ascorbic-acid and Depressive-Disorder--Major

Ascorbic acid, a water-soluble vitamin, is highly concentrated in the brain and participates in neuronal modulation and regulation of central nervous system (CNS) homeostasis. Ascorbic acid has emerged as a neuroprotective compound against neurotoxicants and neurodegenerative diseases, including Alzheimer's disease, multiple sclerosis and amyotrophic lateral sclerosis. Moreover, it improves behavioral and biochemical alterations in psychiatric disorders, including schizophrenia, anxiety, major depressive disorder, and bipolar disorder. Some recent studies have advanced the knowledge on the mechanisms associated with the preventive and therapeutic effects of ascorbic acid by showing that they are linked to improved neurogenesis and synaptic plasticity. This review shows that ascorbic acid has the potential to regulate positively stem cell generation and proliferation. Moreover, it improves neuronal differentiation of precursors cells, promotes adult hippocampal neurogenesis, and has synaptogenic effects that are possibly linked to its protective or therapeutic effects in the brain.

Topics: Adult; Ascorbic Acid; Central Nervous System; Depressive Disorder, Major; Humans; Neurodegenerative Diseases; Neurogenesis

Major depressive disorder (MDD) affects approximately 121 million individuals globally and poses a significant burden to the healthcare system. Around 50-60% of patients with MDD respond adequately to existing treatments that are primarily based on a monoaminergic system. However, the neurobiology of MDD has not been fully elucidated; therefore, it is possible that other biochemical alterations are involved. The glutamatergic system and its associated receptors have been implicated in the pathophysiology of MDD. In fact, the N-methyl-d-aspartate (NMDA) receptor, a glutamate receptor, is a binding or modulation site for both classical antidepressants and new fast-acting antidepressants. Thus, this review aims to present evidence describing the effect of antidepressants that modulate NMDA receptors and the mechanisms that contribute to the antidepressant response.

Topics: Antidepressive Agents; Ascorbic Acid; Depressive Disorder, Major; Glutamates; Glycine Agents; Guanosine; Humans; Receptors, N-Methyl-D-Aspartate

There are some animal studies suggesting the possible role of vitamin C for treating depression. However, the efficacy of vitamin C for treating adult patients with major depressive disorder (MDD) has never been examined.. This 8-week randomized double-blind placebo-controlled clinical trial included adult patients with major depressive disorder according to DSM-IV diagnostic criteria. Twenty-one patients in the treatment group received citalopram plus vitamin C and the 22 patients in the control group received citalopram plus placebo. The Hamilton Depression Rating Scale was used to measure depressive symptoms at baseline, week 2, week 4, and week 8. We also checked for the presence of adverse effects.. While depression symptoms decreased in both groups during this trial, there was no statistically significant difference between the 2 groups (P = .5). The rate of remission, partial response, and complete response was not different between the two groups. The rate of adverse effects were not different between the two groups.. Adding vitamin C to citalopram did not increase the efficacy of citalopram in MDD patients. Vitamin C plus citalopram is as effective as placebo plus citalopram for treating adult patients with suicidal behavior. No serious adverse effect for this combination was identified during this trial.. This trial was registered at http://www.irct.ir . The registration number of this trial was: IRCT201312263930N31 . Date registered: 5 July 2014.

Topics: Adult; Antidepressive Agents; Antioxidants; Ascorbic Acid; Citalopram; Depressive Disorder, Major; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Suicidal Ideation; Suicide; Suicide Prevention; Time Factors; Treatment Outcome; Young Adult

Current antidepressants used to treat pediatric patients have the disadvantage of limited efficacy and potentially serious side effects. The purpose of this study was to assess the efficacy of vitamin C as an adjuvant agent in the treatment of pediatric major depressive disorder in a six-month, double-blind, placebo-controlled pilot trial.. The study group (n=12) was given fluoxetine (10-20 mg/day) plus vitamin C (1000 mg/day) and control group (n=12) administered fluoxetine (10-20 mg/day) plus placebo. The data were analyzed by ANOVA and t-test for independent samples.. Both groups demonstrated significantly improved scores on the Children's Depression Rating Scale (CDRS), the Children's Depression Inventory (CDI), and the Clinical Global Impression (CGI). ANOVA was significantly different on all clinical measurements (group effect, time effect, and interaction), with the exception of group effect and interaction for CGI. Patients treated for six months with fluoxetine and vitamin C showed a significant decrease in depressive symptoms in comparison to the fluoxetine plus placebo group as measured by the CDRS (t=11.36, P<0.0001) and CDI (t=12.27, P<0.0001), but not CGI (t=0.13, P=0.90). No serious adverse effects were observed.. These preliminary results suggest that vitamin C may be an effective adjuvant agent in the treatment of MDD in pediatric patients.

Topics: Adjuvants, Pharmaceutic; Antidepressive Agents; Ascorbic Acid; Child; Depressive Disorder, Major; Double-Blind Method; Female; Fluoxetine; Humans; Male; Pilot Projects

In this study, we investigated the ability of a single coadministration of subeffective doses of ascorbic acid and ketamine to reverse the depressive-like behavior induced by chronic unpredictable stress (CUS) in mice. Moreover, we examined the effect of combined administration of ascorbic acid and ketamine on hippocampal phosphorylation of p70S6K and immunocontents of GLUA1 and PSD-95 in mice submitted to the CUS procedure. CUS procedure was applied for 21 days. Animals received a single coadministration of subeffective doses of ascorbic acid (0.1 mg/kg) and ketamine (0.1 mg/kg) and were subjected to behavioral evaluation 24 h after the treatments. Immediately after the behavioral observations the hippocampi were dissected for Western blotting analyses. Our results revealed that a single administration of subeffective doses of ascorbic acid and ketamine completely reversed the depressive-like behavior induced by CUS, however, this effect was not accompanied by changes in the phosphorylation of p70S6K and immunocontent of GLUA1 or PSD95 in the hippocampus. These findings point to a synergistic antidepressant-like effect of ascorbic acid and ketamine, paving the way for additional studies on the combined use of these compounds for the management of major depressive disorder (MDD).

Topics: Animals; Antidepressive Agents; Ascorbic Acid; Behavior, Animal; Depression; Depressive Disorder, Major; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Female; Hindlimb Suspension; Hippocampus; Ketamine; Locomotion; Mice; Stress, Psychological; Treatment Outcome

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

Considering the involvement of the opioid system in major depressive disorder (MDD), mainly concerning refractory MDD, and the evidence that ascorbic acid may exert a beneficial effect for the treatment of this disorder, this study investigated the involvement of the opioid system in the antidepressant-like effect of ascorbic acid in the tail suspension test (TST). Treatment of Swiss mice with the non-selective opioid receptor antagonist naloxone (1 mg/kg, i.p.) prevented the reduced immobility time caused by ascorbic acid (1 mg/kg, p.o.) in the TST. Additionally, administration of the selective μ1-opioid receptor antagonist, naloxonazine (10 mg/kg, i.p.), also abolished the antidepressant-like action of the same dose of ascorbic acid in the TST. We also investigated the possible relationship between the opioid system and NMDA receptors in the mechanism of action of ascorbic acid or ketamine (0.1 mg/kg, i.p.) in the TST. Treatment of mice with naloxone (1 mg/kg, i.p.) blocked the synergistic antidepressant-like effect of ascorbic acid (0.1 mg/kg. p.o.) and MK-801 (0.001 mg/kg, p.o., a non-competitive NMDA receptor antagonist) in the TST. Combined administration of ketamine and MK-801 induced a synergistic antidepressant-like action, and naloxone partially abolished this effect. Our results indicate that the antidepressant-like effect of ascorbic acid in the TST appears to be dependent on the activation of the opioid system, especially μ1-opioid receptors, which might be an indirect consequence of NMDA receptor inhibition elicited by ascorbic acid administration.

Topics: Analgesics, Opioid; Animals; Antidepressive Agents; Ascorbic Acid; Depressive Disorder, Major; Female; Hindlimb Suspension; Mice; Motor Activity; Narcotic Antagonists; Receptors, Opioid

Topics: Aged; Amyloid beta-Peptides; Ascorbic Acid; Biomarkers; Depressive Disorder, Major; Female; Humans; Male; Metabolomics; Neuropsychological Tests; Peptide Fragments

It has been suggested that dysregulation of γ-aminobutyric acid (GABA)-mediated neurotransmission is involved in the etiology of major depressive disorder and in the action of the fast-acting antidepressant ketamine. Considering that recent evidence has suggested that ascorbic acid may exert an antidepressant-like effect through mechanisms similar to ketamine, this study evaluated the involvement of GABAA and GABAB receptors in the antidepressant-like effect of ascorbic acid, comparing the results with those obtained with ketamine.. To investigate the involvement of GABAA in the antidepressant-like effect of ascorbic acid and ketamine in the tail suspension test (TST), mice were treated with a sub-effective dose of ascorbic acid (0.1mg/kg, po), ketamine (0.1mg/kg, ip) or vehicle and 30minutes later, a sub-effective dose of muscimol (0.1mg/kg, ip, GABAA receptor agonist) or vehicle was administered. In another set of experiments, mice were treated with ascorbic acid (1mg/kg, po, active dose in the TST) or vehicle and 30minutes later, baclofen (1mg/kg, ip, GABAB receptor agonist) was administered. A similar experimental protocol was performed with ketamine (1mg/kg, ip).. The administration of muscimol combined with ascorbic acid or ketamine produced a synergistic antidepressant-like effect in the TST. Moreover, the antidepressant-like effects of ascorbic acid and ketamine were abolished by baclofen. There was no alteration in spontaneous locomotion in any experimental group.. Results indicate that the anti-immobility effect of ascorbic acid and ketamine in TST may involve an activation of GABAA receptors and a possible inhibition of GABAB receptors.

Topics: Animals; Antidepressive Agents; Ascorbic Acid; Depression; Depressive Disorder, Major; Disease Models, Animal; Female; gamma-Aminobutyric Acid; Hindlimb Suspension; Ketamine; Mice; Motor Activity; Receptors, GABA-A; Synaptic Transmission

The aim of the present study was to investigate the oxidative-antioxidative systems and effects of different antidepressants on these systems in patients with major depressive disorder (MDD).. Ninety-six patients with a Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) diagnosis of MDD and 54 healthy controls were included in the study. Plasma malondialdehyde (MDA) levels and susceptibility of red blood cells (RBCs) to oxidation were determined to investigate the oxidative status, plasma vitamin E, vitamin C, serum total carotenoid levels, total antioxidant capacity (TAOC), RBC superoxide dismutase (SOD) and whole blood glutathione peroxidase (GPx) activities were measured to investigate the antioxidative defence before and after 6 weeks of antidepressant treatment.. Plasma MDA levels and susceptibility of RBCs to oxidation were significantly higher in the MDD group compared with the control group. RBC SOD activity was significantly increased in patients with MDD, and furthermore there was a significant positive correlation between the severity of the disease and SOD activity.. MDD is accompanied with oxidative stress; however, oxidative-antioxidative systems do not seem to be affected by 6 weeks of antidepressant treatment.

Topics: Adult; Antidepressive Agents; Antioxidants; Ascorbic Acid; Carotenoids; Depressive Disorder, Major; Erythrocytes; Female; Glutathione Peroxidase; Humans; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Superoxide Dismutase; Time Factors; Uric Acid; Vitamin E