290 results found
Herlinger K, Lingford-Hughes A, 2021, Opioid use disorder and the brain: a clinical perspective, ADDICTION, ISSN: 0965-2140
Kouimtsidis C, Houghton B, Gage H, et 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
Palmer EOC, Ward G, Mota B, et al., 2021, ALCOHOL HANGOVER INDUCES INCREASED NEUROINFLAMMATORY RESPONSE IN A RODENT MODEL, Publisher: WILEY, Pages: 202A-203A, ISSN: 0145-6008
Goldstone AP, Ling YY, Nestor LJ, et 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
Herlinger KE, Ling YY, Nestor LJ, et 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
Introduction & Aims: Alterations in non-drug reward and negative emotional processing are reported in alcohol dependence. This might extend into abstinence, perpetuating relapse. These neurobehavioral endophenotypes may be shared in nicotine dependence and obesity. Our MRC funded Gut Hormones in Addiction (GHADD) study investigated whether acute intravenous infusions of appetitive gut hormones attenuated behavioural components of addiction in abstinent alcohol or nicotine dependence and obesity. This analysis compared non-drug reward and emotional processing between groups at saline visit. Methods: The adult groups studied were: (i) obesity with active dieting (OB, n=25, mean BMI 37.1kg/m2, never smoked, no alcohol use disorder), (ii) ex-smokers (ExS, n=25, BMI 25.3kg/m2, median abstinence 20.7 weeks, no alcohol use disorder), (iii) abstinent alcohol-dependence (AAD, n=26, BMI 25.7kg/m2, abstinence 32.6 weeks , 42% ex-smokers, 46% current smokers), and (iv) healthy controls (HC, n=24, BMI 22.0 kg/m2, single non-infusion visit). Primary outcome measures included fMRI BOLD signal for: (i) win>neutral anticipation during Monetary Incentive Delay Task (MID); (ii) aversive>neutral pictures during Evocative Images Task (EIT) (Paterson et al., 2015). Results: The 3 clinical groups did not differ significantly in age, sex, or years of education; however, the HC were younger (P<0.001). For the MID task, in whole brain analysis of win anticipation (ANOVA, cluster-wise FWE Z>2.6, P<0.05), the AAD group had: lower BOLD signal than HC group in caudate, putamen, supplementary motor area, post-central gyrus, pre-central gyrus, lateral occipital cortex, and superior parietal lobule, lower BOLD signal than ExS in caudate and lateral occipital cortex, but no difference in BOLD signal than OB group; with ExS and OB groups having lower BOLD signal than HC in all regions, apart from caudate for ExS. Age had no effect on BOLD signal in the 3 clinical groups. For the EI
Paterson LM, McGonigle J, Murphy A, et 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
Fonville L, Paterson L, Herlinger K, et 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.
Upthegrove R, de Cates A, Shuttleworth A, et al., 2021, Gender equality in academic publishing: action from the BJPsych, BRITISH JOURNAL OF PSYCHIATRY, Vol: 218, Pages: 128-130, ISSN: 0007-1250
Ashok AH, Myers J, Frost G, et al., 2021, Acute acetate administration increases endogenous opioid levels in the human brain: A [C-11]carfentanil molecular imaging study, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 35, Pages: 606-610, ISSN: 0269-8811
McGinnity CJ, Barros DAR, Hinz R, et al., 2021, Alpha 5 subunit-containing GABA(A) receptors in temporal lobe epilepsy with normal MRI, Brain Communications, Vol: 3, Pages: 1-16, ISSN: 2632-1297
GABAA receptors containing the α5 subunit mediate tonic inhibition and are widely expressed in the limbic system. In animals, activation of α5-containing receptors impairs hippocampus-dependent memory. Temporal lobe epilepsy is associated with memory impairments related to neuron loss and other changes. The less selective PET ligand [11C]flumazenil has revealed reductions in GABAA receptors. The hypothesis that α5 subunit receptor alterations are present in temporal lobe epilepsy and could contribute to impaired memory is untested. We compared α5 subunit availability between individuals with temporal lobe epilepsy and normal structural MRI (‘MRI-negative’) and healthy controls, and interrogated the relationship between α5 subunit availability and episodic memory performance, in a cross-sectional study. Twenty-three healthy male controls (median ± interquartile age 49 ± 13 years) and 11 individuals with MRI-negative temporal lobe epilepsy (seven males; 40 ± 8) had a 90-min PET scan after bolus injection of [11C]Ro15-4513, with arterial blood sampling and metabolite correction. All those with epilepsy and six controls completed the Adult Memory and Information Processing Battery on the scanning day. ‘Bandpass’ exponential spectral analyses were used to calculate volumes of distribution separately for the fast component [VF; dominated by signal from α1 (α2, α3)-containing receptors] and the slow component (VS; dominated by signal from α5-containing receptors). We made voxel-by-voxel comparisons between: the epilepsy and control groups; each individual case versus the controls. We obtained parametric maps of VF and VS measures from a single bolus injection of [11C]Ro15-4513. The epilepsy group had higher VS in anterior medial and lateral aspects of the temporal lobes, the anterior cingulate gyri, the presumed area tempestas (piriform cort
Turton S, Lingford-Hughes A, 2020, Neurobiology and principles of addiction and tolerance, Medicine (United Kingdom), Vol: 48, Pages: 749-753, ISSN: 1357-3039
Substances of abuse dysregulate key brain systems involved in motivation, reward, decision-making and memory. As drug use evolves into a compulsive addiction, there are adaptations in these systems, mediated by a number of different neurotransmitters. The mesolimbic dopaminergic pathway plays a central role in the pleasurable and positive reinforcing effects of drugs. As an individual becomes addicted, there is a shift away from this positive reinforcement to the compulsive, habitual drug-seeking behaviours driven, for example, by cravings or withdrawal symptoms. Although the potential for addiction is common with all drugs of abuse, the underlying mechanisms, neurotransmission systems and adaptations vary between drugs. This review focuses on the neurobiology of addiction and tolerance for alcohol, benzodiazepines, opioids and stimulants.
Cheng H-Y, McGuinness LA, Elbers RG, et al., 2020, Treatment interventions to maintain abstinence from alcohol in primary care: systematic review and network meta-analysis, BMJ-BRITISH MEDICAL JOURNAL, Vol: 371, ISSN: 1756-1833
Herlinger K, Lingford-Hughes A, 2020, Addressing unmet needs in opiate dependence: providing better support for detoxification from OST and advances in relapse prevention, BJPsych Advances, ISSN: 2056-4678
Despite the record breaking levels of opiate related deaths published this year in the UK, pharmacological management of opioid dependence has evolved little since the advent of methadone in 1965. Along with harm minimisation and psychosocial interventions, the mainstay of pharmacological treatment remains opiate substitution therapy (OST) using methadone or buprenorphine, with many patients receiving OST for many years. Even with these treatments, opiate users continue to face mortality risks of 12 times higher than the general population, and emerging evidence suggests that patients who remain on long-term OST present with a range of physical and cognitive impairments. Therefore, with a growing ageing opiate dependent population who would benefit from detoxification from OST, this article will provide an overview of the current situation regarding opioid abuse and current clinical practice, will explore the reasons why availability and acceptability of detoxification pathways are declining, and will discuss emerging pharmacological therapies that could provide benefit in relapse prevention.
Orban C, McGonigle J, Flechais RSA, et al., 2020, Chronic alcohol exposure differentially modulates structural and functional properties of amygdala: A cross-sectional study, ADDICTION BIOLOGY, Vol: 26, ISSN: 1355-6215
Herlinger K, Ling YY, Nestor LJ, et al., 2020, Comparison of food cue reactivity, eating behaviours, mood and impulsivity in obesity, ex-smokers and abstinent alcohol dependence, 33rd Congress of the European-College-of-Neuropsychopharmacology (ECNP), Publisher: ELSEVIER, Pages: S15-S15, ISSN: 0924-977X
Hayes A, Herlinger K, Paterson L, et 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.
Venkataraman A, Turton S, Lingford-Hughes A, 2020, Drug use and associated neuropsychiatric conditions, Oxford Textbook of Neuropsychiatry, Publisher: Oxford University Press, ISBN: 9780198757139
The book meets curriculum requirements for various international training programmes and examinations, and serves as an essential training text book for all psychiatric and neurology trainees worldwide.
Turton S, Myers J, Mick I, et al., 2020, Blunted endogenous opioid release following an oral dexamphetamine challenge in abstinent alcohol dependent individuals, Molecular Psychiatry, Vol: 25, Pages: 1749-1758, ISSN: 1359-4184
Addiction has been proposed as a ‘reward deficient’ state, which is compensated for with substance use. There is growing evidence of dysregulation in the opioid system, which plays a key role in reward, underpinning addiction. Low levels of endogenous opioids are implicated in vulnerability for developing alcohol dependence (AD) and high mu-opioid receptor (MOR) availability in early abstinence is associated with greater craving. This high MOR availability is proposed to be the target of opioid antagonist medication to prevent relapse. However, changes in endogenous opioid tone in AD are poorly characterised and are important to understand as opioid antagonists do not help everyone with AD. We used [11C]carfentanil, a selective MOR agonist positron emission tomography (PET) radioligand, to investigate endogenous opioid tone in AD for the first time. We recruited 13 abstinent male AD and 15 control participants who underwent two [11C]carfentanil PET scans, one before and one 3 h following a 0.5 mg/kg oral dose of dexamphetamine to measure baseline MOR availability and endogenous opioid release. We found significantly blunted dexamphetamine-induced opioid release in 5 out of 10 regions-of-interest including insula, frontal lobe and putamen in AD compared with controls, but no significantly higher MOR availability AD participants compared with HC in any region. This study is comparable to our previous results of blunted dexamphetamine-induced opioid release in gambling disorder, suggesting that this dysregulation in opioid tone is common to both behavioural and substance addictions.
Nutt D, Nestor L, Suckling J, et 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.
Marques TR, Ashok AH, Angelescu I, et al., 2020, GABA-A receptor differences in schizophrenia: a positron emission tomography study using [C-11]Ro154513, Molecular Psychiatry, Vol: 2020, Pages: 1-10, ISSN: 1359-4184
A loss of GABA signaling is a prevailing hypothesis for the pathogenesis of schizophrenia. Preclinical studies indicate that blockade of the α5 subtype of the GABA receptor (α5-GABAARs) leads to behavioral phenotypes associated with schizophrenia, and postmortem evidence indicates lower hippocampal α5-GABAARs protein and mRNA levels in schizophrenia. However, it is unclear if α5-GABAARs are altered in vivo or related to symptoms. We investigated α5-GABAARs availability in antipsychotic-free schizophrenia patients and antipsychotic-medicated schizophrenia patients using [11C]Ro15-4513 PET imaging in a cross-sectional, case–control study design. Thirty-one schizophrenia patients (n = 10 antipsychotic free) and twenty-nine matched healthy controls underwent a [11C]Ro15-4513 PET scan and MRI. The α5 subtype GABA-A receptor availability was indexed using [11C]Ro15-4513 PET imaging. Dynamic PET data were analyzed using the two-tissue compartment model with an arterial plasma input function and total volume of distribution (VT) as the outcome measure. Symptom severity was assessed using the PANSS scale. There was significantly lower [11C]Ro15-4513 VT in the hippocampus of antipsychotic-free patients, but not in medicated patients (p = 0.64), relative to healthy controls (p < 0.05; effect size = 1.4). There was also a significant positive correlation between [11C]Ro15-4513 VT and total PANSS score in antipsychotic-free patients (r = 0.72; p = 0.044). The results suggest that antipsychotic-free patients with schizophrenia have lower α5-GABAARs levels in the hippocampus, consistent with the hypothesis that GABA hypofunction underlies the pathophysiology of the disorder.
Erritzoe D, Ashok AH, Searle GE, et al., 2020, Serotonin release measured in the human brain: A PET study with [11C]CIMBI-36 and d-amphetamine challenge, Neuropsychopharmacology, Vol: 45, Pages: 804-810, ISSN: 0893-133X
Positron emission tomography (PET) enables non-invasive estimation of neurotransmitter fluctuations in the living human brain. While these methods have been applied to dopamine and some other transmitters, estimation of 5-hydroxytryptamine (5-HT; Serotonin) release has proved to be challenging. Here we demonstrate the utility of the novel 5-HT2A receptor agonist radioligand, [11C]CIMBI-36, and a d-amphetamine challenge to evaluate synaptic 5-HT changes in the living human brain. Seventeen healthy male volunteers received [11C]CIMBI-36 PET scans before and 3 hours after an oral dose of d-amphetamine (0.5 mg/kg). Dynamic PET data were acquired over 90 minutes, and the total volume of distribution (VT) in the frontal cortex and the cerebellum derived from a kinetic analysis using MA1. The frontal cortex binding potential (BPNDfrontal) was calculated as (VTfrontal/VTcerebellum)-1. BPNDfrontal = 1- (BPNDfrontalpost-dose/ BPNDfrontalbaseline) was used as an index of 5-HT release. Statistical inference was tested by means of a paired Students t-test evaluating a reduction in post-amphetamine [11C]CIMBI-36 BPNDfrontal .Following d-amphetamine administration, [11C]CIMBI-36 BPNDfrontal was reduced by 14 ± 13 % (p = 0.002). Similar effects were observed in other cortical regions examined in an exploratory analysis.[11C]CIMBI-36 binding is sensitive to synaptic serotonin release in the human brain, and when combined with a d-amphetamine challenge, the evaluation of the human brain serotonin system in neuropsychiatric disorders, such as major depression and Parkinson’s disease is enabled.
Hayes A, Wing V, McGonigle J, et 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  (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
Padmanathan P, Hall K, Moran P, et al., 2020, Prevention of suicide and reduction of self-harm among people with substance use disorder: a systematic review and meta-analysis of randomised controlled trials, Comprehensive Psychiatry, Vol: 96, ISSN: 0010-440X
BACKGROUND: People with substance use disorder (SUD) are at significantly greater risk of suicide compared with the general population. In recent years the number of suicides resulting from drug poisoning in England and Wales has increased. We sought to identify and evaluate the effect of interventions to prevent suicide or reduce self-harm among people with SUD. METHODS: We conducted a systematic review of randomised controlled trials (RCTs) of interventions for people with SUD that included suicide or self-harm-related primary outcomes. We searched Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, PubMed, Embase and Web of Science from inception until 13th January 2019. Studies were assessed for bias using the Cochrane Risk of Bias 2 tool. A random effects meta-analysis of standardised mean differences (SMD) was conducted. RESULTS: We identified six RCTs from four countries (Australia, Iran, the United States of America and the United Kingdom) comprising 468 participants in total. All but one study investigated psychosocial interventions. On average across studies there was weak evidence of a small positive effect of interventions on suicide or self-harm outcomes (d=-0.20, 95% CI=-0.39-0.00). LIMITATIONS: Studies were heterogeneous in terms of population, intervention, controls and outcome. There were some concerns regarding bias for all trials. All trials were liable to type II error. CONCLUSIONS: Evidence is currently lacking regarding the effectiveness of interventions to prevent suicide and reduce self-harm amongst people with SUD.
Limbrick-Oldfield EH, Mick I, Cocks RE, et al., 2020, Neural and neurocognitive markers of vulnerability to gambling disorder: a study of unaffected siblings, Neuropsychopharmacology, Vol: 45, Pages: 292-300, ISSN: 0893-133X
Psychological and neurobiological markers in individuals with gambling disorder (GD) could reflect transdiagnostic vulnerability to addiction or neuroadaptive consequences of long-term gambling. Using an endophenotypic approach to identify vulnerability markers, we tested the biological relatives of cases with GD. Male participants seeking treatment for GD (n = 20) were compared with a male control group (n = 18). Biological siblings of cases with GD (n = 17, unrelated to the current GD group) were compared with a separate control group (n = 19) that overlapped partially with the GD control group. Participants completed a comprehensive assessment of clinical scales, neurocognitive functioning, and fMRI of unexpected financial reward. The GD group displayed elevated levels of self-report impulsivity and delay discounting, and increased risk-taking on the Cambridge Gamble Task. We did not observe impaired motor impulsivity on the stop-signal task. Siblings of GD showed some overlapping effects; namely, elevated impulsivity (negative urgency) and increased risk-taking on the Cambridge Gamble Task. We did not observe any differences in the neural response to win outcomes, either in the GD or sibling analysis compared with their control group. Within the GD group, activity in the thalamus and caudate correlated negatively with gambling severity. Increased impulsivity and risk-taking in GD are present in biological relatives of cases with GD, suggesting these markers may represent pre-existing vulnerability to GD.
Barnes TR, Schizophrenia Consensus Group, 2019, Evidence-based guidelines for the pharmacological treatment of schizophrenia: recommendations from the British Association for Psychopharmacology., Journal of Clinical Psychopharmacology, Vol: 25, Pages: 567-620, ISSN: 0271-0749
These updated guidelines from the British Association for Psychopharmacology replace the original version published in 2011. They address the scope and targets of pharmacological treatment for schizophrenia. A consensus meeting was held in 2017, involving experts in schizophrenia and its treatment. They were asked to review key areas and consider the strength of the evidence on the risk-benefit balance of pharmacological interventions and the clinical implications, with an emphasis on meta-analyses, systematic reviews and randomised controlled trials where available, plus updates on current clinical practice. The guidelines cover the pharmacological management and treatment of schizophrenia across the various stages of the illness, including first-episode, relapse prevention, and illness that has proved refractory to standard treatment. It is hoped that the practice recommendations presented will support clinical decision making for practitioners, serve as a source of information for patients and carers, and inform quality improvement.
Flaus A, Barros DAR, Hinz R, et al., 2019, Decreased GABA-A Receptor Binding in Association With beta-Lactam Antibiotic Use, CLINICAL NUCLEAR MEDICINE, Vol: 44, Pages: 981-982, ISSN: 0363-9762
Flaus A, Riaño Barros DA, Hinz R, et al., 2019, Decreased GABA-A Receptor Binding in Association With β-Lactam Antibiotic Use., Clin Nucl Med, Vol: 44, Pages: 981-982
β-Lactam antibiotics are proconvulsive. In laboratory animals, this effect seems to be predominantly mediated through inhibition of GABA-A receptors, but it has not been demonstrated in humans in vivo. We report images of a [C]Ro15-4513 PET from a 40-year-old man who had completed a 1-week course of flucloxacillin before it. Relative to healthy controls, the participant had significantly lower mean gray matter binding. These novel data suggest that, in humans, the proconvulsive effect of β-lactam antibiotics is mediated via either competition for the same benzodiazepine-binding site as [C]Ro15-4513 or downregulation of GABA-A receptor expression.
Bowden-Jones O, Sinclair J, Lingford-Hughes A, 2019, Psychiatry and the global drugs debate: what every psychiatrist needs to know., British Journal of Psychiatry, Pages: 1-2, ISSN: 0007-1250
There are few topics that divide public opinion as sharply as the use of psychoactive substances and it is easy to see why. Substance use is complex and can be examined from numerous perspectives, including legal, health, economic, cultural and ethical. These varying approaches can lead to a range of different conclusions. Here we explore some of the common approaches adopted towards drug policy and suggest a number of principles, which may inform a psychiatrist's own view.
Wahba M, Sousa S, Watson S, et al., 2019, Neurometabolic approach to treatment-resistant depression Authors' reply, BRITISH JOURNAL OF PSYCHIATRY, Vol: 215, Pages: 568-569, ISSN: 0007-1250
Nestor LJ, Paterson LM, Murphy A, et 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.
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