Imperial College London

ProfessorAnneLingford-Hughes

Faculty of MedicineDepartment of Brain Sciences

Chair in Addiction Biology
 
 
 
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Contact

 

+44 (0)20 7594 8682anne.lingford-hughes Website

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
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316 results found

MacKillop J, Agabio R, Feldstein Ewing SW, Heilig M, Kelly JF, Leggio L, Lingford-Hughes A, Palmer AA, Parry CD, Ray L, Rehm Jet al., 2022, Hazardous drinking and alcohol use disorders., Nat Rev Dis Primers, Vol: 8

Alcohol is one of the most widely consumed psychoactive drugs globally. Hazardous drinking, defined by quantity and frequency of consumption, is associated with acute and chronic morbidity. Alcohol use disorders (AUDs) are psychiatric syndromes characterized by impaired control over drinking and other symptoms. Contemporary aetiological perspectives on AUDs apply a biopsychosocial framework that emphasizes the interplay of genetics, neurobiology, psychology, and an individual's social and societal context. There is strong evidence that AUDs are genetically influenced, but with a complex polygenic architecture. Likewise, there is robust evidence for environmental influences, such as adverse childhood exposures and maladaptive developmental trajectories. Well-established biological and psychological determinants of AUDs include neuroadaptive changes following persistent use, differences in brain structure and function, and motivational determinants including overvaluation of alcohol reinforcement, acute effects of environmental triggers and stress, elevations in multiple facets of impulsivity, and lack of alternative reinforcers. Social factors include bidirectional roles of social networks and sociocultural influences, such as public health control strategies and social determinants of health. An array of evidence-based approaches for reducing alcohol harms are available, including screening, pharmacotherapies, psychological interventions and policy strategies, but are substantially underused. Priorities for the field include translating advances in basic biobehavioural research into novel clinical applications and, in turn, promoting widespread implementation of evidence-based clinical approaches in practice and health-care systems.

Journal article

Vamvakopoulou IA, Fonville L, Hayes A, McGonigle J, Elliott R, Ersche KD, Flechais R, Murphy A, Orban C, Smith DG, Suckling J, Taylor EM, Deakin B, Robbins TW, Nutt D, Lingford-Hughes A, Paterson Let al., 2022, Selective D3 receptor antagonism modulates neural response during negative emotional processing in substance dependence, Frontiers in Psychiatry, Vol: 13, Pages: 1-20, ISSN: 1664-0640

Introduction: Negative affective states contribute to the chronic-relapsingnature of addiction. Mesolimbic dopamine D3 receptors are well placed to modulate emotion and are dysregulated in substance dependence. Selective antagonists might restore dopaminergic hypofunction, thus representing a potential treatment target. We investigated the effects of selective D3 antagonist, GSK598809, on the neural response to negativeemotional processing in substance dependent individuals and healthy controls.Methodology: Functional MRI BOLD response was assessed during an evocative image task, 2h following acute administration of GSK598809 (60mg) or placebo in a multi-site, double-blind, pseudo-randomised, cross-over design. Abstinent drug dependent individuals (DD, n=36) comprising alcohol-only (AO, n=19) and cocaine-alcohol polydrug (PD, n=17) groups, and matched controls (n=32) were presented with aversive and neutral images in a block design (contrast of interest: aversive>neutral). Whole-brain mixed-effects and a priori ROI analyses tested for group and drug effects, with identical models exploring subgroup effects.Results: No group differences in task-related BOLD signal were identified between DD and controls. However, subgroup analysis revealed greater amygdala/insular BOLD signal in PD compared with AO groups. Following drug administration, GSK598809 increased BOLD response across HC and DD groups in thalamus, caudate, putamen, and pallidum, andreduced BOLD response in insular and opercular cortices relative to placebo. Multivariate analyses in a priori ROIs revealed differential effects of D3 antagonism according to subgroup in substantia nigra; GSK598809 increased BOLD response in AO and decreased response in PD groups.Conclusion: Acute GSK598809 modulates the BOLD response to aversive image processing, providing evidence that D3 antagonism may impact emotional regulation. Enhanced BOLD response within D3-rich mesolimbic regions is consistent with its pharmacology a

Journal article

Paterson L, Lingford-Hughes A, Cro S, Phillips R, Mozgunov P, Paterson S, Nahar L, Barker D, Smith Cet al., 2022, FORWARDS-1; An adaptive, single-blind, placebo-controlled ascending dose study of acute baclofen on safety parameters in opioid dependence during methadone-maintenance treatment; a pharmacokinetic-pharmacodynamic study, Trials, Vol: 23, ISSN: 1745-6215

Background:Treatment of opiate addiction with opiate substitution treatment (e.g. methadone) is beneficial. However, some individuals desire or would benefit from abstinence but there are limited options to attenuate problems with opiate withdrawal. Preclinical and preliminary clinical evidence suggests that the GABA-B agonist, baclofen, has the desired properties to facilitate opiate detoxification and prevent relapse. This study aims to understand whether there are any safety issues in administering baclofen to opioid-dependent individuals receiving methadone.Methods:Opiate-dependent individuals (DSM-5 severe opioid use disorder) maintained on methadone will be recruited from addiction services in northwest London (NHS and third sector providers). Participants will be medically healthy with no severe chronic obstructive pulmonary disease or type 2 respiratory failure, no current dependence on other substances (excluding nicotine), no current severe DSM-5 psychiatric disorders, and no contraindications for baclofen or 4800 IU vitamin D (placebo). Eligible participants will be randomised in a 3:1 ratio to receive baclofen or placebo in an adaptive, single-blind, ascending dose design. A Bayesian dose-escalation model will inform the baclofen dose (10, 30, 60, or 90 mg) based on the incidence of ‘dose-limiting toxicity’ (DLT) events and participant-specific methadone dose. A range of respiratory, cardiovascular, and sedative measures including the National Early Warning Score (NEWS2) and Glasgow Coma Scale will determine DLT. On the experimental day, participants will consume their usual daily dose of methadone followed by an acute dose of baclofen or placebo (vitamin D3) ~ 1 h later. Measures including oxygen saturation, transcutaneous CO2, respiratory rate, QTc interval, subjective effects (sedation, drug liking, craving), plasma levels (baclofen, methadone), and adverse events will be obtained using validated questionnaires and examinations periodicall

Journal article

Goldstone AP, Ling YY, Nestor LJ, Pannekoek JN, Ertl N, Herlinger K, Al-Lababidi M, Vanelli F, Chhibbar P, Patel M, Guerrero E, Canizares S, Akavarapu S, Munafo MR, Lingford-Hughes AR, Nutt DJet al., 2022, Effect of acute desacyl ghrelin administration on eating and addictive behaviours: The gut hormone in addiction study, Publisher: WILEY, Pages: 72-73, ISSN: 0145-6008

Conference paper

Agunbiade K, Fonville L, McGonigle J, Elliott R, Ersche KD, Flechais R, Orban C, Murphy A, Smith DG, Suckling J, Taylor EM, Deakin B, Robbins TW, Nutt DJ, Lingford-Hughes AR, Paterson LMet al., 2022, Alterations in white matter microstructure in alcohol and alcohol-polydrug dependence: Associations with lifetime alcohol and nicotine exposure, ADDICTION BIOLOGY, Vol: 27, ISSN: 1355-6215

Journal article

Venkataraman A, Mansur A, Rizzo G, Bishop C, Lewis Y, Kocagoncu E, Lingford-Hughes A, Huiban M, Passchier J, Rowe J, Tsukada H, Brooks D, Martarello L, Comley R, Chen L, Schwarz A, Hargreaves R, Gunn R, Rabiner E, Matthews Pet al., 2022, Widespread cell stress and mitochondrial dysfunction occur in patients with early Alzheimer’s Disease, Science Translational Medicine, Vol: 14, Pages: 1-11, ISSN: 1946-6234

Cell stress and impaired oxidative phosphorylation are central to mechanisms of synaptic loss and neurodegeneration in the cellular pathology of Alzheimer’s disease (AD). In this study, we quantified the in vivo expression of the endoplasmic reticulum stress marker, sigma 1 receptor (S1R), using [11C]SA4503 PET, the mitochondrial complex I (MC1) with [18F]BCPP-EF and the pre-synaptic vesicular protein SV2A with [11C]UCB-J in 12 patients with early AD and in 16 cognitively normal controls. We integrated these molecular measures with assessments of regional brain volumes and cerebral blood flow (CBF) measured with magnetic resonance imaging (MRI) arterial spin labelling. Eight patients with AD were followed longitudinally to estimate the rate of change of the physiological and structural pathology markers with disease progression. The patients showed widespread increases in S1R (≤ 27%) and regional reduction in MC1 (≥ -28%) and SV2A (≥ -25%) radioligand binding, brain volume (≥ -23%), and CBF (≥ -26%). [18F]BCPP-EF PET MC1 binding (≥ -12%) and brain volumes (≥ -5%) showed progressive reductions over 12-18 months, suggesting that they both could be used as pharmacodynamic indicators in early-stage therapeutics trials. Associations of reduced MC1 and SV2A and increased S1R radioligand binding with reduced cognitive performance in AD, although exploratory, suggested a loss of metabolic functional reserve with disease. Our study thus provides in vivo evidence for widespread, clinically relevant cellular stress and bioenergetic abnormalities in early AD.

Journal article

Notley C, Houghton B, Maskrey V, Holland R, Lingford-Hughes A, Punukollu B, Duka T, Kouimtsidis Cet al., 2022, An exploration of identity change in post-detoxification alcohol dependent individuals, Drugs, Habits and Social Policy, Vol: 23, Pages: 48-61, ISSN: 2752-6739

Purpose: Dependent alcohol use is a severe addictive disorder with significant enduring consequences for health and social functioning. This study aims to inductively explore the process of identity change for alcohol dependent people progressing through a “pre-habilitation” intervention, alcohol detoxification and post-detoxification recovery support. Design/methodology/approach: Qualitative study as a part of a process evaluation situated within a UK feasibility trial of a group-based intervention in preparation for structured alcohol detoxification. Semi-structured qualitative interviews (face-to-face or telephone) collected self-reported data on experiences of treatment provision as part of the feasibility trial. Thematic analysis of transcripts and iterative categorisation of identity-related themes and concepts was conducted with verification of analysis undertaken by a second coder. Findings: Identity change was revealed in participant narratives around the meta themes of external (social-identity) and internal (self-identity) concepts. External influences impacting social identity were key, having influenced initiation into alcohol use, influencing acceptance of the stigmatised “alcoholic” label and then being central to the treatment journey. Internal influences on self-identity also impacted on the process of identity change. In recovery, there was hope in discovering a new “normal” identity or rediscovering normality. Originality/value: Analysis demonstrates that moving from regular alcohol use to problematic use is a journey of identity change that is influenced at the macro (cultural), meso (group) and micro (relational) social levels. Throughout the treatment journey, social influences in gaining a new non-drinker identity are key. Findings suggest a need for long-term support through treatment and community-based groups specifically to foster positive identity change that may not have been addressed previously.

Journal article

Evans RA, Leavy OC, Richardson M, Elneima O, McCauley HJC, Shikotra A, Singapuri A, Sereno M, Saunders RM, Harris VC, Houchen-Wolloff L, Aul R, Beirne P, Bolton CE, Brown JS, Choudhury G, Diar-Bakerly N, Easom N, Echevarria C, Fuld J, Hart N, Hurst J, Jones MG, Parekh D, Pfeffer P, Rahman NM, Rowland-Jones SL, Shah AM, Wootton DG, Chalder T, Davies MJ, De Soyza A, Geddes JR, Greenhalf W, Greening NJ, Heaney LG, Heller S, Howard LS, Jacob J, Jenkins RG, Lord JM, Man WD-C, McCann GP, Neubauer S, Openshaw PJM, Porter JC, Rowland MJ, Scott JT, Semple MG, Singh SJ, Thomas DC, Toshner M, Lewis KE, Thwaites RS, Briggs A, Docherty AB, Kerr S, Lone NI, Quint J, Sheikh A, Thorpe M, Zheng B, Chalmers JD, Ho LP, Horsley A, Marks M, Poinasamy K, Raman B, Harrison EM, Wain LV, Brightling CE, Abel K, Adamali H, Adeloye D, Adeyemi O, Adrego R, Aguilar Jimenez LA, Ahmad S, Ahmad Haider N, Ahmed R, Ahwireng N, Ainsworth M, Al-Sheklly B, Alamoudi A, Ali M, Aljaroof M, All AM, Allan L, Allen RJ, Allerton L, Allsop L, Almeida P, Altmann D, Alvarez Corral M, Amoils S, Anderson D, Antoniades C, Arbane G, Arias A, Armour C, Armstrong L, Armstrong N, Arnold D, Arnold H, Ashish A, Ashworth A, Ashworth M, Aslani S, Assefa-Kebede H, Atkin C, Atkin P, Aung H, Austin L, Avram C, Ayoub A, Babores M, Baggott R, Bagshaw J, Baguley D, Bailey L, Baillie JK, Bain S, Bakali M, Bakau M, Baldry E, Baldwin D, Ballard C, Banerjee A, Bang B, Barker RE, Barman L, Barratt S, Barrett F, Basire D, Basu N, Bates M, Bates A, Batterham R, Baxendale H, Bayes H, Beadsworth M, Beckett P, Beggs M, Begum M, Bell D, Bell R, Bennett K, Beranova E, Bermperi A, Berridge A, Berry C, Betts S, Bevan E, Bhui K, Bingham M, Birchall K, Bishop L, Bisnauthsing K, Blaikely J, Bloss A, Bolger A, Bonnington J, Botkai A, Bourne C, Bourne M, Bramham K, Brear L, Breen G, Breeze J, Bright E, Brill S, Brindle K, Broad L, Broadley A, Brookes C, Broome M, Brown A, Brown A, Brown J, Brown J, Brown M, Brown M, Brown V, Brugha T, Brunskill Net al., 2022, Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study, The Lancet Respiratory Medicine, Vol: 10, Pages: 761-775, ISSN: 2213-2600

BackgroundNo effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge.MethodsThe Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing.Findings2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7–9). The proportion of patients reporting full recovery was unchanged between 5 months (501 [25·5%] of 1965) and 1 year (232 [28·9%] of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 [95% CI 0·46–0·99]), obes

Journal article

Hayes A, McGonigle J, Elliott R, Ersche K, Flechais R, Orban C, Murphy A, Smith D, Suckling J, Taylor E, Deakin JF, Robbins T, Nutt D, Lingford-Hughes A, Paterson Let al., 2022, The Relationship Between Reward and Impulsivity in Substance Dependence: An fMRI Study, Publisher: ELSEVIER SCIENCE INC, Pages: S103-S103, ISSN: 0006-3223

Conference paper

Ostinelli EG, Smith K, Zangani C, Ostacher MJ, Lingford-Hughes AR, Hong JSW, Macdonald O, Cipriani Aet al., 2022, COVID-19 and substance use disorders: a review of international guidelines for frontline healthcare workers of addiction services, BMC PSYCHIATRY, Vol: 22

Journal article

Dhital R, Coleman R, Day E, Drummond C, Lingford-Hughes A, Marsden J, Phillips T, Sinclair J, Strang J, Weinman J, Whittlesea C, Widyaratna K, Donoghue Ket al., 2022, Service Users' Views and Experiences of Alcohol Relapse Prevention Treatment and Adherence: New Role for Pharmacists? (Mar, 10.1093/alcalc/agac011, 2022), ALCOHOL AND ALCOHOLISM, Vol: 57, Pages: 642-642, ISSN: 0735-0414

Journal article

Dhital R, Coleman R, Day E, Drummond C, Lingford-Hughes A, Marsden J, Phillips T, Sinclair J, Strang J, Weinman J, Whittlesea C, Widyaratna K, Donoghue Ket al., 2022, Service Users' Views and Experiences of Alcohol Relapse Prevention Treatment and Adherence: New Role for Pharmacists?, ALCOHOL AND ALCOHOLISM, Vol: 57, Pages: 602-608, ISSN: 0735-0414

Journal article

Mozgunov P, Cro S, Lingford-Hughes A, Paterson LM, Jaki Tet al., 2022, A dose-finding design for dual-agent trials with patient-specific doses for one agent with application to an opiate detoxification trial, Pharmaceutical Statistics: the journal of applied statistics in the pharmaceutical industry, Vol: 21, Pages: 476-495, ISSN: 1539-1604

There is a growing interest in early phase dose-finding clinical trials studying combinations of several treatments. While the majority of dose finding designs for such setting were proposed for oncology trials, the corresponding designs are also essential in other therapeutic areas. Furthermore, there is increased recognition of recommending the patient-specific doses/combinations, rather than a single target one that would be recommended to all patients in later phases regardless of their characteristics. In this paper, we propose a dose-finding design for a dual-agent combination trial motivated by an opiate detoxification trial. The distinguishing feature of the trial is that the (continuous) dose of one compound is defined externally by the clinicians and is individual for every patient. The objective of the trial is to define the dosing function that for each patient would recommend the optimal dosage of the second compound. Via a simulation study, we have found that the proposed design results in high accuracy of individual dose recommendation and is robust to the model misspecification and assumptions on the distribution of externally defined doses.

Journal article

Sparasci O, Bhui K, Biswas A, Chamberlain S, Dubicka B, Dudas R, Farooq S, Ford T, Husain N, Jones I, Killaspy H, Lee W, Lingford-Hughes A, Mulholland C, Rubinsztein J, Shankar R, Sharma A, Sinclair L, Stone J, Young Aet al., 2022, Impact of COVID-19 on mental health research: is this the breaking point?, BRITISH JOURNAL OF PSYCHIATRY, ISSN: 0007-1250

Journal article

Grabski M, McAndrew A, Lawn W, Marsh B, Raymen L, Stevens T, Hardy L, Warren F, Bloomfield M, Borissova A, Maschauer E, Broomby R, Price R, Coathup R, Gilhooly D, Palmer E, Gordon-Williams R, Hill R, Harris J, Mollaahmetoglu OM, Curran HV, Brandner B, Lingford-Hughes A, Morgan CJAet al., 2022, Adjunctive Ketamine With Relapse Prevention-Based Psychological Therapy in the Treatment of Alcohol Use Disorder, AMERICAN JOURNAL OF PSYCHIATRY, Vol: 179, Pages: 152-162, ISSN: 0002-953X

Journal article

Venkataraman AV, Bai W, Whittington A, Myers JF, Rabiner EA, Lingford-Hughes A, Matthews PMet al., 2021, Boosting the diagnostic power of amyloid-β PET using a data-driven spatially informed classifier for decision support, Alzheimer's Research and Therapy, Vol: 13, Pages: 1-12, ISSN: 1758-9193

BackgroundAmyloid-β (Aβ) PET has emerged as clinically useful for more accurate diagnosis of patients with cognitive decline. Aβ deposition is a necessary cause or response to the cellular pathology of Alzheimer’s disease (AD). Usual clinical and research interpretation of amyloid PET does not fully utilise all information regarding the spatial distribution of signal. We present a data-driven, spatially informed classifier to boost the diagnostic power of amyloid PET in AD.MethodsVoxel-wise k-means clustering of amyloid-positive voxels was performed; clusters were mapped to brain anatomy and tested for their associations by diagnostic category and disease severity with 758 amyloid PET scans from volunteers in the AD continuum from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). A machine learning approach based on this spatially constrained model using an optimised quadratic support vector machine was developed for automatic classification of scans for AD vs non-AD pathology.ResultsThis classifier boosted the accuracy of classification of AD scans to 81% using the amyloid PET alone with an area under the curve (AUC) of 0.91 compared to other spatial methods. This increased sensitivity to detect AD by 15% and the AUC by 9% compared to the use of a composite region of interest SUVr.ConclusionsThe diagnostic classification accuracy of amyloid PET was improved using an automated data-driven spatial classifier. Our classifier highlights the importance of considering the spatial variation in Aβ PET signal for optimal interpretation of scans. The algorithm now is available to be evaluated prospectively as a tool for automated clinical decision support in research settings.

Journal article

Venkataraman A, Bishop C, Mansur A, Rizzo G, Lewis Y, Kocagoncu E, Lingford-Hughes A, Huiban M, Passchier J, Rowe JB, Tsukada H, Brooks DJ, Martarello L, Comley RA, Chen L, Hargreaves R, Schwarz AJ, Gunn RN, Rabiner E, Matthews PMet al., 2021, Imaging synaptic microstructure and synaptic loss in vivo in early Alzheimer’s Disease, Publisher: Cold Spring Harbor Laboratory

Background Synaptic loss and neurite dystrophy are early events in Alzheimer’s Disease (AD). We aimed to characterise early synaptic microstructural changes in vivo.Methods MRI neurite orientation dispersion and density imaging (NODDI) and diffusion tensor imaging (DTI) were used to image cortical microstructure in both sporadic, late onset, amyloid PET positive AD patients and healthy controls (total n = 28). We derived NODDI measures of grey matter extracellular free water (FISO), neurite density (NDI) and orientation dispersion (ODI), which provides an index of neurite branching and orientation, as well as more conventional DTI measures of fractional anisotropy (FA), mean/axial/radial diffusivity (MD, AD, RD, respectively). We also performed [11C]UCB-J PET, which provides a specific measure of the density of pre-synaptic vesicular protein SV2A. Both sets of measures were compared to regional brain volumes.Results The AD patients showed expected relative decreases in regional brain volumes (range, -6 to - 23%) and regional [11C]UCB-J densities (range, -2 to -25%). Differences between AD and controls were greatest in the hippocampus. NODDI microstructural measures showed greater FISO (range, +26 to +44%) in AD, with little difference in NDI (range, -1 to +7%) and mild focal changes in ODI (range, -4 to +3%). Regionally greater FISO and lower [11C]UCB-J binding were correlated across grey matter in patients (most strongly in the caudate, r2 = 0.37, p = 0.001). FISO and DTI RD were strongly positively associated, particularly in the hippocampus (r2 = 0.98, p < 7.4 × 10−9). After 12-18 months we found a 5% increase in FISO in the temporal lobe, but little change across all ROIs in NDI and ODI. An exploratory analysis showed higher parietal lobe FISO was associated with lower language scores in people with AD.Conclusions We interpreted the increased extracellular free water as a possible consequence of glial activation. The dynamic range of disease

Working paper

Herlinger K, Lingford-Hughes A, 2021, Addressing unmet needs in opiate dependence: supporting detoxification and advances in relapse prevention, BJPSYCH ADVANCES, Vol: 27, Pages: 362-372, ISSN: 2056-4678

Journal article

Nutt D, Hayes A, Fonville L, Zafar R, Palmer EOC, Paterson L, Lingford-Hughes Aet al., 2021, Alcohol and the Brain, NUTRIENTS, Vol: 13

Journal article

Evans RA, McAuley H, Harrison EM, Shikotra A, Singapuri A, Sereno M, Elneima O, Docherty AB, Lone NI, Leavy OC, Daines L, Baillie JK, Brown JS, Chalder T, De Soyza A, Diar Bakerly N, Easom N, Geddes JR, Greening NJ, Hart N, Heaney LG, Heller S, Howard L, Hurst JR, Jacob J, Jenkins RG, Jolley C, Kerr S, Kon OM, Lewis K, Lord JM, McCann GP, Neubauer S, Openshaw PJM, Parekh D, Pfeffer P, Rahman NM, Raman B, Richardson M, Rowland M, Semple MG, Shah AM, Singh SJ, Sheikh A, Thomas D, Toshner M, Chalmers JD, Ho L-P, Horsley A, Marks M, Poinasamy K, Wain LV, Brightling CE, PHOSP-COVID Collaborative Groupet al., 2021, Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study, The Lancet Respiratory Medicine, Vol: 9, Pages: 1275-1287, ISSN: 2213-2600

BACKGROUND: The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. METHODS: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9-6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40-59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health bur

Journal article

Palmer EOC, Trender W, Tyacke RJ, Hampshire A, Lingford-Hughes Aet al., 2021, Impact of COVID-19 restrictions on alcohol consumption behaviours, BJPsych Open, Vol: 7, Pages: 1-7, ISSN: 2056-4724

BackgroundWe aimed to evaluate how coronavirus (COVID-19) restrictions had altered individual's drinking behaviours, including consumption, hangover experiences, and motivations to drink, and changing levels of depression and anxiety.MethodWe conducted an online cross-sectional self-report survey. Whole group analysis compared pre- versus post-COVID restrictions. A correlation coefficient matrix evaluated the associations between all outcome scores. Self-report data was compared with Alcohol Use Disorders Identification Test (AUDIT) scores from the 2014 Adult Psychiatric Morbidity Survey. Multiple linear modelling (MLM) was calculated to identify factors associated with increasing AUDIT scores and post-restriction AUDIT scores.ResultsIn total, 346 individuals completed the survey, of which 336 reported drinking and were therefore analysed. After COVID-19 restrictions 23.2% of respondents reported an increased AUDIT score, and 60.1% a decreased score. AUDIT score change was positively correlated with change in depression (P < 0.01, r = 0.15), anxiety (P < 0.01, r = 0.15) and drinking to cope scores (P < 0.0001, r = 0.35). MLM revealed that higher AUDIT scores were associated with age, mental illness, lack of a garden, self-employed or furloughed individuals, a confirmed COVID-19 diagnosis and smoking status.ConclusionsCOVID-19 restrictions decreased alcohol consumption for the majority of individuals in this study. However, a small proportion increased their consumption; this related to drinking to cope and increased depression and anxiety.

Journal article

Venkataraman A, Mansur A, Rizzo G, Bishop C, Lewis Y, Kocagoncu E, Lingford-Hughes A, Huiban M, Passchier J, Rowe J, Tsukada H, Brooks DJ, Martarello L, Comley RA, Chen L, Schwarz AJ, Hargreaves R, Gunn R, Rabiner E, Matthews PMet al., 2021, Widespread cell stress and mitochondrial dysfunction in early Alzheimer’s Disease, Publisher: MedRxiv

Cell stress and impaired oxidative phosphorylation are central to mechanisms of synaptic loss and neurodegeneration in the cellular pathology of Alzheimer’s disease (AD). We quantified the in vivo density of the endoplasmic reticulum stress marker, the sigma 1 receptor (S1R) using [11C]SA4503 PET, as well as that of mitochondrial complex I (MC1) with [18F]BCPP-EF and the pre-synaptic vesicular protein SV2A with [11C]UCB-J in 12 patients with early AD and in 16 cognitively normal controls. We integrated these molecular measures with assessments of regional brain volumes and brain perfusion (CBF) measured with MRI arterial spin labelling. 8 AD patients were followed longitudinally to estimate rates of change with disease progression over 12-18 months. The AD patients showed widespread increases in S1R (≤ 27%) and regional decreases in MC1 (≥ -28%), SV2A (≥ -25%), brain volume (≥ -23%), and CBF (≥ -26%). [18F]BCPP-EF PET MC1 density (≥ -12%) and brain volumes (≥ -5%) were further reduced at follow up in brain regions consistent with the differences between AD patients and controls at baseline. Exploratory analyses showing associations of MC1, SV2A and S1R density with cognitive changes at baseline and longitudinally with AD, but not in controls, suggested a loss of metabolic functional reserve with disease. Our study thus provides novel in vivo evidence for widespread cellular stress and bioenergetic abnormalities in early AD and that they may be clinically meaningful.

Working paper

Herlinger K, Lingford-Hughes A, 2021, Opioid use disorder and the brain: a clinical perspective, ADDICTION, Vol: 117, Pages: 495-505, ISSN: 0965-2140

Journal article

Kouimtsidis C, Houghton B, Gage H, Notley C, Maskrey V, Clark A, Holland R, Lingford-Hughes A, Punukollu B, Touray M, Duka Tet al., 2021, A feasibility trial of an intervention in alcohol dependence for structured preparation before detoxification versus usual care: the SPADe trial results, PILOT AND FEASIBILITY STUDIES, Vol: 7

Journal article

Herlinger KE, Ling YY, Nestor LJ, Pannekoek J, Al Lababidi M, Ertl N, Vanelli F, Chhibbar P, Guerrero E, Canizares S, Akavarapu S, Munafo MR, Lingford-Hughes AR, Nutt DJ, Goldstone APet al., 2021, Comparison of monetary reward anticipation and negative emotional processing in obesity, ex-smokers and abstinent alcohol dependence, 44th Annual Meeting Research Society on Alcoholism / International Society for Behavioral Research on Alcoholism, Publisher: Wiley, Pages: 241A-241A, ISSN: 0145-6008

Conference paper

Paterson LM, McGonigle J, Murphy A, Giribaldi B, Elliott R, Ersche KD, Flechais R, Orban C, Smith DG, Suckling J, Taylor EM, Deakin JFW, Robbins TW, Nutt DJ, Lingford-Hughes ARet al., 2021, INVESTIGATING NEURAL CORRELATES OF SUBSTANCE DEPENDENCE AND THEIR PHARMACOLOGICAL MODULATION; NEW AVENUES TO TREATMENT AND PREDICTORS OF RELAPSE, Publisher: WILEY, Pages: 20A-20A, ISSN: 0145-6008

Conference paper

Palmer EOC, Ward G, Mota B, Tyacke R, Nutt D, Lingford-Hughes A, Ward R, Sastre Met al., 2021, ALCOHOL HANGOVER INDUCES INCREASED NEUROINFLAMMATORY RESPONSE IN A RODENT MODEL, Publisher: WILEY, Pages: 202A-203A, ISSN: 0145-6008

Conference paper

Goldstone AP, Ling YY, Nestor LJ, Pannekoek JN, Vanelli F, Herlinger K, Ertl N, Al-Lababidi M, Chhibbar P, Guerrero E, Akavarapu S, Canizares S, Munafo MR, Lingford-Hughes AR, Nutt DJet al., 2021, EFFECT OF ACUTE DESACYL GHRELIN ADMINISTRATION ON EATING AND ADDICTIVE BEHAVIOURS: THE GUT HORMONE IN ADDICTION STUDY, Publisher: WILEY, Pages: 51A-51A, ISSN: 0145-6008

Conference paper

Fonville L, Paterson L, Herlinger K, Hayes A, Hill R, Nutt D, Lingford-Hughes Aet al., 2021, Functional evaluation of NK1 antagonism on cue reactivity in opiate dependence; an fMRI study, Drug and Alcohol Dependence, Vol: 221, Pages: 1-7, ISSN: 0376-8716

BackgroundOpiate addiction is a major health challenge with substantial societal cost. Though harm minimisation strategies have been effective, there is a growing need for new treatments for detoxification and relapse prevention. Preclinical research has found neurokinin 1 (NK1) receptors have prominent effects on opiate reward and reinforcement, and human studies have found NK1 antagonism led to reductions in craving and withdrawal. However, its effect on brain mechanisms in opiate addiction has not yet been examined.MethodsThis study aims to assess the impact of NK1 antagonist aprepitant on heroin cue-elicited changes in blood-oxygenation level dependent (BOLD) signal in opiate dependent individuals undergoing detoxification. Participants will attend two scanning sessions and receive a single dose of aprepitant (320 mg) and a placebo in a randomised, cross-over design. During functional magnetic resonance imaging participants will undergo two runs of a cue reactivity task, which consists of passive viewing of drug cues or neutral cues in a block design fashion. We hypothesise that NK1 antagonism will attenuate the BOLD response to drug cues in the caudate nucleus and amygdala. Regions of interest were selected based on NK1 receptor density and their role in cue reactivity and craving.

Journal article

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