Search

Introduction: Decreased plasma BDNF (pBDNF) levels have been proposed as a biomarker in the illness phases of mood disorders. This cross-sectional study aimed to evaluate the pBDNF and BDNF promoters' DNA methylation levels in workers exposed to occupational stress and suffering from work-related stress disorders. Methods: the pBDNF and BDNF exon I and IV promoters' methylation levels were measured by specific immunoassays and methylation-sensitive high-resolution melting (MS-HRM) in 62 patients with adjustment disorders (AD), 79 patients with major depressive disorder (MDD) and 44 healthy controls. Occupational stress was evaluated in the patients and controls using the Job Content Questionnaire (JCQ). Results: the pBDNF levels were significantly higher in the MDD (p < 0.001) and AD (p < 0.0001) patients than in the controls. The MDD patients showed significantly lower pBDNF levels than the AD ones (p = 0.01). The BDNF exon I and IV promoters' methylation levels were significantly higher in the MDD patients than in the AD ones (exon I promoter: p = 0.0001, exon IV promoter: p < 0.0001) and controls (exon I promoter: p = 0.0001, exon IV promoter: p < 0.0001). In the patients, but not in the controls, the BDNF promoters' methylation levels showed significant negative correlations with occupational stress. Conclusions: BDNF could play a key role in the pathophysiology of stress-related disorders and the peripheral elevation of it observed in patients exposed to occupational stress could suggest a protective mechanism for neurons from stress-mediated damage. The elevation of the pBDNF levels, even in MDD, may characterize a "reactive" subtype of depressive episode, while the significant elevation of the BDNF promoters' methylation levels in depressed patients could indicate a predisposition to more severe illness under stress. Further research is needed, focusing on biomarkers for stress-related disorders as a potential tool for the diagnosis and prevention of occupational diseases. [ABSTRACT FROM AUTHOR]

Post-traumatic stress disorder (PTSD) is a highly disabling mental disorder arising after traumatism exposure, often revealing critical and complex courses when comorbidity with bipolar disorder (BD) occurs. To search for PTSD or depression biomarkers that would help clinicians define BD presentations, this study aimed at preliminarily evaluating circulating brain-derived-neurotrophic factor (BDNF) levels in BD subjects with PTSD or experiencing a major depressive episode versus controls. Two bloodstream BDNF components were specifically investigated, the storage (intraplatelet) and the released (plasma) ones, both as adaptogenic/repair signals during neuroendocrine stress response dynamics. Bipolar patients with PTSD (n = 20) or in a major depressive episode (n = 20) were rigorously recruited together with unrelated healthy controls (n = 24) and subsequently examined by psychiatric questionnaires and blood samplings. Platelet-poor plasma (PPP) and intraplatelet (PLT) BDNF were measured by ELISA assays. The results showed markedly higher intraplatelet vs. plasma BDNF, confirming platelets' role in neurotrophin transport/storage. No between-group PPP-BDNF difference was reported, whereas PLT-BDNF was significantly reduced in depressed BD patients. PLT-BDNF negatively correlated with mood scores but not with PTSD items like PPP-BDNF, which instead displayed opposite correlation trends with depression and manic severity. Present findings highlight PLT-BDNF as more reliable at detecting depression than PTSD in BD, encouraging further study into BDNF variability contextually with immune-inflammatory parameters in wider cohorts of differentially symptomatic bipolar patients. [ABSTRACT FROM AUTHOR]

Introduction: Recent evidence reported mental health issues in university students such as anxiety and depressive symptoms and poor sleep quality. Decreased plasma brain-derived neurotrophic factor (BDNF) levels have been proposed as a biomarker of depressive symptoms, whereas cortisol levels are an index of energy mobilization and stress and have been linked to sleep quality. Given that salivary biomarkers represent an interesting new field of research, the aim of this cross-sectional study was to evaluate salivary BDNF and cortisol levels in university students to assess whether they have associations with psychological disturbances such as anxiety and depressive symptoms, sleep quality, and stress level. Methods: Salivary BDNF and cortisol levels were measured by specific immunoassays in 70 students whose mental health was also evaluated on the same day through the evaluation of anxiety and depression symptoms (Goldberg scale), sleep quality (Pittsburg Sleep Quality Index and Athens Insomnia Scale), and stress (self-perceived stress scale) and healthy lifestyle habits (alcohol consumption, smoking, regular exercise, and body mass index) were also measured. Multivariate regression analyses were performed in order to identify the strengths of associations between psychological alterations and the concentrations of BDNF, cortisol, and other variables. Results: Salivary BDNF levels were significantly higher in students with more depressive symptoms, whereas no significant differences were found for cortisol levels. When performing the binary logistic regression model, BDNF levels are included as a predictor variable for a high-depressive-symptoms burden (p < 0.05). Students with worse sleep quality on the Pittsburg Scale had higher cortisol levels (p < 0.05). The subdomains of sleep latency and sleep medication were those significantly associated with salivary cortisol levels in logistic regression analyses (OR = 15.150, p = 0.028). Sleep medication only appeared to be related to cortisol levels (OR = 185.142, p = 0.019). Perceived stress levels and anxiety symptoms were not associated with BDNF or cortisol levels. Conclusions: BDNF could play a key role in the pathophysiology of mood-related disorders, and elevation of its peripheral levels could contribute to protecting neurons from the development of mental illness. Higher salivary cortisol levels measured in the morning are accompanied by poorer sleep quality. More research is needed, focusing on salivary biomarkers of disorders related to depressive symptoms and poor sleep quality as a potential tool for the diagnosis and prevention of mental illness. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) is implicated in the etiology and treatment response in major depressive disorder (MDD). However, peripheral BDNF concentrations have not been compared across different MDD stages. Bright light therapy (BLT) offers some potential in treatment-resistant depression (TRD), but its effects on BDNF levels are unknown. This study included a cross-sectional analysis of plasma BDNF concentration in females with TRD, unmedicated MDD patients, and healthy controls (HC), and measurements of longitudinal BLT effects on plasma BDNF levels in TRD patients. The present study included 55 drug-naïve, first-episode patients, 25 drug-free recurrent-episode MDD patients, 71 HC participants, and 54 TRD patients. Patients were rated by Hamilton Depression Rating Scale (HAMD)-17 and the Montgomery–Åsberg Depression Rating Scale (MADRS). Patients with TRD received BLT during 4 weeks. The total HAMD-17 and MADRS scores decreased following BLT. All patient groups had lower plasma BDNF than HC, but BDNF levels did not differ between first- and recurrent-episode BDNF patients and TRD patients before or after BLT. However, responders and remitters to BLT had higher post-treatment plasma BDNF concentrations than patients who did not achieve response or remission. The changes in plasma BDNF levels may be candidates for biomarkers of treatment response to BLT in TRD patients. [ABSTRACT FROM AUTHOR]

This study seeks to offer a contribution to the method of subtyping major depressed patients by exploring the possible relationships between circulating brain-derived neurotrophic factor (BDNF), different peripheral inflammatory/metabolic markers in the blood and clinical characteristics. Thirty-nine patients, thoroughly diagnosed according to the DSM-5 criteria, underwent a comprehensive set of evaluations encompassing structured interviews, rating scales and a panel of blood tests. Correlation and comparison analyses were carried out by means of non-parametric statistical tests. Concurrently, a principal component analysis was performed to explain biochemical variance. The findings of our research unveiled that leukocyte counts, their ratios and other inflammatory parameters are positively correlated with depression scores. Moreover, we found variations within the BDNF pools of depressed patients. Specifically, higher levels of platelet-poor plasma BDNF (PPP-BDNF) were correlated with augmented inflammatory markers in patients showing specific episode characteristics, whereas reduced platelet BDNF (PLT-BDNF) provided a better indication of the changes that were linked to a diagnosis of long-term depression. Our findings suggest that PPP-BDNF and PLT-BDNF might differentiate depression conditions. They also imply usefulness in appraising peripheral biomarker profiles in patients for a deeper characterization of major depressive episodes. At the same time, it is plausible that they might constitute novel avenues for developing more tailored therapeutic strategies for patients with MDs. [ABSTRACT FROM AUTHOR]

Simple Summary: Biological clocks regulate the timing of numerous body functions in adaption to daily repeating cycles in the environment, such as the sleep–wake phases that are trained by the cycling changes of night and day light. The identification of a deceased victim is a critical component in a forensic investigation, but it can be significantly hampered by the condition of the dead body and the lack of personal records and documents. This review links current knowledge on the molecular mechanisms of biological rhythms to forensically relevant aspects, including the time period since death, cause of death, the use of insects for forensics, sex and age of a person, ethnic background and development. Putting these findings in context demonstrates how the analysis of molecular clock analysis could be used as tool for future personal identification in forensic investigations. Biological clocks set the timing for a large number of essential processes in the living human organism. After death, scientific evidence is required in forensic investigations in order to collect as much information as possible on the death circumstances and personal identifiers of the deceased victim. We summarize the associations between the molecular mechanisms of biological rhythms and forensically relevant aspects, including post-mortem interval and cause of death, entomological findings, sex, age, ethnicity and development. Given their importance during lifetime, biological rhythms could be potential tools to draw conclusions on the death circumstances and the identity of a deceased person by mechanistic investigations of the different biological clocks in a forensic context. This review puts the known effects of biological rhythms on the functions of the human organism in context with potential applications in forensic fields of interest, such as personal identification, entomology as well as the determination of the post-mortem interval and cause of death. [ABSTRACT FROM AUTHOR]

Major depressive disorder is a leading cause of disability worldwide and a major contributor to the overall global burden of disease. While there are several options for antidepressant treatment, only about 40–60% of patients respond to initial monotherapy, while 30–40% of patients may even show resistance to treatment. This article offers a narrative review of those studies evaluating the predictive properties of various blood-based baseline biomarkers regarding treatment responses to the pharmacological, stimulation, or behavioral treatment of patients with treatment-resistant depression (TRD). Our results show that overall, there is only a very limited number of studies assessing baseline peripheral biomarkers regarding treatment response in TRD. Although there is some evidence for the predictive significance of particular biomarkers (e.g., IL-6, CRP, BDNF), the majority of the results are either single-study reports or studies with conflicting results. This may contribute to the wide variety of treatment protocols and different TRD definition criteria, the small number of patients included, and the existence of different biological phenotypes of the disorder used within the various studies. Taken together, there does not yet appear to be any specific baseline peripheral biomarker with sufficient discriminative predictive validity that can be used in the routine clinical practice of TRD. The discovery of new biomarkers and the better clinical characterization of known biomarkers could support the better classification and staging of TRD, the development of personalized treatment algorithms with higher rates of remission and fewer side effects, and the development of new precision drugs for specific subgroups of patients. [ABSTRACT FROM AUTHOR]

COVID-19 (COronaVIrus Disease 19) is an infectious disease also known as an acute respiratory syndrome caused by the SARS-CoV-2. Although in children and adolescents SARS-CoV-2 infection produces mostly mild or moderate symptoms, in a certain percentage of recovered young people a condition of malaise, defined as long-COVID-19, remains. To date, the risk factors for the development of long-COVID-19 are not completely elucidated. Neurotrophins such as NGF (Nerve Growth Factor) and BDNF (Brain-Derived Neurotrophic Factor) are known to regulate not only neuronal growth, survival and plasticity, but also to influence cardiovascular, immune, and endocrine systems in physiological and/or pathological conditions; to date only a few papers have discussed their potential role in COVID-19. In the present pilot study, we aimed to identify NGF and BDNF changes in the serum of a small cohort of male and female adolescents that contracted the infection during the second wave of the pandemic (between September and October 2020), notably in the absence of available vaccines. Blood withdrawal was carried out when the recruited adolescents tested negative for the SARS-CoV-2 ("post-infected COVID-19"), 30 to 35 days after the last molecular test. According to their COVID-19 related outcomes, the recruited individuals were divided into three groups: asymptomatics, acute symptomatics and symptomatics that over time developed long-COVID-19 symptoms ("future long-COVID-19"). As a control group, we analyzed the serum of age-matched healthy controls that did not contract the infection. Inflammatory biomarkers (TNF-α, TGF-β), MCP-1, IL-1α, IL-2, IL-6, IL-10, IL-12) were also analyzed with the free oxygen radicals' presence as an oxidative stress index. We showed that NGF serum content was lower in post-infected-COVID-19 individuals when compared to healthy controls; BDNF levels were found to be higher compared to healthy individuals only in post-infected-COVID-19 symptomatic and future long-COVID-19 girls, leaving the BDNF levels unchanged in asymptomatic individuals if compared to controls. Oxidative stress and inflammatory biomarkers were unchanged in male and female adolescents, except for TGF-β that, similarly to BDNF, was higher in post-infected-COVID-19 symptomatic and future long-COVID-19 girls. We predicted that NGF and/or BDNF could be used as early biomarkers of COVID-19 morbidity in adolescents. [ABSTRACT FROM AUTHOR]

The search for a biological marker predicting the future failure or success of electroconvulsive therapy (ECT) remains highly challenging for patients with treatment-resistant depression. Evidence suggests that Brain-Derived Neurotrophic Factor (BDNF), a protein known to be involved in brain plasticity mechanisms, can play a key role in both the clinical efficacy of ECT and the pathophysiology of depressive disorders. We hypothesized that mature BDNF (mBDNF), an isoform of BDNF involved in the neural plasticity and survival of neural networks, might be a good candidate for predicting the efficacy of ECT. Total BDNF (tBDNF) and mBDNF levels were measured in 23 patients with severe treatment-resistant depression before (baseline) they received a course of ECT. More precisely, tBDNF and mBDNF measured before ECT were compared between patients who achieved the criteria of remission after the ECT course (remitters, n = 7) and those who did not (non-remitters, n = 16). We found that at baseline, future remitters displayed significantly higher mBDNF levels than future non-remitters (p = 0.04). No differences were observed regarding tBDNF levels at baseline. The multiple logistic regression model controlled for age and sex revealed that having a higher baseline mBDNF level was significantly associated with future remission after ECT sessions (odd ratio = 1.38; 95% confidence interval = 1.07–2.02, p = 0.04). Despite the limitations of the study, current findings provide additional elements regarding the major role of BDNF and especially the mBDNF isoform in the clinical response to ECT in major depression. [ABSTRACT FROM AUTHOR]

The anti-inflammatory, antifibrotic and antimicrobial activities of curcumin (CUR) are missed because of its low solubility in aqueous media, low bioavailability, and structural lability upon oral intake. Soft nanoparticles such as nanoliposomes are not efficient as CUR carriers, since crystalline CUR is expelled from them to physiological media. Nanostructures to efficiently trap and increase the aqueous solubility of CUR are needed to improve both oral or nebulized delivery of CUR. Here we showed that SRA1 targeted nanoarchaeosomes (nATC) [1:0.4 w:w:0.04] archaeolipids, tween 80 and CUR, 155 ± 16 nm sized of −20.7 ± 3.3 z potential, retained 0.22 mg CUR ± 0.09 per 12.9 mg lipids ± 4.0 (~600 μM CUR) in front to dilution, storage, and nebulization. Raman and fluorescence spectra and SAXS patterns were compatible with a mixture of enol and keto CUR tautomers trapped within the depths of nATC bilayer. Between 20 and 5 µg CUR/mL, nATC was endocytosed by THP1 and A549 liquid–liquid monolayers without noticeable cytotoxicity. Five micrograms of CUR/mL nATC nebulized on an inflamed air–liquid interface of A549 cells increased TEER, normalized the permeation of LY, and decreased il6, tnfα, and il8 levels. Overall, these results suggest the modified pharmacodynamics of CUR in nATC is useful for epithelia repair upon inflammatory damage, deserving further deeper exploration, particularly related to its targeting ability. [ABSTRACT FROM AUTHOR]