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Mood disorders, i.e. major depressive disorder (MDD) and bipolar disorders, are leading sources of disability worldwide. Currently available treatments do not yield remission in approximately a third of patients with a mood disorder. This is in part because these treatments do not target a specific core pathology underlying these heterogeneous disorders. In recent years, abnormal inflammatory processes have been identified as putative pathophysiological mechanisms and treatment targets in mood disorders, particularly among individuals with treatment-resistant conditions.
In this selective review, we aimed to summarise recent advances in the field of immunopsychiatry, including emerging pathophysiological models and findings from treatment ttrials of immunomodulatory agents for both MDD and bipolar disorders.
We performed a literature review by searching Medline for clinical trials of immunomodulating agents as monotherapy or adjunctive treatments in MDD and bipolar disorders. Included studies are randomised controlled trials (RCTs), cluster RCTs or cross-over trials of immunomodulating agents that had an active comparator or a placebo-arm.
Current evidence shows an association between inflammation and mood symptoms. However, there is conflicting evidence on whether this link is causal.
Future studies should focus on identifying specific neurobiological underpinnings for the putative causal association between an activated inflammatory response and mood disorders. Results of these studies are needed before further treatment trials of immunomodulatory agents can be justified.
The aim of this study was to determine whether schizophrenic patients' impairment in semantic verbal fluency tasks is due to difficulties in organizing their search or, in other words, in organizing output in terms of clusters of meaningfully related words. Consecutive association of words belonging to subcategories of the semantic task was defined as semantic clustering. A categorical verbal fluency task was first administered to 100 healthy subjects and then to 22 schizophrenic patients and 22 healthy subjects matched for sex, age and education. In the normal population, semantic clustering was found to be involved in word generation. A large number of semantic clusters indicated efficient organization of semantic knowledge and led to better word production. Schizophrenic patients showed impaired verbal fluency and generated a smaller number of semantic clusters than the control subjects. These findings point to a defect in self-initiation of semantic categorization in schizophrenia.
Neuropsychiatric symptoms, also referred to as ‘BPSD’ (Behavioural and Psychological Symptoms of Dementia), are now proposed as a major component of the dementia syndrome and are as clinically significant as disorders of cognition. Behavioural changes are not only important at a symptomatic level but could be a key feature for the future disease modifying therapies.
For clinical trials, the following points have been suggested by members of BPSD European Alzheimer Disease Consortium (EADC):
- to limit the use of BNPI total score
- to use NPI sub syndrome or single item score
- to use in combination with the NPI specific behavioural domains scale
For clinical practice, results from the cohort such as the REAL.Fr study help to stress
the importance neuropsychiatric symptoms in AD patients. 686 AD patients included
A majority of patients at any stage of the disease presented with one or several behavioral and psychological disturbances. Apathy concerned 43% of patients and, with or without depression, was associated with more pronounced deficits in global cognition, everyday life and instrumental abilities, nutritional status and with a higher burden level. A high level of psychotropic prescription, especially with antidepressant, was observed in patients with apathy. In a multivariate analysis taking into account the cognitive and functional variables of AD, apathy and depression were the only significant predictors of psychotropic prescription.
Other results coming from the 4 year follow up assessment will also be presented.
There is wide acknowledgement that apathy is an important behavioural syndrome in Alzheimer’s disease and in various neuropsychiatric disorders. In light of recent research and the renewed interest in the correlates and impacts of apathy, and in its treatments, it is important to develop criteria for apathy that will be widely accepted, have clear operational steps, and that will be easily applied in practice and research settings. Meeting these needs is the focus of the task force work reported here.
The task force includes members of the Association Française de Psychiatrie Biologique, the European Psychiatric Association, the European Alzheimer’s Disease Consortium and experts from Europe, Australia and North America. An advanced draft was discussed at the consensus meeting (during the EPA conference in April 7th 2008) and a final agreement reached concerning operational definitions and hierarchy of the criteria.
Apathy is defined as a disorder of motivation that persists over time and should meet the following requirements. Firstly, the core feature of apathy, diminished motivation, must be present for at least four weeks; secondly two of the three dimensions of apathy (reduced goal-directed behaviour, goal-directed cognitive activity, and emotions) must also be present; thirdly there should be identifiable functional impairments attributable to the apathy. Finally, exclusion criteria are specified to exclude symptoms and states that mimic apathy.
Chronic social isolation in the elderly may be related with diverse psychiatric disorders: chronic depressive episode, paranoia-type personality, and late non-schizophrenic psychosis.
In order to separate psychotic depression and non-schizophrenic psychosis with depressive mood, there is a need for more clearly defined criteria.
We report the case of a 68 yrs. women living alone at home for more than twenty years, with a complete social isolation for two years. This behaviour was found associated with severe delusion: she unreasonably felt persecuted by her flat's owner and she dissimulated an extensive basocellular carcinoma on her face threatening her life. A history of a short depressive episode at the time of her divorce was only found, as she demonstrated at initial assessment many paranoia personality traits. A review of literature on this disorders’ association was therefore undertaken.
Evolution after admission revealed the lack of effectiveness of antipsychotic treatment on delusion, but some efficiency of antidepressant. Nevertheless, personality traits remained unaffected by care. Literature on the association between mood disorders and non-schizophrenic psychosis is rare, and we suggest some criteria that may account for psychotic depression and be useful to treatment choice.
In the absence of a history of chronic mood or psychotic disorder, it is hypothesised that paranoia symptoms may account more for a psychotic depression than for late paranoid schizophrenia. This may have consequences for therapeutic strategy.
A suicide attempt is an major event that creates harm on both family and close relatives, that can be measured in terms of traumatic stress and medico-economic impact (costs). Each year, 3.750.000 French people are concerned by a suicide attempt of a relative (or close person).
Male or female, older than 16, being a relative of a suicide attempter (i.e. living in the same house as the suicide attempter). 171 families were included (171 suicide attempters and 171 « family informants »). These subjects were compared to IRDES datas on French population (Institute of Research and Documentation on Health Economy ; sample of 20.000 subjects, representing 95% of the French families). All subjects were reassessed by phone at 3 month and 1 year.
80% of the relatives declare “being fine” at 1 year; the 20% that declare being “not so well” are important to qualify, the sooner after the suicide attempt. An explicative model trying to evaluate the risk of being “not so well” at 1 year is possible ; this model is highly represented by the psychotraumatic impact of the confrontation with the suicide attempt.
On the economic plan, we can observe a great stability in healthcare contacts at 1 year (hospitalizations, GP or Specialists contacts, other kind of care contact…), contrasting with a big increase in medication use (× 2.37 in comparison with IRDES population); all the medication types being concerned, psychotropic and others.
The question of a self-medication partly unconscious is raised.
Severe depression after mid-life has significant clinical, cognitive or functional consequences. These related dimensions may have a different evolution under treatment, and their assessment may be useful to evaluate treatment efficiency.
To measure differential treatment effect on clinical, cognitive and functional dimensions in elderly severe depression.
The relation between these three dimensions has been examined from the inclusion through six weeks of treatment
Three different treatment (antidepressant, ECT and rTMS) were proposed to ten patients aged more than 60. The clinical, cognitive and functional dimensions were compared at inclusion and J42, and their evolution was also measured. At the end, we tried to assess trends for difference between the three types of treatment. Three types of evaluation were performed: clinical (depression, anxiety and apathy), neuropsychological (memory, attentional and executive functioning) and functional (activities of daily life, autonomy).
This preliminary study put in evidence a common pre-treatment profile of depressive symptoms (mood disorder), cognitive (executive difficulties) and functional (loss of autonomy, physical problems) abilities. Clinical improvement was associated with similar cognitive and functional progression, whatever therapeutic method was proposed.
Repetitive evaluation of symptomatology, cognitive performance and everyday life functioning seems to have a major importance in post midlife depressive episodes. It might be useful to determine if non-pharmacological treatment may result in a different evolution of these dimensions.
White-matter abnormalities are sometimes associated with mood disorders, and atypical depression may be related with a leukodystrophy.
A case report of a treatment-resistant depression with cognitive deficits and extensive white-matter hyperintensities suggested a literature review on this unattended association.
A 33 yrs. woman was recovered in our psychiatric ward with a recurrent depressive disorder, partially resistant to antidepressant for eleven years. MADRS score was 26 at admission, without significant anxiety or psychotic symptoms. After 12 days, she presented delirium with neurological localisation symptoms. MRI examination put in evidence confluent hypersignal of white matter with demyelinisation, without grey-matter lesion. No biological or enzymatic abnormalities were detected. A severe executive dysfunction with information slowing was detected on neuropsychological assessment. We performed a literature review on the association of depression and leukodystrophy.
The presented case is a probable Childhood Ataxia with Cerebral Hypomyelination (CACH) syndrome lately revealed by treatment-resistant depression. It represents 30% of all causes of leukodystrophy, and as it is described typically in a childhood form, an onset at adulthood has also been reported, sometimes with foreground behavioural and affective disorders. in that form, it may present with a treatment-resistant and atypical depression.
Treatment-resistant depression in young people with an atypical presentation may be related with an extensive white-matter disease, and a complete evaluation including MRI, biological, enzymatic, neuropsychological assessments, is therefore recommended.
The role of social factors in suicidal behaviour is long established. There is growing evidence supporting the Interpersonal Theory of Suicide (ITS), as developed by Joiner et al., which postulates that two psychological dimensions linked to thwarted fundamental interpersonal needs, perceived burdensomeness and thwarted belongingness are linked to the onset of suicidal desire. The Interpersonal Needs Questionnaire (INQ) has been designed to assess those dimensions for use in research on the aetiology of suicidal behaviour and as a component of risk assessment in clinical settings. There is currently no available French version.
Our objective was to provide a French adaptation of the INQ. We translated the INQ, and then examined the construct validity of INQ-F in a clinical setting.
The INQ was translated and administered to 50 patients admitted for suicide attempt or suicidal ideation. Scales with validated French versions were used to assess the following dimensions: suicide risk (Ducher Suicide Risk Assessment Scale (RSD), depression (BDI-SF and MADRS), hopelessness (Beck Hopelessness Scale (BHS) and social vulnerability (EPICES).
INQ-F was significantly correlated with suicide risk (rho= .737, p < .001), depression, hopelessness and social isolation. Internal consistency was high (Cronbach's alpha = .9137).
Our results support the construct validity of the INQ-F, although complementary studies are needed to further establish it, as well as the relevance of the ITS for suicide risk assessment in clinical settings.
Constant strain rate nanoindentation hardness measurements at high sustained strain rates cannot be made in conventional nanoindentation testing systems using the commonly employed continuous stiffness measurement technique (CSM) because of the “plasticity error” recently reported by Merle et al. [Acta Mater.134, 167 (2017)]. To circumvent this problem, here we explore an alternative testing and analysis procedure based on quasi-static loading and an independent knowledge of the Young's modulus, which is easily obtained by standard nanoindentation testing. In theory, the method applies to any indentation strain rate, but in practice, an upper limit on the rate arises from hardware limitations in the testing system. The new methodology is developed and applied to measurements made with an iMicro nanoindenter (KLA, Inc.), in which strain rates up to 100 s−1 were successfully achieved. The origins of the hardware limitations are documented and discussed.
A new carbon isotope record for two high-latitude sedimentary successions that span the Jurassic–Cretaceous boundary interval in the Sverdrup Basin of Arctic Canada is presented. This study, combined with other published Arctic data, shows a large negative isotopic excursion of organic carbon (δ13Corg) of 4‰ (V-PDB) and to a minimum of −30.7‰ in the probable middle Volgian Stage. This is followed by a return to less negative values of c. −27‰. A smaller positive excursion in the Valanginian Stage of c. 2‰, reaching maximum values of −24.6‰, is related to the Weissert Event. The Volgian isotopic trends are consistent with other high-latitude records but do not appear in δ13Ccarb records of Tethyan Tithonian strata. In the absence of any obvious definitive cause for the depleted δ13Corg anomaly, we suggest several possible contributing factors. The Sverdrup Basin and other Arctic areas may have experienced compositional evolution away from open-marine δ13C values during the Volgian Age due to low global or large-scale regional sea levels, and later become effectively coupled to global oceans by Valanginian time when sea level rose. A geologically sudden increase in volcanism may have caused the large negative δ13Corg values seen in the Arctic Volgian records but the lack of precise geochronological age control for the Jurassic–Cretaceous boundary precludes direct comparison with potentially coincident events, such as the Shatsky Rise. This study offers improved correlation constraints and a refined C-isotope curve for the Boreal region throughout latest Jurassic and earliest Cretaceous time.
Erysiphe alphitoides causes oak powdery mildew, an example of disease in a wild perennial plant that has shown dramatic changes over a century in Europe. There are several hypotheses for this: pathogen evolution towards lower virulence, a reciprocal increase in oak population resistance, and environmental factors. We show that understanding the pathosystem requires accounting of both seasonality and the occurrence of a pathogen complex, with several cryptic fungal species differing in their life-history traits. Observational data suggest that severity of annual epidemics is linked to interannual pathogen transmission, including winter survival and the infection success of the primary inoculum in spring. Climate-driven phenological synchrony between host and pathogen in spring appears to be critical. Several cryptic Erysiphe species are associated with the disease and co-occur at multiple spatial scales. A semi-discrete model combining a SIR model in the epidemic phase and a discrete-time model between years, based on a within–between season transmission trade-off, describes seasonality and the coexistence of pathogen species. We discuss model refinement by the introduction of host population age classes and other modelling approaches for the evolution of pathogen virulence and host resistance in a changing environment.
Constant strain rate nanoindentation is a popular technique for probing the local mechanical properties of materials but is usually restricted to strain rates ≤0.1 s−1. Faster indentation potentially results in an overestimation of the hardness because of the plasticity error associated with the continuous stiffness measurement (CSM) method. This can have significant consequences in some applications, such as the measurement of strain rate sensitivity. The experimental strain rate range can be extended by increasing the harmonic frequency of the CSM oscillation. However, with commercial instruments, this is achievable only by identifying higher CSM frequencies at which the testing system is dynamically well behaved. Using these principles, a commercial system operated at the unusually high harmonic frequency of 1570 Hz was successfully used to characterize of the strain rate sensitivity of a Zn22Al superplastic alloy at strain rates up to 1 s−1, i.e., an order of magnitude higher than with standard methods.
Habitat prioritization and corridor restoration are important steps for reconnecting fragmented habitats and species populations, and spatial modelling approaches are useful in identifying suitable habitat for elusive tropical rainforest mammals. The Endangered Bornean banteng Bos javanicus lowi, a wild bovid endemic to Borneo, occurs in habitat that is highly fragmented as a result of extensive agricultural expansion. Based on the species’ historical distribution in Sabah (Malaysia), we conducted camera-trap surveys in 14 forest reserves during 2011–2016. To assess suitable habitat for the banteng we used a presence-only maximum entropy (MaxEnt) approach with 11 spatial predictors, including climate, infrastructure, land cover and land use, and topography variables. We performed a least-cost path analysis using Linkage Mapper, to understand the resistance to movement through the landscape. The surveys comprised a total of 44,251 nights of camera trapping. We recorded banteng presence in 11 forest reserves. Key spatial predictors deemed to be important in predicting suitable habitat included soil associations (52.6%), distance to intact and logged forests (11.8%), precipitation in the driest quarter (10.8%), distance to agro-forest and regenerating forest (5.7%), and distance to oil palm plantations (5.1%). Circa 11% of Sabah had suitable habitat (7,719 km2), of which 12.2% was in protected forests, 60.4% was in production forests and 27.4% was in other areas. The least-cost path model predicted 21 linkages and a relatively high movement resistance between core habitats. Our models provide information about key habitat and movement resistance for bantengs through the landscape, which is crucial for constructive conservation strategies and land-use planning.
When a promising natural enemy of a key pest exists locally, it is a common practice in biological control (BC) to rear and release it for supplementary control in the targeted agroecosystem even though significant knowledge gaps concerning pre/post release may still exist. Incorporating genetic information into BC research fills some of these gaps. Habrobracon hebetor, a parasitoid of many economically important moths that infest stored and field crops worldwide is commonly used, particularly against the millet head miner (MHM), a key pest of millet in Sahelian countries. To advance our knowledge on how H. hebetor that occurs naturally in open-field cropping systems and grain stores as well as being mass-produced and released for MHM control, performs in millet agroecosystems in Niger we evaluated its population genetics using two mitochondrial and 21 microsatellite markers. The field samples were genetically more diverse and displayed heterozygote excess. Very few field samples had faced significant recent demographic bottlenecks. The mating system (i.e. nonrandom mating with complementary sex determination) of this species may be the major driver of these findings rather than bottlenecks caused by the small number of individuals released and the scarcity of hosts during the longlasting dry season in Niger. H. hebetor population structure was represented by several small patches and genetically distinct individuals. Gene flow occurred at local and regional scales through human-mediated and natural short-distance dispersal. These findings highlight the importance of the mating system in the genetic diversity and structure of H. hebetor populations, and contribute to our understanding of its reported efficacy against MHM in pearl millet fields.
Livestock farming is criticized for negatively impacting the environment, concerns about animal welfare and the impact of excessive meat consumption on human health. However, livestock farming provides other underappreciated and poorly communicated benefits to society in terms of employment, product quality, cultural landscapes and carbon storage by grasslands. Few attempts have been made so far to simultaneously consider the services and impacts provided by livestock production. Here, we propose an integrated graphical tool, called the ‘barn’ to explicitly summarize the synergies and trade-offs between services and impacts provided by livestock farming. It illustrates livestock farming interacting with its physical, economic and social environment along five interfaces: (i) Markets, (ii) Work and employment, (iii) Inputs, (iv) Environment and climate, (v) Social and cultural factors. This graphical tool was then applied by comparing two contrasting livestock production areas (high livestock density v. grassland-based), and the dominant v. a niche system within a crop-livestock area. We showed the barn could be used for cross-comparisons of services and impacts across livestock production areas, and for multi-level analysis of services and impacts of livestock farming within a given area. The barn graphically summarizes the ecological and socio-economic aspects of livestock farming by explicitly representing multiple services and impacts of different systems in a simple yet informative way. Information for the five interfaces relies on available quantitative assessments from the literature or data sets, and on expert-knowledge for more qualitative factors, such as social and cultural ones. The ‘barn’ can also inform local stakeholders or policy-makers about potential opportunities and threats to the future of livestock farming in specific production areas. It has already been used as a pedagogical tool for teaching the diversity of services and impacts of livestock systems across Europe and is currently developed as a serious game for encouraging knowledge exchange and sharing different viewpoints between stakeholders.
The Endangered proboscis monkey Nasalis larvatus is endemic to the island of Borneo. Habitat loss is a major threat to this species, and an understanding of long-term demographic trends is crucial for its conservation. We assessed the population trends and group sizes of proboscis monkeys over 10 years in the Lower Kinabatangan floodplain in Sabah, Malaysian Borneo. Comparisons of observed populations between 2004 and 2014 revealed significantly reduced group sizes, which is probably a result of forest fragmentation. Three long-term studies over 34–73 months in specific areas showed fluctuating estimated densities in each area, but no overall population increase or decrease. Riparian forests are the most important habitat for these monkeys, and one reason for the relatively stable population could be that there were only minor losses of forest along rivers during 2004–2014 because protected areas have been established in the region in 2005. However, proboscis monkey habitat remains under threat in areas allocated for oil palm, and protection of these areas is paramount to maintaining this population.
Livestock is a major driver in most rural landscapes and economics, but it also polarises debate over its environmental impacts, animal welfare and human health. Conversely, the various services that livestock farming systems provide to society are often overlooked and have rarely been quantified. The aim of analysing bundles of services is to chart the coexistence and interactions between the various services and impacts provided by livestock farming, and to identify sets of ecosystem services (ES) that appear together repeatedly across sites and through time. We review three types of approaches that analyse associations among impacts and services from local to global scales: (i) detecting ES associations at system or landscape scale, (ii) identifying and mapping bundles of ES and impacts and (iii) exploring potential drivers using prospective scenarios. At a local scale, farming practices interact with landscape heterogeneity in a multi-scale process to shape grassland biodiversity and ES. Production and various ES provided by grasslands to farmers, such as soil fertility, biological regulations and erosion control, benefit to some extent from the functional diversity of grassland species, and length of pasture phase in the crop rotation. Mapping ES from the landscape up to the EU-wide scale reveals a frequent trade-off between livestock production on one side and regulating and cultural services on the other. Maps allow the identification of target areas with higher ecological value or greater sensitivity to risks. Using two key factors (livestock density and the proportion of permanent grassland within utilised agricultural area), we identified six types of European livestock production areas characterised by contrasted bundles of services and impacts. Livestock management also appeared to be a key driver of bundles of services in prospective scenarios. These scenarios simulate a breakaway from current production, legislation (e.g. the use of food waste to fatten pigs) and consumption trends (e.g. halving animal protein consumption across Europe). Overall, strategies that combine a reduction of inputs, of the use of crops from arable land to feed livestock, of food waste and of meat consumption deliver a more sustainable food future. Livestock as part of this sustainable future requires further enhancement, quantification and communication of the services provided by livestock farming to society, which calls for the following: (i) a better targeting of public support, (ii) more precise quantification of bundles of services and (iii) better information to consumers and assessment of their willingness to pay for these services.