gamradt, Stefanie; Hasselmann, Helge; Taenzer, Aline; Brasanac, Jelena; Stiglbauer, Victoria; Sattler, Arne; Sajitz-Hermstein, Max; Kierszniowska, Sylwia; Ramien, Caren; Nowacki, Jan; Mascarell-Maricic, Lea; Wingenfeld, Katja; Piber, Dominique; Ströhle, Andreas; Kotsch, Katja; Paul, Friedemann; Otte, Christian; Gold, Stefan M.

doi:10.1016/j.isci.2021.103312

Cited by 18 publications

(10 citation statements)

References 35 publications

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“…Over the last decade, different studies have reported ETC dysfunction in BD. However, in vivo cellular mitochondrial respiration has been assessed in subjects with major depressive disorders 25 and BD 26,27 and compared it with mitochondrial respiration in HC, but has not been studied in different phases of BD. In addition, these studies have been conducted with small samples.…”

Section: Introductionmentioning

confidence: 99%

Reduced mitochondrial respiratory capacity in patients with acute episodes of bipolar disorder: Could bipolar disorder be a state‐dependent mitochondrial disease?

Giménez‐Palomo,

Guitart‐Mampel,

Meseguer

et al. 2023

Acta Psychiatr Scand

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BackgroundBipolar disorder (BD) is a chronic and recurrent disease characterized by acute mood episodes and periods of euthymia. The available literature postulates that a biphasic dysregulation of mitochondrial bioenergetics might underpin the neurobiology of BD. However, most studies focused on inter‐subject differences rather than intra‐subject variations between different mood states. To test this hypothesis, in this preliminary proof‐of‐concept study, we measured in vivo mitochondrial respiration in patients with BD during a mood episode and investigated differences compared to healthy controls (HC) and to the same patients upon clinical remission.MethodsThis longitudinal study recruited 20 patients with BD admitted to our acute psychiatric ward with a manic (n = 15) or depressive (n = 5) episode, and 10 matched HC. We assessed manic and depressive symptoms using standardized psychometric scales. Different mitochondrial oxygen consumption rates (OCRs: Routine, Leak, electron transport chain [ETC], Rox) were assessed during the acute episode (T0) and after clinical remission (T1) using high‐resolution respirometry at 37°C by polarographic oxygen sensors in a two‐chamber Oxygraph‐2k system in one million of peripheral blood mononuclear cells (PMBC). Specific OCRs were expressed as mean ± SD in picomoles of oxygen per million cells. Significant results were adjusted for age, sex, and body mass index.ResultsThe longitudinal analysis showed a significant increase in the maximal oxygen consumption capacity (ETC) in clinical remission (25.7 ± 16.7) compared to the acute episodes (19.1 ± 11.8, p = 0.025), and was observed separately for patients admitted with a manic episode (29.2 ± 18.9 in T1, 22.3 ± 11.9 in T0, p = 0.076), and at a trend‐level for patients admitted with a depressive episode (15.4 ± 3.9 in T1 compared to 9.4 ± 3.2 in T0, p = 0.107). Compared to HC, significant differences were observed in ETC in patients with a bipolar mood episode (H = 11.7; p = 0.003). Individuals with bipolar depression showed lower ETC than those with a manic episode (t = −3.7, p = 0.001). Also, significant differences were observed in ETC rates between HC and bipolar depression (Z = 1.000, p = 0.005).ConclusionsBioenergetic and mitochondrial dysregulation could be present in both manic and depressive phases in BD and, importantly, they may restore after clinical remission. These preliminary results suggest that mitochondrial respiratory capacity could be a biomarker of illness activity and clinical response in BD. Further studies with larger samples and similar approaches are needed to confirm these results and identify potential biomarkers in different phases of the disease.

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Section: Introductionmentioning

confidence: 99%

Reduced mitochondrial respiratory capacity in patients with acute episodes of bipolar disorder: Could bipolar disorder be a state‐dependent mitochondrial disease?

Giménez‐Palomo,

Guitart‐Mampel,

Meseguer

et al. 2023

Acta Psychiatr Scand

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“…This immune signature was also linked to elevated serum markers such as CRP, characterizing a subgroup of "inflamed" depression. Moreover, the degree of alterations in mitochondria such as respiratory chain function appears to differ between cell populations of the adaptive and innate immune system when compared between patients with MDD and closely matched healthy controls [9] (see Fig. 1d).…”

Section: Cd4 T Cells Cd8 T Cells Monocytesmentioning

confidence: 98%

“…This effect is particularly pronounced in a subgroup of patients, as shown by comparisons between "uninflamed" and "inflamed" subtypes of MDD (based on clustering of peripheral cellular immune markers), see [8]. d In MDD, impairments of mitochondrial reserve (as measured by oxygen consumption rate) were more pronounced in purified T cells than in monocytes (based on [9]). e Mitochondrial dysfunction in CD4 T cells specifically has been demonstrated to induce depression/anxiety-like behavior in mice (based on [10]).…”

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confidence: 98%

Cellular specificity of mitochondrial and immunometabolic features in major depression

et al. 2022

Self Cite

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Converging lines of evidence from human studies and experimental models have recently suggested a putative pathogenetic role of mitochondrial biology in neuropsychiatric disorders including depression. However, mitochondrial regulation is tissue-specific and varies substantially between subsets of cell populations, particularly in the immune system, where mitochondrial bioenergetics and dynamics drive cell function. Thus, while the peripheral immune system is an attractive biomarker candidate due to its easy accessibility in humans and its likely involvement in mood disorders, investigations in this area will require detailed workup of cellular specificity and functional implications to gain insight into potentially druggable pathobiological substrates.

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“…A higher LDL/HDL ratio was found in MDD patients along with a reduction in omega-3 fatty acids levels [ 47 , 60 ] and a positive correlation between the Montgomery-Åsberg Depression Rating Scale (MADRS) score and serum levels of LDL, triglycerides, cholesterol, free cholesterol, phospholipids and apolipoprotein B before treatment [ 50 ]. Furthermore, a study that compared eight weeks of treatment with fluoxetine found reduced ApoB (lipoprotein B)/ApoA1 (lipoprotein A1) [ 58 ].…”

Section: Reviewmentioning

confidence: 99%

Metabolomics of Major Depressive Disorder: A Systematic Review of Clinical Studies

Costa¹,

Carneiro²,

Alves³

et al. 2022

Cureus

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Although the understanding of the pathophysiology of major depressive disorder (MDD) has advanced greatly, this has not been translated into improved outcomes. To date, no biomarkers have been identified for the diagnosis, prognosis, and therapeutic management of MDD. Thus, we aim to review the biomarkers that are differentially expressed in MDD. A systematic review was conducted in January 2022 in the PubMed/MEDLINE, Scopus, Embase, PsycINFO, and Gale Academic OneFile databases for clinical studies published from January 2001 onward using the following terms: "Depression" OR "Depressive disorder" AND "Metabolomic." Multiple metabolites were found at altered levels in MDD, demonstrating the involvement of cellular signaling metabolites, components of the cell membrane, neurotransmitters, inflammatory and immunological mediators, hormone activators and precursors, and sleep controllers. Kynurenine and acylcarnitine were identified as consistent with depression and response to treatment. The most consistent evidence found was regarding kynurenine and acylcarnitine. Although the data obtained allow us to identify how metabolic pathways are affected in MDD, there is still not enough evidence to propose changes to current diagnostic and therapeutic actions. Some limitations are the heterogeneity of studies on metabolites, methods for detection, analyzed body fluids, and treatments used. The experiments contemplated in the review identified increased or reduced levels of metabolites, but not necessarily increased or reduced the activity of the associated pathways. The information acquired through metabolomic analyses does not specify whether the changes identified in the metabolites are a cause or a consequence of the pathology.

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Reduced mitochondrial respiration in T cells of patients with major depressive disorder

Cited by 18 publications

References 35 publications

Reduced mitochondrial respiratory capacity in patients with acute episodes of bipolar disorder: Could bipolar disorder be a state‐dependent mitochondrial disease?

Reduced mitochondrial respiratory capacity in patients with acute episodes of bipolar disorder: Could bipolar disorder be a state‐dependent mitochondrial disease?

Cellular specificity of mitochondrial and immunometabolic features in major depression

Metabolomics of Major Depressive Disorder: A Systematic Review of Clinical Studies

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