N-Acetylcysteine as a novel rapidly acting anti-suicidal agent: A pilot naturalistic study in the emergency setting

Hans, Davinder; Rengel, A.; Hans, Jaspreet; Bassett, Darryl; Hood, Sean

doi:10.1371/journal.pone.0263149

Cited by 8 publications

(6 citation statements)

References 40 publications

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“…NAC readily crosses the blood-brain barrier providing a cysteine substrate for GSH synthesis in the brain, in addition to acting directly as a scavenger of ROS ( 40 ). Hans et al ( 41 ) suggest that NAC may have potential use as an adjunct to fast-acting treatment in MDD. Although preliminary, our findings appear to imply reduced glutathione as a potential biomarker or etiologic factor among women at risk of suicide, with therapeutic implications.…”

Section: Discussionmentioning

confidence: 99%

Can glutathione be a biomarker for suicide risk in women 18 months postpartum?

et al. 2023

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BackgroundSuicide risk is prominent among the problems affecting populations, mainly due to the broad family, psychosocial and economic impact. Most individuals at suicidal risk have some mental disorder. There is considerable evidence that psychiatric disorders are accompanied by the activation of neuro-immune and neuro-oxidative pathways. The aim of the study is to evaluate the serum levels of oxidative stress biomarkers in women at risk of suicide after 18 months of postpartum.MethodsThis is a case-control study, nested within a cohort study. From this cohort, 45 women [15 without mood disorders and 30 with mood disorders (Major depression and Bipolar disorder)] were selected at 18 months postpartum, the depression and suicide risk were assessed using the Mini-International Neuropsychiatric Interview Plus (MINI-Plus) instrument, module A and C, respectively. Blood was collected and stored for later analysis of the reactive species (DCFH), superoxide dismutase (SOD), and glutathione reduced (GSH). For data analysis, the SPSS program was used. To compare the nominal covariates with the outcome GSH levels, the Student’s t-test or analysis of variance (ANOVA) was used. Spearman’s correlation was performed for analysis between the quantitative covariates and the outcome. To analyze the interaction between the factors, multiple linear regression was performed. Bonferroni analysis was used as an additional/secondary result to visualize differences in glutathione levels according to risk severity. After the adjusted analysis, p-values < 0.05 were considered statistically significant.ResultsThe percentage of suicide risk observed in our sample of women at 18 months postpartum was 24.4% (n = 11). After adjusting for the independent variables, only the presence of suicide risk remained associated with the outcome (β = 0.173; p = 0.007), low levels of GSH at 18 months after postpartum. Likewise, we verified the difference in GSH levels according to the degree of suicide risk, observing a significant association between the differences in glutathione means in the group of women with moderate to high risk compared to the reference group (no suicide risk) (p = 0.009).ConclusionOur findings suggest that GSH may be a potential biomarker or etiologic factor in women at moderate to high risk of suicide.

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Section: Discussionmentioning

confidence: 99%

Can glutathione be a biomarker for suicide risk in women 18 months postpartum?

et al. 2023

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“…Evidence as an adjunctive therapy to reduce symptoms of Bipolar Affective Disorder, MDD, and Schizophrenia [187]. Enhanced coping mechanisms, not only for addressing acute stressors but possibly also for mitigating the impact of persistent stress-inducing factors [188].…”

Section: N-acetyl Cysteinementioning

confidence: 99%

Advancements Exploring Major Depressive Disorder: Insights on Oxidative Stress, Serotonin Metabolism, BDNF, HPA Axis Dysfunction, and Pharmacotherapy Advances

Correia,

Vale

2024

IJTM

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Major depressive disorder (MDD), a prevalent mental illness, is marked by a complex mixture of biological factors. This review focuses on the roles of oxidative stress, tryptophan-serotonin metabolism, brain-derived neurotrophic factor (BDNF), and the hypothalamic–pituitary–adrenal (HPA) axis in MDD’s pathophysiology. Oxidative stress, defined as an imbalance between pro-oxidants and antioxidants, is closely linked to MDD’s neurobiological changes. The tryptophan (TRP)-/serotonin (5-HT) metabolic pathway is also known to be crucial in mood regulation, with its dysregulation being a central aspect of MDD. Additionally, BDNF, key for neuronal growth and plasticity, often shows alterations in MDD patients, supporting its role in the disorder’s progression. Furthermore, the HPA axis, which manages stress response, is frequently disrupted in MDD, further contributing to its complex pathology. In addition to exploring these biological mechanisms, this review also explores the pharmacotherapy of MDD, including new advances. These advancements in treatment strategies are crucial for managing MDD effectively. Understanding these mechanisms and the latest pharmacological interventions is essential for developing more effective treatments for MDD.

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“…When studying chronic NAC administration in murine models, Wright et al noted an antidepressant-like effect on both wildtype and Huntington-disease murine models, which was noted to be due to decreased mitochondrial oxidative stress [ 33 ]. Further assessing the potential uses of NAC in depression, various studies assessing depression using the Montgomery–Asberg Depression Rating Scale (MADRS) have observed NAC administration to improve depressive symptoms [ 34 , 35 , 36 ]. These studies suggest a potential for NAC administration as an adjunct therapeutic in MDD.…”

Section: Major Depressive Disordermentioning

confidence: 99%

Potential Role of Glutathione Antioxidant Pathways in the Pathophysiology and Adjunct Treatment of Psychiatric Disorders

Poladian

Navasardyan

Narinyan

et al. 2023

Clinics and Practice

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Oxidative stress is defined as the imbalance between the production of free radicals and their removal by antioxidants, leading to accumulation and subsequent organ and tissue damage. Antioxidant status and its role in the accumulation of free radicals has been observed in a number of psychological disorders. Glutathione is commonly referred to as the principal antioxidant of the brain and, therefore, plays a critical role in maintaining redox homeostasis. Reduced levels of glutathione in the brain increase its vulnerability to oxidative stress, and may be associated with the development and progression of several psychiatric disorders. Within this review, we focus on analyzing potential associations between the glutathione antioxidant pathway and psychiatric disorders: major depressive disorder, schizophrenia, bipolar disorder, and generalized anxiety disorder. Our research suggests that studies regarding these four disorders have shown decreased levels of GSH in association with diseased states; however, conflicting results note no significant variance in glutathione pathway enzymes and/or metabolites based on diseased state. In studying the potential of NAC administration as an adjunct therapy, various studies have shown NAC to augment therapy and/or aid in symptomatic management for psychiatric disorders, while contrasting results exist within the literature. Based on the conflicting findings throughout this review, there is room for study regarding the potential role of glutathione in the development and progression of psychiatric disorders. Our findings further suggest a need to study such pathways with consideration of the interactions with first-line pharmacotherapy, and the potential use of antioxidants as supplemental therapy.

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N-Acetylcysteine as a novel rapidly acting anti-suicidal agent: A pilot naturalistic study in the emergency setting

Cited by 8 publications

References 40 publications

Can glutathione be a biomarker for suicide risk in women 18 months postpartum?

Can glutathione be a biomarker for suicide risk in women 18 months postpartum?

Advancements Exploring Major Depressive Disorder: Insights on Oxidative Stress, Serotonin Metabolism, BDNF, HPA Axis Dysfunction, and Pharmacotherapy Advances

Potential Role of Glutathione Antioxidant Pathways in the Pathophysiology and Adjunct Treatment of Psychiatric Disorders

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