Highlights • Chronic stress activates NLRP3 complex in rodent brain; • NLRP3 is activated in peripheral blood mononuclear cells of patients with MDD; • Antidepressant compounds decrease NLRP3 ...activation; • Increased IL-1β and IL-18 are frequently associated with depressive symptoms;
The importance of tryptophan as a precursor for neuroactive compounds has long been acknowledged. The metabolism of tryptophan along the kynurenine pathway and its involvement in mental disorders is ...an emerging area in psychiatry. We performed a meta-analysis to examine the differences in kynurenine metabolites in major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). Electronic databases were searched for studies that assessed metabolites involved in the kynurenine pathway (tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxykynurenine, and their associate ratios) in people with MDD, SZ, or BD, compared to controls. We computed the difference in metabolite concentrations between people with MDD, BD, or SZ, and controls, presented as Hedges' g with 95% confidence intervals. A total of 101 studies with 10,912 participants were included. Tryptophan and kynurenine are decreased across MDD, BD, and SZ; kynurenic acid and the kynurenic acid to quinolinic acid ratio are decreased in mood disorders (i.e., MDD and BD), whereas kynurenic acid is not altered in SZ; kynurenic acid to 3-hydroxykynurenine ratio is decreased in MDD but not SZ. Kynurenic acid to kynurenine ratio is decreased in MDD and SZ, and the kynurenine to tryptophan ratio is increased in MDD and SZ. Our results suggest that there is a shift in the tryptophan metabolism from serotonin to the kynurenine pathway, across these psychiatric disorders. In addition, a differential pattern exists between mood disorders and SZ, with a preferential metabolism of kynurenine to the potentially neurotoxic quinolinic acid instead of the neuroprotective kynurenic acid in mood disorders but not in SZ.
Recent studies have suggested that mitochondrial dysfunction and dysregulated neuroinflammatory pathways are involved in the pathophysiology of major depressive disorder (MDD). Here, we aimed to ...assess the differences in markers of mitochondrial dynamics, mitophagy, general autophagy, and apoptosis in peripheral blood mononuclear cells (PBMCs) of MDD patients (n = 77) and healthy controls (HCs, n = 24). Moreover, we studied inflammation engagement as a moderator of mitochondria dysfunctions on the severity of depressive symptoms. We found increased levels of Mfn-2 (p < 0.001), short Opa-1 (S-Opa-1) (p < 0.001) and Fis-1 (p < 0.001) in MDD patients, suggesting an increase in the mitochondrial fragmentation. We also found that MDD patients had higher levels of Pink-1 (p < 0.001), p62/SQSTM1 (p < 0.001), LC3B (p = 0.002), and caspase-3 active (p = 0.001), and lower levels of parkin (p < 0.001) compared with HCs. Moreover, we showed that that MDD patients with higher CRP levels had higher levels of Mfn-2 (p = 0.001) and LC3B (p = 0.002) when compared with MDD patients with low CRP. Another notable finding was that the severity of depressive symptoms in MDD is associated with changes in protein levels in pathways related to mitochondrial dynamics and mitophagy, and can be dependent on the inflammatory status. Overall, our study demonstrated that a disruption in the mitochondrial dynamics network could initiate a cascade of abnormal changes relevant to the critical pathological changes during the course of MDD and lead to poor outcomes.
Abstract Background Depression is frequently reported in association with COPD. However, the prevalence of depression in these patients ranges largely. This study aimed to systematically review the ...prevalence of depression in COPD and controls and to explore remaining causes of inter-study variability in the reported prevalence. Methods a systemic review of the literature and a meta-analysis was performed to evaluate the source of variability in the reported rates of depression in stable COPD. Main eligibility criteria were: controlled studies with a sample size >100, outpatients with COPD diagnosed by spirometry and, use of a validated depression screening instrument. Results From 1613 studies identified, eight controlled studies were included in the review. The number of participants in the pooled studies was of 5.552 COPD subjects and 5.211 controls. Using stricter criteria for study selection reduced the variability of the depression prevalence in COPD and controls, which was 27.1% 25.9–28.3 in COPD subjects and 10.0% 9.2–10.8 in the control group. The pooled odds ratio and 95% CI was 3.74 2.4–5.9. However, the heterogeneity across studies was high. Possible explanatory factor included sample sizes, COPD/controls ratio, smoker's/nonsmokers ratio) and qualitative differences (source of subjects, instruments to screen depression, COPD severity, smoking status, and comorbidities). Conclusion The study highlights the variability in estimates of depression prevalence in COPD. It could be explained by methodological differences across the included studies. This suggests that a standardization is critical to improve precision of the estimates.
Bipolar disorder (BD) is a chronic mental illness characterized by changes in mood that alternate between mania and hypomania or between depression and mixed states, often associated with functional ...impairment. Although effective pharmacological and non-pharmacological treatments are available, several patients with BD remain symptomatic. The advance in the understanding of the neurobiology underlying BD could help in the identification of new therapeutic targets as well as biomarkers for early detection, prognosis, and response to treatment in BD. In this review, we discuss genetic, epigenetic, molecular, physiological and neuroimaging findings associated with the neurobiology of BD. Despite the advances in the pathophysiological knowledge of BD, the diagnosis and management of the disease are still essentially clinical. Given the complexity of the brain and the close relationship between environmental exposure and brain function, initiatives that incorporate genetic, epigenetic, molecular, physiological, clinical, environmental data, and brain imaging are necessary to produce information that can be translated into prevention and better outcomes for patients with BD.
Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19), which has been declared a public health emergency of international interest, with ...confirmed cases in most countries. COVID-19 presents manifestations that can range from asymptomatic or mild infections up to severe manifestations that lead to hospitalization and death. A growing amount of evidence indicates that the virus may cause neuroinvasion. Postmortem brain study findings have included edema, hemorrhage, hydrocephalus, atrophy, encephalitis, infarcts, swollen axons, myelin loss, gliosis, neuronal satellitosis, hypoxic-ischemic damage, arteriolosclerosis, leptomeningeal inflammation, neuronal loss, and axon degeneration. In addition, the COVID-19 pandemic is causing dangerous effects on the mental health of the world population, some of which can be attributed to its social impact (social distancing, financial issues, and quarantine). There is also a concern that environmental stressors, enhanced by psychological factors, are contributing to the emergence of psychiatric outcomes during the pandemic. Although clinical studies and diagnosing SARS-CoV-2-related neurological disease can be challenging, they are necessary to help define the manifestations and burden of COVID-19 in neurological and psychiatric symptoms during and after the pandemic. This review aims to present the neurobiology of coronavirus and postmortem neuropathological hallmarks.
Treatment-resistant bipolar depression (TRBD) has been reported in about one-quarter of patients with bipolar disorders, and few interventions have shown clear and established effectiveness. We ...conducted a narrative review of the published medical literature to identify papers discussing treatment-resistant depression concepts and novel interventions for bipolar depression that focus on TRBD. We searched for potentially relevant English-language articles published in the last decade. Selected articles (based on the title and abstract) were retrieved for a more detailed evaluation. A number of promising new interventions, both pharmacological and non-pharmacological, are being investigated for TRBD treatment, including ketamine, lurasidone, D-cycloserine, pioglitazone, N-acetylcysteine, angiotensin-converting enzyme inhibitors, angiotensin II type 1 receptor blockers, cyclooxygenase 2 inhibitors, magnetic seizure therapy, intermittent theta-burst stimulation, deep transcranial magnetic stimulation, vagus nerve stimulation therapy, and deep brain stimulation. Although there is no consensus about the concept of TRBD, better clarification of the neurobiology associated with treatment non-response could help identify novel strategies. More research is warranted, mainly focusing on personalizing current treatments to optimize response and remission rates.
To explore the association between social cognition and previous suicide attempts and non-suicidal self-injurious behavior in adults with unipolar depressive disorders.
Seventy-two patients ...undergoing outpatient treatment for unipolar depression were enrolled in this cross-sectional study. Theory of mind was assessed using the Hinting Task and the Revised Reading the Mind in the Eyes Test. Empathy was evaluated using the Interpersonal Reactivity Index. Lifetime suicide attempts and non-suicidal self-injurious behavior were assessed using the Columbia Suicide Risk Rating Scale. Participants with and without these suicide-related outcomes were compared in terms of social cognition.
Patients with previous suicide attempts performed worse on the Reading the Mind in the Eyes Test (p = 0.017). Patients with a history of non-suicidal self-injurious behavior were younger (p = 0.005), had a younger age at first depressive episode (p = 0.017), and scored higher on personal distress in the Interpersonal Reactivity Index (p = 0.027). Only personal distress remained independently associated with non-suicidal self-injurious behavior in multivariable analysis (p = 0.038).
Among patients with depression, those with previous suicide attempts or non-suicidal self-injurious behavior showed worse social cognition. These results encourage future research on social cognition deficits as clinical markers of suicide-related behaviors and as targets for interventions.
OBJECTIVEThe stigma toward individuals with mental disorders is highly prevalent, not only in the general population but among health care providers as well. The aim of this study was to identify ...subgroups based on stigmatizing beliefs related to psychiatric disorders among Brazilian psychiatrists, as well as to investigate their association with clinical and personality characteristics. METHODSLatent cluster analysis was used to find subgroups of cases in multivariate data according to a psychotic (schizophrenia) and a nonpsychotic disorder (attention-deficit hyperactivity disorder). The clusters for each psychiatric disorder were compared according to sociodemographic, emotional traits, and personality characteristics. RESULTSA total of 779 psychiatrists answered the questionnaire. Three different subgroups of stigma levels were identified regarding schizophrenia: the highest (n=202 51.7%), intermediate (108 27.6%), and the lowest (81 20.7%). Participants from the highest stigma group had a significantly longer time since graduation, higher anxiety-state scores, and lower positive affect. Two subgroups were identified with respect to attention-deficit hyperactivity disorder, although there were no differences between them in sociodemographic or clinical variables. CONCLUSIONThere were more subgroups of stigmatizing beliefs regarding psychotic disorders. Individual characteristics, such as those related to trait anxiety and affect, can be associated with high stigma toward schizophrenia.
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