ascorbic-acid and Depressive-Disorder

Stress-related disorders, such as depression and anxiety, present marked deficits in behavioral and cognitive functions related to reward. These are highly prevalent disabling conditions with high social and economic costs. Furthermore, a significant percentage of affected individuals cannot benefit from clinical intervention, opening space for new treatments. Although the literature data have reported limited and variable results regarding oxidative stress-related endpoints in stress-related disorders, the possible neuroprotective effect of antioxidant compounds, such as ascorbic acid (vitamin C), emerges as a possible therapy strategy for psychiatric diseases. Here, we briefly present background information on biological activity of ascorbic acid, particularly functions related to the CNS homeostasis. Additionaly, we reviewed the available information on the role of ascorbic acid in stress-related diseases, focusing on supplementation and depletion studies. The vitamin C deficiency is widely associated to stress-related diseases. Although the efficacy of this vitamin in anxiety spectrum disorders is less stablished, several studies showed that ascorbic acid supplementation produces antidepressant effect and improves mood. Interestingly, the modulation of monoaminergic and glutamatergic neurotransmitter systems is postulated as pivotal target for the antidepressant and anxiolytic effects of this vitamin. Given that ascorbic acid supplementation produces fast therapeutic response with low toxicity and high tolerance, it can be considered as a putative candidate for the treatment of mood and anxiety disorders, especially those that are refractory to current treatments. Herein, the literature was reviewed considering the potential use of ascorbic acid as an adjuvant in the treatment of anxiety and depression.

Topics: Animals; Antioxidants; Anxiety; Anxiety Disorders; Ascorbic Acid; Depression; Depressive Disorder; Humans; Neuroprotective Agents; Stress, Psychological

Studies have suggested that depression was accompanied by oxidative stress dysregulation, including abnormal total antioxidant capacity (TAC), antioxidants, free radicals, oxidative damage and autoimmune response products. This meta-analysis aims to analyse the clinical data quantitatively by comparing the oxidative stress markers between depressed patients and healthy controls.. A search was conducted to collect the studies that measured the oxidative stress markers in depressed patients. Studies were searched in Embase, Medline, PsychINFO, Science direct, CBMDisc, CNKI and VIP from 1990 to May 2015. Data were subjected to meta-analysis by using a random effects model for examining the effect sizes of the results. Bias assessments, heterogeneity assessments and sensitivity analyses were also conducted.. 115 articles met the inclusion criteria. Lower TAC was noted in acute episodes (AEs) of depressed patients (p<0.05). Antioxidants, including serum paraoxonase, uric acid, albumin, high-density lipoprotein cholesterol and zinc levels were lower than controls (p<0.05); the serum uric acid, albumin and vitamin C levels were increased after antidepressant therapy (p<0.05). Oxidative damage products, including red blood cell (RBC) malondialdehyde (MDA), serum MDA and 8-F2-isoprostanes levels were higher than controls (p<0.05). After antidepressant medication, RBC and serum MDA levels were decreased (p<0.05). Moreover, serum peroxide in free radicals levels were higher than controls (p<0.05). There were no differences between the depressed patients and controls for other oxidative stress markers.. This meta-analysis supports the facts that the serum TAC, paraoxonase and antioxidant levels are lower, and the serum free radical and oxidative damage product levels are higher than controls in depressed patients. Meanwhile, the antioxidant levels are increased and the oxidative damage product levels are decreased after antidepressant medication. The pathophysiological relationships between oxidative stress and depression, and the potential benefits of antioxidant supplementation deserve further research.

Topics: Albumins; Antidepressive Agents; Antioxidants; Aryldialkylphosphatase; Ascorbic Acid; Biomarkers; Case-Control Studies; Cross-Sectional Studies; Depression; Depressive Disorder; F2-Isoprostanes; Humans; Lipid Peroxidation; Lipoproteins, HDL; Malondialdehyde; Oxidative Stress; Uric Acid

We have investigated the effects of supplementation of the diet with the antioxidant vitamins C and E on several functions of the immune response of aged women. Ten healthy women and 20 women (72 +/- 6 years old) suffering two diseases often associated with age (10 with major depression disorders, MDD, and 10 with coronary heart disease, CHD) were administered 1 g of vitamin C and 200 mg of vitamin E daily for 16 weeks. Blood samples were collected before and after treatment for measurement of several immunological functions, namely proliferative response of lymphocytes to the mitogen phytohemagglutinin (20 mg/L) and phagocytic functions of polymorphonuclear (PMN) neutrophils, i.e., adherence to vascular endothelium, chemotaxis, phagocytosis of latex beads, and superoxide anion production. In addition, we also determined the levels of serum cortisol and lipid peroxides. Intake of vitamins resulted in a significant increase in the lymphoproliferative capacity and in the phagocytic functions of PMN neutrophils as well as in a significant decrease of serum levels of lipid peroxides and cortisol, both in the healthy aged women and in the aged women with MDD or CHD. These findings suggest an important role of antioxidant supplementation in the improvement of immune function in aged females as well as in the prevention and treatment of specific diseases associated with age that are quite prevalent in the developed countries.

Topics: Aged; Antioxidants; Ascorbic Acid; Chemotaxis; Coronary Disease; Depressive Disorder; Female; Humans; Hydrocortisone; Immune System; Lipid Peroxidation; Lymphocyte Activation; Lymphocytes; Neutrophils; Phagocytosis; Superoxides; Vitamin E

In animal experiments, neuroprotective, anticonvulsive and antidepressant-like properties have been increasingly attributed to administrations of ascorbic acid (AA, vitamin C) in at least medium (low millimolar) doses, which however await validation in well controlled clinical studies. In mammalian cortical and subcortical neurons, small to modest acidification (<0.4-0.5 pH-units) is belonging to the key strategies for controlling local excitability and is associated with neuroprotection, e.g. by limiting excitotoxicity. Such acidifications are furthermore involved in the mechanisms of some anticonvulsants and antidepressants. As AA-transport and regulation of intracellular pH (pHi) are closely interwoven on the level of special transmembrane solute carriers, I suppose that the aforementioned beneficial AA-effects might be based upon a discrete "hormetic" acidification of cortical and or subcortical neurons via an AA-mediated weakening of their pHi-regulation. This assumption is supported by findings in non-neuronal cells suggesting both, intracellular acidification and inhibition of a core-element of the pHi-regulation apparatus by millimolar AA. In mammalian subcortical neurons, there is already first evidence of a modest acidification after adding low millimolar AA.

Topics: Alzheimer Disease; Animals; Anticonvulsants; Antidepressive Agents; Antioxidants; Ascorbic Acid; Brain; Carrier Proteins; Cations; Dehydroascorbic Acid; Depressive Disorder; Epilepsy; Humans; Hydrogen-Ion Concentration; Intracellular Fluid; Mammals; Mechanistic Target of Rapamycin Complex 1; Nerve Tissue Proteins; Neurons; Neuroprotective Agents; Oxidation-Reduction

Adolescents with depression are at risk for negative long-term consequences and recurrence of depression. Many do not receive nor access treatment, especially Latino youth. New treatment approaches are needed. This study examined the feasibility and acceptability of a stepped collaborative care treatment model (SCIPT-A) for adolescents with depression utilizing interpersonal psychotherapy for adolescents (IPT-A) and antidepressant medication (if needed) compared to Enhanced Treatment as Usual (E-TAU) in urban pediatric primary care clinics serving primarily Latino youth. Results suggest the SCIPT-A model is feasible, acceptable and potentially beneficial for urban Latino adolescents. Clinicians delivered the SCIPT-A model with fidelity using supervision successfully implemented in a community setting.

Topics: Adolescent; Antidepressive Agents; Ascorbic Acid; Cooperative Behavior; Depressive Disorder; Depressive Disorder, Major; Female; Ferrous Compounds; Hispanic or Latino; Humans; Male; Mental Health Services; Patient Acceptance of Health Care; Pediatrics; Pilot Projects; Primary Health Care; Psychotherapy; Urban Population

Diabetes mellitus and depression are the common comorbid disorders affecting humans worldwide. There is an unmet need to develop therapeutic strategies to treat both diabetes mellitus and comorbid depression. The present study evaluated the effectiveness of metformin and ascorbic acid against type 2 diabetes mellitus and comorbid depression in rats. Four groups of diabetic rats were orally administered with vehicle (1mL/kg), metformin (25mg/kg), ascorbic acid (25mg/kg), or combination of metformin (25mg/kg) and ascorbic acid (25mg/kg) for 11 consecutive days. Diabetes was induced by single-dose administration of streptozotocin (65mg/kg, i.p.) with nicotinamide (120mg/kg, i.p.). Comorbid depression was induced by five inescapable foot-shocks (2mA, 2ms duration) at 10s intervals on days 1, 5, 7, and 10. One group of healthy rats received only vehicles to serve as nondiabetic control group. On day 11, animals were sacrificed, and blood and brain samples were collected from each rat following forced swim test. Plasma glucose, insulin, and corticosterone levels were estimated in plasma. The levels of monoamines, proinflammatory cytokines, and oxidative stress were measured in prefrontal cortex. The combination therapy significantly reduced immobility period, glucose, and corticosterone levels relative to diabetes with comorbid depression group. Furthermore, the combination therapy increased the levels of insulin and monoamines, and caused a significant reductions in oxidative stress and proinflammatory cytokines. In conclusion, the present study revealed that metformin and ascorbic acid combination therapy could be a potential strategy to treat type 2 diabetes mellitus and comorbid depression.

Topics: Animals; Ascorbic Acid; Biogenic Monoamines; Blood Glucose; Comorbidity; Corticosterone; Cytokines; Depression; Depressive Disorder; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Disease Models, Animal; Drug Therapy, Combination; Insulin; Male; Metformin; Oxidative Stress; Rats; Rats, Inbred Strains

Degeneration of substantia nigra dopaminergic neurons is a key pathological change of Parkinson's disease (PD), and its motor consequences have been widely recognized. Recently, mood disorders associated with PD have begun to attract a great deal of interest, however, their pathogenesis remains unclear. PD is associated with not only degenerative changes in dopaminergic neurons in the substantia nigra but also changes in serotonergic neurons in the raphe nuclei. The abnormalities in central 5-hydroxytryptamine (5-HT) neurotransmission are thought to play a key role in the pathogenesis of depression. The lateral habenula (LHb) is closely related to the substantia nigra and raphe nuclei, and its hyperactivity is closely related to the pathogenesis of depression. In this study, we screened rats with depressive-like behaviors from PD model animals and found that cytochrome c oxidase activity in the LHb of these rats was twice that seen in the control rats. In the forced swim test, LHb lesions caused a decrease in depressive-like behavior of PD rats as indexed by decreased immobility times and increased climbing times. Additionally, LHb lesions caused an enhance in 5-HT levels in the raphe nuclei. These results suggest that LHb lesions may improve depressive-like behavior in PD rats by increasing 5-HT levels in the raphe nuclei. Thus, LHb contributes to the depressive-like behavior in PD rats via mediating the effects of dopaminergic neurons in the substantia nigra on serotonergic neurons in the raphe nuclei.

Topics: Animals; Ascorbic Acid; Depressive Disorder; Dopamine; Electric Stimulation; Electron Transport Complex IV; Exploratory Behavior; Habenula; Male; Motor Activity; Neuropsychological Tests; Oxidopamine; Parkinsonian Disorders; Random Allocation; Raphe Nuclei; Rats, Wistar; Serotonin

Studies have demonstrated an association between stressful conditions and the onset of clinical depression. Considering the antidepressant-like properties of ascorbic acid in both experimental and clinical approaches, we evaluated the beneficial effect of this vitamin on restraint stress-induced behavioral and neurochemical alterations. Acute restraint stress caused a depressive-like behavior in the forced swimming test, accompanied by increased lipid peroxidation (cerebral cortex and hippocampus); increased superoxide dismutase (cerebral cortex and hippocampus), glutathione reductase (cerebral cortex), and glutathione peroxidase (cerebral cortex and hippocampus) activities; and elevated expression of Bcl-2 (hippocampus). Oral administration of ascorbic acid (1 mg/kg) or fluoxetine (10 mg/kg) 1 h before restraint stress prevented the stress-induced increase on immobility time in the forced swimming test. Moreover, this vitamin reduced lipid peroxidation to control levels and restored the activity of superoxide dismutase, glutathione reductase, and glutathione peroxidase. Ascorbic acid had no effect on the increased level of Bcl-2 induced by stress. Glutathione levels, glycogen synthase kinase-3β phosphorylation, and Bax expression were not altered by stress or ascorbic acid administration. Besides reinforcing the antioxidant potential of ascorbic acid, our results support the notion that oxidative stress plays a role in the pathogenesis and treatment of stress-induced depression.

Topics: Animals; Antioxidants; Ascorbic Acid; bcl-2-Associated X Protein; Cerebral Cortex; Depressive Disorder; Female; Glutathione Peroxidase; Glutathione Reductase; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Hippocampus; Lipid Metabolism; Mice; Motor Activity; Oxidation-Reduction; Proto-Oncogene Proteins c-bcl-2; Stress, Psychological; Superoxide Dismutase; Swimming; Transcription, Genetic; Vitamins

Stress is a potent risk factor for depression, yet the underlying mechanism is not clearly understood. In the present study, we explored the mechanism of development and maintenance of depression in a stress-induced animal model. Mice restrained for 2 h daily for 14 d showed distinct depressive behavior, and the altered behavior persisted for >3 months in the absence of intervention. Acute restraint induced a surge of oxidative stress in the brain, and stress-induced oxidative stress progressively increased with repetition of stress. In vitro, the stress hormone glucocorticoid generated superoxide via upregulation of NADPH oxidase. Consistently, repeated restraints increased the expression of the key subunits of NADPH oxidase, p47phox and p67phox, in the brain. Moreover, stressed brains markedly upregulated the expression of p47phox to weak restress evoked in the poststress period, and this molecular response was reminiscent of amplified ROS surge to restress. Pharmacological inhibition of NADPH oxidase by the NADPH oxidase inhibitor apocynin during the stress or poststress period completely blocked depressive behavior. Consistently, heterozygous p47phox knock-out mice (p47phox(+/-)) or molecular inhibition of p47phox with Lenti shRNA-p47phox in the hippocampus suppressed depressive behavior. These results suggest that repeated stress promotes depressive behavior through the upregulation of NADPH oxidase and the resultant metabolic oxidative stress, and that the inhibition of NADPH oxidase provides beneficial antidepression effects.

Topics: Acetophenones; Analysis of Variance; Animals; Antidepressive Agents, Tricyclic; Antioxidants; Ascorbic Acid; Brain; Cell Line; Corticosterone; Depressive Disorder; Disease Models, Animal; Drug Administration Schedule; Gene Expression Regulation, Enzymologic; Green Fluorescent Proteins; Hindlimb Suspension; Hippocampus; Humans; Hydrogen Peroxide; Imipramine; Lipid Peroxidation; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; NADPH Oxidases; Neuroblastoma; Neurons; Phosphoproteins; Reactive Oxygen Species; Restraint, Physical; RNA, Messenger; RNA, Small Interfering; Social Behavior; Superoxides; Swimming; Time Factors

Topics: Antioxidants; Ascorbic Acid; Depressive Disorder; Humans; Hypericum; Phytotherapy; Plants, Medicinal; Preoperative Care; Research Design; Treatment Failure

A 29-year-old man was admitted to hospital, unconscious and with extensive bleedings in skin and muscles. For many weeks he had been practically starving himself with suicidal intent. Physical examination revealed signs of anaemia and gingivitis with hypertrophy of the tooth borders and bleeding gums, as well as bright blood on rectal examination. There were extensive ecchymoses and petechiae, especially in the legs. Some of the body hair was corkscrew-curly. Haemoglobin level was 7.2 g/dl, mean corpuscular volume 93 fl, reticulocyte count 29/1000. The Rumpel-Leede test was abnormal (60 petechiae/4 cm2), as were the vitamin C level (0.026 mg/dl whole blood) and the ascorbic acid tolerance test. As these findings indicated scurvy, vitamin C was administered, 1 g daily intravenously for 5 days, followed by 500 mg daily by mouth. Remarkable improvement was apparent as early as 72 hours after onset of treatment. The endogenous depression, the underlying cause of the suicide attempt, was treated with clomipramine. When the patient was discharged after 13 days his physical and mental state was much improved.

Topics: Adult; Ascorbic Acid; Clomipramine; Depressive Disorder; Erythrocyte Count; Erythrocyte Indices; Hemoglobins; Humans; Male; Reticulocytes; Scurvy; Self-Injurious Behavior; Starvation; Suicide, Attempted

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Depressive Disorder; Erythrocytes; Female; Folic Acid; Humans; Male; Vitamin B 12

Topics: Aged; Aged, 80 and over; Aging, Premature; Ascorbic Acid; Depression; Depressive Disorder; Procaine; Substance-Related Disorders; Vitamin B Complex

Topics: Adrenocorticotropic Hormone; Ascorbic Acid; Central Nervous System; Depression; Depressive Disorder; Humans; Vitamins