COVID-19, Anxiety, and Body Mass Index Increase Leptin Levels: a Cross-sectional Multicentric Study.

Although many efforts have been made to understand the pathophysiological mechanisms of COVID-19, critical gaps remain to be explored. This study aimed to investigate potential alterations in adipokine levels (specifically adiponectin, leptin, and resistin) among individuals with COVID-19. Within this population, we further assessed the association between these markers with both, body mass index (BMI) and psychiatric symptoms. This cross-sectional study included an age- and sex-matched sample of adults with COVID-19 (cases) and without COVID-19 (controls). We evaluated the severity of psychiatric symptoms, BMI, and adipokines. Individuals with COVID-19 presented greater BMI, stress levels, and leptin levels when compared to controls. Leptin levels were greater in individuals with moderate/severe COVID-19 as compared to individuals with COVID-19 who were asymptomatic or having mild symptoms. Leptin levels were positively correlated with BMI, severity of depressive and anxiety symptoms, and stress levels in the total sample. Leptin levels were also positively correlated with BMI, severity of anxiety symptoms, and stress levels in controls. In cases, there was a positive correlation between adiponectin and the severity of depressive symptoms and stress levels and leptin/resistin with BMI. A linear regression model revealed that BMI, severity of anxiety symptoms, and the diagnosis of COVID-19 are independently associated with increased leptin levels. Thus, leptin levels seem to be impacted by the COVID-19 infection, anxiety, and BMI.

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.

A narrative review on invasive brain stimulation for treatment-resistant depression

While most patients with depression respond to pharmacotherapy and psychotherapy, about one-third will present treatment resistance to these interventions. For patients with treatment-resistant depression (TRD), invasive neurostimulation therapies such as vagus nerve stimulation, deep brain stimulation, and epidural cortical stimulation may be considered. We performed a narrative review of the published literature to identify papers discussing clinical studies with invasive neurostimulation therapies for TRD. After a database search and title and abstract screening, relevant English-language articles were analyzed. Vagus nerve stimulation, approved by the U.S. Food and Drug Administration as a TRD treatment, may take several months to show therapeutic benefits, and the average response rate varies from 15.2-83%. Deep brain stimulation studies have shown encouraging results, including rapid response rates (> 30%), despite conflicting findings from randomized controlled trials. Several brain regions, such as the subcallosal-cingulate gyrus, nucleus accumbens, ventral capsule/ventral striatum, anterior limb of the internal capsule, medial-forebrain bundle, lateral habenula, inferior-thalamic peduncle, and the bed-nucleus of the stria terminalis have been identified as key targets for TRD management. Epidural cortical stimulation, an invasive intervention with few reported cases, showed positive results (40-60% response), although more extensive trials are needed to confirm its potential in patients with TRD.

A narrative review on invasive brain stimulation for treatment-resistant depression.

While most patients with depression respond to pharmacotherapy and psychotherapy, about one-third will present treatment resistance to these interventions. For patients with treatment-resistant depression (TRD), invasive neurostimulation therapies such as vagus nerve stimulation, deep brain stimulation, and epidural cortical stimulation may be considered. We performed a narrative review of the published literature to identify papers discussing clinical studies with invasive neurostimulation therapies for TRD. After a database search and title and abstract screening, relevant English-language articles were analyzed. Vagus nerve stimulation, approved by the U.S. Food and Drug Administration as a TRD treatment, may take several months to show therapeutic benefits, and the average response rate varies from 15.2-83%. Deep brain stimulation studies have shown encouraging results, including rapid response rates (> 30%), despite conflicting findings from randomized controlled trials. Several brain regions, such as the subcallosal-cingulate gyrus, nucleus accumbens, ventral capsule/ventral striatum, anterior limb of the internal capsule, medial-forebrain bundle, lateral habenula, inferior-thalamic peduncle, and the bed-nucleus of the stria terminalis have been identified as key targets for TRD management. Epidural cortical stimulation, an invasive intervention with few reported cases, showed positive results (40-60% response), although more extensive trials are needed to confirm its potential in patients with TRD.

Relationship of Oxidative Stress as a Link between Diabetes Mellitus and Major Depressive Disorder.

Both conditions, major depressive disorder (MDD) and diabetes mellitus (DM) are chronic and disabling diseases that affect a very significant percentage of the world's population. Studies have been shown that patients with DM are more susceptible to develop depression, when compared to the general population. The opposite also happens; MDD could be a risk factor for DM development. Some mechanisms have been proposed to explain the pathophysiological mechanisms involved with these conditions, such as excess of glucocorticoids, hyperglycemia, insulin resistance, and inflammation. These processes can lead to an increase in damage to biomolecules and a decrease in antioxidant defense capacity, leading to oxidative stress.

Early Maternal Deprivation Induces Microglial Activation, Alters Glial Fibrillary Acidic Protein Immunoreactivity and Indoleamine 2,3-Dioxygenase during the Development of Offspring Rats.

Maternal deprivation (MD) induces behavioral changes and impacts brain circuits that could be associated with the pathophysiology of depression. This study investigated the markers of microglia and astrocyte activation as well as indoleamine 2,3-dioxygenase (IDO) expression in developmental programming after early life MD (on postnatal days (PNDs) 20, 30, 40, and 60). On PND 60, the rats that were subjected to MD displayed depressive-like behavior. On PND 10, it was found that there was a decrease in the level of glial fibrillary acidic protein (GFAP) immunopositive cells, a decrease in the level of IDO expression, and an increase in the level of Iba-1 (microglial marker) in the hippocampus of rats that were subjected to MD. On PND 20, levels of GFAP were also found to have decreased in the hippocampus, and there was an increase in the level of Iba-1 in the hippocampus. AIF-1 (microglial marker) expression was observed in the PFC following MD. On PND 30, the levels of Iba-1 remained elevated. On PND 40, the levels of GFAP were found to have increased in the hippocampus of rats that were subjected to MD. On PND 60, the levels of GFAP and AIF-1 remained elevated following MD. These results suggest that early life stress induces negative developmental programming in rats, as demonstrated by depressive-like behavior in adult life. Moreover, MD increases microglial activation in both early and late developmental phases. The levels of GFAP and IDO decreased in the early stages but were found to be higher in later developmental periods. These findings suggest that MD could differentially affect the expression of the IDO enzyme, astrocytes, and microglial activation depending on the neurodevelopmental period. The onset of an inflammatory state from resident brain cells could be associated with the activation of the kynurenine pathway and the development of depressive behavior in adulthood.

Resilience Dysregulation in Major Depressive Disorder: Focus on Glutamatergic Imbalance and Microglial Activation.

BACKGROUND: Many studies have been shown an important role of glutamatergic system as well microglial activation in the pathophysiology of major depressive disorder (MDD). In humans most resistant to the development of psychiatric disorders, including MDD, are observed a greater degree of resilience resulting from stress. Less resilience is associated with neuroendocrine and neuroinflammatory markers, as well as with glutamatergic system dysregulation. Thus, this review we highlighted findings from literature identifying the function of glutamatergic system, microglial activation and inflammation in resilience. METHODS: We conducted a review of computerized databases from 1970 to 2017. RESULTS: There is an association between microglial activation and glutamatergic system activation with stress vulnerability and resilience. CONCLUSIONS: Glutamate neurotransmission, including neurotransmitter synthesis, signalling, and glutamate receptor functions and expression all seem to be involved with both stress vulnerability and resilience. Moreover, inflammation and microglial activation mediate individual differences in resilience and the risk of stress-induced MDD.

Early life experience contributes to the developmental programming of depressive-like behaviour, neuroinflammation and oxidative stress.

This study used an animal model of depression induced by maternal care deprivation (MCD) to investigate whether depressive behaviour, neuroinflammation and oxidative stress were underlying factors in developmental programming after early life stress. At postnatal days (PND) 20, 30, 40, and 60, individual subsets of animals were evaluated in behavioural tests and then euthanized to assess cytokine levels and oxidative stress parameters in the prefrontal cortex (PFC), hippocampus and serum. The results showed that MCD did not induce behavioural changes at PND 30 and 40. However, at PND 20 and 60, the rats displayed a depressive-like behaviour in the forced swimming test, without changes in locomotor spontaneous activity. In the brain and serum, the levels of pro-inflammatory cytokines (interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α)) were increased, and the anti-inflammatory cytokine (interleukin-10) level was reduced throughout developmental programming (PND 20, 30, 40 and 60). Protein carbonyl levels increased in the brain at PND 30, 40 and 60. Superoxide dismutase (SOD) activity was decreased during all developmental programming phases evaluated in the brain. Catalase (CAT) activity was decreased at PND 20, 40 and 60 in the brain. Our results revealed that "critical episodes" in early life stressful events are able to induce behavioural alterations that persist into adulthood and can stimulate inflammation and oxidative damage in both central and peripheral systems, which are required for distinct patterns of resilience against psychiatric disorders later in life.