An increasingly influential perspective conceptualizes both obesity and overeating as a food addiction accompanied by corresponding brain changes. Because there are far-reaching implications for ...clinical practice and social policy if it becomes widely accepted, a critical evaluation of this model is important. We examine the current evidence for the link between addiction and obesity, identifying several fundamental shortcomings in the model, as well as weaknesses and inconsistencies in the empirical support for it from human neuroscientific research.
The infection fatality rate of COVID-19 is several-fold higher than that of seasonal influenza,2 and infection can lead to persisting illness, including in young, previously healthy people (ie, long ...COVID).3 It is unclear how long protective immunity lasts,4 and, like other seasonal coronaviruses, SARS-CoV-2 is capable of re-infecting people who have already had the disease, but the frequency of re-infection is unknown.5 Transmission of the virus can be mitigated through physical distancing, use of face coverings, hand and respiratory hygiene, and by avoiding crowds and poorly ventilated spaces. PK reports personal fees from Kymab, outside the submitted work; PK also has a patent ‘Monoclonal antibodies to treat and prevent infection by SARS-CoV-2 (Kymab)’ pending and is a scientific advisor to the Serology Working Group (Public Heath England), Testing Advisory Group (Department of Health and Social Care) and the Vaccines Task force (Department for Business, Energy and Industrial Strategy). CS reports grants from BMS, Ono-Pharmaceuticals, and Archer Dx (collaboration in minimal residual disease sequencing technologies), outside the submitted work; personal fees from Bristol Myers Squibb, Roche-Ventana, Ono Pharmaceutical, GlaxoSmithKline, Novartis, Celgene, Illumina, MSD, Sarah Canon Research Institute, Genentech, Bicycle Therapeutics, and Medicixi, outside the submitted work; personal fees and stock options from GRAIL and Achilles Therapeutics, outside the submitted work; and stock options from Epic Biosciences and Apogen Biotechnologies, outside the submitted work.
While returning to school as soon as possible is imperative for the education, social development, and mental and physical welfare of children, not enough has been done to make schools safer for ...students and staff.1 Without additional mitigations, increases in transmission are likely, this time with more infectious and possibly more virulent variants, resulting in further lockdowns, school closures, and absenteeism. Yet the evidence cited for these arguments has serious limitations.4,5 Primary and secondary school closures have been associated with substantial reductions over time in the effective reproduction number (Rt) across many countries (including England) and time periods.6,7 In contrast, data from the Office for National Statistics' (ONS) 2020 COVID-19 Infection Survey show that the prevalence of infection among children aged 2–10 years (2%) and 11–16 years (3%) rose above the prevalence for all other age groups before the 2020 Christmas break (appendix p 4). Multi-layered mitigations can substantially reduce the risk of transmission within schools and into households.13 In the panel we summarise a set of recommendations that are in line with guidelines from the US Centers for Disease Control and Prevention (CDC) and practised in many countries to reduce the risk of transmission in schools and mitigate the impact of COVID-19 on children and families.
Anorexia nervosa (AN) and bulimia nervosa (BN) are associated with altered brain structure and function, as well as increased habitual behavior. This neurobehavioral profile may implicate ...neurochemical changes in the pathogenesis of these illnesses. Altered glutamate, myo-inositol and N-acetyl aspartate (NAA) concentrations are reported in restrictive AN, yet whether these extend to binge-eating disorders, or relate to habitual traits in affected individuals, remains unknown. We therefore used single-voxel proton magnetic resonance spectroscopy to measure glutamate, myo-inositol, and NAA in the right inferior lateral prefrontal cortex and the right occipital cortex of 85 women n = 22 AN (binge-eating/purging subtype; AN-BP), n = 33 BN, n = 30 controls. To index habitual behavior, participants performed an instrumental learning task and completed the Creature of Habit Scale. Women with AN-BP, but not BN, had reduced myo-inositol and NAA concentrations relative to controls in both regions. Although patient groups had intact instrumental learning task performance, both groups reported increased routine behaviors compared to controls, and automaticity was related to reduced prefrontal glutamate and NAA participants with AN-BP. Our findings extend previous reports of reduced myo-inositol and NAA levels in restrictive AN to AN-BP, which may reflect disrupted axonal-glial signaling. Although we found inconsistent support for increased habitual behavior in AN-BP and BN, we identified preliminary associations between prefrontal metabolites and automaticity in AN-BP. These results provide further evidence of unique neurobiological profiles across binge-eating disorders.
Learning to optimally predict rewards requires agents to account for fluctuations in reward value. Recent work suggests that individuals can efficiently learn about variable rewards through ...adaptation of the learning rate, and coding of prediction errors relative to reward variability. Such adaptive coding has been linked to midbrain dopamine neurons in nonhuman primates, and evidence in support for a similar role of the dopaminergic system in humans is emerging from fMRI data. Here, we sought to investigate the effect of dopaminergic perturbations on adaptive prediction error coding in humans, using a between-subject, placebo-controlled pharmacological fMRI study with a dopaminergic agonist (bromocriptine) and antagonist (sulpiride). Participants performed a previously validated task in which they predicted the magnitude of upcoming rewards drawn from distributions with varying SDs. After each prediction, participants received a reward, yielding trial-by-trial prediction errors. Under placebo, we replicated previous observations of adaptive coding in the midbrain and ventral striatum. Treatment with sulpiride attenuated adaptive coding in both midbrain and ventral striatum, and was associated with a decrease in performance, whereas bromocriptine did not have a significant impact. Although we observed no differential effect of SD on performance between the groups, computational modeling suggested decreased behavioral adaptation in the sulpiride group. These results suggest that normal dopaminergic function is critical for adaptive prediction error coding, a key property of the brain thought to facilitate efficient learning in variable environments. Crucially, these results also offer potential insights for understanding the impact of disrupted dopamine function in mental illness.
To choose optimally, we have to learn what to expect. Humans dampen learning when there is a great deal of variability in reward outcome, and two brain regions that are modulated by the brain chemical dopamine are sensitive to reward variability. Here, we aimed to directly relate dopamine to learning about variable rewards, and the neural encoding of associated teaching signals. We perturbed dopamine in healthy individuals using dopaminergic medication and asked them to predict variable rewards while we made brain scans. Dopamine perturbations impaired learning and the neural encoding of reward variability, thus establishing a direct link between dopamine and adaptation to reward variability. These results aid our understanding of clinical conditions associated with dopaminergic dysfunction, such as psychosis.
ObjectivesTo assess the potential impacts of successive lockdown-easing measures in England, at a point in the COVID-19 pandemic when community transmission levels were relatively high.DesignWe ...developed a Bayesian model to infer incident cases and reproduction number (R) in England, from incident death data. We then used this to forecast excess cases and deaths in multiple plausible scenarios in which R increases at one or more time points.SettingEngland.ParticipantsPublicly available national incident death data for COVID-19 were examined.Primary outcomeExcess cumulative cases and deaths forecast at 90 days, in simulated scenarios of plausible increases in R after successive easing of lockdown in England, compared with a baseline scenario where R remained constant.ResultsOur model inferred an R of 0.75 on 13 May when England first started easing lockdown. In the most conservative scenario modelled where R increased to 0.80 as lockdown was eased further on 1 June and then remained constant, the model predicted an excess 257 (95% CI 108 to 492) deaths and 26 447 (95% CI 11 105 to 50 549) cumulative cases over 90 days. In the scenario with maximal increases in R (but staying ≤1), the model predicts 3174 (95% CI 1334 to 6060) excess cumulative deaths and 421 310 (95% CI 177 012 to 804 811) cases. Observed data from the forecasting period aligned most closely to the scenario in which R increased to 0.85 on 1 June, and 0.9 on 4 July.ConclusionsWhen levels of transmission are high, even small changes in R with easing of lockdown can have significant impacts on expected cases and deaths, even if R remains ≤1. This will have a major impact on population health, tracing systems and healthcare services in England. Following an elimination strategy rather than one of maintenance of R ≤1 would substantially mitigate the impact of the COVID-19 epidemic within England.
Purpose
It is unclear how hospitals are responding to the mental health needs of the population in England, against a backdrop of diminishing resources. We aimed to document patterns in hospital ...activity by psychiatric disorder and how these have changed over the last 22 years.
Methods
In this observational time series analysis, we used routinely collected data on all NHS hospitals in England from 1998/99 to 2019/20. Trends in hospital admissions and bed days for psychiatric disorders were smoothed using negative binomial regression models with year as the exposure and rates (per 1000 person-years) as the outcome. When linear trends were not appropriate, we fitted segmented negative binomial regression models with one change-point. We stratified by gender and age group children (0–14 years); adults (15 years +).
Results
Hospital admission rates and bed days for all psychiatric disorders decreased by 28.4 and 38.3%, respectively. Trends were not uniform across psychiatric disorders or age groups. Admission rates mainly decreased over time, except for anxiety and eating disorders which doubled over the 22-year period, significantly increasing by 2.9% (AAPC = 2.88; 95% CI: 2.61–3.16;
p
< 0.001) and 3.4% (AAPC = 3.44; 95% CI: 3.04–3.85;
p
< 0.001) each year. Inpatient hospital activity among children showed more increasing and pronounced trends than adults, including an increase of 212.9% for depression, despite a 63.8% reduction for adults with depression during the same period.
Conclusion
In the last 22 years, there have been overall reductions in hospital activity for psychiatric disorders. However, some disorders showed pronounced increases, pointing to areas of growing need for inpatient psychiatric care, especially among children.
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.
There has been a resurgence of interest in the field of reward processing in schizophrenia in recent years, aided by insights from functional neuroimaging. We examine how disturbances in ...reward-related processes relate to the pathophysiology and symptomatology of this disorder.
Behavioural and functional neuroimaging studies in psychosis demonstrate impairments in the representation of reward value and in reward-related learning and a failure to motivate behaviour for incentives. These impairments are linked to abnormal mesocorticolimbic and mesostriatal function.
Abnormalities in reward processing offer insights into the symptomatology of schizophrenia and its underlying neurobiology. Further investigation is required into the specificity of these deficits to particular symptom expression and to what extent they are improved by antipsychotic treatment.
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