Current Perspectives on Pharmacological and Non-Pharmacological Interventions for the Inflammatory Mechanism of Unipolar Depression

Dogaru, Ioana-Alexandra; Puiu, Maria; Manea, Mirela; Dionisie, Vlad

doi:10.3390/brainsci12101403

Cited by 13 publications

(10 citation statements)

References 211 publications

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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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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

View full text Add to dashboard Cite

show abstract

“…The classical antidepressant hypothesis, known as the monoamine theory, uses monoamine oxidase inhibitors (MAOIs) and selective serotonin reuptake inhibitors (SSRIs) to restore low monoamine levels in the brain [ 48 ], while serotonin and norepinephrine reuptake inhibitors (SNRIs) are also used to treat MDD [ 49 ], but individual response varies significantly. Long-term follow-up studies have identified a higher risk of weight gain in individuals prescribed antidepressants, highlighting the need for personalized treatment approaches that consider an individual’s BMI or adiposity [ 50 ].…”

Section: Mdd Stress and Neuropsychoimmunitymentioning

confidence: 99%

Personalized Medicine of Omega-3 Fatty Acids in Depression Treatment in Obese and Metabolically Dysregulated Patients

Chen

Chang

et al. 2023

JPM

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The co-occurrence of depression and obesity has become a significant public health concern worldwide. Recent studies have shown that metabolic dysfunction, which is commonly observed in obese individuals and is characterized by inflammation, insulin resistance, leptin resistance, and hypertension, is a critical risk factor for depression. This dysfunction may induce structural and functional changes in the brain, ultimately contributing to depression’s development. Given that obesity and depression mutually increase each other’s risk of development by 50–60%, there is a need for effective interventions that address both conditions. The comorbidity of depression with obesity and metabolic dysregulation is thought to be related to chronic low-grade inflammation, characterized by increased circulating levels of pro-inflammatory cytokines and C-reactive protein (CRP). As pharmacotherapy fails in at least 30–40% of cases to adequately treat major depressive disorder, a nutritional approach is emerging as a promising alternative. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are a promising dietary intervention that can reduce inflammatory biomarkers, particularly in patients with high levels of inflammation, including pregnant women with gestational diabetes, patients with type 2 diabetes mellitus, and overweight individuals with major depressive disorder. Further efforts directed at implementing these strategies in clinical practice could contribute to improved outcomes in patients with depression, comorbid obesity, and/or metabolic dysregulation.

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“…Unipolar depression (Major Depressive Disorder-MDD) has generally been found to stimulate a pro-inflammatory Th1 response (IL-1, IL-2, soluble IL-2 receptor (-sIL-2R), IL-6, C-Reactive Protein (CRP), TNF-α, and IFN-γ), with a subsequent increase in tryptophan catabolites (the kynurenine pathway) [17,22,23]. Cytokines can be produced by astrocytes and microglia in the brain or diffuse to the brain from the periphery through a leaky blood-brain barrier (BBB), active transport, endothelial cell activation, cytokine receptor binding, or via vagus nerve interaction in the gut, especially when cytokine levels are elevated [21].…”

Section: Immunology Microbes and Psychiatric Disordersmentioning

confidence: 99%

“…Therefore, elevated pro-inflammatory cytokine levels reduce frontal brain activity [19], which may lead to symptoms of depression in immunogenetically susceptible patients [11]. Indeed, depression treatment significantly decreases the levels of some cytokines, including IL-1 [25], and treatment with anti-inflammatory substances, such as minocycline or N-acetyl cysteine (NAC) [22], may improve clinical outcomes in depression.…”

Section: Immunology Microbes and Psychiatric Disordersmentioning

confidence: 99%

The Immunoseasonal Theory of Psychiatric Disorders

Waszkiewicz

2023

JCM

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Although the influence of the weather on the well-being and mental health of psychiatric patients has been widely seen, the relationships between various seasonal weather factors and depressive, manic, anxiety, and psychotic states have not been systematized in the literature. The current article describes the seasonal changes in weather-related immune responses and their impact on the development of episodes of depression, mania, psychosis, and anxiety, highlighting the T-helper 1 (Th1) and Th2 immune balance as their potential trigger. In autumn–winter depression, the hyperactivation of the Th1 system, possibly by microbial/airborne pathogens, may lead to the inflammatory inhibition of prefrontal activity and the subcortical centers responsible for mood, drive, and motivation. Depressive mood periods are present in most people suffering from schizophrenia. In the spring and summertime, when the compensating anti-Th1 property of the Th2 immune system is activated, it decreases the Th1 response. In individuals immunogenetically susceptible to psychosis and mania, the inhibition of Th1 by the Th2 system may be excessive and lead to Th2-related frontal and subcortical hyperactivation and subsequent psychosis. In people suffering from bipolar disorder, hyperintense changes in white matter may be responsible for the partial activation of subcortical areas, preventing full paranoid psychosis. Thus, psychosis may be mood-congruent in affective disorders.

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Current Perspectives on Pharmacological and Non-Pharmacological Interventions for the Inflammatory Mechanism of Unipolar Depression

Cited by 13 publications

References 211 publications

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

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

Personalized Medicine of Omega-3 Fatty Acids in Depression Treatment in Obese and Metabolically Dysregulated Patients

The Immunoseasonal Theory of Psychiatric Disorders

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