Perceived stress in obsessive-compulsive disorder is related with obsessive but not cmpulsive symptoms

Obsessive–compulsive disorder (OCD) is achronic psychiatric disorder characterized by recurrent intrusive thoughts and/or repetitive compulsory behaviors. This psychiatric disorder is known to be stress responsive, as symptoms increase during periods of stress but also because stressful events may precede the onset of OCD. However, only a few and inconsistent reports have been published about the stress perception and the stress-response in these patients. Herein, we have characterized the correlations of OCD symptoms with basal serum cortisol levels and scores in a stress perceived questionnaire (PSS-10). The present data reveals that cortisol levels and the stress scores in the PSS-10 were significantly higher in OCD patients that in controls. Moreover, stress levels self-reported by patients using the PSS-10 correlated positively with OCD severity in the Yale–Brown Obsessive–Compulsive Scale (Y–BOCS). Interestingly, PSS-10 scores correlated with the obsessive component, but not with the compulsive component, of Y–BOCS. These results confirm that stress is relevant in the context of OCD, particularly for the obsessive symptomatology.Pedro Morgado is supported by a fellowship “SFRH/SINTD/60129/2009” funded by FCT – Foundation for Science and Technology. Supported by FEDER funds through Operational program for competitive factors – COMPETE and by national funds through FCT –Foundation for Science and Technology to project “PTDC/SAU-NSC/111814/2009.

Generic dynamics of 4-dimensional C2 Hamiltonian systems

We study the dynamical behaviour of Hamiltonian flows defined on 4-dimensional compact symplectic manifolds. We find the existence of a C2-residual set of Hamiltonians for which every regular energy surface is either Anosov or it is in the closure of energy surfaces with zero Lyapunov exponents a.e. This is in the spirit of the Bochi-Mane dichotomy for area-preserving diffeomorphisms on compact surfaces and its continuous-time version for 3-dimensional volume-preserving flows

Hyperbolicity through stable shadowing for generic geodesic flows

We prove that the closure of the closed orbits of a generic geodesic flow on a closed Riemannian n >= 2 dimensional manifold is a uniformly hyperbolic set if the shadowing property holds C2-robustly on the metric. We obtain analogous results using weak specification and the shadowing property allowing bounded time reparametrization.The authors were partially supported by the Project ‘New trends in Lyapunov exponents’ (PTDC/MAT-PUR/29126/2017). MB was partially supported by FCT - ‘Fundação para a Ciência e a Tecnologia’, through Centro de Matemática e Aplicações (CMA-UBI), Universidade da Beira Interior, project UID/MAT/00212/2013. JLD was partially supported by the Project CEMAPRE - UID/MULTI/00491/2019 financed by FCT/MCTES through national funds. MJT was partially supported by the Research Centre of Mathematics of the University of Minho with the Portuguese Funds from the Fundação para a Ciência e a Tecnologia, through the Project UID/MAT/00013/2013

Age-related qualitative shift in emotional behaviour : paradoxical findings after re-exposure of rats in the elevated-plus maze

Several variables, including age, are known to influence anxiety. Previous exposure to the elevated-plus maze (EPM) is known to modify emotional behaviour as retesting in the EPM at a standard age of 3 months increases open-arm avoidance and attenuates the effects of anxiolytic drugs. This study analysed whether similar results are obtained when older animals are subjected to these experimental paradigms. Overall, increasing age was associated with more signs of anxiety. Additionally, we observed a paradoxical behaviour pattern in aged-subjects that were re-exposed to the EPM, with mid-aged and old rats failing to display open arm avoidance (OAA) in the second trial; this qualitative shift in emotional behaviour was not associated with decreased locomotion. An examination of how age influences responsiveness to anxiolytic drugs, with or without previous maze experience, was also conducted. Midazolam (0.5 and 1 mg/kg) proved anxiolytic in maize-naive young animals; in marked contrast, in older animals midazolam at 1 mg/kg resulted in sedation but not anxiolyis. One trial tolerance to midazolam was evident in animals of both ages that were subjected to a second EPM trial; the latter phenomenon was apparently accentuated in older animals as they do not show open arm avoidance upon re-exposure to the EPM. These data suggest that the age-associated ‘resistance’ to anxiolytic drugs might be related to a qualitative shift in emotional behaviour

Morphological correlates of corticosteroid-induced changes in prefrontal cortex-dependent behaviors

Imbalances in the corticosteroid milieu have been implicated in several neuropsychiatric disorders, including depression and schizo-phrenia. Prefrontal cortex (PFC) dysfunction is also a hallmark of these conditions, causing impairments in executive functions such as behavioral flexibility and working memory. Recent studies have suggested that the PFC might be influenced by corticosteroids released during stress. To test this possibility, we assessed spatial working memory and behavioral flexibility in rats submitted to chronic adrenalectomy or treatment with corticosterone (25 mg/kg) or the synthetic glucocorticoid dexamethasone (300 μg/kg); the behavioral analysis was complemented by stereological evaluation of the PFC (prelimbic, infralimbic, and anterior cingulate regions), the adjacent retrosplenial and motor cortices, and the hippocampal formation. Dexamethasone treatment resulted in a pronounced impairment in working memory and behavioral flexibility, effects that correlated with neuronal loss and atrophy of layer II of the infralimbic, prelimbic, and cingulate cortices. Exposure to corticosterone produced milder impairments in behavioral flexibility, but not in working memory, and reduced the volume of layer II of all prefrontal areas. Interestingly, adrenalectomy-induced deleterious effects only became apparent on the reverse learning task and were not associated with structural alterations in the PFC. None of the experimental procedures influenced the morphology of retrosplenial or motor cortices, but stereological measurements confirmed previously observed effects of corticosteroids on hippocampal structure. Our results describe, for the first time, that imbalances in the corticosteroid environment can induce degeneration of specific layers of the PFC; these changes appear to be the morphological correlate of corticosteroid-induced impairment of PFC-dependent behavior(s).German Academic Exchange - grant Acções Integradas Luso-Alemãs.Portuguese Rectors’ Conference

Intelligent control for accurate position tracking of electrohydraulic actuators

A novel intelligent control scheme is presented for accurate position tracking of electrohydraulic servo actuators. The proposed control law is designed by means of a non-linear control approach and includesan adaptive neural network to provide the basic intelligent features. Online learning, instead of off-line supervised training, is proposed to update the weight vector of the neural network. Moreover, the adoption of a composite error signal as the only input to the neural network allows a significant reduction in the computational complexity of the algorithm. Rigorous proofs for the boundedness and convergence properties of the closed-loop signals are provided. Experimental results obtained with an electrohydraulic system demonstrate the efficacy of the proposed controller, even considering the highly non-linear and uncertain plant dynamics.</p

A Trans-Dimensional Approach to the Behavioral Aspects of Depression

Depression, a complex mood disorder, displays high comorbidity with anxiety and cognitive disorders. To establish the extent of inter-dependence between these behavioral domains, we here undertook a systematic analysis to establish interactions between mood [assessed with the forced-swimming (FST) and sucrose consumption tests (SCT)], anxiety [elevated-plus maze (EPM) and novelty suppressed feeding (NSF) tests] and cognition (spatial memory and behavioral flexibility tests) in rats exposed to unpredictable chronic-mild-stress (uCMS). Expectedly, uCMS induced depressive-like behavior, a hyperanxious phenotype and cognitive impairment; with the exception of the measure of anxiety in the EPM, these effects were attenuated by antidepressants (imipramine, fluoxetine). Measures of mood by the FST and SCT were strongly correlated, whereas no significant correlations were found between the different measures of anxiety (EPM and NSF); likewise, measures of cognition by spatial memory and behavioral flexibility tests were poorly correlated. Inter-domain analysis revealed significant correlations between mood (FST and SCT) and anxiety-like behavior (NSF, but not EPM). Furthermore, significant correlations were found between cognitive performance (reverse learning task) and mood (FST and SCT) and anxiety-like behavior (NSF). These results demonstrate interactions between different behavioral domains that crosscut the disciplines of psychiatry and neurology

The sweet drive test : refining phenotypic characterization of anhedonic behavior in rodents

Measuring anhedonic behavior in rodents is a challenging task as current methods display only moderate sensitivity to detect anhedonic phenotype and, consequently, results from different labs are frequently incongruent. Herein we present a newly-developed test, the Sweet Drive Test (SDT), which integrates food preference measurement in a non-aversive environment, with ultrasonic vocalizations (USVs) recording. Animals were placed in a soundproofed black arena, under red light illumination, and allowed to choose between regular and sweet food pellets. During the test trials, 50 KHz USVs, previously described to be associated with positive experiences, were recorded. In a first experimental approach, we demonstrate the ability of SDT to accurately characterize anhedonic behavior in animals chronically exposed to stress. In a subsequent set of experiments, we show that this paradigm has high sensitivity to detect mood-improving effects of antidepressants. The combined analysis of both food preference and the number of 50 KHz vocalizations in the SDT provides also a valuable tool to discriminate animals that responded to treatment from non-responder animals.We thank S. Borges and A. J. Rodrigues for advice and assistance in the USVs recording procedures and analysis, and H. Almeida and J. J. Cerqueira for comments and suggestions on the experimental design. Furthermore, we thank P. Costa for assistance with 3D reconstruction images. Antonio Mateus-Pinheiro, Patricia Patricio, Monica Morais, and Nuno D. Alves received fellowships from the Portuguese Foundation for Science and Technology (FCT). This study was co-funded by the Life- and Health Sciences Research Institute (ICVS), and ON.2-O NOVO NORTE-North Portugal Regional Operational Programme 2007/2013, of the National Strategic Reference Framework (NSRF) 2007/2013, through the European Regional Development Fund (ERDF)

Growth assessment of Helicobacter pylori in liquidmedium – effect of aggregation

Helicobacter pylori is a pathogenic organism associated with gastric diseases. It is described that H. pylori can change morphology when exposed to adverse conditions and H. pylori cells can aggregate in clusters when in liquid culture. Such phenomenon makes it difficult to assess growth using the conventional methods. The development of robust methods to assess growth in a more reliable way is needed. In the present work a method that allows efficient cell disaggregation was developed.Fundação para a Ciência e Tecnologia (FCT) PhD Grant (SFRH/BD/47596/2008

Do genes and environment meet to regulate cerebrospinal fluid dynamics? Relevance for schizophrenia

Schizophrenia is a neurodevelopment disorder in which the interplay of genes and environment contributes to disease onset and establishment. The most consistent pathological feature in schizophrenic patients is an enlargement of the brain ventricles. Yet, so far, no study has related this finding with dysfunction of the choroid plexus (CP), the epithelial cell monolayer located within the brain ventricles that is responsible for the production of most of the cerebrospinal fluid (CSF). Enlarged brain ventricles are already present at the time of disease onset (young adulthood) and, of notice, isolated mild ventriculomegaly detected in utero is associated with subsequent mild neurodevelopmental abnormalities similar to those observed in children at high risk of developing schizophrenia. Here we propose that altered CP/CSF dynamics during neurodevelopment may be considered a risk, causative and/or participating factor for development of schizophrenia.Nadine C. Santos and Fernanda Marques are recipients of postdoctoral fellowships by the Switchbox project (European Commission FP7 initiative grant HEALTH-F2-2010-259772) and the Fundação para a Ciência e Tecnologia (FCT, Portugal), respectively