10,931 research outputs found
Psychiatric face of COVID-19
No full textThe Coronavirus Disease 2019 (COVID-19) represents a severe multiorgan pathology which, besides cardio-respiratory manifestations, affects the function of the central nervous system (CNS). The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similarly to other coronaviruses demonstrate neurotropism; the viral infection of the brain stem may complicate the course of the disease through damaging central cardio-respiratory control. The systemic inflammation as well as neuroinflammatory changes are associated with massive increase of the brain pro-inflammatory molecules, neuroglial reactivity, altered neurochemical landscape and pathological remodelling of neuronal networks. These organic changes, emerging in concert with environmental stress caused by experiences of intensive therapy wards, pandemic fears and social restrictions, promote neuropsychiatric pathologies including major depressive disorder, bipolar disorder (BD), various psychoses, obsessive-compulsive disorder and post-traumatic stress disorder. The neuropsychiatric sequelae of COVID-19 represent serious clinical challenge that has to be considered for future complex therapies. © 2020, The Author(s)
Impaired glucose metabolism in bipolar patients and response to mood stabilizer treatments
No full textBackground: Metabolic dysfunctions in patients with bipolar disorder (BD) are critical factors that interfere with outcome, but only one study evaluated the influence of glucose dysmetabolism on the response to treatment with lithium. We aimed to investigate the potential impact of glucose metabolic status on clinical characteristics of BD patients and their response to treatment with different mood stabilizers in monotherapy or in combination. Methods: 45 BD patients with insulin resistance (IR) or type 2 diabetes mellitus (DM2) and 46 patients with normal glucose metabolism, treated with mood stabilizers for at least one year were assessed by diagnostic and rating instruments. Their clinical characteristics were compared and an ordinal logistic regression model was adopted to identify possible predictors of response to mood stabilizer treatments. Results: Compared to patients with normal glucose metabolism, BD patients with impaired glucose metabolism showed a worse clinical presentation of their psychiatric illness and a worse response to mood stabilizers. Ordinal logistic regression analysis evidenced that impaired glucose metabolism was the only predictor of poor response to mood stabilizers (OR 4.3; 95% CI: 1.7–11.1; p < 0.002). Limitations: Cross-sectional design and the relatively small sample size, are the main limitations of our study. Conclusions: Our findings expand literature data suggesting that BD patients with impaired glucose metabolism are at a greater risk of not responding to lithium as well as to different mood stabilizer treatments
Clinical, genetic, and brain imaging predictors of risk for bipolar disorder in high-risk individuals
No full textIntroduction: Early detection and intervention in bipolar disorder (BD) might reduce illness severity, slow its progression, and, in specific cases, even ward off the full-blown disorder. Therefore, identifying at-risk individuals and targeting them promptly before the illness onset is of the utmost importance. In the last decades, there has been a significant effort aimed at identifying genetic and molecular factors able to modulate risk and pharmacological outcomes. Areas covered: We performed a narrative review of articles aimed at identifying clinical, genetics, molecular, and brain imaging markers of BD specifically focusing on samples of individuals at high-risk for BD. Special emphasis was put on studies applying an integrative design, e.g. studies combining different markers such as genetic and brain imaging. Expert opinion: Findings from studies in risk individuals are still too sparse to allow drawing definite conclusions. However, the high potentiality of longitudinal studies in individuals considered at risk to develop BD supports the need for more efforts. Future investigations should focus on more homogeneous subpopulations and evaluate the cross-linking between clinical, genetic, and brain morphostructural/functional neuroimaging characteristics as predictors of risk for BD
Recommended from our members
Emmett L. Bennett, Jr. Offprint Collection
No full textThe scholarly library of Emmett L. Bennett, Jr. compiled in the course of his Editorship of the journal Nestor (founded in 1957). The collection includes scholarly publications (offprints) and manuscripts sent by prospective authors to Dr. Bennett. Includes a Finding Aid (PDF and Word) and Catalog (an Excel document for each of two record groups: offprints collected up to 1995, and offprints collected from 1995-2011). Both the Finding Aid and Catalog are provided to facilitate researchers' searches for offprints by author, title, journal, year, and subject.Classic
How could retinoids fit into Alzheimer's therapy?
No full textRetinoids are a class of natural and synthetic molecules structurally and/or functionally related to all-trans-retinoic acid (ATRA), a metabolite of Vitamin A (retinol). The retinoid system controls the expression of hundreds of genes, including transcription factors, enzymes, structural proteins, cell surface receptors, neurotransmitters, hormones and growth factors, hence modulating cell proliferation, differentiation, morphogenesis and immunity. The retinoid-associated signaling plays a critical role in neurodevelopment and remains active in the adult central nervous system, thus assuming high relevance in the context of neurodegeneration. The ability of retinoids to exert antioxidant effects, decrease β-amyloid (Aβ) accumulation, improve neurotransmission, suppress neuroinflammation and promote neural regeneration is discussed. Although retinoids with their pleiotropic activity are revealing a promising approach for the management of Alzheimer's disease (AD), timing as well as appropriate dosage and safety still remain a challenge. In particular, assuming that the end-stage lesions (senile plaques and neurofibrillary tangles) are an adaptive response to oxidative stress underlying AD, late administration of retinoids could paradoxically suppress a protective mechanism by inhibiting Aβ deposits
Cannabidiol in vivo blunts beta-amyloid induced neuroinflammation by suppressing IL-1beta and iNOS expression
No full textHow effective are mood stabilizers in treating bipolar patients comorbid with cPTSD? Results from an observational study
No full textBackground Multiple traumatic experiences, particularly in childhood, may predict and be a risk factor for the development of complex post-traumatic stress disorder (cPTSD). Unfortunately, individuals with bipolar disorder (BP) are more likely to have suffered traumatic events than the general population. Consequently, cPTSD could be comorbid with BD, and this may negatively affect psychopathological manifestations. To date, no one has explored whether such comorbidity also affects the response to treatment with mood stabilizers in BD patients.Results Here, a cross-sectional study was carried out by comparing the response to treatment, measured by the Alda scale, in a cohort of 344 patients diagnosed with BD type I and II, screened for the presence (or absence) of cPTSD using the International Trauma Questionnaire. The main result that emerged from the present study is the poorer response to mood stabilizers in BD patients with comorbid cPTSD compared with BD patients without cPTSD.Conclusions The results collected suggest the need for an add-on therapy focused on trauma in BD patients. This could represent an area of future interest in clinical research, capable of leading to more precise and quicker diagnoses as well as suggesting better tailored and more effective treatments
S100B induces tau protein hyperphosphorylation via Dickopff-1 up-regulation and disrupts the Wnt pathway in human neural stem cells.
No full textPrevious studies suggest that levels of the astrocyte-derived S100B protein, such as those occurring in brain extra-cellular spaces consequent to persistent astroglial activation, may have a pathogenetic role in Alzheimer's disease (AD). Although S100B was reported to promote beta amyloid precursor protein overexpression, no clear mechanistic relationship between S100B and formation of neurofibrillary tangles (NFTs) is established. This in vitro study has been aimed at investigating whether S100B is able to disrupt Wnt pathway and lead to tau protein hyperphosphorylation. Utilizing Western blot, electrophoretic mobility shift assay, supershift and reverse transcriptase-polymerase chain reaction techniques, it has been demonstrated that micromolar S100B concentrations stimulate c-Jun N-terminal kinase (JNK) phosphorylation through the receptor for advanced glycation ending products, and subsequently activate nuclear AP-1/cJun transcription, in cultured human neural stem cells. In addition, as revealed by Western blot, small interfering RNA and immunofluorescence analysis, S100B-induced JNK activation increased expression of Dickopff-1 that, in turn, promoted glycogen synthase kinase 3 beta phosphorylation and beta-catenin degradation, causing canonical Wnt pathway disruption and tau protein hyperphosphorylation. These findings propose a previously unrecognized link between S100B and tau hyperphosphorylation, suggesting S100B can contribute to NFT formation in AD and in all other conditions in which neuroinflammation may have a crucial role
S100B induces tau protein hyperphosphorylation via Dickopff-1 up-regulation and disrupts the Wnt pathway in human neural stem cells
No full textPrevious studies suggest that levels of the astrocyte-derived S100B protein, such as those occurring in brain extra-cellular spaces consequent to persistent astroglial activation, may have a pathogenetic role in Alzheimer's disease (AD). Although S100B was reported to promote beta amyloid precursor protein overexpression, no clear mechanistic relationship between S100B and formation of neurofibrillary tangles (NFTs) is established. This in vitro study has been aimed at investigating whether S100B is able to disrupt Wnt pathway and lead to tau protein hyperphosphorylation. Utilizing Western blot, electrophoretic mobility shift assay, supershift and reverse transcriptase-polymerase chain reaction techniques, it has been demonstrated that micromolar S100B concentrations stimulate c-Jun N-terminal kinase (JNK) phosphorylation through the receptor for advanced glycation ending products, and subsequently activate nuclear AP-1/cJun transcription, in cultured human neural stem cells. In addition, as revealed by Western blot, small interfering RNA and immunofluorescence analysis, S100B-induced JNK activation increased expression of Dickopff-1 that, in turn, promoted glycogen synthase kinase 3beta phosphorylation and beta-catenin degradation, causing canonical Wnt pathway disruption and tau protein hyperphosphorylation. These findings propose a previously unrecognized link between S100B and tau hyperphosphorylation, suggesting S100B can contribute to NFT formation in AD and in all other conditions in which neuroinflammation may have a crucial role
- …
