ABSTRACT
Comparing one's appearance to other people's and believing in an ideal body shape can negatively impact an individual. The probability of developing ED in individuals with high body dissatisfaction is higher than in the general population, leading to long-term emotional and metabolic damage. Populational studies on the prevalence of ED in Brazil are scarce in the literature. The research was carried out through the Google Forms website and evaluated risk of eating disorders through the Eating Attitude Test, degree of body dissatisfaction in the sample through the Body Shape Questionnaire and the Internet Addiction Test was used to evaluate time spent on the internet. The results showed that 84.5% of the sample were female and 62.3% of the individuals had eutrophic by the Body Mass Index. About 40.2% of the population studied had abnormal attitudes towards food, indicating a possible risk of developing ED, and 62.5% of the sample did not show body dissatisfaction. Regarding internet use, 10.8% had problematic internet use. The presence of risky eating attitudes was more prevalent in participants dissatisfied with their bodies. In addition, participants with problematic internet use had a higher risk for EDs.
Subject(s)
Feeding and Eating Disorders , Social Media , Humans , Female , Male , Feeding and Eating Disorders/epidemiology , Feeding and Eating Disorders/psychology , Brazil/epidemiology , Adult , Young Adult , Surveys and Questionnaires , Risk Factors , Coal Mining , Adolescent , Body Image/psychology , Middle Aged , Body Mass Index , Prevalence , Time Factors , Cross-Sectional Studies , Body Dissatisfaction/psychologyABSTRACT
Over the last six decades, lithium has been considered the gold standard treatment for the long-term management of bipolar disorder due to its efficacy in preventing both manic and depressive episodes as well as suicidal behaviors. Nevertheless, despite numerous observed effects on various cellular pathways and biologic systems, the precise mechanism through which lithium stabilizes mood remains elusive. Furthermore, there is recent support for the therapeutic potential of lithium in other brain diseases. This review offers a comprehensive examination of contemporary understanding and predominant theories concerning the diverse mechanisms underlying lithium's effects. These findings are based on investigations utilizing cellular and animal models of neurodegenerative and psychiatric disorders. Recent studies have provided additional support for the significance of glycogen synthase kinase-3 (GSK3) inhibition as a crucial mechanism. Furthermore, research has shed more light on the interconnections between GSK3-mediated neuroprotective, antioxidant, and neuroplasticity processes. Moreover, recent advancements in animal and human models have provided valuable insights into how lithium-induced modifications at the homeostatic synaptic plasticity level may play a pivotal role in its clinical effectiveness. We focused on findings from translational studies suggesting that lithium may interface with microRNA expression. Finally, we are exploring the repurposing potential of lithium beyond bipolar disorder. These recent findings on the therapeutic mechanisms of lithium have provided important clues toward developing predictive models of response to lithium treatment and identifying new biologic targets. SIGNIFICANCE STATEMENT: Lithium is the drug of choice for the treatment of bipolar disorder, but its mechanism of action in stabilizing mood remains elusive. This review presents the latest evidence on lithium's various mechanisms of action. Recent evidence has strengthened glycogen synthase kinase-3 (GSK3) inhibition, changes at the level of homeostatic synaptic plasticity, and regulation of microRNA expression as key mechanisms, providing an intriguing perspective that may help bridge the mechanistic gap between molecular functions and its clinical efficacy as a mood stabilizer.
Subject(s)
Lithium Compounds , Humans , Animals , Lithium Compounds/pharmacology , Lithium Compounds/therapeutic use , Antimanic Agents/pharmacology , Antimanic Agents/therapeutic use , Bipolar Disorder/drug therapy , Neuronal Plasticity/drug effects , Glycogen Synthase Kinase 3/metabolism , Glycogen Synthase Kinase 3/antagonists & inhibitorsABSTRACT
The present study aimed to investigate the effects of paradoxical sleep deprivation (PSD) on behavioral and oxidative stress parameters in the brain and serum of mice submitted to the animal model of hyperglycemia induced by alloxan, mimicking the main symptom of diabetes mellitus (DM). Adults C57BL/6 male and female mice received an injection of alloxan, and ten days later, the animals were submitted to the PSD for 36â¯h. The animals' behavioral parameters were evaluated in the open-field test. Oxidative stress parameters [Diacetyldichlorofluorescein (DCF), Thiobarbituric acid reactive substances (TBARS), Superoxide dismutase (SOD), and Glutathione] were assessed in the frontal cortex, hippocampus, striatum, and serum. The PSD increased the male and female mice locomotion, but the alloxan's pre-administration prevented the PSD-induced hyperactivity. In addition, the male mice receiving alloxan and submitted to the PSD had elevated latency time in the first quadrant and the number of fecal boli, demonstrating increased anxiety-like behavior. The HPA-axis was hyperactivating in male and female mice pre-administered alloxan and/or PSD-submitted animals. The oxidative stress parameters were also increased in the serum of the animals administered alloxan and/or sleep-deprived mice. Despite alloxan or PSD leading to behavioral or biochemical alterations, the one did not potentiate the other in mice. However, more studies are necessary to identify the link between sleep and hyperglycemia.
Subject(s)
Brain , Disease Models, Animal , Hyperglycemia , Mice, Inbred C57BL , Oxidative Stress , Sleep Deprivation , Animals , Sleep Deprivation/metabolism , Sleep Deprivation/physiopathology , Sleep Deprivation/blood , Male , Oxidative Stress/physiology , Female , Hyperglycemia/metabolism , Brain/metabolism , Mice , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/physiopathology , Alloxan , Thiobarbituric Acid Reactive Substances/metabolism , Superoxide Dismutase/metabolism , Glutathione/metabolism , Glutathione/bloodABSTRACT
BACKGROUND: RECOVER is a randomized sham-controlled trial of vagus nerve stimulation and the largest such trial conducted with a psychiatric neuromodulation intervention. OBJECTIVE: To describe pre-implantation baseline clinical characteristics and treatment history of patients with unipolar, major depressive disorder (MDD), overall and as a function of exposure to interventional psychiatric treatments (INTs), including electroconvulsive therapy, transcranial magnetic stimulation, and esketamine. METHODS: Medical, psychiatric, and treatment records were reviewed by study investigators and an independent Study Eligibility Committee prior to study qualification. Clinical characteristics and treatment history (using Antidepressant Treatment History [Short] Form) were compared in those qualified (N = 493) versus not qualified (N = 228) for RECOVER, and among the qualified group as a function of exposure to INTs during the current major depressive episode (MDE). RESULTS: Unipolar MDD patients who qualified for RECOVER had marked TRD (median of 11.0 lifetime failed antidepressant treatments), severe disability (median WHODAS score of 50.0), and high rate of baseline suicidality (77% suicidal ideation, 40% previous suicide attempts). Overall, 71% had received at least one INT. Compared to the no INT group, INT recipients were younger and more severely depressed (QIDS-C, QIDS-SR), had greater suicidal ideation, earlier diagnosis of MDD, and failed more antidepressant medication trials. CONCLUSIONS: RECOVER-qualified unipolar patients had marked TRD and marked treatment resistance with most failing one or more prior INTs. Treatment with ≥1 INTs in the current MDE was associated with earlier age of MDD onset, more severe clinical presentation, and greater treatment resistance relative to patients without a history of INT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03887715.
Subject(s)
Depressive Disorder, Major , Depressive Disorder, Treatment-Resistant , Transcranial Magnetic Stimulation , Humans , Male , Female , Depressive Disorder, Major/therapy , Middle Aged , Adult , Depressive Disorder, Treatment-Resistant/therapy , Electroconvulsive Therapy , Vagus Nerve Stimulation , Antidepressive Agents/therapeutic use , Ketamine , Treatment OutcomeABSTRACT
BACKGROUND: Treatment of refractory bipolar disorder (BD) is extremely challenging. Deep brain stimulation (DBS) holds promise as an effective treatment intervention. However, we still understand very little about the mechanisms of DBS and its application on BD. AIM: The present study aimed to investigate the behavioural and neurochemical effects of ventral tegmental area (VTA) DBS in an animal model of mania induced by methamphetamine (m-amph). METHODS: Wistar rats were given 14 days of m-amph injections, and on the last day, animals were submitted to 20 min of VTA DBS in two different patterns: intermittent low-frequency stimulation (LFS) or continuous high-frequency stimulation (HFS). Immediately after DBS, manic-like behaviour and nucleus accumbens (NAc) phasic dopamine (DA) release were evaluated in different groups of animals through open-field tests and fast-scan cyclic voltammetry. Levels of NAc dopaminergic markers were evaluated by immunohistochemistry. RESULTS: M-amph induced hyperlocomotion in the animals and both DBS parameters reversed this alteration. M-amph increased DA reuptake time post-sham compared to baseline levels, and both LFS and HFS were able to block this alteration. LFS was also able to reduce phasic DA release when compared to baseline. LFS was able to increase dopamine transporter (DAT) expression in the NAc. CONCLUSION: These results demonstrate that both VTA LFS and HFS DBS exert anti-manic effects and modulation of DA dynamics in the NAc. More specifically the increase in DA reuptake driven by increased DAT expression may serve as a potential mechanism by which VTA DBS exerts its anti-manic effects.
Subject(s)
Deep Brain Stimulation , Disease Models, Animal , Mania , Methamphetamine , Rats, Wistar , Ventral Tegmental Area , Animals , Ventral Tegmental Area/drug effects , Ventral Tegmental Area/metabolism , Methamphetamine/pharmacology , Male , Rats , Mania/therapy , Mania/chemically induced , Central Nervous System Stimulants/pharmacology , Nucleus Accumbens/drug effects , Nucleus Accumbens/metabolism , Dopamine/metabolism , Dopamine Plasma Membrane Transport Proteins/metabolism , Motor Activity/drug effects , Motor Activity/physiology , Bipolar Disorder/therapy , Bipolar Disorder/chemically inducedABSTRACT
BACKGROUND: Older people are the fastest-growing age group, with the highest risk of cognitive impairment. This study assessed the prevalence and associated factors with cognitive impairment in community-dwelling older people. METHODS: Older people were interviewed and accomplished through sociodemographic and health questionnaires. The quantitative variables were described by mean and standard deviation or median and interquartile range. The significance level adopted was 5 % (p < 0.05). The association between the quantitative variables was evaluated using the Pearson or Spearman correlation coefficients. RESULTS: The research population comprised 165 long-lived adults aged ≥80. The youngest one was 80, and the oldest one was 94 years old. The participants were 84.8 ± 3.6 years old, female (63 %) with a mean of education of 2.9 ± 1.8 years. A poor performance in the Mini-Mental State Examination (MMSE) was found in 58 (35.2 %) individuals when adjusted for educational level. After adjustment for confounding factors, body mass index (BMI) (p = 0.09), total older adults' income (up to 1 minimum wage [mw], p = 0.023; over 1 to 2 mw, p = 0.023), functional disability (Moderate dependence 75 %, p = 0.038; Moderate dependence 50 %, p = 0.081; Moderate dependence 25 %, p = 0.054), and the anxiety scale (p = 0.032), remained associated with cognitive impairment. CONCLUSIONS: This study showed that BMI, total older adults' income, functional disability, and anxiety are related to cognitive impairment in long-lived adults. This study has some limitations, such as the fact that it is a cross-sectional study, the reduced number of individuals, and the fact that there were no comparisons among different ages and populations.
Subject(s)
Cognitive Dysfunction , Humans , Female , Aged , Aged, 80 and over , Prevalence , Cross-Sectional Studies , Cognitive Dysfunction/psychology , Independent Living/psychology , Educational StatusABSTRACT
AIM: To investigate the factor structure, reliability, and validity of the Brazilian version of the Abbreviated Suicidal Narrative Inventory (SNI-38). METHODS: We used an anonymous online questionnaire of the SNI-38 and self-report measures administered between November 2020 and October 2021 in the Brazilian community. Participants were recruited through social media advertisements. Confirmatory factor analysis was carried out to test the factor structure of the SNI-38. In addition, we examined internal consistency, and convergent validity against stressful life events, the suicide crisis syndrome, suicidal ideation, and suicide attempts. RESULTS: 2660 participants were included. The eight-factor model SNI-38 had a good model fit (χ2[637] = 7,473.98, p < .001, CFI = .99, TLI = .99, RMSEA = .07, SRMR = .06); all items were significantly and positively loaded onto their respective factors (factor loadings ≥ .45). Reliability was good to high in all subscales except goal disengagement. Additionally, all subscales - except goal disengagement - were correlated positively which the suicide crisis syndrome, stressful life events, lifetime/past-month suicidal ideation, and lifetime suicide attempts. CONCLUSIONS: These findings provide preliminary support for the validity of the Brazilian version of the SNI-38, being an appropriate and valid tool for measuring suicidal narrative among Brazilian samples.
ABSTRACT
Major Depressive Disorder continues to remain one of the most prevalent psychiatric diseases globally. Despite multiple trials of conventional therapies, a subset of patients fail to have adequate benefit to treatment. Deep brain stimulation (DBS) is a promising treatment in this difficult to treat population and has shown strong antidepressant effects across multiple cohorts. Nearly two decades of work have provided insights into the potential for chronic focal stimulation in precise brain targets to modulate pathological brain circuits that are implicated in the pathogenesis of depression. In this paper we review the rationale that prompted the selection of various brain targets for DBS, their subsequent clinical outcomes and common adverse events reported. We additionally discuss some of the pitfalls and challenges that have prevented more widespread adoption of this technology as well as future directions that have shown promise in improving therapeutic efficacy of DBS in the treatment of depression.
ABSTRACT
OBJECTIVE: To examine the factor structure, reliability, and validity of the Brazilian version of the Suicide Crisis Inventory (SCI-2) among Brazilian adults. METHODS: The SCI-2 was cross-culturally adapted into Portuguese and administered to 2,265 individuals in the Brazilian community. Confirmatory factor analyses, internal consistency, and convergent and criterion validity against the suicidal narrative, stressful life events, suicidal ideation, and suicide attempts were examined. RESULTS: The revised one-factor model of the SCI-2 resulted in adequate, but not optimal, model fit (χ2[1539] = 31,442.79, p < .001, CFI = .99, TLI = .99, RMSEA = .09, SRMR = .05). The revised five-factor model, on the other hand, demonstrated good fit (χ2[1529] = 14,174.86, p < .001, CFI = 1.00, TLI = 1.00, RMSEA = .06, SRMR = .04). Comparison of these two models indicated that the five-factor exhibited a superior model fit to the one-factor model. The SCI-2 total and subscales showed strong internal consistency, good convergent, and criterion validity in relation to stressful life events, suicidal narrative (except goal disengagement subscale), suicidal ideation, and suicide attempts. CONCLUSIONS: These findings indicate that the Brazilian version of the SCI-2 is a valid tool for measuring symptoms of the Suicide Crisis Syndrome.
ABSTRACT
Suicide attempt (SA) risk is elevated in individuals with bipolar disorder (BD), and DNA methylation patterns may serve as possible biomarkers of SA. We conducted epigenome-wide association studies (EWAS) of blood DNA methylation associated with BD and SA. DNA methylation was measured at >700,000 positions in a discovery cohort of n = 84 adults with BD with a history of SA (BD/SA), n = 79 adults with BD without history of SA (BD/non-SA), and n = 76 non-psychiatric controls (CON). EWAS revealed six differentially methylated positions (DMPs) and seven differentially methylated regions (DMRs) between BD/SA and BD/non-SA, with multiple immune-related genes implicated. There were no epigenome-wide significant differences when BD/SA and BD/non-SA were each compared to CON, and patterns suggested that epigenetics differentiating BD/SA from BD/non-SA do not differentiate BD/non-SA from CON. Weighted gene co-methylation network analysis and trait enrichment analysis of the BD/SA vs. BD/non-SA contrast further corroborated immune system involvement, while gene ontology analysis implicated calcium signalling. In an independent replication cohort of n = 48 BD/SA and n = 47 BD/non-SA, fold changes at the discovery cohort's significant sites showed moderate correlation across cohorts and agreement on direction. In both cohorts, classification accuracy for SA history among individuals with BD was highest when methylation at the significant CpG sites as well as information from clinical interviews were combined, with an AUC of 88.8% (CI = 83.8-93.8%) and 82.1% (CI = 73.6-90.5%) for the combined epigenetic-clinical classifier in the discovery and replication cohorts, respectively. Our results provide novel insight to the role of immune system functioning in SA and BD and also suggest that integrating information from multiple levels of analysis holds promise to improve risk assessment for SA in adults with BD.
Subject(s)
Bipolar Disorder , Adult , Humans , Bipolar Disorder/genetics , Epigenome , Suicide, Attempted , Genome-Wide Association Study , Epigenesis, Genetic , DNA MethylationABSTRACT
BACKGROUND: Major depression has a complex and multifactorial etiology constituted by the interaction between genetic and environmental factors in its development. OBJECTIVE: The aim of this study was to evaluate the effects of sodium butyrate (SD) on epigenetic enzyme alterations in rats subjected to animal models of depression induced by maternal deprivation (MD) or chronic mild stress (CMS). METHODS: To induce MD, male Wistar rats were deprived of maternal care during the first 10 days of life. To induce CMS, rats were subjected to the CMS for 40 days. Adult rats were then treated with daily injections of SD for 7 days. Animals were subjected to the forced swimming test (FST), and then, histone deacetylase (HDAC), histone acetyltransferase (HAT), and DNA methyltransferase (DNMT) activities were evaluated in the brain. RESULTS: MD and CMS increased immobility time in FST and increased HDAC and DNMT activity in the animal brains. SD reversed increased immobility induced by both animal models and the alterations in HDAC and DNMT activities. There was a positive correlation between enzyme activities and immobility time for both models. HDAC and DNMT activities also presented a positive correlation between themselves. CONCLUSION: These results suggest that epigenetics can play an important role in major depression pathophysiology triggered by early or late life stress and its treatment.
Subject(s)
Antidepressive Agents , Brain , Butyric Acid , Epigenesis, Genetic , Maternal Deprivation , Rats, Wistar , Stress, Psychological , Animals , Male , Stress, Psychological/drug therapy , Butyric Acid/pharmacology , Butyric Acid/therapeutic use , Epigenesis, Genetic/drug effects , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Rats , Brain/drug effects , Brain/metabolism , Disease Models, Animal , Histone Deacetylases/metabolism , Depression/drug therapy , Histone Acetyltransferases/metabolism , Swimming/psychologySubject(s)
Depressive Disorder, Major , Electroconvulsive Therapy , Ketamine , Humans , Depressive Disorder, Major/therapy , Depressive Disorder, Major/drug therapy , Electroconvulsive Therapy/adverse effects , Electroconvulsive Therapy/methods , Ketamine/adverse effects , Ketamine/therapeutic use , Ketamine/administration & dosage , Systematic Reviews as Topic , Meta-Analysis as TopicABSTRACT
The present study aimed to evaluate if sepsis sensitizes behavioural and biochemical responses induced by m-amphetamine. For this, Wistar rats were submitted to the cecal ligation and puncture. After 30 days of cecal ligation and puncture procedure, the animals were submitted to a single intraperitoneal injection of saline or m-amphetamine (.25, .50, or 1.0 mg/kg). Locomotor behaviour was assessed 2 h after the administration. Interleukin (IL)-1ß, IL-6, IL-10, tumour necrosis factor-α, dopamine-cAMP-regulated phosphoprotein of 32,000 kDa (DARPP-32) and neuronal calcium sensor (NCS-1) levels were evaluated in the frontal cortex, hippocampus and striatum. Also, brain-derived neurotrophic factor (BDNF), neuronal growth factor and glial-derived neurotrophic factor levels were assessed in the hippocampus. M-amphetamine alone (.25 and 1.0 mg/kg) increased rats' locomotion and exploratory behaviour compared with the Sham + Sal. Animals from the cecal ligation and puncture + m-amphetamine (.5 and/or 1.0 mg/kg) group showed an increase in locomotion, exploratory and risk-like behaviour when compared with the Sham + Saline group and with its respective Sham groups. Cecal ligation and puncture increased interleukin levels compared with the Sham + Sal. However, cecal ligation and puncture animals that received m-amphetamine (1 mg/kg) increased even more, these inflammatory parameters compared with the Sham + Sal and the cecal ligation and puncture + saline group. M-amphetamine at lower doses increased neurotrophic factors, but higher doses decreased these parameters in the brain of cecal ligation and puncture rats. M-amphetamine dose-dependently increased DARPP-32 and NCS-1 levels in cecal ligation and puncture rats in some structures. In conclusion, these results demonstrate that sepsis sensitizes behavioural amphetamine responses while inducing inflammatory and neurotrophic vulnerability in the cecal ligation and puncture model.
Subject(s)
Amphetamine , Sepsis , Rats , Animals , Rats, Wistar , Amphetamine/pharmacology , Punctures , Disease Models, AnimalABSTRACT
Objective: To evaluate the factor structure, reliability, and validity of the Brazilian version of the Suicide Crisis Inventory-2 (SCI-2) among Brazilian adults. Methods: The SCI-2 was cross-culturally adapted into Portuguese and administered to 2,265 Brazilian participants. Confirmatory factor analysis (CFA) was used to assess factor structure, internal consistency, convergent validity, and criterion validity by using measures such as suicidal narratives, stressful life events, suicidal ideation, and suicide attempts. Results: The revised one-factor model of the SCI-2 demonstrated an adequate, although not optimal, model fit (χ2[1539] = 31,442.79, p < 0.001, comparative fit index [CFI] = 0.99, Tucker-Lewis index [TLI] = 0.99, root mean square error of approximation [RMSEA] = 0.09, standardized root mean residual [SRMR] = 0.05). The revised five-factor model, on the other hand, demonstrated good fit (χ2[1529] = 14,174.86, p < 0.001, CFI = 1.00, TLI = 1.00, RMSEA = 0.06, SRMR = 0.04). Comparison of these two models indicated that the five-factor model had a better fit than the one-factor model. Both the total and subscale scores of the SCI-2 showed strong internal consistency and good convergent and criterion validity in relation to stressful life events, suicidal narratives (excluding the goal disengagement subscale), suicidal ideation, and suicide attempts. Conclusion: Our findings suggest that the Brazilian version of the SCI-2 is a valid tool for assessing symptoms of suicidal crisis syndrome.
ABSTRACT
BACKGROUND: Stressful life events are associated with higher odds of suicidal thoughts and behaviors. Furthermore, stressful life events can trigger specific symptoms, including the suicidal narrative and suicide crisis syndrome, resulting in an increased risk of suicidal thoughts and behaviors. This study examined the moderating role of suicide risk in the relationship between stressful life events, the suicidal narrative, and the suicide crisis syndrome. METHODS: 2,260 adults completed an online survey recruited through advertisements on social media. The level of emotional distress was assessed through the Suicide Narrative Inventory, Suicide Crisis Inventory-2, Stressful Life Events Questionnaire, and Mini International Neuropsychiatric Interview. The PROCESS macro (Hayes) was used to analyze the moderation models. RESULTS: Stressful life events were positively correlated with the suicidal narrative and suicide crisis syndrome. The effects of stressful life events on suicidal narrative and suicide crisis syndrome were strongest when suicide risk was low and weakest when suicide risk was high. CONCLUSIONS: These findings suggest that including stressful life events as part of suicide risk assessment in general and clinical settings is critical to managing treatment for suicidal thoughts and developing adaptive coping.
ABSTRACT
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.
ABSTRACT
Notwithstanding advances in understanding the pathophysiology of major depressive disorder (MDD), no single mechanism can explain all facets of this disorder. An expanding body of evidence indicates a putative role for the inflammatory response. Several meta-analyses showed an increase in systemic peripheral inflammatory markers in individuals with MDD. Numerous conditions and circumstances in the modern world may promote chronic systemic inflammation through mechanisms, including alterations in the gut microbiota. Peripheral cytokines may reach the brain and contribute to neuroinflammation through cellular, humoral, and neural pathways. On the other hand, antidepressant drugs may decrease peripheral levels of inflammatory markers. Anti-inflammatory drugs and nutritional strategies that reduce inflammation also could improve depressive symptoms. The present study provides a critical review of recent advances in the role of inflammation in the pathophysiology of MDD. Furthermore, this review discusses the role of glial cells and the main drivers of changes associated with neuroinflammation. Finally, we highlight possible novel neurotherapeutic targets for MDD that could exert antidepressant effects by modulating inflammation.