953 research outputs found
Social Avoidance in Depression:A Study Using a Social Decision-Making Task
Depression significantly affects interpersonal functioning. Social avoidance may play an important role in depression, limiting opportunities and social skills acquisition, contributing to the maintenance of social difficulties. In the last few years, the need for studying social interactions using interactive tasks has been highlighted. This study investigated social avoidance in unmedicated depressed (n = 26) and matched healthy control (n = 26) participants, using a novel computerized social decision-making task (the TEAM task). In this task, participants choose between a social option (playing in a team with a coplayer) and an individual option (playing alone). Although the social option is more profitable from a material point of view, it can also be challenging because of social comparison and guilt feelings for failing the team. It was found that the higher the rank of the coplayer, the stronger the negative emotions (shame, guilt) reported by participants and the more they opted for the individual option. Depressed participants reported significantly less positive (happiness) and more negative (shame, guilt, disappointment) feelings regarding the task. Importantly, depressed participants chose the individual option significantly more often than controls, which led to lower gains in this group. Furthermore, as the task progressed, controls selected the individual option less often, whereas depressed participants selected the individual option more often. Our findings illustrate the importance of social avoidance in depression and how this behavior can lead to negative consequences. They also highlight the role of social comparison and guilt-related processes in underlying social avoidance in depression. (PsycINFO Database Record (c) 2019 APA, all rights reserved
Localized removal of the Au–Si eutectic bonding layer for the selective release of microstructures
Analgesia e sedação durante a instalação do cateter central de inserção periférica em neonatos
Nonlinear complexity analysis of brain fMRI signals in schizophrenia
Peer reviewedPublisher PD
A randomized controlled trial of sucrose and/or pacifier as analgesia for infants receiving venipuncture in a pediatric emergency department
<p>Abstract</p> <p>Background</p> <p>Although sucrose has been accepted as an effective analgesic agent for procedural pain in neonates, previous studies are largely in the NICU population using the procedure of heel lance. This is the first report of the effect of sucrose, pacifier or the combination thereof for the procedural pain of venipuncture in infants in the pediatric emergency department population.</p> <p>Methods</p> <p>The study design was a double (sucrose) and single blind (pacifier), placebo-controlled randomized trial – factorial design carried out in a pediatric emergency department. The study population was infants, aged 0 – 6 months. Eighty-four patients were randomly assigned to one of four groups: a) sucrose b) sucrose & pacifier c) control d) control & pacifier. Each child received 2 ml of either 44% sucrose or sterile water, by mouth. The primary outcome measure: FLACC pain scale score change from baseline. Secondary outcome measures: crying time and heart rate change from baseline.</p> <p>Results</p> <p>Sucrose did not significantly reduce the FLACC score, crying time or heart rate. However sub-group analysis revealed that sucrose had a much greater effect in the younger groups. Pacifier use reduced FLACC score (not statistically significant), crying times (statistically significant) but not heart rate. Subgroup analysis revealed a mean crying time difference of 76.52 seconds (p < 0.0171) (0–1 month) and 123.9 seconds (p < 0.0029) (1–3 month). For subgroup age > 3 months pacifier did not have any significant effect on crying time. Age adjusted regression analysis revealed that both sucrose and pacifier had significant effects on crying time. Crying time increased with both increasing age and increasing gestational age.</p> <p>Conclusion</p> <p>Pacifiers are inexpensive, effective analgesics and are easy to use in the PED for venipuncture in infants aged 0–3 months. The benefits of sucrose alone as an analgesic require further investigation in the older infant, but sucrose does appear to provide additional benefit when used with a pacifier in this age group.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN15819627</p
Phosphorylation controls autoinhibition of cytoplasmic linker protein-170
Author Posting. © American Society for Cell Biology, 2010. This article is posted here by permission of American Society for Cell Biology for personal use, not for redistribution. The definitive version was published in Molecular Biology of the Cell 21 (2010): 2661-2673, doi:10.1091/mbc.E09-12-1036.Cytoplasmic linker protein (CLIP)-170 is a microtubule (MT) plus-end-tracking protein that regulates MT dynamics and links MT plus ends to different intracellular structures. We have shown previously that intramolecular association between the N and C termini results in autoinhibition of CLIP-170, thus altering its binding to MTs and the dynactin subunit p150Glued (J. Cell Biol. 2004: 166, 1003–1014). In this study, we demonstrate that conformational changes in CLIP-170 are regulated by phosphorylation that enhances the affinity between the N- and C-terminal domains. By using site-directed mutagenesis and phosphoproteomic analysis, we mapped the phosphorylation sites in the third serine-rich region of CLIP-170. A phosphorylation-deficient mutant of CLIP-170 displays an "open" conformation and a higher binding affinity for growing MT ends and p150Glued as compared with nonmutated protein, whereas a phosphomimetic mutant confined to the "folded back" conformation shows decreased MT association and does not interact with p150Glued. We conclude that phosphorylation regulates CLIP-170 conformational changes resulting in its autoinhibition.This work was supported by National
Institutes of Health grant GM-25062 (to G.G.B.); Netherlands Organization for
Scientific Research grants (to A. A. and N. G.); a Cancer Genomics Centre
grant (to J.v.H.); and Presidential Program of Russian Academy of Sciences
and RFBP grant 05-04-4915 (to E.S.N.)
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Can understanding reward help illuminate anhedonia?
Purpose of review: The goal of this paper is to examine how reward processing might help us understand the symptom of anhedonia.
Recent findings: There are extensive reviews exploring the relationship between responses to rewarding stimuli and depression. These often include a discussion on anhedonia and how this might be underpinned in particular by dysfunctional reward processing. However, there is no specific consensus on whether studies to date have adequately examined the various sub-components of reward processing or how these might relate in turn to various aspects of anhedonia symptoms.
Summary: The approach to understanding the symptom of anhedonia should be to examine all the sub-components of reward processing at the subjective and objective behavioural and neural level, with well validated tasks that can be replicated. Investigating real life experiences of anhedonia and how theses might be predicted by objective lab measures is also needed in future research
Abnormal reward prediction-error signalling in antipsychotic naive individuals with first-episode psychosis or clinical risk for psychosis.
Ongoing research suggests preliminary, though not entirely consistent, evidence of neural abnormalities in signalling prediction errors in schizophrenia. Supporting theories suggest mechanistic links between the disruption of these processes and the generation of psychotic symptoms. However, it is unknown at what stage in the pathogenesis of psychosis these impairments in prediction-error signalling develop. One major confound in prior studies is the use of medicated patients with strongly varying disease durations. Our study aims to investigate the involvement of the meso-cortico-striatal circuitry during reward prediction-error signalling in earliest stages of psychosis. We studied patients with first-episode psychosis (FEP) and help-seeking individuals at-risk for psychosis due to sub-threshold prodromal psychotic symptoms. Patients with either FEP (n = 14), or at-risk for developing psychosis (n = 30), and healthy volunteers (n = 39) performed a reinforcement learning task during fMRI scanning. ANOVA revealed significant (p < 0.05 family-wise error corrected) prediction-error signalling differences between groups in the dopaminergic midbrain and right middle frontal gyrus (dorsolateral prefrontal cortex, DLPFC). FEP patients showed disrupted reward prediction-error signalling compared to controls in both regions. At-risk patients showed intermediate activation in the midbrain that significantly differed from controls and from FEP patients, but DLPFC activation that did not differ from controls. Our study confirms that FEP patients have abnormal meso-cortical signalling of reward-prediction errors, whereas reward-prediction-error dysfunction in the at-risk patients appears to show a more nuanced pattern of activation with a degree of midbrain impairment but preserved cortical function
Confidence and psychosis: a neuro-computational account of contingency learning disruption by NMDA blockade.
A state of pathological uncertainty about environmental regularities might represent a key step in the pathway to psychotic illness. Early psychosis can be investigated in healthy volunteers under ketamine, an NMDA receptor antagonist. Here, we explored the effects of ketamine on contingency learning using a placebo-controlled, double-blind, crossover design. During functional magnetic resonance imaging, participants performed an instrumental learning task, in which cue-outcome contingencies were probabilistic and reversed between blocks. Bayesian model comparison indicated that in such an unstable environment, reinforcement learning parameters are downregulated depending on confidence level, an adaptive mechanism that was specifically disrupted by ketamine administration. Drug effects were underpinned by altered neural activity in a fronto-parietal network, which reflected the confidence-based shift to exploitation of learned contingencies. Our findings suggest that an early characteristic of psychosis lies in a persistent doubt that undermines the stabilization of behavioral policy resulting in a failure to exploit regularities in the environment.FV was supported by the Groupe Pasteur Mutualité. RG was supported by the Fondation pour la Recherche Médicale and the Fondation Bettencourt Schueller. SP is supported by a Marie Curie Intra-European fellowship (FP7-PEOPLE-2012-IEF). AF was supported by National Health and Medical Research Council grants (IDs : 1050504 and 1066779) and an Australian Research Council Future Fellowship (ID: FT130100589). This work was supported by the Wellcome Trust and the Bernard Wolfe Health Neuroscience Fund.This is the final version of the article. It first appeared from the Nature Publishing Group via http://dx.doi.org/10.1038/mp.2015.7
Abnormal Frontostriatal Activity During Unexpected Reward Receipt in Depression and Schizophrenia: Relationship to Anhedonia.
Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states.Supported by a MRC Clinician Scientist award (G0701911), a Brain and Behaviour Research Foundation Young Investigator, and an Isaac Newton Trust award to Dr Murray; an award to Dr Segarra from the Secretary for Universities and Research of the Ministry of Economy and Knowledge of the Government of Catalonia and the European Union; by the University of Cambridge Behavioural and Clinical Neuroscience Institute, funded by a joint award from the Medical Research Council and Wellcome Trust (G1000183 and 093875/Z/10Z respectively); by awards from the Wellcome Trust (095692) and the Bernard Wolfe Health Neuroscience Fund to Professor Fletcher, and by awards from the Wellcome Trust Institutional Strategic Support Fund (097814/Z/11) and Cambridge NIHR Biomedical Research Centre. The authors are grateful for the help of clinical staff in CAMEO, in the Cambridge Rehabilitation and Recovery service and Pathways, and in the Cambridge IAPT service, for help with participant recruitment.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/npp.2015.37
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