The study of age at onset of mental health disorders is technically and conceptually difficult. It is important to consider these age distributions in order to understand causes and mechanisms of ...illness and to intervene at an appropriate juncture for primary and secondary prevention. This article reviews some of the approaches to studying age at onset, sets out the evidence to support the assertion that adult mental disorders begin in adolescence, and finds that perhaps half of all adult mental health disorders have begun by the teenage years. The paper then discusses whether this fits what is known about the developmental neurobiology of the brain and introduces the implications for mental health services.
Oxidative Stress Sies, Helmut; Berndt, Carsten; Jones, Dean P
Annual review of biochemistry,
06/2017, Letnik:
86, Številka:
1
Journal Article
Recenzirano
Oxidative stress is two sided: Whereas excessive oxidant challenge causes damage to biomolecules, maintenance of a physiological level of oxidant challenge, termed oxidative eustress, is essential ...for governing life processes through redox signaling. Recent interest has focused on the intricate ways by which redox signaling integrates these converse properties. Redox balance is maintained by prevention, interception, and repair, and concomitantly the regulatory potential of molecular thiol-driven master switches such as Nrf2 Keap1 or NF-κB IκB is used for system-wide oxidative stress response. Nonradical species such as hydrogen peroxide (H
2
O
2
) or singlet molecular oxygen, rather than free-radical species, perform major second messenger functions. Chemokine-controlled NADPH oxidases and metabolically controlled mitochondrial sources of H
2
O
2
as well as glutathione- and thioredoxin-related pathways, with powerful enzymatic back-up systems, are responsible for fine-tuning physiological redox signaling. This makes for a rich research field spanning from biochemistry and cell biology into nutritional sciences, environmental medicine, and molecular knowledge-based redox medicine.
Singly ionized ytterbium, with ultranarrow optical clock transitions at 467 and 436 nm, is a convenient system for the realization of optical atomic clocks and tests of present-day variation of ...fundamental constants. We present the first direct measurement of the frequency ratio of these two clock transitions, without reference to a cesium primary standard, and using the same single ion of Yb+171. The absolute frequencies of both transitions are also presented, each with a relative standard uncertainty of 6x10-16. Combining our results with those from other experiments, we report a threefold improvement in the constraint on the time variation of the proton-to-electron mass ratio, mu super(.)/ mu =0.2(1.1)x10-16 yr-1, along with an improved constraint on time variation of the fine structure constant, alpha super(.)/ alpha =-0.7(2.1)x10-17 yr-1
Global forest restoration targets have been set, yet policy makers and land managers lack guiding principles on how to invest limited resources to achieve them. We conducted a meta-analysis of 166 ...studies in naturally regenerating and actively restored forests worldwide to answer: (1) To what extent do floral and faunal abundance and diversity and biogeochemical functions recover? (2) Does recovery vary as a function of past land use, time since restoration, forest region, or precipitation? (3) Does active restoration result in more complete or faster recovery than passive restoration? Overall, forests showed a high level of recovery, but the time to recovery depended on the metric type measured, past land use, and region. Abundance recovered quickly and completely, whereas diversity recovered slower in tropical than in temperate forests. Biogeochemical functions recovered more slowly after agriculture than after logging or mining. Formerly logged sites were mostly passively restored and generally recovered quickly. Mined sites were nearly always actively restored using a combination of planting and either soil amendments or recontouring topography, which resulted in rapid recovery of the metrics evaluated. Actively restoring former agricultural land, primarily by planting trees, did not result in consistently faster or more complete recovery than passively restored sites. Our results suggest that simply ending the land use is sufficient for forests to recover in many cases, but more studies are needed that directly compare the value added of active versus passive restoration strategies in the same system. Investments in active restoration should be evaluated relative to the past land use, the natural resilience of the system, and the specific objectives of each project.
Cocaine addiction is a major public health problem that is particularly difficult to treat. Without medically proven pharmacological treatments, interventions to change the maladaptive behavior of ...addicted individuals mainly rely on psychosocial approaches. Here we report on impairment in cocaine-addicted patients to act purposefully toward a given goal and on the influence of extended training on their behavior. When patients were rewarded for their behavior, prolonged training improved their response rate toward the goal but simultaneously rendered them insensitive to the consequences of their actions. By contrast, overtraining of avoidance behavior had no effect on patient performance. Our findings illustrate the ineffectiveness of punitive approaches and highlight the potential for interventions that focus on improving goal-directed behavior and implementing more desirable habits to replace habitual drug-taking.
A growing body of preclinical evidence indicates that addiction to cocaine is associated with neuroadaptive changes in frontostriatal brain systems. Human studies in cocaine-dependent individuals ...have shown alterations in brain structure, but it is less clear how these changes may be related to the clinical phenotype of cocaine dependence characterized by impulsive behaviours and compulsive drug-taking. Here we compared self-report, behavioural and structural magnetic resonance imaging data on a relatively large sample of cocaine-dependent individuals (n = 60) with data on healthy volunteers (n = 60); and we investigated the relationships between grey matter volume variation, duration of cocaine use, and measures of impulsivity and compulsivity in the cocaine-dependent group. Cocaine dependence was associated with an extensive system of abnormally decreased grey matter volume in orbitofrontal, cingulate, insular, temporoparietal and cerebellar cortex, and with a more localized increase in grey matter volume in the basal ganglia. Greater duration of cocaine dependence was correlated with greater grey matter volume reduction in orbitofrontal, cingulate and insular cortex. Greater impairment of attentional control was associated with reduced volume in insular cortex and increased volume of caudate nucleus. Greater compulsivity of drug use was associated with reduced volume in orbitofrontal cortex. Cocaine-dependent individuals had abnormal structure of corticostriatal systems, and variability in the extent of anatomical changes in orbitofrontal, insular and striatal structures was related to individual differences in duration of dependence, inattention and compulsivity of cocaine consumption.
► We develop a framework which documents relationships between greenspace and health. ► The framework highlights key mediators which underpin the relationship. ► Moderators affect the relationship, ...such as socio-economic status and greenspace type. ► The framework can be used to inform and improve planning of research studies.
A growing body of evidence investigates whether access to greenspace, such as parks and woodland, is beneficial to well-being. Potential health benefits of greenspace exposure include opportunity for activities within the space and psychological benefits of viewing and interacting with nature. However, empirical research evidence on the effects of greenspace exposure shows mixed findings. Hence we suggest that the key questions of “if, why and how?” greenspace influences health remain largely unanswered. We argue that researchers have inadequately considered the causal pathways which drive the relationship. In particular, an improved understanding is needed of potential mediators and moderators. In this paper we draw on social–ecological theories and a review of the literature to develop a novel theoretical framework which summarises current knowledge about hypothetical causal pathways between access to greenspace and health outcomes. The framework highlights how mediators – such as use of greenspace and perceptions of the living environment – drive associations between access and both physical and psychological health outcomes. We propose key moderators based on evidence that associations between greenspace and health differ by demographic factors such as gender, ethnicity and socio-economic status, living context, greenspace type and climate. We discuss the evidence for how and why these factors act as moderators and consider the implications which arise from this improved understanding of the relationship between greenspace and health. In conclusion, we discuss how the framework can be used to inform planning of research studies, and how it may be developed in the future as more evidence emerges.
The functional interpretation of high throughput metabolomics by mass spectrometry is hindered by the identification of metabolites, a tedious and challenging task. We present a set of computational ...algorithms which, by leveraging the collective power of metabolic pathways and networks, predict functional activity directly from spectral feature tables without a priori identification of metabolites. The algorithms were experimentally validated on the activation of innate immune cells.
Tau pathology, neuroinflammation, and neurodegeneration are key aspects of Alzheimer's disease. Understanding whether these features predict cognitive decline, alone or in combination, is crucial to ...develop new prognostic measures and enhanced stratification for clinical trials. Here, we studied how baseline assessments of in vivo tau pathology (measured by 18F-AV-1451 PET), neuroinflammation (measured by 11C-PK11195 PET) and brain atrophy (derived from structural MRI) predicted longitudinal cognitive changes in patients with Alzheimer's disease pathology. Twenty-six patients (n = 12 with clinically probable Alzheimer's dementia and n = 14 with amyloid-positive mild cognitive impairment) and 29 healthy control subjects underwent baseline assessment with 18F-AV-1451 PET, 11C-PK11195 PET, and structural MRI. Cognition was examined annually over the subsequent 3 years using the revised Addenbrooke's Cognitive Examination. Regional grey matter volumes, and regional binding of 18F-AV-1451 and 11C-PK11195 were derived from 15 temporo-parietal regions characteristically affected by Alzheimer's disease pathology. A principal component analysis was used on each imaging modality separately, to identify the main spatial distributions of pathology. A latent growth curve model was applied across the whole sample on longitudinal cognitive scores to estimate the rate of annual decline in each participant. We regressed the individuals' estimated rate of cognitive decline on the neuroimaging components and examined univariable predictive models with single-modality predictors, and a multi-modality predictive model, to identify the independent and combined prognostic value of the different neuroimaging markers. Principal component analysis identified a single component for the grey matter atrophy, while two components were found for each PET ligand: one weighted to the anterior temporal lobe, and another weighted to posterior temporo-parietal regions. Across the whole-sample, the single-modality models indicated significant correlations between the rate of cognitive decline and the first component of each imaging modality. In patients, both stepwise backward elimination and Bayesian model selection revealed an optimal predictive model that included both components of 18F-AV-1451 and the first (i.e. anterior temporal) component for 11C-PK11195. However, the MRI-derived atrophy component and demographic variables were excluded from the optimal predictive model of cognitive decline. We conclude that temporo-parietal tau pathology and anterior temporal neuroinflammation predict cognitive decline in patients with symptomatic Alzheimer's disease pathology. This indicates the added value of PET biomarkers in predicting cognitive decline in Alzheimer's disease, over and above MRI measures of brain atrophy and demographic data. Our findings also support the strategy for targeting tau and neuroinflammation in disease-modifying therapy against Alzheimer's disease.
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