97 research outputs found

    Localization and Glassy Dynamics Of Many-Body Quantum Systems

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    When classical systems fail to explore their entire configurational space, intriguing macroscopic phenomena like aging and glass formation may emerge. Also closed quanto-mechanical systems may stop wandering freely around the whole Hilbert space, even if they are initially prepared into a macroscopically large combination of eigenstates. Here, we report numerical evidences that the dynamics of strongly interacting lattice bosons driven sufficiently far from equilibrium can be trapped into extremely long-lived inhomogeneous metastable states. The slowing down of incoherent density excitations above a threshold energy, much reminiscent of a dynamical arrest on the verge of a glass transition, is identified as the key feature of this phenomenon. We argue that the resulting long-lived inhomogeneities are responsible for the lack of thermalization observed in large systems. Such a rich phenomenology could be experimentally uncovered upon probing the out-of-equilibrium dynamics of conveniently prepared quantum states of trapped cold atoms which we hereby suggest

    Mice with reduced DAT levels recreate seasonal-induced switching between states in bipolar disorder.

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    Developing novel therapeutics for bipolar disorder (BD) has been hampered by limited mechanistic knowledge how sufferers switch between mania and depression-how the same brain can switch between extreme states-described as the "holy grail" of BD research. Strong evidence implicates seasonally-induced switching between states, with mania associated with summer-onset, depression with winter-onset. Determining mechanisms of and sensitivity to such switching is required. C57BL/6J and dopamine transporter hypomorphic (DAT-HY 50% expression) mice performed a battery of psychiatry-relevant behavioral tasks following 2-week housing in chambers under seasonally relevant photoperiod extremes. Summer-like and winter-like photoperiod exposure induced mania-relevant and depression-relevant behaviors respectively in mice. This behavioral switch paralleled neurotransmitter switching from dopamine to somatostatin in hypothalamic neurons (receiving direct input from the photoperiod-processing center, the suprachiasmatic nucleus). Mice with reduced DAT expression exhibited hypersensitivity to these summer-like and winter-like photoperiods, including more extreme mania-relevant (including reward sensitivity during reinforcement learning), and depression-relevant (including punishment-sensitivity and loss-sensitivity during reinforcement learning) behaviors. DAT mRNA levels switched in wildtype littermate mice across photoperiods, an effect not replicated in DAT hypomorphic mice. This inability to adjust DAT levels to match photoperiod-induced neurotransmitter switching as a homeostatic control likely contributes to the susceptibility of DAT hypormophic mice to these switching photoperiods. These data reveal the potential contribution of photoperiod-induced neuroplasticity within an identified circuit of the hypothalamus, linked with reduced DAT function, underlying switching between states in BD. Further investigations of the circuit will likely identify novel therapeutic targets to block switching between states

    Abilities to explicitly and implicitly infer intentions from actions in adults with autism spectrum disorder

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    Previous research suggests that Autism Spectrum Disorder (ASD) might be associated with impairments on implicit but not explicit mentalizing tasks. However, such comparisons are made difficult by the heterogeneity of stimuli and the techniques used to measure mentalizing capabilities. We tested the abilities of 34 individuals (17 with ASD) to derive intentions from others’ actions during both explicit and implicit tasks and tracked their eye-movements. Adults with ASD displayed explicit but not implicit mentalizing deficits. Adults with ASD displayed typical fixation patterns during both implicit and explicit tasks. These results illustrate an explicit mentalizing deficit in adults with ASD, which cannot be attributed to differences in fixation patterns

    Mother–infant interaction in schizophrenia:Transmitting risk or resilience? A systematic review of the literature

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    Purpose: The parent–infant relationship is an important context for identifying very early risk and resilience factors and targets for the development of preventative interventions. The aim of this study was to systematically review studies investigating the early caregiver–infant relationship and attachment in offspring of parents with schizophrenia. Methods: We searched computerized databases for relevant articles investigating the relationship between early caregiver–infant relationship and outcomes for offspring of a caregiver with a diagnosis of schizophrenia. Studies were assessed for risk of bias. Results: We identified 27 studies derived from 10 cohorts, comprising 208 women diagnosed with schizophrenia, 71 with other psychoses, 203 women with depression, 59 women with mania/bipolar disorder, 40 with personality disorder, 8 with unspecified mental disorders and 119 non-psychiatric controls. There was some evidence to support disturbances in maternal behaviour amongst those with a diagnosis of schizophrenia and there was more limited evidence of disturbances in infant behaviour and mutuality of interaction. Conclusions: Further research should investigate both sources of resilience and risk in the development of offspring of parents with a diagnosis of schizophrenia and psychosis. Given the lack of specificity observed in this review, these studies should also include maternal affective disorders including depressive and bipolar disorders

    Excessive substance use in bipolar disorder is associated with impaired functioning rather than clinical characteristics, a descriptive study

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    <p>Abstract</p> <p>Background</p> <p>There is a strong association between bipolar disorder (BD) and substance use disorder (SUD). The clinical and functional correlates of SUD in BD are still unclear and little is known about the role of excessive substance use that does not meet SUD criteria. Thus, the aims of the current study were to investigate lifetime rates of illicit substance use in BD relative to the normal population and if there are differences in clinical and functional features between BD patients with and without excessive substance use.</p> <p>Methods</p> <p>125 consecutively recruited BD in- and outpatients from the Oslo University Hospitals and 327 persons randomly drawn from the population in Oslo, Norway participated. Clinical and functional variables were assessed. Excessive substance use was defined as DSM-IV SUD and/or excessive use according to predefined criteria.</p> <p>Results</p> <p>The rate of lifetime illicit substance use was significantly higher among patients compared to the reference population (OR = 3.03, CI = 1.9-4.8, p < .001). Patients with excessive substance use (45% of total) had poorer educational level, occupational status, GAF-scores and medication compliance, with a trend towards higher suicidality rates, compared to patients without. There were no significant group differences in current symptom levels or disease course between groups.</p> <p>Conclusion</p> <p>The percentage of patients with BD that had tried illicit substances was significantly higher than in the normal population. BD patients with excessive substance use clearly had impaired functioning, but not a worse course of illness compared to patients without excessive substance use. An assessment of substance use beyond SUD criteria in BD is clinically relevant.</p

    A Biological Global Positioning System: Considerations for Tracking Stem Cell Behaviors in the Whole Body

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    Many recent research studies have proposed stem cell therapy as a treatment for cancer, spinal cord injuries, brain damage, cardiovascular disease, and other conditions. Some of these experimental therapies have been tested in small animals and, in rare cases, in humans. Medical researchers anticipate extensive clinical applications of stem cell therapy in the future. The lack of basic knowledge concerning basic stem cell biology-survival, migration, differentiation, integration in a real time manner when transplanted into damaged CNS remains an absolute bottleneck for attempt to design stem cell therapies for CNS diseases. A major challenge to the development of clinical applied stem cell therapy in medical practice remains the lack of efficient stem cell tracking methods. As a result, the fate of the vast majority of stem cells transplanted in the human central nervous system (CNS), particularly in the detrimental effects, remains unknown. The paucity of knowledge concerning basic stem cell biology—survival, migration, differentiation, integration in real-time when transplanted into damaged CNS remains a bottleneck in the attempt to design stem cell therapies for CNS diseases. Even though excellent histological techniques remain as the gold standard, no good in vivo techniques are currently available to assess the transplanted graft for migration, differentiation, or survival. To address these issues, herein we propose strategies to investigate the lineage fate determination of derived human embryonic stem cells (hESC) transplanted in vivo into the CNS. Here, we describe a comprehensive biological Global Positioning System (bGPS) to track transplanted stem cells. But, first, we review, four currently used standard methods for tracking stem cells in vivo: magnetic resonance imaging (MRI), bioluminescence imaging (BLI), positron emission tomography (PET) imaging and fluorescence imaging (FLI) with quantum dots. We summarize these modalities and propose criteria that can be employed to rank the practical usefulness for specific applications. Based on the results of this review, we argue that additional qualities are still needed to advance these modalities toward clinical applications. We then discuss an ideal procedure for labeling and tracking stem cells in vivo, finally, we present a novel imaging system based on our experiments

    Cardiac resynchronization therapy guided by cardiovascular magnetic resonance

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    Cardiac resynchronization therapy (CRT) is an established treatment for patients with symptomatic heart failure, severely impaired left ventricular (LV) systolic dysfunction and a wide (> 120 ms) complex. As with any other treatment, the response to CRT is variable. The degree of pre-implant mechanical dyssynchrony, scar burden and scar localization to the vicinity of the LV pacing stimulus are known to influence response and outcome. In addition to its recognized role in the assessment of LV structure and function as well as myocardial scar, cardiovascular magnetic resonance (CMR) can be used to quantify global and regional LV dyssynchrony. This review focuses on the role of CMR in the assessment of patients undergoing CRT, with emphasis on risk stratification and LV lead deployment

    Convergent functional genomic studies of omega-3 fatty acids in stress reactivity, bipolar disorder and alcoholism

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    Omega-3 fatty acids have been proposed as an adjuvant treatment option in psychiatric disorders. Given their other health benefits and their relative lack of toxicity, teratogenicity and side effects, they may be particularly useful in children and in females of child-bearing age, especially during pregnancy and postpartum. A comprehensive mechanistic understanding of their effects is needed. Here we report translational studies demonstrating the phenotypic normalization and gene expression effects of dietary omega-3 fatty acids, specifically docosahexaenoic acid (DHA), in a stress-reactive knockout mouse model of bipolar disorder and co-morbid alcoholism, using a bioinformatic convergent functional genomics approach integrating animal model and human data to prioritize disease-relevant genes. Additionally, to validate at a behavioral level the novel observed effects on decreasing alcohol consumption, we also tested the effects of DHA in an independent animal model, alcohol-preferring (P) rats, a well-established animal model of alcoholism. Our studies uncover sex differences, brain region-specific effects and blood biomarkers that may underpin the effects of DHA. Of note, DHA modulates some of the same genes targeted by current psychotropic medications, as well as increases myelin-related gene expression. Myelin-related gene expression decrease is a common, if nonspecific, denominator of neuropsychiatric disorders. In conclusion, our work supports the potential utility of omega-3 fatty acids, specifically DHA, for a spectrum of psychiatric disorders such as stress disorders, bipolar disorder, alcoholism and beyond
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