Stress levels, psychological symptoms, and C-reactive protein levels in COVID-19: A cross-sectional study.

BACKGROUND: Although many studies have pointed out a possible relationship between COVID-19 and the presence of psychiatric disorders, the majority of the studies have significant limitations. This study investigates the influence of COVID-19 infection on mental health. METHODS: This cross-sectional study included an age- and sex-matched sample of adult individuals positive (cases) or negative (controls) for COVID-19. We evaluated the presence of psychiatric conditions and C-reactive protein (CRP). RESULTS: Findings showed greater severity of depressive symptoms, higher levels of stress, and greater CRP in cases. The severity of depressive and insomnia symptoms, as well as the CRP were more remarkable in individuals with moderate/severe COVID-19. We found a positive correlation between stress and severity of anxiety, depression, and insomnia in individuals with or without COVID-19. There was a positive correlation between CRP levels and severity of depressive symptoms in cases and controls, and a positive correlation between CRP levels and the severity of anxiety symptoms and stress levels only in individuals with COVID-19. Individuals with COVID-19 and depression had greater CRP than those with COVID-19 without current major depressive disorder. LIMITATIONS: We cannot infer causality because this is a cross-sectional study, and the majority of COVID-19 sample was asymptomatic or had mild symptoms, which may limit the generalizability of our findings for moderate/severe cases. CONCLUSIONS: Individuals with COVID-19 showed greater severity of psychological symptoms, which may impact on the development of psychiatric disorders in the future. CPR seem to be a promising biomarker for earlier detection of post-COVID depression.

ω-3 and folic acid act against depressive-like behavior and oxidative damage in the brain of rats subjected to early- or late-life stress.

OBJECTIVES: To investigate the antidepressant and antioxidant effects of omega-3, folic acid and n-acetylcysteine (NAC) in rats which were subjected to early or late life stress. METHODS: Early stress was induced through maternal deprivation (MD), while late life stress was induced using the chronic mild stress (CMS) protocol. Young rats which were subjected to MD and the adult rats which were subjected to CMS were treated with omega-3 fatty acids (0.72 g/kg), NAC (20 mg/kg) or folic acid (50 mg/kg) once/day, for a period of 20 days. Then, the animals' immobility times were evaluated using the forced swimming test. Oxidative stress parameters were evaluated in the brain. RESULTS: Depressive-like behavior induced by CMS was prevented by NAC and folic acid, and depressive-like behavior induced by MD was prevented by NAC, folic acid and omega-3. NAC, folic acid and omega-3 were able to exert antioxidant effects in the brain of rats subjected to CMS or MD. These preventive treatments decreased the levels of protein carbonylation and lipid peroxidation, and also decreased the concentrations of nitrite/nitrate and reduced the activity of myeloperoxidase activity in the rat brain which was induced by CMS or MD. NAC, folic acid and omega-3 increased superoxide dismutase and catalase activities in the rat brain subjected to early or late life stress. CONCLUSIONS: NAC, omega-3 and folic acid may present interesting lines of treatment based on their antioxidant properties, which cause an inhibition of behavioral and brain changes that occur from stressful life events.

Acute treatment with ketamine and chronic treatment with minocycline exert antidepressant-like effects and antioxidant properties in rats subjected different stressful events.

Despite decades of research, the fundamental neurochemical and molecular mechanisms underlying the major depressive disorder (MDD) are still poorly understood, and current antidepressant treatments have limited clinical efficacy. In clinical conditions, the rapprochement between the disease and the corrective actions of drugs in laboratory animals is essential for developing effective therapies. Thus, the aim of this study was to evaluate the antidepressant effects of ketamine (N-metil-d-asparte (NMDA) receptor antagonist), minocycline (tetracycline antibiotic), and amitriptyline (classical antidepressant), on behavior and oxidative stress parameters in animals submitted to the chronic mild stress (CMS) and maternal deprivation protocols. For this aim, male Wistar rats were submitted to maternal deprivation or CMS. To induce maternal deprivation, Wistar rats were deprived of maternal care during the first 10 days of life. To induce CMS, Wistar rats were submitted to the CMS for 40 days. To reverse the effects of stress, treatment was done intraperitoneally with a single dose of ketamine (15 mg/kg), and minocycline (25 mg/kg) and amitriptyline (10 mg/kg) by 20 days. After treatment, the animals were submitted to the forced swimming test and then analyzed oxidative stress parameters in the prefrontal cortex (PFC), hippocampus, amygdala and nucleus accumbens (NAc). Treatment with ketamine, minocycline and amitriptyline were able to exert antidepressant effects in the forced swimming test. However, these antidepressant effects were dependent on the stress model by which the animals were exposed. In certain brain regions some treatment strategies had a pro-oxidant effect. Though, most of the strategies used in this study had antioxidant effects, as reported by a decrease on protein and lipid damage, nitrite/nitrate concentration and myeloperoxidase activity. In addition, an increase in the antioxidant superoxide dismutase (SOD) and catalase (CAT) enzymes activities were also evident after treatments. In conclusion, the antidepressant effects of ketamine and minocycline, in the present study, may be associated, at least in part, with its antioxidant and neuroprotective effects in animals subjected to maternal deprivation or CMS.

Mechanism of synergistic action on behavior, oxidative stress and inflammation following co-treatment with ketamine and different antidepressant classes.

BACKGROUND: Major depressive disorder (MDD) affects many people in the world. However, around 40% of patients do not respond to any pharmacological drugs. An alternative is to use a combination of different pharmacological groups or the combination of a classical antidepressant with a substance that can potentiate its effect. Thus, this study aimed to investigate the synergistic interactions between different antidepressants, including fluoxetine, quetiapine and lamotrigine in combination with ketamine, a N-methyl-d-aspartate (NMDA) receptor antagonist. METHODS: Wistar rats were acutely treated with fluoxetine (1.25mg/kg), quetiapine (5mg/kg), and lamotrigine (5.0mg/kg) alone or in combination with ketamine (5.0mg/kg), and then subjected to behavioral tests. In addition, oxidative damage and antioxidant capacity were assessed in the rat brain, and pro-inflammatory cytokines levels were evaluated in the serum. RESULTS: It was observed a synergistic effect of ketamine in combination with fluoxetine on the immobility time in the forced swimming test, indicating an antidepressant effect. Other antidepressant did not show effects when administrated alone or joint to ketamine. The combination of ketamine with other antidepressants, particularly quetiapine, in some brain regions induced an increase in damage to lipids and proteins. However, the combination of ketamine with fluoxetine increased the antioxidant activity of superoxide dismutase, and decreased oxidative damage, thus suggesting a neuroprotective effect of the combination of these drugs. The combination of ketamine with fluoxetine or lamotrigine reduced pro-inflammatory cytokines levels. CONCLUSION: In conclusion, ketamine induced antioxidant or pro-antioxidant effects dependent of antidepressant classes or brain area.

Immune System Modulators with Antidepressant Effects: Evidence from Animal Models.

BACKGROUND: Major depressive disorder (MDD) is associated with high mortality and morbidity rates, and currently, approximately 340 million people worldwide suffer from depression at some point in life. In view of the growing socio-economic and clinical impact, several studies have focused on the etiopathology of MDD, suggesting that not only the monoaminergic system but also other brain mechanisms may be involved in the pathophysiology of MDD. Recent studies have shown a link between inflammation and MDD and have also demonstrated that antidepressants and antiinflammatory drugs can act to reduce inflammation, thereby improving depressive symptoms. Animal models of depression are indispensable for studying the pathophysiology of this disorder and new treatments for it. Further, studies have shown that rodent models of depression are also associated with elevated levels of inflammation in the periphery and brain. OBJECTIVE: This review will highlight the role of immune inflammation in MDD and the significance of immune system modulators with antidepressant effects in the treatment of MDD, based on studies using animal models of depression.

Quetiapine treatment reverses depressive-like behavior and reduces DNA methyltransferase activity induced by maternal deprivation.

Stress in early life has been appointed as an important phenomenon in the onset of depression and poor response to treatment with classical antidepressants. Furthermore, childhood trauma triggers epigenetic changes, which are associated with the pathophysiology of major depressive disorder (MDD). Treatment with atypical antipsychotics such as quetiapine, exerts therapeutic effect for MDD patients and induces epigenetic changes. This study aimed to analyze the effect of chronic treatment with quetiapine (20mg/kg) on depressive-like behavior of rats submitted to maternal deprivation (MD), as well as the activity of histone acetylation by the enzymes histone acetyl transferases (HAT) and deacetylases (HDAC) and DNA methylation, through DNA methyltransferase enzyme (DNMT) in the prefrontal cortex (PFC), nucleus accumbens (NAc) and hippocampus. Maternally deprived rats had a depressive-like behavior in the forced swimming test and an increase in the HDAC and DNMT activities in the hippocampus and NAc. Treatment with quetiapine reversed depressive-like behavior and reduced the DNMT activity in the hippocampus. This is the first study to show the antidepressant-like effect of quetiapine in animals subjected to MD and a protective effect by quetiapine in reducing epigenetic changes induced by stress in early life. These results reinforce an important role of quetiapine as therapy for MDD.

Minocycline protects against oxidative damage and alters energy metabolism parameters in the brain of rats subjected to chronic mild stress.

Studies have been suggested that minocycline can be a potential new agent for the treatment of depression. In addition, both oxidative stress and energy metabolism present an important role in pathophysiology of depression. So, the present study was aimed to evaluate the effects of minocycline on stress oxidative parameters and energy metabolism in the brain of adult rats submitted to the chronic mild stress protocol (CMS). After CMS Wistar, both stressed animals as controls received twice ICV injection of minocycline (160 µg) or vehicle. The oxidative stress and energy metabolism parameters were assessed in the prefrontal cortex (PF), hippocampus (HIP), amygdala (AMY) and nucleus accumbens (Nac). Our findings showed that stress induced an increase on protein carbonyl in the PF, AMY and NAc, and mynocicline injection reversed this alteration. The TBARS was increased by stress in the PF, HIP and NAc, however, minocycline reversed the alteration in the PF and HIP. The Complex I was incrased in AMY by stress, and minocycline reversed this effect, however reduced Complex I activity in the NAc; Complex II reduced in PF and AMY by stress or minocycline; the Complex II-III increased in the HIP in stress plus minocycline treatment and in the NAc with minocycline; in the PF and HIP there were a reduced in Complex IV with stress and minocycline. The creatine kinase was reduced in AMY and NAc with stress and minocycline. In conclusion, minocycline presented neuroprotector effects by reducing oxidative damage and regulating energy metabolism in specific brain areas.