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• What is the primary question addressed by this study? This study explores the association between chronic BZD use and FDG-PET brain metabolism in the MEMENTO clinical cohort of nondemented older adults with isolated memory complaint or mild cognitive impairment. • What is the main finding of this study? The authors found that brain metabolism was significantly greater in chronic BZD users compared to non-users in the whole brain and in the right amygdala, independent of potential confounders. • What is the meaning of the finding? Chronic BZD use may induce a compensatory mechanism which consists in a global metabolism upregulation in the brain, with a specific focus on the right amygdala as a specific target for BZD action. We sought to examine the association between chronic Benzodiazepine (BZD) use and brain metabolism obtained from 2-deoxy-2-fluoro-D-glucose (FDG) positron emission tomography (PET) in the MEMENTO clinical cohort of nondemented older adults with an isolated memory complaint or mild cognitive impairment at baseline. Our analysis focused on 3 levels: (1) the global mean brain standardized uptake value (SUVR), (2) the Alzheimer's disease (AD)-specific regions of interest (ROIs), and (3) the ratio of total SUVR on the brain and different anatomical ROIs. Cerebral metabolism was obtained from 2-deoxy-2-fluoro-D-glucose-FDG-PET and compared between chronic BZD users and nonusers using multiple linear regressions adjusted for age, sex, education, APOE ε 4 copy number, cognitive and neuropsychiatric assessments, history of major depressive episodes and antidepressant use. We found that the SUVR was significantly higher in chronic BZD users (n = 192) than in nonusers (n = 1,122) in the whole brain (beta = 0.03; p = 0.038) and in the right amygdala (beta = 0.32; p = 0.012). Trends were observed for the half-lives of BZDs (short- and long-acting BZDs) (p = 0.051) and Z-drug hypnotic treatments (p = 0.060) on the SUVR of the right amygdala. We found no significant association in the other ROIs. Our study is the first to find a greater global metabolism in chronic BZD users and a specific greater metabolism in the right amygdala. Because the acute administration of BZDs tends to reduce brain metabolism, these findings may correspond to a compensatory mechanism while the brain adapts with global metabolism upregulation, with a specific focus on the right amygdala. [ABSTRACT FROM AUTHOR]

The first-line management of behavioral and psychological symptoms of dementia (BPSD) is based on nonpharmacologic interventions such as the provision of guidance and medical support to caregivers. However, accessibility to specialized care and medical resources is often scarce. The ongoing COVID-19 pandemic has compromised the delivery of outpatient care (notably in order to minimize the risk of disease transmission), thus making it essential to provide other means of accessing care for these patient populations. The use of telemedicine (TM) may be a means of increasing access to specialist care for patients with disabilities and poor access to health services, such as those with BPSD. The aim of this study is to provide a review of the literature on the use of TM for treatment and follow-up of patients with BPSD and their caregivers. We searched the PUBMED, EMBASE and CINAHL for articles published between January 1st, 2000, and December 31st, 2020, on the applicability of TM support for people with BPSD and their caregivers. We included open-label studies, qualitative studies, and randomized controlled trials . We did not include studies on the use of TM during the COVID-19 pandemic. A total of 22 publications were included and reviewed. TM was found to 1) be acceptable and feasible for both patients and caregivers, 2) decrease the frequency and intensity of BPSD, and 3) improve the caregiver's perceived wellbeing and mental health. Videoconferencing was effective for patient-centered interventions in nursing homes. Telephone-based interventions were more relevant when they were targeted at caregivers. The published studies are lacking in scope and high-quality studies are now needed to confirm these findings and assess TM's cost-effectiveness and ability to improve the management of patients with BPSD. In view of the ongoing COVID-19 pandemic, remote solutions for assessing and monitoring individuals with BPSD are urgently needed - particularly those living in rural areas and so-called "medical deserts." [ABSTRACT FROM AUTHOR]

To design faster and more energy-efficient systems, numerous inexact arithmetic operators have been proposed, generally obtained by modifying the logic structure of conventional circuits. However, as the quality of service of an application has to be ensured, these operators need to be precisely characterized to be usable in commercial or real-life applications. The characterization of the error induced by inexact operators is commonly achieved with exhaustive or stochastic bit-accurate gate-level simulations. However, for high bit-widths, the time and memory required for such simulations become prohibitive. To overcome these limitations, a new characterization framework for inexact operators is proposed. The proposed framework characterizes the error induced by inexact operators in terms of mean error distance, error rate and maximum error distance, allowing to completely define the error probability mass function. By exploiting statistical properties of the approximation error, the number of simulations needed for precise characterization is minimized. From user-defined confidence requirements, the proposed method computes the minimal number of simulations to obtain the desired accuracy on the characterization for the error rate and mean error distance. The maximum error distance value is then extracted from the simulated samples using the extreme value theory. For 32-bit adders, the proposed method reduces the number of simulations needed up to a few tens of thousands points. • A framework to characterize the error of inexact circuits is proposed. • The asked estimation quality allows trading-off the number of simulations. • The method is based on inferential statistics and extreme value theory. • The error rate, mean and maximum error distance are estimated. [ABSTRACT FROM AUTHOR]

Background: Orthostatic hypotension (OH) is highly prevalent in the elderly, and this population can be exposed to serious complications, including falls and cognitive disorders, as well as overall mortality. However, the pathophysiology of OH is still poorly understood, and innovative methods of cerebral blood flow (CBF) assessment have been required to accurately investigate cerebrovascular reactivity in OH.Objectives: We want to compare brain tissue pulsatility (BTP) changes during an orthostatic challenge in elderly patients over 80 with and without OH.Materials and Methods: Forty-two subjects aged 80 and over were recruited from the geriatric unit of the Hospital of Tours, France, and were divided into two groups according to the result of an orthostatic challenge. The noninclusion criteria were any general unstable medical condition incompatible with orthostatic challenge, having no temporal acoustic window, severe cognitive impairment (Mini Mental Status Examination <15), history of stroke, and legal guardianship. We used the novel and highly sensitive ultrasound technique of tissue pulsatility imaging to measure BTP changes in elderly patients with (n = 22) and without OH (n = 17) during an orthostatic challenge.Results: We found that the mean brain tissue pulsatility related to global intracranial pulsatility, but not maximum brain tissue pulsatility related to large arteries pulsatility, decreased significantly in OH patients, with a delay compared with the immediate drop in peripheral blood pressure.Conclusion: Global pulsatile CBF changes and small vessels pulsatility, rather than changes in only large arteries, may be key mechanisms in OH to account for the links between OH and cerebrovascular disorders. [ABSTRACT FROM AUTHOR]

Bone marrow biopsy (BMB) is a common procedure in haematology used for the diagnosis and evaluation of response treatment. Because the procedure is difficult for haematologists to perform, patients often experience pain and stress. On Control, a system device, was introduced in the 2000s and uses a drill-powered needle to perform BMB. The aim of this study was to compare the quality of BMB, based on the length of the trephine, the number of interosseous spaces and the interpretability of the examination, obtained from manual BMB vs. drill-powered BMB. The secondary objectives were to evaluate the patient's pain and anxiety, and the haematologist's perceived difficulty in performing BMB. This was a retrospective study conducted between June 2016 and June 2017 in the Henri Becquerel Cancer Centre in Rouen, France. A total of 439 patients were included in the study; the sex ratio (M:F) was 1.34 and 70.2% underwent a drill-powered BMB. A significant difference was observed concerning trephine length (14.30 ± 5.58 mm with the drill-powered system vs. 11.18 ± 4.43 mm with manual BMB, p < 0.0001) and the number of interosseous spaces (9.49 ± 5.35 vs. 7.93 ± 4.01, respectively, p = 0.01). The interpretability of the examination did not differ between the two procedures (p = 0.9). On Control, the drill-powered system for BMB, is widely distributed in North America and Europe, but this procedure is not yet generally applied. Although this procedure is costly, the ongoing development of this technique, because of its performance, is beneficial especially to obese patients. • The drill-powered system device On Control was introduced in the 2000s. • Better than manual device as for trephine length and number of interosseous spaces • The interpretability of the examination did not differ between the two methods. • It is a costly and performant method, beneficial especially in obese patients. [ABSTRACT FROM AUTHOR]

The article discusses the ethical issues in the management of patients with psychological and behavioral symptoms of dementia during the implementation of coronavirus disease 2019 (COVID-19) preventive measures in France.

Depression is recognized as a predictor of increased cardiac morbidity and mortality. In addition, depressed patients exhibit an increase in the serum markers of endothelial dysfunction and platelet activation involved in the cascade of events leading to atherosclerosis. The purpose of this study was to determine the early and late-onset expression of various vascular markers in a rodent model of depression. Male DBA (an inbred strain of mice)/2J mice were exposed to either 7 weeks of controlled living conditions or unpredictable chronic mild stress (UCMS), and subsequently given daily fluoxetine (10 mg/kg) or NaCl (9%) during the last 5 weeks of the experiment. Depressive-like behavior was evaluated by using motivational and self-care behavior, including the assessment of the animal's coat state and grooming behavior. Enzyme-linked immunoassay was used to quantify matrix metalloproteinase-9 (MMP-9), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and plasminogen activator inhibitor-1 (PAI-1) expression either immediately after the end of the UCMS procedure (short term condition) or 10 months later (long-term condition). Results indicate that 1) UCMS procedure induces a short-term depressive-like behavior in mice, defined as coat state deterioration, an effect that is prevented by fluoxetine treatment; 2) UCMS procedure has no effect on the short-term expression of the studied markers; however, UCMS increases expression of plasminogen activator inhibitor-1 only in the long-term group; 3) fluoxetine treatment is unable to counteract this UCMS-induced change; 4) aging induces behavioral perturbation, defined as a decrease in grooming motivation, and an increase of all the vascular markers in both control and UCMS groups and 5) pretreatment with fluoxetine has no protective effects on aging-induced behavioral and vascular alterations. Thus, in this model of depression-like behavior, UCMS appears to induce late-onset physiological changes, which are consistent with human studies indicating that depression is a risk factor for the development of heart disease. [ABSTRACT FROM AUTHOR]

Abstract: Pulsatile motion of brain parenchyma results from cardiac and breathing cycles and consists in a rapid displacement in systole, with slow diastolic recovery. Based on the vascular depression concept and recent studies where a correlation was found between cerebral haemodynamics and depression in the elderly, we emitted the hypothesis that tissue brain motion due to perfusion is correlated to elderly depression associated with cardiovascular risk factors. Tissue Pulsatlity Imaging (TPI) is a new ultrasound technique developed firstly at the University of Washington to assess the brain tissue motion. We used TPI technique to measure the brain displacement of two groups of elderly patients with diabetes as a vascular risk factor. The first group is composed of 11 depressed diabetic patients. The second group is composed of 12 diabetic patients without depressive symptoms. Transcranial acquisitions were performed with a 1.8 MHz ultrasound phased array probe through the right temporal bone window. The acquisition of six cardiac cycles was realized on each patient with a frame rate of 23 frames/s. Displacements estimation was performed by off-line analysis. A significant decrease in brain pulsatility was observed in the group of depressed patients compared to the group of non depressed patients. Mean displacement magnitude was about 44±7 μm in the first group and 68±13 μm in the second group. [Copyright &y& Elsevier]

Background: The term “vascular depression” has been proposed to describe a subset of depressive disorders that occurs in old age as a consequence of cerebrovascular disease. However, depression has been shown to result from other cardiovascular diseases such as coronary heart diseases, as well as to precipitate, worsen or precede vascular diseases. Depression also increases the likelihood of the incidence of vascular risk factors such as diabetes. Aims: To review clinical and epidemiological evidence linking geriatric depression and vascular diseases, and to discuss the potential mechanisms that could underlie this association. Method: Systematic review of the literature of the last 5 years through Medline database search. Results: Papers report the following potential ways of association: (1) there is a direct influence of vascular disease, in particular, arteriosclerosis, on the incidence of depression; (2) depressive disorders have a direct impact on the cardiovascular system; (3) depression and vascular disease share either a common pathophysiological process or genetic determinants. Discussion: Depression can be understood as the direct consequence of brain damage in neurodegenerative disorders such as Parkinson''s or Huntington''s diseases. Similarly, vascular depression is mostly considered to be the consequence of microvascular lesions on prefrontal and subcortical regions. However, this functional neuroanatomical model offers no explanation for cases where depression has been shown to precede vascular diseases. Since cardiovascular diseases develop in a context of acquired environmental factors together with genetically determined disease, it may be postulated that geriatric depression could both result from brain lesions of vascular origin and also share some pathogenic or genetic determinants. [Copyright &y& Elsevier]

Objective: To test the effect of changing referral mode to Consultation–Liaison Psychiatry (C–L Psychiatry) by implementing early screening with systematic multidisciplinary management for emotional disorders in noncognitively impaired medical inpatients. Method: A prospective pre- and postintervention controlled study in the internal medicine division of a university hospital. Results: Out of 515 patients admitted to the internal medicine ward during the study period, 176 were included in the study and gave their informed consent (male=63%); 81 in the control group and 95 in the intervention group. Except for the increase in referral rate to the C–L Psychiatry service (4–32%), there were no significant differences between the baseline and intervention periods either in terms of length of stay in the internal medicine ward and of use and costs of medical resources, or in terms of patients'' satisfaction as regards attention paid to psychosocial issues during hospitalization. Conclusion: As a result of changing referral mode to C–L Psychiatry, the lack of effect on length of stay and on medical consumption of medically ill inpatients should be considered in the context of the briefness of the hospitalization periods encountered. Furthermore, the change in referral process does not seem to increase patients'' perception of the quality of care provided. [Copyright &y& Elsevier]

Increasing evidence suggests that brain pulsatility is involved in the pathophysiology of various neurological and psychiatric disorders. However, it remains unclear whether high brain pulsatility is damaging to or protective of the brain in normal conditions, and this could depend on the age of the individual and the methods used to measure brain pulsatility. The goal of our study was to investigate associations between subcortical volumes and brain pulsatility as assessed with ultrasound in healthy young adults using both a conventional method (transcranial Doppler pulsatility index [TCD-PI]) and the innovative method of tissue pulsatility imaging (TPI), which allows a high level of detection of small brain movements (micrometers). Twenty-five females aged 18-55 with no history of significant medical disorder underwent magnetic resonance imaging and ultrasound assessment. The volumes of six subcortical regions known to be particularly sensitive to change in cerebral blood flow were measured and compared with brain pulsatility as assessed with TCD-PI and TPI. TCD-PI and TPI measures positively correlated with all subcortical regions, with the caudate nucleus having the strongest association. Linear regressions found that TCD-PI and TPI measures of brain pulsatility explained 16% to 67% of the variance of the subcortical volumes. Our results suggest that a greater pulsatility as assessed with ultrasound in healthy young adults may constitute a protective factor for brain structure. Ultrasound measures of brain pulsatility may be appropriate to provide costless, non-invasive, portable and highly sensitive markers of cerebral blood flow pulsatility related to brain structure. [ABSTRACT FROM AUTHOR]

Background Mechanisms involved in brain changes observed in major depression have been poorly investigated in clinical populations. Changes in cerebral blood flow (CBF) have been found in depressed patients and constitute a potential mechanism by which brain volume varies in depression. We have tested the association of cerebral blood flow velocity (CBFV) as assessed with Transcranial Doppler (TCD) and cerebral blood flow (CBF) as assessed with Arterial Spin Labeling Magnetic Resonance Imaging (ASL-MRI) with Total Brain Volume (TBV) and the volume of seven subcortical regions, in currently depressed and long-term remitted patients. In addition, we have evaluated other potential confounders for the association depression/brain volume, including dimensional symptoms of depression, cardiovascular risk factors (CVRF) and antidepressants. Methods Seventy-five individuals were recruited, divided in 3 equal groups (currently depressed, remitted individuals and healthy controls) and were submitted to clinical assessment, MRI and Transcranial Doppler. Results CBFV was positively correlated with TBV, Hippocampus and Thalamus volume, but only in remitted patients, who tend to have larger brains compared to both currently depressed and controls. CVRF were negatively associated with brain volumes in the 3 groups and antidepressant use was associated with larger Thalamus. We found no association between brain volumes and CBF as assessed with ASL-MRI, anhedonia, anxiety or psychomotor retardation. Discussion Greater CBFV may be a physiological mechanism by which brain is enlarged in remitted patients. Future studies should consider CBFV, CVRF and antidepressants as possible confounders for the association depression/brain volumes, especially in remitted patients. [ABSTRACT FROM AUTHOR]

Patients suffering from treatment-resistant depression (TRD) are at risk of suicide. Sleep and circadian rhythm alterations are widely recognized as core symptoms of major depressive disorder and are associated with suicidal ideation. Thus, sleep and circadian rhythm alterations may be targeted to prevent suicide. Patients were recruited from a prospective cohort of the French network of TRD expert centers. Mood, sleep and circadian rhythms were assessed at baseline; suicidal risk was assessed both at baseline and during a one-year follow-up with standardized subjective questionnaires. Excessive daytime sleepiness (adjusted odds ratio aOR = 1.7(1–3.3), p = 0.04) and daytime dysfunction (aOR = 1.81(1.16–2.81), p = 0.0085) increased the risk of suicidal thoughts over the one-year follow-up period in patients with TRD after adjustment on age, gender, depression, trauma, anxiety, impulsivity, current daily tobacco smoking and body mass index. Hypnotics intake is associated with a reduced risk of suicidal ideation at one-year follow-up after the same adjustments (OR = 0.73(0.56–0.95), p = 0.019). Other associations between sleep quality or circadian rhythms and suicidal ideations at either baseline or one year did not remain significant in multivariate analyses after the same adjustments. Sleep assessments were based on self-reported questionnaires rather than objective measures. Daytime sleepiness and dysfunction are predictors of suicidal ideations, whereas hypnotics intake is associated with a reduced risk of suicidal ideations. Diurnal symptoms of sleep disturbances are therefore red flags to target for preventing suicide in depressed patients, and hypnotics seem efficient in preventing suicide for patients with TRD. • Patients suffering from TRD are at risk of suicide and sleep alterations may be targeted to prevent suicide. • Diurnal symptoms of sleep disturbances are red flags to target for preventing suicide in depressed patients. • Hypnotics intake is associated with a reduced risk of suicidal ideations for patients with TRD. • These findings provides new insights into the link between suicide and sleep, alertness and biological clock. [ABSTRACT FROM AUTHOR]

Previous cross-sectional studies found excessive Brain Tissue Pulsations (BTP) in mid-life depression, which could constitute a mechanism of brain damage in depression. However, it remains unclear whether successful antidepressant therapy restores BTP amplitudes. In this prospective study, we investigated longitudinal changes in BTP in patients with a major depressive episode (MDE), among responders and non-responders to escitalopram. Fifty-two individuals with a MDE, free of antidepressants at baseline, were included in an 8-week open-labeled escitalopram trial. Ultrasound Tissue Pulsatility Imaging (TPI) was applied to measure resting BTP and BTP reactivity in an orthostatic challenge, at baseline and at week 8. TPI data were available for 48 participants divided into responders (n = 28, 58.3%) and non-responders (n = 20, 41.7%) according to change in the MADRS score. MaxBTP significantly decreased between baseline and week 8, only in responders. In addition, changes in MaxBTP during the orthostatic challenge were no longer significant at week 8 but only in responders. Because excessive BTP constitutes a potential mechanism for brain damage, our results suggest that a successful pharmacotherapy could benefit patients to lower the risk of brain damage in individuals with depression, a population exposed to stroke, small arteries disease and brain atrophy. TPI could provide a surrogate biomarker to monitor antidepressant response and brain health in depression in clinical routine. • Excessive Brain Tissue Pulsations (BTP) was previously observed in depression. • We investigated prospective changes in BTP in an 8-week escitalopram trial. • We found that BTP decreased with successful pharmacotherapy. • Besides, BTP reactivity with orthostasis was no longer significant in responders. • BTP may provide a neuroimaging marker for monitoring brain health in depression. [ABSTRACT FROM AUTHOR]

In addition to heredity, exposure to early-life adversity is an important predisposing risk factor of suicidal behaviour. Although the association between Childhood Trauma (CT) and suicide risk is well documented, interactions between CT and suicidal behaviour in Treatment-Resistant Depression (TRD) populations have received little coverage. This study aimed to evaluate i) association between CT and suicidal behaviour in a TRD population, and ii) the role of personality traits and impulsiveness as potential factors of mediation in these associations. Patients were recruited from a cohort of the French network of TRD expert centers. Depressive symptom severity, CT, suicidal behaviour, personality traits, and impulsiveness were assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS), the Childhood Trauma Questionnaire (CTQ), the Columbia Suicide Severity Rating Scale (CSSRS), the Structured Clinical Interview for DSM-IV, the Big Five Inventory, and the Barratt Impulsivness Scale (BIS) respectively. Among the 256 patients with a baseline CTQ, in relation to suicide risk for the current depressive episode, we found an association with the total CTQ scores mediated by the intensity of the current episode in a model adjusted for age and sex (total effect: β = 0.171; p = 0.011, direct effect: β = 0.135; p = 0.043; indirect effect: β = 0.036; p = 0.048). Focusing on CT subtypes, we detected an association between suicide risk and physical neglect in a model adjusted for age and sex (β = 0.301; p = 0.002), without any mediation by the intensity of the current episode. There was no mediation effect from personality traits nor impulsiveness. With regards to CSSRS to assess suicidal ideation, we did not find any association with the total CTQ score and CT subtype scores. We report a strong association between suicidal behaviour and CT (in particular childhood physical neglect) in a TRD population. [ABSTRACT FROM AUTHOR]

It remains unclear whether benzodiazepines (BZDs) constitute a risk factor for Alzheimer's disease (AD). In this study, we investigated associations between chronic use of BZDs and brain amyloid load, a hallmark of AD, in 268 nondemented older individuals. F18-florbetapir positron emission tomography scans were performed to assess amyloid load as measured by standardized uptake value ratios, which were compared between chronic BZD users and nonusers using adjusted multiple linear regressions. Short- versus long-acting BZDs were also considered in the analyses. Standardized uptake value ratios were significantly lower in BZD users (n = 47) than in nonusers (n = 221), independent of multiple adjustments. The effect was stronger for short-acting BZDs than for long-acting BZDs. This is the first large clinical study showing a reduced brain amyloid load in chronic BZD users, especially with short-acting BZDs. Our results do not support the view of BZD use as a risk factor for AD and instead support the involvement of pharmacological mechanisms related to neuronal hyperactivity, neuroinflammation, and sleep quality as potential targets for blocking amyloid accumulation. • Amyloid load was significantly lower in benzodiazepine (BZD) users than in nonusers. • The effect was stronger for short-acting BZDs than for long-acting BZDs. • Our results do not support the view of BZDs as risk factors for Alzheimer's disease. • Pharmacological mechanisms related to BZDs may provide targets for blocking amyloid. [ABSTRACT FROM AUTHOR]

Follicular helper T-cell lymphomas (TFHL) have an aggressive course with a poor outcome. European and US guidelines recommend anthracycline-based chemotherapy as a first-line treatment, but the 5-year overall survival rate is still approximately 30%. We describe here the features of a cohort of TFHL patients who experienced prolonged survival despite the absence of specific treatment or the initiation of steroid-based therapy. In our study, we describe 15 adult patients who suffered from TFHL and had not received intensive chemotherapy at diagnosis for any reason. Biopsies of these cases were centrally reviewed, and the mutational pattern was determined using next-generation sequencing. These 15 patients had the classic clinical, biological and pathological features of TFHL, angioimmunoblastic-type. TET2 mutations were found in 83% of patients; RHOA G17V, IDH2 R172 and DNMT3A mutations were found in 67%, 42% and 33% of the patients, respectively. Among the 15 patients, 8 did not receive any treatment, and 7 received steroid-based treatment. Ten patients had progression (5 in each group). Four patients died (3 of them from the progression of their lymphoma). The median follow-up in our cohort was 53 months. The 5-year OS was 66%, 100% for untreated patients and 29% for the others. In those 2 groups, the median time to treatment initiation was 22 months from diagnosis. We described a series of 15 well-characterized TFHL patients with an indolent outcome, suggesting that a watch-and-wait approach can be proposed in selected patients. Identifying factors predicting such evolution is warranted. • Follicular helper T-cell lymphomas have an aggressive course with a poor outcome. • We describe 15 TFHL patients with an indolent outcome without specific treatment. • The 15 patients had the classic clinicobiological and pathological features of TFHL. • A watch-and-wait approach can be proposed in selected patients with TFHLs. [ABSTRACT FROM AUTHOR]

Highlights • Role of inflammatory markers in pathophysioogy of depressive illness remains elusive. • UCMS model of depression leads to a depressive-like state which is reversible by antidepressant pharmacotherapy. • UCMS also causes activation of microglia inside mice brain • Antagonsist of P2X7 receptors, Brilliant Blue G (BBG), reverses UCMS induced behavioral and biochemical changes in mice. • BBG reinstated the dysregulated HPA axis but didn’t affect the adult hippocampal neurogenesis like Fluoxetine. Abstract A polymorphism in the P2RX7 gene that encodes for the P2X7 ionotropic ATP-gated receptor (P2X7R) protein has been shown to be associated with an increased risk for developing depressive illnesses. However, the role of P2X7R in depression is still unclear. To better understand the role of P2X7R and its subsequent impact on microglial activation, we compared the effect of the P2X7R antagonist Brilliant Blue G (BBG) with that of fluoxetine in an unpredictable chronic mild stress (UCMS) model of depression in mice. Our results indicate that BBG (50 mg/kg body weight in 0.9% NaCl, 10 ml/kg/day) successfully reversed the degradation of coat states and nest-building scores induced by exposure to UCMS, similar to the conventional antidepressant fluoxetine (15 mg/kg body weight in 0.9% NaCl, 10 ml/kg/day). BBG also reversed the UCMS-induced microglial activation in cortical and hippocampal regions and the basal nuclei of mouse brains and corrected the UCMS-induced hypothalamo-pituitary-adrenal (HPA) axis dysregulation. In contrast to fluoxetine, however, BBG treatment did not increase the density of doublecortin-positive cells in the dentate gyrus, indicating that BBG had no impact on hippocampal neurogenesis. These results suggest that P2X7R is involved in recovery from depressive-like states caused by exposure to UCMS in a mechanism that involves restoration of the HPA axis but not hippocampal neurogenesis. These results add to the evidence that P2X7R antagonist agents may have potential value in the pharmacological management of depression. [ABSTRACT FROM AUTHOR]

Tobacco smoking has been associated with suicide, impulsivity and depression in non-clinical populations with differences across sexes. To determine the role of tobacco smoking in Treatment-Resistant Depression (TRD) according to sex in a precision-medicine approach. The FACE-TRD cohort is a national cohort of TRD patients recruited in 13 resistant depression expert centers between 2014 and 2021 and followed-up at 6 months. A standardized one-day long comprehensive battery was carried out, including trained-clinician and patient-reported outcomes, and patients were reevaluated at 6 months on their smoking and psychiatric hospitalization outcomes. 355 TRD participants were included (222 women). The smoking rate was much higher in TRD women compared to the French general population (34% vs 24%) while it was comparable for men (approximately 29%). In multivariate analyses, compared to non-smoking women, female smokers had significantly increased number of lifetime psychiatric hospitalizations (standardized beta B = 0.232, p = 0.014) and electro-convulsive therapy (adjusted odds ratio (aOR) = 2.748, p = 0.005), increased suicidal ideations (aOR = 4.047, p = 0.031), history of suicide attempt (aOR = 1.994, p = 0.033), and increased impulsivity (B = 0.210, p = 0.006) and were more frequently treated by benzodiazepines (aOR = 1.848, p = 0.035) and third- or fourth-line TRD treatments (antipsychotics aOR = 2.270, p = 0.006, mood stabilizers aOR = 2.067 p = 0.044). Tobacco smoking at baseline was predictive of psychiatric hospitalization within 6 months in persistent smoking women (aOR = 2.636, p = 0.031). These results were not replicated in men, for whom tobacco smoking was only associated with increased clinician-rated and self-reported depressive symptoms (respectively B = 0.207, p = 0.022 and B = 0.184, p = 0.048). The smoking cessation rate at 6 months was higher in women than in men (12% vs. 7%). No patient was administered nicotine substitute or varenicline at the two timepoints. Combining these results and those of the literature, we recommend that active tobacco cessation should be promoted in TRD to improve depression, suicide and impulsivity especially in women. Female smokers appear as a specific population with heavier mental health outcomes that should be specifically addressed. • In this study, we show that tobacco smoking may play a role in treatment-resistant depression. • In women, the prevalence of tobacco smoking is much higher than in the general population. • In women, smoking is associated with suicidality, impulsivity and wih resistance to antidepressants. • In men tobacco smoking is associated with increased depressive symptoms. • Tobacco smoking cessation rates at 6 months are insufficient. [ABSTRACT FROM AUTHOR]

Abstract: Unipolar depression is one of the leading causes of disability. The pathophysiology of depression is poorly understood. Evidence suggests that inflammation is associated with depression. For instance, pro-inflammatory cytokines are found to be elevated in the peripheral blood of depressed subjects. Cytokine immunotherapy itself is known to induce depressive symptoms. While the epidemiological and biochemical relationship between inflammation and depression is strong, little is known about the possible existence of neuroinflammation in depression. The use of animal models of depression such as the Unpredictable Chronic Mild Stress (UCMS) has already contributed to the elucidation of the pathophysiological mechanisms of depression such as decreased neurogenesis and HPA axis alterations. We used this model to explore the association of depressive-like behavior in mice with changes in peripheral pro-inflammatory cytokines IL-1β, TNFα and IL-6 level as well as the neuroinflammation by quantifying CD11b expression in brain areas known to be involved in the pathophysiology of depression. These areas include the cerebral cortex, the nucleus accumbens, the bed nucleus of the stria terminalis, the caudate putamen, the amygdala and the hippocampus. The results indicate that microglial activation is significantly increased in the infralimbic, cingulate and medial orbital cortices, nucleus accumbens, caudate putamen, amygdala and hippocampus of the mouse brain as a function of UCMS, while levels of pro-inflammatory cytokines did not differ among the groups. This finding suggests that neuroinflammation occurs in depression and may be implicated in the subject''s behavioral response. They also suggest that UCMS could be a potentially reliable model to study depression-induced neuroinflammation. [Copyright &y& Elsevier]

Abstract: Major depression is an independent risk factor for the development of cardiovascular disease. This impact of depression on vascular function seems to be mediated by the endothelial dysfunction, defined as an impairment of endothelium-dependent vasorelaxation, which represents a reliable predictor of atherosclerosis and has been regularly found to be associated with depression. This study aimed at investigating aortic vascular reactivity in mice submitted to the unpredictable chronic mild stress (UCMS) procedure, a reliable model of depression. The results confirm the effectiveness of the UCMS procedure to induce neuroendocrine, physical and behavioral depression-like alterations as well as a significant decrease of acetylcholine-induced vasorelaxation without any effect on phenylephrine-induced vasoconstriction. In this study, we reveal an altered vascular reactivity in an animal model of depression, demonstrating an endothelial dysfunction reminiscent to the one found in depressed patients. [Copyright &y& Elsevier]

Abstract: Posttraumatic stress disorder (PTSD) has been frequently associated with volumetric reductions of grey matter structures (e.g. hippocampus and anterior cingulate), but these results remain controversial, especially in female non-combat-related samples. The present study aimed at exploring whole-brain structures in women with sexual abuse-related PTSD on the basis of cortical and subcortical structure comparisons to a matched pair sample that was well-controlled. Seventeen young women who had experienced sexual abuse and who had a diagnosis of chronic PTSD based on the Clinician Administered PTSD Scale for DSM-IV and 17 healthy controls individually matched for age and years of education were consecutively recruited. Both groups underwent structural magnetic resonance imaging and psychiatric assessment of the main disorders according to Axis I of DSM-IV. The resulting scans were analyzed using automated cortical and subcortical volumetric quantifications. Compared with controls, PTSD subjects displayed normal global and regional brain volumes and cortical thicknesses. Our results indicate preserved subcortical volumes and cortical thickness in a sample of female survivors of sexual abuse with PTSD. The authors discuss potential differences between neural mechanisms of sexual abuse-related PTSD and war-related PTSD. [ABSTRACT FROM AUTHOR]

Abstract: The present study aimed to investigate olfactory anhedonia and olfactory negative alliesthesia in depressed patients. Two odorants, one with pleasant (vanillin), and one with unpleasant (butyric acid) hedonic valence were evaluated by 30 depressed inpatients and 30 controls (healthy subjects, matched by age and gender). Participants explored the hedonic valence, intensity (discrimination) and perceived quality (identification) of 16 different stimuli (3 concentrations of odorants, their 9 combinations, and 1 control containing distilled water). The hedonic perception showed that patients perceived the unpleasant odorant as significantly more unpleasant than controls (olfactory negative alliesthesia). Concerning the intensity ratings, controls were able to discriminate between all concentrations of odorants, while patients discriminated between the different concentrations only for the unpleasant component and not for the vanillin (olfactory anhedonia). Regarding the identification task in an iso-intense unmixed odorants mixture, patients perceived significantly less the pleasant odorant than the unpleasant one (olfactory anhedonia), whereas controls perceived both odorants equally well. These results support the notion of an olfactory perception impairment in depression. Further studies are needed to replicate these findings and to confirm that such olfactory anhedonia or/and olfactory negative alliesthesia could be a state or a trait of depression. [Copyright &y& Elsevier]

Abstract: Cognitive deficits are well documented in psychiatric disorders, particularly in schizophrenia and depression. Cognitive activity roots in perceptions. However, research on sensorial alterations in psychiatric conditions has mainly focused on visual or auditory processes and less on olfaction. Here, we examine data on olfactory deficits in psychiatric patients using a systematic review of recent publications. Schizophrenic patients are mainly characterized by no reliable change in odour sensitivity and by a deficit in odour identification, recognition and discrimination. Depressed patients principally exhibit a deficit in the hedonic aspects of this perception, even if, in some case, alterations in sensitivity or identification are also found. Changes in odour perception are also found in dementia and in some neurodegenerative disease, but in this case alterations concern all aspects of the sensorial experience (detection threshold, identification and recognition). Taken together, these data indicate that olfactory abnormalities might be a marker of psychiatric conditions, with a specific pattern for each disease. [Copyright &y& Elsevier]

Abstract: Objective: Delirium is highly prevalent in general hospitals but remains underrecognized and undertreated despite its association with increased morbidity, mortality, and health services utilization. To enhance its management, we developed guidelines covering all aspects, from risk factor identification to preventive, diagnostic, and therapeutic interventions in adult patients. Methods: Guidelines, systematic reviews, randomized controlled trials (RCT), and cohort studies were systematically searched and evaluated. Based on a synthesis of retrieved high-quality documents, recommendation items were submitted to a multidisciplinary expert panel. Experts scored the appropriateness of recommendation items, using an evidence-based, explicit, multidisciplinary panel approach. Each recommendation was graded according to this process'' results. Results: Rated recommendations were mostly supported by a low level of evidence (1.3% RCT and systematic reviews, 14.3% nonrandomized trials vs. 84.4% observational studies or expert opinions). Nevertheless, 71.1% of recommendations were considered appropriate by the experts. Prevention of delirium and its nonpharmacological management should be fostered. Haloperidol remains the first-choice drug, whereas the role of atypical antipsychotics is still uncertain. Conclusions: While many topics addressed in these guidelines have not yet been adequately studied, an explicit panel and evidence-based approach allowed the proposal of comprehensive recommendations for the prevention and management of delirium in general hospitals. [Copyright &y& Elsevier]

Major Depressive Disorder is particularly frequent among physically ill inpatients. Despite the considerable human burden and financial costs, Major Depressive Disorder remains under-detected and under-treated. To improve this situation, clinical practice guidelines for the management of Major Depressive Disorder were developed for patients in the general hospital. They were adapted from existing good quality guidelines. A literature search has been conducted to identify guidelines and systematic reviews about the management of Major Depressive Disorder. The quality of the existing guidelines was evaluated by means of the AGREE instrument (Appraisal of Guidelines for Research and Evaluation). Complementary literature searches were necessary to answer questions such as “depression and physical illness” or “antidepressants and somatic medication”. The guidelines were discussed by a multidisciplinary internal panel. The final version was reviewed by an external panel. This paper presents the development process and a summary of these guidelines for the management of Major Depressive Disorder. The adaptation of good quality guidelines to local needs requires much time, effort and skills. Easier ways for the adaptation and use of high quality guidelines at the local level may result from better coordination, organization and updating of guidelines at a national or supranational level. [Copyright &y& Elsevier]

Increasing evidence suggests that ultrasound (US) imaging may provide biomarkers and therapeutic options in mental disorders. We systematically reviewed the literature to provide a global overview of the possibilities of US for psychiatry. Original English language articles published between January 2000 and September 2019 were identified through databases searching and analyzed to summarize existing evidence according to PRISMA methodology. A total of 81 articles were included. Various US techniques and markers have been used in mental disorders, including Transcranial Doppler and Intima-Media Thickness. Most of the studies have focused on characterizing the pathophysiology of mental disorders, especially vascular physiology. Studies on therapeutic applications are still scarce. US imaging has proved to be useful in characterizing vascular impairment and structural and functional brain changes in mental disorders. Preliminary findings also suggest potential interests for therapeutic applications. Growing evidence suggests that US imaging could provide a non-invasive, portable and low-cost tool for pathophysiological characterization, prognostic assessment and therapeutic applications in mental disorders. • We reviewed literature on Ultrasound (US) imaging and therapy in Psychiatry. • We found 81 studies using various US techniques in various mental disorders. • US have been mostly used to characterize the pathophysiology of mental disorders. • US imaging has the potential to provide biomarkers for mental disorders. • Preliminary findings suggest therapeutic options with US for mental disorders. [ABSTRACT FROM AUTHOR]

Abstract: We used Tissue Pulsatility Imaging (TPI) to compare the Brain Tissue Pulsatility (BTP) in depressed (n =11) and non-depressed (n =13) type-2 diabetic non-demented patients aged 50years and older. Both maximum and mean BTP were significantly decreased in depressed diabetic subjects compared to non-depressed diabetic subjects. [Copyright &y& Elsevier]