Prefrontal Glutathione Levels in Major Depressive Disorder Are Linked to a Lack of Positive Affect

Tuura, Ruth O’Gorman; Buchmann, Andreas; Ritter, Christopher; Hase, Adrian; Haynes, Melanie; Noeske, Ralph; Hasler, Gregor

doi:10.3390/brainsci13101475

Cited by 5 publications

(1 citation statement)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When analyzing GSH levels in the prefrontal cortex of postmortem patients diagnosed with MDD, researchers observed lower levels of the metabolite when compared to healthy controls [58]. A recent study has assessed in vivo GSH levels in the prefrontal cortex by magnetic resonance, finding them to be increased in patients with current MDD, when compared to those with past MDD and healthy controls [61]. Decreased levels of GSH were found in the occipital region of patients with anhedonia compared to age− and sex-matched controls [62].…”

Section: Discussionmentioning

confidence: 99%

Targeted Analysis of Plasma Polar Metabolites in Postmenopausal Depression

Naufel,

Pedroso,

de Souza

et al. 2024

Metabolites

View full text Add to dashboard Cite

Depression will be the disease with the highest incidence worldwide by 2030. Data indicate that postmenopausal women have a higher incidence of mood disorders, and this high vulnerability seems to be related to hormonal changes and weight gain. Although research evaluating the profile of metabolites in mood disorders is advancing, further research, maintaining consistent methodology, is necessary to reach a consensus. Therefore, the objective of the present study was to carry out an exploratory analysis of the plasma polar metabolites of pre- and postmenopausal women to explore whether the profile is affected by depression. The plasma analysis of 50 polar metabolites was carried out in a total of 67 postmenopausal women, aged between 50 and 65 years, either without depression (n = 25) or with depression symptoms (n = 42), which had spontaneous onset of menopause and were not in use of hormone replacement therapy, insulin, or antidepressants; and in 42 healthy premenopausal women (21 without depression and 21 with depression symptoms), aged between 40 and 50 years and who were not in use of contraceptives, insulin, or antidepressants. Ten metabolites were significantly affected by depression symptoms postmenopause, including adenosine (FDR = 3.778 × 10−14), guanosine (FDR = 3.001 × 10−14), proline (FDR = 1.430 × 10−6), citrulline (FDR = 0.0001), lysine (FDR = 0.0004), and carnitine (FDR = 0.0331), which were down-regulated, and dimethylglycine (FDR = 0.0022), glutathione (FDR = 0.0048), creatine (FDR = 0.0286), and methionine (FDR = 0.0484) that were up-regulated. In premenopausal women with depression, oxidized glutathione (FDR = 0.0137) was down-regulated, and dimethylglycine (FDR = 0.0406) and 4-hydroxyproline (FDR = 0.0433) were up-regulated. The present study provided new data concerning the consequences of depression on plasma polar metabolites before and after the establishment of menopause. The results demonstrated that the postmenopausal condition presented more alterations than the premenopausal period and may indicate future measures to treat the disturbances involved in both menopause and depression.

show abstract

Section: Discussionmentioning

confidence: 99%

Targeted Analysis of Plasma Polar Metabolites in Postmenopausal Depression

Naufel,

Pedroso,

de Souza

et al. 2024

Metabolites

View full text Add to dashboard Cite

show abstract

Medial prefrontal cortex neurotransmitter abnormalities in posttraumatic stress disorder with and without comorbidity to major depression

Swanberg,

Prinsen,

Averill

et al. 2024

NMR in Biomedicine

View full text Add to dashboard Cite

Posttraumatic stress disorder (PTSD) is a chronic psychiatric condition that follows exposure to a traumatic stressor. Though previous in vivo proton (1H) MRS) research conducted at 4 T or lower has identified alterations in glutamate metabolism associated with PTSD predisposition and/or progression, no prior investigations have been conducted at higher field strength. In addition, earlier studies have not extensively addressed the impact of psychiatric comorbidities such as major depressive disorder (MDD) on PTSD‐associated 1H‐MRS‐visible brain metabolite abnormalities. Here we employ 7 T 1H MRS to examine concentrations of glutamate, glutamine, GABA, and glutathione in the medial prefrontal cortex (mPFC) of PTSD patients with MDD (PTSD+MDD+; N = 6) or without MDD (PTSD+MDD−; N = 5), as well as trauma‐unmatched controls without PTSD but with MDD (PTSD−MDD+; N = 9) or without MDD (PTSD−MDD−; N = 18). Participants with PTSD demonstrated decreased ratios of GABA to glutamine relative to healthy PTSD−MDD− controls but no single‐metabolite abnormalities. When comorbid MDD was considered, however, MDD but not PTSD diagnosis was significantly associated with increased mPFC glutamine concentration and decreased glutamate:glutamine ratio. In addition, all participants with PTSD and/or MDD collectively demonstrated decreased glutathione relative to healthy PTSD−MDD− controls. Despite limited findings in single metabolites, patterns of abnormality in prefrontal metabolite concentrations among individuals with PTSD and/or MDD enabled supervised classification to separate them from healthy controls with 80+% sensitivity and specificity, with glutathione, glutamine, and myoinositol consistently among the most informative metabolites for this classification. Our findings indicate that MDD can be an important factor in mPFC glutamate metabolism abnormalities observed using 1H MRS in cohorts with PTSD.

show abstract