Modelling the impact of lockdown-easing measures on cumulative COVID-19 cases and deaths in England.

OBJECTIVES: To 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. DESIGN: We 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. SETTING: England. PARTICIPANTS: Publicly available national incident death data for COVID-19 were examined. PRIMARY OUTCOME: Excess 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. RESULTS: Our 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. CONCLUSIONS: When 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

Sugar addiction: the state of the science.

PURPOSE: As obesity rates continue to climb, the notion that overconsumption reflects an underlying 'food addiction' (FA) has become increasingly influential. An increasingly popular theory is that sugar acts as an addictive agent, eliciting neurobiological changes similar to those seen in drug addiction. In this paper, we review the evidence in support of sugar addiction. METHODS: We reviewed the literature on food and sugar addiction and considered the evidence suggesting the addictiveness of highly processed foods, particularly those with high sugar content. We then examined the addictive potential of sugar by contrasting evidence from the animal and human neuroscience literature on drug and sugar addiction. RESULTS: We find little evidence to support sugar addiction in humans, and findings from the animal literature suggest that addiction-like behaviours, such as bingeing, occur only in the context of intermittent access to sugar. These behaviours likely arise from intermittent access to sweet tasting or highly palatable foods, not the neurochemical effects of sugar. CONCLUSION: Given the lack of evidence supporting it, we argue against a premature incorporation of sugar addiction into the scientific literature and public policy recommendations.Wellcome Trust (Senior Fellowship award)This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00394-016-1229-

Birth weight, family history of diabetes and diabetes onset in schizophrenia.

INTRODUCTION:The prevalence of diabetes in schizophrenia is twice that in the general population, but there are few reliable predictors of which individuals will develop glucose dysregulation. OBJECTIVE:To test if abnormal birth weight (either too low or too high) and parental diabetes, both variables that can be ascertained in the clinic, can predict diabetes onset in patients with schizophrenia. RESEARCH DESIGN AND METHODS:Electronic records of a cohort of 190 clozapine-treated patients (37% treated for more than 20 years) and Cox regression survival analysis (with any type of glucose dysregulation as the event) to account for differences in length of treatment before the event and age at clozapine treatment initiation. RESULTS:Age at clozapine initiation (Exp(B)=1.098; p<0.001), family history of diabetes (Exp(B)=2.299; p=0.049) and birth weight2 (Exp(B)=0.999; p=0.013) were significant predictors of glucose dysregulation onset, while gender was not (Exp(B)=0.1.350; p=0.517). Among individuals with 10 years of follow-up, 80% of those with both abnormal birth weight and a family history of diabetes developed diabetes compared with 56% with only abnormal birth weight, 40% with only a family history of diabetes and 20% in those with neither. CONCLUSIONS:Since 48% of cases had at least one risk factor and 6% had both risk factors, there is a substantial proportion of patients for whom preventive strategies could be implemented

Dopamine modulates the neural representation of subjective value of food in hungry subjects.

Although there is a rich literature on the role of dopamine in value learning, much less is known about its role in using established value estimations to shape decision-making. Here we investigated the effect of dopaminergic modulation on value-based decision-making for food items in fasted healthy human participants. The Becker-deGroot-Marschak auction, which assesses subjective value, was examined in conjunction with pharmacological fMRI using a dopaminergic agonist and an antagonist. We found that dopamine enhanced the neural response to value in the inferior parietal gyrus/intraparietal sulcus, and that this effect predominated toward the end of the valuation process when an action was needed to record the value. Our results suggest that dopamine is involved in acting upon the decision, providing additional insight to the mechanisms underlying impaired decision-making in healthy individuals and clinical populations with reduced dopamine levels.This is the author's accepted manuscript. The final version is available from the Society for Neuroscience in the Journal of Neuroscience at http://www.jneurosci.org/content/34/50/16856.abstract

Association of birth weight and the development of antipsychotic induced adiposity in individuals with treatment resistant schizophrenia.

Though weight gain is a common side effect of antipsychotic treatment, there are no useful predictors of which patients are likely to be affected and to what degree. It has been shown that exposure to adverse conditions during intra-uterine life confers a vulnerability to the development of later life metabolic complications and low birth weight for gestational age has been shown to be a robust marker of such prenatal adversity. We hypothesised that patients with schizophrenia with a lower birth weight will have increased vulnerability to the weight inducing effects of antipsychotic treatment. The relationship between birth weight and total and central adiposity, measured as body mass index (BMI) and waist-to-hip ratio (WHR) respectively, was examined in three groups: drug naïve first episode of psychosis (FEP) patients (n=41), treatment resistant schizophrenia (TRS) patients (n=42) and matched healthy volunteers (n=72). All analyses were controlled for age, gender and duration of treatment exposure. We found that a lower birth weight was associated with higher BMI and WHR only in TRS patients but not in FEP or controls, suggesting that prenatal adversity, as indicated by the surrogate marker of a lower birth weight, confers an increased vulnerability to clozapine induced weight gain.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.euroneuro.2016.03.00

Brain networks underlying vulnerability and resilience to drug addiction.

Regular drug use can lead to addiction, but not everyone who takes drugs makes this transition. How exactly drugs of abuse interact with individual vulnerability is not fully understood, nor is it clear how individuals defy the risks associated with drugs or addiction vulnerability. We used resting-state functional MRI (fMRI) in 162 participants to characterize risk- and resilience-related changes in corticostriatal functional circuits in individuals exposed to stimulant drugs both with and without clinically diagnosed drug addiction, siblings of addicted individuals, and control volunteers. The likelihood of developing addiction, whether due to familial vulnerability or drug use, was associated with significant hypoconnectivity in orbitofrontal and ventromedial prefrontal cortical-striatal circuits-pathways critically implicated in goal-directed decision-making. By contrast, resilience against a diagnosis of substance use disorder was associated with hyperconnectivity in two networks involving 1) the lateral prefrontal cortex and medial caudate nucleus and 2) the supplementary motor area, superior medial frontal cortex, and putamen-brain circuits respectively implicated in top-down inhibitory control and the regulation of habits. These findings point toward a predisposing vulnerability in the causation of addiction, related to impaired goal-directed actions, as well as countervailing resilience systems implicated in behavioral regulation, and may inform novel strategies for therapeutic and preventative interventions.This research was funded by a Medical Research Council (MRC) grant (G0701497), financially supported by the NIHR Cambridge Biomedical Research Centre, and conducted within the Behavioural and Clinical Neuroscience Institute (BCNI). CM was supported by the Wellcome Trust grant to KDE (105602/Z/14/Z) and the NIHR Cambridge Biomedical Research Centre. JS was partly supported by the NIHR CLAHRC East of England and by the Charles University PRVOUK programme P38. TWR is a recipient of a Wellcome Trust Senior Investigator Award (104631/z/14/z). TWR discloses consultancy with Cambridge Cognition, Greenfield Bioventures and Unilever; he receives royalties for CANTAB from Cambridge Cognition, research grants from Shionogi and GlaxoSmithKline and editorial honoraria from Springer Verlag and Elsevier. ETB is a National Institute for Health Research Senior Investigator

The role of oxytocin in the facial mimicry of affiliative vs. non-affiliative emotions.

The present paper builds upon a growing body of work documenting oxytocin's role in social functioning, to test whether this hormone facilitates spontaneous mimicry of others' emotional expressions. In a double-blind, randomized trial, adult Caucasian males (n = 145) received a nasal spray of either oxytocin or placebo before completing a facial mimicry task. Facial expressions were coded using automated face analysis. Oxytocin increased mimicry of facial features of sadness (lips and chin, but not areas around the eyes), an affiliative reaction that facilitates social bonding. Oxytocin also increased mimicry of happiness, but only for individuals who expressed low levels of happiness in response to neutral faces. Overall, participants did not reliably mimic expressions of fear and anger, echoing recent theoretical accounts of emotional mimicry as dependent on the social context. In sum, our findings suggest that oxytocin facilitates emotional mimicry in ways that are conducive to affiliation, pointing to a possible pathway through which oxytocin promotes social bonding

The Presence of Real Food Usurps Hypothetical Health Value Judgment in Overweight People.

To develop more ecologically valid models of the neurobiology of obesity, it is critical to determine how the neural processes involved in food-related decision-making translate into real-world eating behaviors. We examined the relationship between goal-directed valuations of food images in the MRI scanner and food consumption at a subsequent ad libitum buffet meal. We observed that 23 lean and 40 overweight human participants showed similar patterns of value-based neural responses to health and taste attributes of foods. In both groups, these value-based responses in the ventromedial PFC were predictive of subsequent consumption at the buffet. However, overweight participants consumed a greater proportion of unhealthy foods. This was not predicted by in-scanner choices or neural response. Moreover, in overweight participants alone, impulsivity scores predicted greater consumption of unhealthy foods. Overall, our findings suggest that, while the hypothetical valuation of the health of foods is predictive of eating behavior in both lean and overweight people, it is only the real-world food choices that clearly distinguish them.This study was supported by the Bernard Wolfe Health Neuroscience Fund (HZ, PCF), the Wellcome Trust (NM, HZ, PCF), the Medical Research Council grant U105960389 (ALA, KMD, SAJ) and the Department of Health Policy Research Program (Policy Research Unit in Behaviour and Health [PR-UN-0409-10109]) (TMM, SEF).This is the final version of the article. It first appeared from the Society for Neuroscience via https://doi.org/10.1523/ENEURO.0025-16.201