Imperial College London

DrLouisePaterson

Faculty of MedicineDepartment of Brain Sciences

Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 7028l.paterson

 
 
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Location

 

Burlington DanesHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

60 results found

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

Orban C, McGonigle J, Flechais RSA, Paterson LM, Elliott R, Erritzoe D, Ersche KD, Murphy A, Nestor LJ, Passetti F, Reed LJ, Ribeiro AS, Smith DG, Suckling J, Taylor EM, Waldman AD, Wing VC, Deakin JFW, Robbins TW, Nutt DJ, Lingford-Hughes ARet al., 2020, Chronic alcohol exposure differentially modulates structural and functional properties of amygdala: A cross-sectional study, ADDICTION BIOLOGY, Vol: 26, ISSN: 1355-6215

Journal article

Hayes A, Herlinger K, Paterson L, Lingford-Hughes Aet al., 2020, The neurobiology of substance use and addiction: evidence from neuroimaging and relevance to treatment, BJPsych Advances, Pages: 1-12, ISSN: 2056-4678

Addiction is a global health problem with a chronic relapsing nature for which there are few treatment options. In the past few decades, neuroimaging has allowed us to better understand the neurobiology of addiction. Functional neuroimaging paradigms have been developed to probe the neural circuits underlying addiction, including reward, inhibitory control, stress, emotional processing and learning/memory networks. Functional neuroimaging has also been used to provide biological support for the benefits of psychosocial and pharmacological interventions, although evidence remains limited and often inconclusive in this area, which may contribute to the variability in treatment efficacy. In this article, we discuss the changing definitions and clinical criteria that describe and classify addictive disorders. Using examples from functional neuroimaging studies we summarise the neurobiological mechanisms that underpin drug use, dependence, tolerance, withdrawal and relapse. We discuss the links between functional neuroimaging and treatment, outline clinical management in the UK and give an overview of future directions in research and addiction services.

Journal article

Nutt D, Nestor L, Suckling J, Ersche K, Murphy A, McGonigle J, Orban C, Paterson L, Reed L, Taylor E, Flechais R, Smith D, Bullmore E, Elliott R, Deakin B, Rabiner I, Lingford Hughes A, Sahakian B, Robbins T, Nutt Det al., 2020, Disturbances across whole brain networks during reward anticipation in an abstinent addiction population., NeuroImage: Clinical, Vol: 27, Pages: 1-10, ISSN: 2213-1582

The prevalent spatial distribution of abnormalities reported in cognitive fMRI studies in addiction suggests there are extensive disruptions across whole brain networks. Studies using resting state have reported disruptions in network connectivity in addiction, but these studies have not revealed characteristics of network functioning during critical psychological processes that are disrupted in addiction populations. Analytic methods that can capture key features of whole brain networks during psychological processes may be more sensitive in revealing additional and widespread neural disturbances in addiction, that are the provisions for relapse risk, and targets for medication development. The current study compared a substance addiction (ADD; n = 83) group in extended abstinence with a control (CON; n = 68) group on functional MRI (voxel-wise activation) and global network (connectivity) measures related to reward anticipation on a monetary incentive delay task. In the absence of group differences on MID performance, the ADD group showed reduced activation predominantly across temporal and visual regions, but not across the striatum. The ADD group also showed disruptions in global network connectivity (lower clustering coefficient and higher characteristic path length), and significantly less connectivity across a sub-network comprising frontal, temporal, limbic and striatal nodes. These results show that an addiction group in extended abstinence exhibit localised disruptions in brain activation, but more extensive disturbances in functional connectivity across whole brain networks. We propose that measures of global network functioning may be more sensitive in highlighting latent and more widespread neural disruptions during critical psychological processes in addiction and other psychiatric disorders.

Journal article

Hayes A, Wing V, McGonigle J, Turton S, Elliot R, Ersche KD, Flechais R, Orban C, Murphy A, Smith DG, Suckling J, Taylor EM, Deakin JF, Robbins TW, Nutt DJ, Lingford-Hughes AR, Paterson LMet al., 2020, The relationship between reward processing and impulsivity in addiction: a functional magnetic resonance imaging study, ECNP Workshop on Junior Scientists in Europe, Publisher: ELSEVIER, Pages: S70-S71, ISSN: 0924-977X

Introduction: Evidence suggests that abnormalities in reward processing and increased impulsivity contribute to the pathophysiology of addiction. However, the relationship between the two is currently not well characterised. This study used fMRI to investigate the BOLD response during reward and inhibitory control tasks and how such responses were associated with subjective and behavioural measures of impulsivity in abstinent alcohol, cocaine and polydrug addiction. We hypothesized a negative correlation between non-drug related reward anticipation and impulsivity measures in polydrug and alcohol dependence compared with healthy controls owing to increased impulsivity and thus more inhibitory control effort needed to maintain successful abstinence.Methods: Abstinent alcohol dependent (AD, n=27), polydrug dependent (PD, n=57) and healthy control (HC, n=65) participants were recruited [1] (REC number 11/H0707/9). Participants completed a battery of impulsivity measures; the Barratt Impulsiveness Scale (BIS-11) and the Urgency, Premeditation, (lack of), Perseverance (lack of), Sensation Seeking, Positive Urgency, Impulsive Behaviour Scale (UPPS-P) to measure trait impulsivity, the Kirby Delay Discounting task to measure choice impulsivity and the Stop Signal Task (SST) to measure impulsive action. Participants also underwent fMRI scanning (3-T) using the monetary incentive delay (MID) and Go/No-go (GNG) tasks. An a-priori region of interest approach was used to image BOLD response during the following contrasts: reward anticipation>neutral anticipation and no-go/go in the rIFG, OFC and caudate. Data was analysed using ANOVA or Kruskal- Wallis tests (with Tukey or Mann-Whitney U post-hoc tests respectively) and Pearson's or Spearman's rank correlations, as appropriate. Holm-Bonferroni correction was applied.Results: There were significant group differences in the BIS-11 (p<0.001), UPPS-P (p<0.001) and Kirby Delay Discounting task (p=0.002). Appropriate post-hoc

Conference paper

Nestor LJ, Paterson LM, Murphy A, McGonigle J, Orban C, Reed L, Taylor E, Flechais R, Smith D, Bullmore ET, Ersche KD, Suckling J, Elliott R, Deakin B, Rabiner I, Lingford Hughes A, Sahakian BJ, Robbins TW, Nutt DJet al., 2019, Naltrexone differentially modulates the neural correlates of motor impulse control in abstinent alcohol-dependent and poly-substance dependent individuals, European Journal of Neuroscience, Vol: 50, Pages: 2311-2321, ISSN: 0953-816X

Identifying key neural substrates in addiction disorders for targeted drug development remains a major challenge for clinical neuroscience. One emerging target is the opioid system, where substance‐dependent populations demonstrate prefrontal opioid dysregulation that predicts impulsivity and relapse. This may suggest that disturbances to the prefrontal opioid system could confer a risk for relapse in addiction due to weakened “top‐down” control over impulsive behaviour. Naltrexone is currently licensed for alcohol dependence and is also used clinically for impulse control disorders. Using a go/no‐go (GNG) task we examined the effects of acute naltrexone on the neural correlates of successful motor impulse control in abstinent alcoholics (AUD), abstinent poly substance‐dependent (poly‐SUD) individuals, and controls during a randomized double blind placebo controlled fMRI study. In the absence of any differences on GNG task performance, the AUD group showed a significantly greater BOLD response compared to the control group in lateral and medial prefrontal regions during both placebo and naltrexone treatments; effects that were positively correlated with alcohol abstinence. There was also a dissociation in the positive modulating effects of naltrexone in the orbitofrontal cortex (OFC) and anterior insula cortex (AIC) of the AUD and poly‐SUD groups respectively. Self‐reported trait impulsivity in the poly‐SUD group also predicted the effect of naltrexone in the AIC. These results suggest that acute naltrexone differentially amplifies neural responses within two distinct regions of a salience network during successful motor impulse control in abstinent AUD and poly‐SUD groups, which are predicted by trait impulsivity in the poly‐SUD group.

Journal article

De Beaurepaire R, Sinclair JMA, Heydtmann M, Addolorato G, Aubin H-J, Beraha EM, Caputo F, Chick JD, de la Selle P, Franchitto N, Garbutt JC, Haber PS, Jaury P, Lingford-Hughes AR, Morley KC, Muller CA, Owens L, Pastor A, Paterson LM, Pelissier F, Rolland B, Stafford A, Thompson A, van den Brink W, Leggio L, Agabio Ret al., 2019, The use of Baclofen as a treatment for alcohol use disorder: A clinical practice perspective, Frontiers in Psychiatry, Vol: 9, ISSN: 1664-0640

Alcohol use disorder (AUD) is a brain disorder associated with high rates of mortality and morbidity worldwide. Baclofen, a selective gamma-aminobutyric acid-B (GABA-B) receptor agonist, has emerged as a promising drug for AUD. The use of this drug remains controversial, in part due to uncertainty regarding dosing and efficacy, alongside concerns about safety. To date there have been 15 randomized controlled trials (RCTs) investigating the use of baclofen in AUD; three using doses over 100 mg/day. Two additional RCTs have been completed but have not yet been published. Most trials used fixed dosing of 30–80 mg/day. The other approach involved titration until the desired clinical effect was achieved, or unwanted effects emerged. The maintenance dose varies widely from 30 to more than 300 mg/day. Baclofen may be particularly advantageous in those with liver disease, due to its limited hepatic metabolism and safe profile in this population. Patients should be informed that the use of baclofen for AUD is as an “off-label” prescription, that no optimal fixed dose has been established, and that existing clinical evidence on efficacy is inconsistent. Baclofen therapy requires careful medical monitoring due to safety considerations, particularly at higher doses and in those with comorbid physical and/or psychiatric conditions. Baclofen is mostly used in some European countries and Australia, and in particular, for patients who have not benefitted from the currently used and approved medications for AUD.

Journal article

Lingford-Hughes A, Durant C, Paterson L, Turton S, Venkataraman A, Wilson S, Myers J, Muthukumaraswamy S, Mick I, Paterson S, Jones T, Nahar L, Cordero R, Nutt Det al., 2018, Using baclofen to explore GABA-B receptor function in alcohol dependence: insights from pharmacokinetic and pharmacodynamic measures, Frontiers in Psychiatry, Vol: 9, ISSN: 1664-0640

Background: The role of GABA-B neurotransmission in addiction has recently received increased attention, with clinical trials indicating that baclofen, a GABA-B receptor agonist, may reduce alcohol consumption, craving and promote abstinence. However, the optimal dose to treat alcohol dependence is unclear with patients requesting and tolerating much higher doses of baclofen, compared with other clinical uses. We assessed the pharmacokinetics and pharmacodynamics (PK/PD) of baclofen to provide insight into GABA-B sensitivity in this patient group, relative to controls.Methods: Male healthy volunteers (controls, n = 12) and abstinent alcohol dependent individuals (AD, n = 8) received single oral doses of baclofen or placebo in a 3-way crossover design. Controls received placebo/10 mg/60 mg baclofen in a randomized, double-blind design, AD received placebo/60 mg/90 mg baclofen in a single-blind design. PK/PD measures were recorded at baseline and multiple time-points up to 6 h post-dosing, including plasma baclofen, plasma growth hormone (GH), Subjective High Assessment Scale (SHAS) and biphasic alcohol effects scale (BAES). Repeated measures ANOVA analysis explored “change from baseline” dose, time, group, and interaction effects, t-tests compared peak effects.Results: Dose-dependent effects of baclofen on PK and PD measures were observed in both control and AD groups. Whilst there were no significant group differences in any baclofen PK parameters (t1/2, tmax, Cmax, AUC), marked differences in PD effects were clearly evident. In controls, 60 mg baclofen significantly increased total SHAS and BAES scores, and significantly increased plasma GH levels compared with placebo, with peak effects at 60–120 min, in line with its PK profile. In AD, 60 mg baclofen had limited effects on these parameters; SHAS scores, BAES scores and plasma GH levels were significantly blunted compared with controls (significant group*time interactions P = 0.0014, 0.0015 and P

Journal article

Agabio R, Sinclair JMA, Addolorato G, Aubin H-J, Beraha EM, Caputo F, Chick JD, de La Selle P, Franchitto N, Garbutt JC, Haber PS, Heydtmann M, Jaury P, Lingford-Hughes AR, Morley KC, Mueller CA, Owens L, Pastor A, Paterson LM, Pelissier F, Rolland B, Stafford A, Thompson A, van den Brink W, de Beaurepaire R, Leggio Let al., 2018, Baclofen for the treatment of alcohol use disorder: the Cagliari Statement, Lancet Psychiatry, Vol: 5, Pages: 957-960, ISSN: 2215-0366

Journal article

Savulich G, Riccelli R, Passamonti L, Correia M, Deakin JFW, Elliott R, Flechais RSA, Lingford-Hughes AR, McGonigle J, Murphy A, Nutt NJ, Orban C, Paterson LM, Reed LJ, Smith DG, Suckling J, Tait R, Taylor E, Sahakian BJ, Robbins TW, Ersche KDet al., 2017, THE ICCAM PLATFORM: TO INVESTIGATE THE NEUROPHARMACOLOGY OF BRAIN PROCESSES RELEVANT TO ADDICTION, Publisher: OXFORD UNIV PRESS, ISSN: 0735-0414

Conference paper

Murphy A, Nestor LJ, McGonigle J, Paterson L, Boyapati V, Ersche KD, Flechais R, Kuchibatla S, Metastasio A, Orban C, Passetti F, Reed L, Smith D, Suckling J, Taylor E, Robbins TW, Lingford-Hughes A, Nutt DJ, Deakin JFW, Elliott Ret al., 2017, Acute D3 Antagonist GSK598809 Selectively Enhances Neural Response During Monetary Reward Anticipation in Drug and Alcohol Dependence (vol 42, pg 1049, 2017), NEUROPSYCHOPHARMACOLOGY, Vol: 42, Pages: 1925-1926, ISSN: 0893-133X

Journal article

Savulich G, Riccelli R, Passamonti L, Correia M, Deakin JFW, Elliott R, Flechais RSA, Lingford-Hughes AR, McGonigle J, Murphy A, Nutt DJ, Orban C, Paterson LM, Reed LJ, Smith DG, Suckling J, Tait R, Taylor EM, Sahakian BJ, Robbins TW, Ersche KDet al., 2017, Effects of naltrexone are influenced by childhood adversity during negative emotional processing in addiction recovery, TRANSLATIONAL PSYCHIATRY, Vol: 7, ISSN: 2158-3188

Naltrexone is an opioid receptor antagonist used in the management of alcohol dependence. Although the endogenous opioid system has been implicated in emotion regulation, the effects of mu-opioid receptor blockade on brain systems underlying negative emotional processing are not clear in addiction. Individuals meeting criteria for alcohol dependence alone (n=18, alcohol) and in combination with cocaine and/or opioid dependence (n=21, alcohol/drugs) and healthy individuals without a history of alcohol or drug dependence (n=21) were recruited. Participants were alcohol and drug abstinent before entered into this double-blind, placebo-controlled, randomized, crossover study. Functional magnetic resonance imaging was used to investigate brain response while viewing aversive and neutral images relative to baseline on 50 mg of naltrexone and placebo. We found that naltrexone modulated task-related activation in the medial prefrontal cortex and functional connectivity between the anterior cingulate cortex and the hippocampus as a function of childhood adversity (for aversive versus neutral images) in all groups. Furthermore, there was a group-by-treatment-by-condition interaction in the right amygdala, which was mainly driven by a normalization of response for aversive relative to neutral images under naltrexone in the alcohol/drugs group. We conclude that early childhood adversity is one environmental factor that influences pharmacological response to naltrexone. Pharmacotherapy with naltrexone may also have some ameliorative effects on negative emotional processing in combined alcohol and drug dependence, possibly due to alterations in endogenous opioid transmission or the kappa-opioid receptor antagonist actions of naltrexone.

Journal article

Savulich G, Riccelli R, Passamonti L, Correia M, Deakin JFW, Elliott R, Flechais RSA, Lingford-Hughes AR, McGonigle J, Murphy A, Nutt D, Orban C, Paterson LM, Reed LJ, Smith DG, Suckling J, Tait R, Taylor EM, Sahakian BJ, Robbins TW, Ersche KDet al., 2017, Effects of naltrexone are influenced by childhood adversity during negative emotional processing in addiction recovery, European-College-of-Neuropsychopharmacology (ECNP) Workshop for Junior Scientists in Europe, Publisher: ELSEVIER SCIENCE BV, Pages: S59-S60, ISSN: 0924-977X

Conference paper

Morris LS, Baek K, Tait R, Elliott R, Ersche KD, Flechais R, McGonigle J, Murphy A, Nestor LJ, Orban C, Passetti F, Paterson LM, Rabiner I, Reed L, Smith D, Suckling J, Taylor EM, Bullmore ET, Lingford-Hughes AR, Deakin B, Nutt DJ, Sahakian BJ, Robbins TW, Voon V, ICCAM Consortiumet al., 2017, Naltrexone ameliorates functional network abnormalities in alcohol-dependent individuals., Addiction Biology, Vol: 23, Pages: 425-436, ISSN: 1369-1600

Naltrexone, an opioid receptor antagonist, is commonly used as a relapse prevention medication in alcohol and opiate addiction, but its efficacy and the mechanisms underpinning its clinical usefulness are not well characterized. In the current study, we examined the effects of 50-mg naltrexone compared with placebo on neural network changes associated with substance dependence in 21 alcohol and 36 poly-drug-dependent individuals compared with 36 healthy volunteers. Graph theoretic and network-based statistical analysis of resting-state functional magnetic resonance imaging (MRI) data revealed that alcohol-dependent subjects had reduced functional connectivity of a dispersed network compared with both poly-drug-dependent and healthy subjects. Higher local efficiency was observed in both patient groups, indicating clustered and segregated network topology and information processing. Naltrexone normalized heightened local efficiency of the neural network in alcohol-dependent individuals, to the same levels as healthy volunteers. Naltrexone failed to have an effect on the local efficiency in abstinent poly-substance-dependent individuals. Across groups, local efficiency was associated with substance, but no alcohol exposure implicating local efficiency as a potential premorbid risk factor in alcohol use disorders that can be ameliorated by naltrexone. These findings suggest one possible mechanism for the clinical effects of naltrexone, namely, the amelioration of disrupted network topology.

Journal article

Murphy A, Nestor LJ, McGonigle J, Paterson L, Boyapati V, Ersche KD, Flechais R, Kuchibatla S, Metastasio A, Orban C, Passetti F, Reed L, Smith D, Suckling J, Taylor E, Robbins TW, Lingford-Hughes A, Nutt DJ, Deakin JF, Elliott Ret al., 2017, Acute D3 antagonist GSK598809 selectively enhances neural response during monetary reward anticipation in drug and alcohol dependence, Neuropsychopharmacology, Vol: 42, Pages: 1049-1057, ISSN: 1740-634X

Evidence suggests that disturbances in neurobiological mechanisms of reward and inhibitory control maintain addiction and provoke relapse during abstinence. Abnormalities within the dopamine system may contribute to these disturbances and pharmacologically targeting the D3 dopamine receptor (DRD3) is therefore of significant clinical interest. We used functional magnetic resonance imaging to investigate the acute effects of the DRD3 antagonist GSK598809 on anticipatory reward processing, using the monetary incentive delay task (MIDT), and response inhibition using the Go/No-Go task (GNGT). A double-blind, placebo-controlled, crossover design approach was used in abstinent alcohol dependent, abstinent poly-drug dependent and healthy control volunteers. For the MIDT, there was evidence of blunted ventral striatal response to reward in the poly-drug-dependent group under placebo. GSK598809 normalized ventral striatal reward response and enhanced response in the DRD3-rich regions of the ventral pallidum and substantia nigra. Exploratory investigations suggested that the effects of GSK598809 were mainly driven by those with primary dependence on alcohol but not on opiates. Taken together, these findings suggest that GSK598809 may remediate reward deficits in substance dependence. For the GNGT, enhanced response in the inferior frontal cortex of the poly-drug group was found. However, there were no effects of GSK598809 on the neural network underlying response inhibition nor were there any behavioral drug effects on response inhibition. GSK598809 modulated the neural network underlying reward anticipation but not response inhibition, suggesting that DRD3 antagonists may restore reward deficits in addiction.

Journal article

Murphy A, Nestor LJ, McGonigle J, Paterson L, Boyapati V, Ersche KD, Flechais R, Kuchibatla S, Metastasio A, Orban C, Passetti F, Reed L, Smith D, Suckling J, Taylor E, Obbins TWR, Lingford-Hughes A, Nutt DJ, Deakin JFW, Elliott Ret al., 2017, Acute D3 Antagonist GSK598809 Selectively Enhances Neural Response During Monetary Reward Anticipation in Drug and Alcohol Dependence (vol 42, pg 1049, 2017), NEUROPSYCHOPHARMACOLOGY, Vol: 42, Pages: 1559-1559, ISSN: 0893-133X

Journal article

McGonigle J, Murphy A, Paterson LM, Reed LJ, Nestor L, Nash J, Elliott R, Ersche KD, Flechais RS, Newbould R, Orban C, Smith DG, Taylor EM, Waldman AD, Robbins TW, Deakin JW, Nutt DJ, Lingford-Hughes AR, Suckling J, ICCAM Platformet al., 2016, The ICCAM platform study: An experimental medicine platform for evaluating new drugs for relapse prevention in addiction. Part B: fMRI description, Journal of Psychopharmacology, Vol: 31, Pages: 3-16, ISSN: 1461-7285

OBJECTIVES: We aimed to set up a robust multi-centre clinical fMRI and neuropsychological platform to investigate the neuropharmacology of brain processes relevant to addiction - reward, impulsivity and emotional reactivity. Here we provide an overview of the fMRI battery, carried out across three centres, characterizing neuronal response to the tasks, along with exploring inter-centre differences in healthy participants. EXPERIMENTAL DESIGN: Three fMRI tasks were used: monetary incentive delay to probe reward sensitivity, go/no-go to probe impulsivity and an evocative images task to probe emotional reactivity. A coordinate-based activation likelihood estimation (ALE) meta-analysis was carried out for the reward and impulsivity tasks to help establish region of interest (ROI) placement. A group of healthy participants was recruited from across three centres (total n=43) to investigate inter-centre differences. PRINCIPLE OBSERVATIONS: The pattern of response observed for each of the three tasks was consistent with previous studies using similar paradigms. At the whole brain level, significant differences were not observed between centres for any task. CONCLUSIONS: In developing this platform we successfully integrated neuroimaging data from three centres, adapted validated tasks and applied whole brain and ROI approaches to explore and demonstrate their consistency across centres.

Journal article

Lim TV, Ricceli R, Passamonti L, Deakin JFW, Elliot R, Flechais RSA, Lingford-Hughes AR, McGonigle J, Murphy A, Nutt DJ, Orban C, Paterson LM, Reed LJ, Sahakian BJ, Savulich G, Smith DG, Suckling J, Taylor EM, Robbins TW, Ersche KDet al., 2016, Endogenous opioid blockade modulates neural networks implicated in attentional and behavioural control in individuals recovering from alcohol and drug dependence, 29th Congress of the European-College-of-Neuropsychopharmacology (ECNP), Publisher: ELSEVIER SCIENCE BV, Pages: S696-S697, ISSN: 0924-977X

Conference paper

Nestor LJ, Murphy A, McGonigle J, Orban C, Reed L, Taylor E, Flechais R, Paterson LM, Smith D, Bullmore ET, Ersche KD, Suckling J, Tait R, Elliott R, Deakin B, Rabiner I, Lingford-Hughes A, Nutt DJ, Sahakian B, Robbins TW, ICCAM Consortiumet al., 2016, Acute naltrexone does not remediate fronto-striatal disturbances in alcoholic and alcoholic polysubstance-dependent populations during a monetary incentive delay task, Addiction Biology, Vol: 22, Pages: 1576-1589, ISSN: 1369-1600

There is a concerted research effort to investigate brain mechanisms underlying addiction processes that may predicate the development of new compounds for treating addiction. One target is the brain's opioid system, because of its role in the reinforcing effects of substances of abuse. Substance-dependent populations have increased numbers of the mu opioid receptor (MOR) in fronto-striatal regions that predict drug relapse, and demonstrate disturbances in these regions during the processing of non-drug rewards. Naltrexone is currently licensed for alcohol and opiate dependence, and may remediate such disturbances through the blockade of MORs in fronto-striatal reward circuitry. Therefore, we examined the potential acute modulating effects of naltrexone on the anticipation of, and instrumental responding for, non-drug rewards in long-term abstinent alcoholics, alcoholic poly substance-dependent individuals and controls using a monetary incentive delay (MID) task during a randomized double blind placebo controlled functional MRI study. We report that the alcoholic poly substance-dependent group exhibited slower and less accurate instrumental responding compared to alcoholics and controls that was less evident after acute naltrexone treatment. However, naltrexone treatment was unable to remediate disturbances within fronto-striatal regions during reward anticipation and 'missed' rewards in either substance-dependent group. While we have not been able to identify the underlying neural mechanisms for improvement observed with naltrexone in the alcoholic poly-substance dependent group, we can confirm that both substance-dependent groups exhibit substantial neural deficits during an MID task, despite being in long-term abstinence.

Journal article

Taylor EM, Murphy A, Boyapati V, Ersche KD, Flechais R, Kuchibatla S, McGonigle J, Metastasio A, Nestor L, Orban C, Passetti F, Paterson L, Smith D, Suckling J, Tait R, Lingford-Hughes AR, Robbins TW, Nutt DJ, Deakin JFW, Elliott Ret al., 2016, Impulsivity in abstinent alcohol and polydrug dependence: a multidimensional approach, Psychopharmacology, Vol: 233, Pages: 1487-1499, ISSN: 1432-2072

Journal article

Paterson LM, Flechais RSA, Murphy A, Reed LJ, Abbott S, Boyapati V, Elliott R, Erritzoe D, Ersche KD, Faluyi Y, Faravelli L, Fernandez-Egea E, Kalk NJ, Kuchibatla SS, McGonigle J, Metastasio A, Mick I, Nestor L, Orban C, Passetti F, Rabiner EA, Smith DG, Suckling J, Tait R, Taylor EM, Waldman AD, Robbins TW, Deakin JFW, Nutt DJ, Lingford-Hughes ARet al., 2015, The Imperial College Cambridge Manchester (ICCAM) platform study: an experimental medicine platform for evaluating new drugs for relapse prevention in addiction. Part A: study description, Journal of Psychopharmacology, Vol: 29, Pages: 943-960, ISSN: 1461-7285

Drug and alcohol dependence are global problems with substantial societal costs. There are few treatments for relapse prevention and therefore a pressing need for further study of brain mechanisms underpinning relapse circuitry. The Imperial College Cambridge Manchester (ICCAM) platform study is an experimental medicine approach to this problem: using functional magnetic resonance imaging (fMRI) techniques and selective pharmacological tools, it aims to explore the neuropharmacology of putative relapse pathways in cocaine, alcohol, opiate dependent, and healthy individuals to inform future drug development. Addiction studies typically involve small samples because of recruitment difficulties and attrition. We established the platform in three centres to assess the feasibility of a multisite approach to address these issues. Pharmacological modulation of reward, impulsivity and emotional reactivity were investigated in a monetary incentive delay task, an inhibitory control task, and an evocative images task, using selective antagonists for µ-opioid, dopamine D3 receptor (DRD3) and neurokinin 1 (NK1) receptors (naltrexone, GSK598809, vofopitant/aprepitant), in a placebo-controlled, randomised, crossover design. In two years, 609 scans were performed, with 155 individuals scanned at baseline. Attrition was low and the majority of individuals were sufficiently motivated to complete all five sessions (n=87). We describe herein the study design, main aims, recruitment numbers, sample characteristics, and explain the test hypotheses and anticipated study outputs.

Journal article

Savulich G, Ersche KD, Deakin B, Elliott R, Flechais R, Lingford-Hughes A, McGonigle J, Murphy A, Nestor L, Nutt DJ, Paterson L, Reed L, Sahakian BJ, Suckling J, Tait R, Robbins TWet al., 2015, The modulatory effects of naltrexone on the underlying neural network in alcohol and drug dependence: an FMRI study, 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism, Publisher: Wiley, Pages: 253A-253A, ISSN: 0145-6008

Conference paper

Taylor EM, Murphy A, Ersche KD, Flechais R, Lingford-Hughes AR, Paterson L, Nutt DJ, Robbins TW, Deakin JW, Elliott Ret al., 2015, Neuropsychological, self-report and neurocognitive measures of impulsivity in substance-dependent individuals compared to controls, ECNP Workshop for Junior Scientists in Europe, Publisher: ELSEVIER SCIENCE BV, Pages: S85-S86, ISSN: 0924-977X

Conference paper

Brust P, Deuther-Conrad W, Donat CK, Barthel H, Riss P, Paterson L, Hoepping A, Sabri O, Cumming Pet al., 2014, Preclinical aspects of nicotinic acetylcholine receptor imaging., PET and SPECT of Neurobiological Systems, Editors: Dierckx, Otte, de Vries, van Waarde, Luiten, Publisher: Springer-Verlag Berlin Heidelberg

Book chapter

Paterson LM, Kornum BR, Nutt DJ, Pike VW, Knudsen GMet al., 2013, 5-HT radioligands for human brain imaging with PET and SPECT, MEDICINAL RESEARCH REVIEWS, Vol: 33, Pages: 54-111, ISSN: 0198-6325

Journal article

Durant CF, Wilson SJ, Lightman S, Nutt DJ, Paterson LM, Rich AS, Malizia ALet al., 2012, Sleep and the HPA axis; the effect on sleep of two doses of hydrocortisone administered as a bolus during the day in healthy volunteers, 21st Congress of the European-Sleep-Research-Society, Publisher: WILEY-BLACKWELL, Pages: 24-24, ISSN: 0962-1105

Conference paper

Paterson LM, Nutt DJ, Wilson SJ, 2011, Sleep and its disorders in translational medicine, J.Psychopharmacol., Vol: 25, Pages: 1226-1234

The study of sleep is a useful approach to studying the brain in psychiatric disorders and in investigating the effects of psychotropic drugs. Sleep physiology lends itself well to pharmacological and physiological manipulation, as it has the advantage of a functional output, the electroencephalograph, which is common to all mammals, and can be measured in freely moving (or naturally sleeping) animals under controlled laboratory conditions or in a naturalistic home environment. The complexity of sleep architecture varies between species but all share features which are comparable. In addition, sleep architecture is sensitive to changes in brain neurotransmitters such as serotonin, so cross-species sleep measurement can be combined with pharmacological manipulation to investigate the receptor mechanisms controlling sleep-wake regulation and sleep architecture in response to known and novel agents. Translational approaches such as these have improved our understanding of sleep circuitry and facilitated the development of new treatments for sleep disorders, particularly insomnia. This review provides examples of how research findings within the sleep field have been translated between animal models, healthy volunteers and patient populations with particular focus on the serotonergic system

Journal article

Durant CF, Wilson SJ, Lightman S, Nutt DJ, Paterson LM, Rich A, Malizia ALet al., 2011, DOSE RELATED SLEEP CHANGES IN HEALTHY VOLUNTEERS AFTER TWO DOSES OF HYDROCORTISONE: A DOUBLE BLIND PLACEBO CONTROLLED STUDY, Summer Meeting of the British-Association-for-Psychopharmacology, Publisher: SAGE PUBLICATIONS LTD, Pages: A56-A56, ISSN: 0269-8811

Conference paper

Tyacke RJ, Durant CF, Paterson LM, Dineen P, Bachurova G, Wilson S, Nutt DJ, Malizia ALet al., 2011, EFFECTS OF ACUTE INHALATION OF VAPORIZED CANNABIS OR PLACEBO ON CARDIOVASCULAR AND SACCADIC EYE MOVEMENT MEASURES: A PILOT STUDY, Summer Meeting of the British-Association-for-Psychopharmacology, Publisher: SAGE PUBLICATIONS LTD, Pages: A37-A37, ISSN: 0269-8811

Conference paper

Wilson SJ, Paterson LM, Durant CF, Sinclair L, Rich AS, Wood B, Lightman S, Nutt DJ, Malizia ALet al., 2011, ACUTE EFFECTS OF HIGH DOSE HYDROCORTISONE ON SLEEP IN PATIENTS WITH TREATMENT RESISTANT DEPRESSION: A DOUBLE BLIND PLACEBO CONTROLLED STUDY, Summer Meeting of the British-Association-for-Psychopharmacology, Publisher: SAGE PUBLICATIONS LTD, Pages: A23-A23, ISSN: 0269-8811

Conference paper

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