Tradução comentada: fatores de risco três meses após a UCI

Mestrado em Tradução EspecializadaO trabalho consiste na tradução e no relatório da tradução de um artigo científico da área da medicina, relativo aos efeitos secundários ocorridos três meses depois do tratamento na Unidade de Cuidados Intensivos. Pretende-se identificar e comentar os principais problemas de tradução. A criação de um glossário com a terminologia específica encontrada no texto de partida foi de suma importância para ultrapassar e resolver os problemas terminológicos.The work consists in the translation and translation report of a scientific research on the secondary effects that occurred three months after the treatment in the Intensive Care Unit. The objective is to identify and overcome the main translation problems. The creation of a glossary containing the specific terminology found in the source text was of great importance, helping to overcome and solve the terminology problems

Neuroimaging Correlates of Resilience to Traumatic Events—A Comprehensive Review

Improved understanding of the neurobiological correlates of resilience would be an important step toward recognizing individuals at risk of developing post-traumatic stress disorder (PTSD) or other trauma-related diseases, enabling both preventative measures and individually tailored therapeutic approaches. Studies on vulnerability factors allow drawing conclusions on resilience. Structural changes of cortical and subcortical structures, as well as alterations in functional connectivity and functional activity, have been demonstrated to occur in individuals with PTSD symptoms. Relevant areas of interest are hippocampus, amygdala, insula, anterior cingulate cortex, and prefrontal cortex, as well as related brain networks, such as the default-mode, salience, and central executive network. This review summarizes the existing literature and integrates findings from cross-sectional study designs with two-group designs (trauma exposed individuals with and without PTSD), three-group designs (with an additional group of unexposed, healthy controls), twin-studies and longitudinal studies. In terms of structural findings, decreased hippocampal volume in PTSD individuals might be either a vulnerability factor or a result of trauma exposure, or both. Reduced anterior cingulate cortex and prefrontal cortex volumes seem to be predisposing factors for increased vulnerability. Regarding functional connectivity, increased amygdala connectivity has been demonstrated selectively in PTSD individuals, as well as increased default-mode-network and salience network connectivity. In terms of functional activity, increased amygdala and anterior cingulate cortex activities, and decreased prefrontal cortex activity as a response to external stimuli have been associated with higher vulnerability. Increased prefrontal cortex activity seemed to be a protective factor. Selecting adequate study designs, optimizing the diagnostic criteria, as well as differentiating between types of trauma and accounting for other factors, such as gender-specific differences, would be well-served in future research. Conclusions on potential preventative measures, as well as clinical applications, can be drawn from the present literature, but more studies are needed

Multimodule Web-Based COVID-19 Anxiety and Stress Resilience Training (COAST): Single-Cohort Feasibility Study With First Responders

BACKGROUND Since the emergence of COVID-19, health care workers and first responders have been at a high risk for mental health symptoms owing to their exposure to the virus and increased work stress during the pandemic. Although interventions exist to address mental health issues following exposure to disasters, emergencies, and humanitarian crises, considerably less is known about web-based unguided interventions to help mitigate the negative impacts of such events. Additionally, in contexts in which emergencies reduce access to in-person care, remote forms of support are critical, yet there are limited studies on the use of such interventions. Evidence-based, easy-to-use, scalable interventions are direly needed for this population. OBJECTIVE This study aimed to develop and test the feasibility of an unguided electronic mental health program, COVID-19 Anxiety and Stress Resilience Training (COAST), tailored to first responders and health care personnel, based on scientific evidence and empirically based techniques. METHODS We developed COVID-19-specific training modules focusing on several domains that are previously reported as key to resilience and stress recovery: self-efficacy, mindfulness, sleep quality, and positive thinking. The program was made available to 702 first responders between May and August 2020, during the COVID-19 pandemic. Sociodemographic, work-, and COVID-19-related information was collected, and psychometric questionnaires were completed. We examined user acceptance and user activity, including module choice and participant feedback. RESULTS In total, 52 of 702 (7%) first responders to whom we reached out used the program at least once. COAST use was independent of age, sex, or baseline levels of self-efficacy, mindful awareness, sleep quality, and positive thinking (for all, P>.39). First responders who had tested positive and those who had been quarantined were more likely to engage in the program. A click count analysis per module showed that participants used the self-efficacy and mindfulness modules most often, with 382 and 122 clicks, respectively, over 15 weeks. Overall, first responders expressed satisfaction with the program. CONCLUSIONS Engagement of first responders in the multimodule web-based COAST program was feasible and the first responder cohort expressed overall satisfaction with the program. Those in more difficult circumstances, including those in quarantine and those who tested positive, may be more likely to engage in such programs. Further controlled studies could pave the way for efficacy studies and the development of additional modules, including just-in-time interventions or blended interventions combining individual use of an unguided self-help intervention, such as COAST, with subsequent individual psychotherapy for those who continue to experience stress and psychological symptoms

Disentangling craving‐ and valence‐related brain responses to smoking cues in individuals with nicotine use disorder

Tobacco smoking is one of the leading causes of preventable death and disease worldwide. Most smokers want to quit, but relapse rates are high. To improve current smoking cessation treatments, a better understanding of the underlying mechanisms of nicotine dependence and related craving behaviour is needed. Studies on cue-driven cigarette craving have been a particularly useful tool for investigating the neural mechanisms of drug craving. Here, functional neuroimaging studies in humans have identified a core network of craving-related brain responses to smoking cues that comprises of amygdala, anterior cingulate cortex, orbitofrontal cortex, posterior cingulate cortex and ventral striatum. However, most functional Magnetic Resonance Imaging (fMRI) cue-reactivity studies do not adjust their stimuli for emotional valence, a factor assumed to confound craving-related brain responses to smoking cues. Here, we investigated the influence of emotional valence on key addiction brain areas by disentangling craving- and valence-related brain responses with parametric modulators in 32 smokers. For one of the suggested key regions for addiction, the amygdala, we observed significantly stronger brain responses to the valence aspect of the presented images than to the craving aspect. Our results emphasize the need for carefully selecting stimulus material for cue-reactivity paradigms, in particular with respect to emotional valence. Further, they can help designing future research on teasing apart the diverse psychological dimensions that comprise nicotine dependence and, therefore, can lead to a more precise mapping of craving-associated brain areas, an important step towards more tailored smoking cessation treatments. Keywords: craving; cue-reactivity; functional Magnetic Resonance Imaging; neuroimaging; nicotine use disorder; smoking

Insular dysfunction within the salience network is associated with severity of symptoms and aberrant inter-network connectivity in major depressive disorder

Major depressive disorder (MDD) is characterized by altered intrinsic functional connectivity within (intra-iFC) intrinsic connectivity networks (ICNs),such as the Default Mode- (DMN),Salience- (SN) and Central Executive Network (CEN). It has been proposed that aberrant switching between DMN-mediated self-referential and CEN-mediated goal-directed cognitive processes might contribute to MDD, possibly explaining patients' difficulties to disengage the processing of self-focused, often negatively biased thoughts. Recently, it has been shown that the right anterior insula (rAl) within the SN is modulating DMN/CEN interactions. Since structural and functional alterations within the Al have been frequently reported in MDD, we hypothesized that aberrant intra-iFC in the SN's rAl is associated with both aberrant iFC between DMN and CEN (inter-iFC) and severity of symptoms in MDD. Twenty-five patients with MDD and 25 healthy controls were assessed using resting-state fMRI (rs-fMRI) and psychometric examination. High-model-order independent component analysis (ICA) of rs-fMRI data was performed to identify ICNs including DMN, SN, and CEN. Intra-iFC within and inter-iFC between distinct subsystems of the DMN, SN, and CEN were calculated, compared between groups and correlated with the severity of symptoms. Patients with MDD showed (1) decreased intra-iFC within the SN's rAl,(2) decreased inter-iFC between the DMN and CEN, and (3) increased inter-iFC between the SN and DMN. Moreover, decreased intra-iFC in the SN's rAl was associated with severity of symptoms and aberrant DMN/CEN interactions, with the latter losing significance after correction for multiple comparisons. Our results provide evidence for a relationship between aberrant intra-iFC in the salience network's rAl, aberrant DMN/CEN interactions and severity of symptoms, suggesting a link between aberrant salience mapping, abnormal coordination of DMN/CEN based cognitive processes and psychopathology in MDD

Age- and Gender Dependent Liver Fat Content in a Healthy Normal BMI Population as Quantified by Fat-Water Separating DIXON MR Imaging

OBJECTIVES To establish age- and sex-dependent values of magnetic resonance (MR) liver fat-signal fraction (FSF) in healthy volunteers with normal body-mass index (BMI). METHODS 2-point mDIXON sequences (repetition time/echo time, 4.2msec/1.2msec, 3.1msec) at 3.0 Tesla MR were acquired in 80 healthy volunteers with normal BMI (18.2 to 25.7 kg/m2) between 20 and 62 years (10 men/10 women per decade). FSF was measured in 5 liver segments (segment II, III, VI, VII, VIII) based on mean signal intensities in regions of interest placed on mDIXON-based water and fat images. Multivariate general linear models were used to test for significant differences between BMI-corrected FSF among age subgroups. Pearson and Spearman correlations between FSF and several body measures were calculated. RESULTS Mean FSF (%) ± standard deviations significantly differed between women (3.91 ± 1.10) and men (4.69 ± 1.38) and varied with age for women/men (p-value: 0.002/0.027): 3.05 ± 0.49/3.74 ± 0.60 (age group 20-29), 3.75 ± 0.66/4.99 ± 1.30 (30-39), 4.76 ± 1.16/5.25 ± 1.97 (40-49) and 4.09 ± 1.26/4.79 ± 0.93 (50-62). FSF differences among age subgroups were significant for women only (p = 0.003). CONCLUSIONS MR-based liver fat content is higher in men and peaks in the fifth decade for both genders

Insular dysfunction reflects altered between-network connectivity and severity of negative symptoms in schizophrenia during psychotic remission

Schizophrenia is characterized by aberrant intrinsic functional connectivity (iFC) within and between intrinsic connectivity networks (ICNs), including the Default Mode- (DMN), Salience- (SN), and Central Executive Network (CEN). The anterior insula (AI) of the SN has been demonstrated to modulate DMN/CEN interactions. Recently, we found that the dependence of DMN/CEN interactions on SN's right AI activity is altered in patients with schizophrenia in acute psychosis and related to psychotic symptoms, indicating a link between aberrant AI, DMN, CEN, and psychosis. However, since structural alterations of the insula are also present during psychotic remission and associated with negative symptoms, impaired AI interaction might be relevant even for psychotic remission and corresponding symptoms. Twelve patients with schizophrenia during psychotic remission (SR) and 12 healthy controls were assessed using resting-state fMRI and psychometric examination. High-model-order independent component analysis of fMRI data revealed ICNs including DMN, SN, and CEN. Scores of iFC within (intra-iFC) and between (inter-iFC) distinct subsystems of the DMN, SN, and CEN were calculated, compared between groups and correlated with the severity of symptoms. Intra-iFC was altered in patients SN, DMN, and CEN, including decreased intra-iFC in the left AI within the SN. Patients' inter-iFC between SN and CEN was increased and correlated with the severity of negative symptoms. Furthermore, decreased intra-iFC of the left AI correlated with both severity of negative symptoms and increased inter-iFC between SN and CEN. Our result provides first evidence for a relationship between AI dysfunction and altered between-network interactions in schizophrenia during psychotic remission, which is related to the severity of negative symptoms. Together with our previous results, data suggest specific SN/DMN/CEN reorganization in schizophrenia with distinct insular pathways for distinct symptom dimensions

Reduced apparent fiber density in the white matter of premature-born adults

Premature-born adults exhibit lasting white matter alterations as demonstrated by widespread reduction in fractional anisotropy (FA) based on diffusion-weighted imaging (DWI). FA reduction, however, is non-specific for microscopic underpinnings such as aberrant myelination or fiber density (FD). Using recent advances in DWI, we tested the hypothesis of reduced FD in premature-born adults and investigated its link with the degree of prematurity and cognition. 73 premature- and 89 mature-born adults aged 25–27 years underwent single-shell DWI, from which a FD measure was derived using convex optimization modeling for microstructure informed tractography (COMMIT). Premature-born adults exhibited lower FD in numerous tracts including the corpus callosum and corona radiata compared to mature-born adults. These FD alterations were associated with both the degree of prematurity, as assessed via gestational age and birth weight, as well as with reduced cognition as measured by full-scale IQ. Finally, lower FD overlapped with lower FA, suggesting lower FD underlie unspecific FA reductions. Results provide evidence that premature birth leads to lower FD in adulthood which links with lower full-scale IQ. Data suggest that lower FD partly underpins FA reductions of premature birth but that other processes such as hypomyelination might also take place

Investigating the association of ventral and dorsal striatal dysfunction during reward anticipation with negative symptoms in patients with schizophrenia and healthy individuals

Background Negative symptoms are a core feature of schizophrenia and also found in healthy individuals in subclinical forms. According to the current literature the two negative symptom domains, apathy and diminished expression may have different underlying neural mechanisms. Previous observations suggest that striatal dysfunction is associated with apathy in schizophrenia. However, it is unclear whether apathy is specifically related to ventral or dorsal striatal alterations. Here, we investigated striatal dysfunction during reward anticipation in patients with schizophrenia and a non-clinical population, to determine whether it is associated with apathy. Methods Chronic schizophrenia patients (n = 16) and healthy controls (n = 23) underwent an event- related functional MRI, while performing a variant of the Monetary Incentive Delay Task. The two negative symptom domains were assessed in both groups using the Brief Negative Symptoms Scale. Results In schizophrenia patients, we saw a strong negative correlation between apathy and ventral and dorsal striatal activation during reward anticipation. In contrast, there was no correlation with diminished expression. In healthy controls, apathy was not correlated with ventral or dorsal striatal activation during reward anticipation. Conclusion This study replicates our previous findings of a correlation between ventral striatal activity and apathy but not diminished expression in chronic schizophrenia patients. The association between apathy and reduced dorsal striatal activity during reward anticipation suggests that impaired action-outcome selection is involved in the pathophysiology of motivational deficits in schizophrenia

Magnetic Resonance Echo Planar Neuroimaging – Methodological Advances and Current applications in Psychiatry

Although the burden of mental disorders continues to grow worldwide, their neurobiology still remains insufficiently understood. Over the last quarter century, methodological advances in neuroimaging have transformed the field of neuroscience. The advent of magnetic resonance imaging (MRI) and more particularly the development of echo planar imaging (EPI) pulse sequences, enabled novel applications, including functional magnetic resonance imaging (fMRI) and diffusion weighted/tensor imaging (DWI/DTI). Together, both methods allow for a characterization of the neuronal circuitry, which may serve as a specific biomarker for mental disorders. However, the functional architecture of the human brain remains elusive, while methodological limitations are still hampering our scientific progress. The six articles selected for this habilitation thesis address different aspects of EPI based MR neuroimaging with an emphasis on two main aspects: First, the application of fMRI in clinical populations with mental illness to explore associations between the functional connectome and behaviour, disease course and/or neuropathology. Second, the development and optimization of novel DWI/DTI approaches and their subsequent validation in peripheral neuronal structures. Using fMRI, we found a relationship between altered subcortical-cortical functional connectivity and psychotic symptoms in patients with schizophrenia, described an association between aberrant graph-theoretical network- topology and the course of disease in patients with depression and demonstrated an intricate interaction between brain activity during rest, task, cognitive performance and amyloid-β (Aβ) as measured with Aβ-specific positron-emission tomography in patients with prodromal Alzheimer’s disease. In addition, we validated the reproducibility of a novel DWI/DTI approach with optimized slice-wise shimming, tested the feasibility and performance of DTI in fine neuronal structures applying a novel readout segmented EPI and evaluated to which extent the acquisition can be accelerated without impeding the data quality. With its two main focuses within the framework of MR EPI neuroimaging, this work presents potential applications of already established methods to investigate the neurobiology underlying mental disorders as well as novel methodological developments in MR neuroimaging. The integration of methodological developments and applications in clinical research settings according to hypotheses derived from clinical observations may allow for the detection of biomarkers, which might have an influence on diagnostics and clinical decision making in the future