Publications
324 results found
Lennox B, Yeeles K, Jones PB, et al., 2019, Intravenous immunoglobulin and rituximab versus placebo treatment of antibody-associated psychosis: study protocol of a randomised phase IIa double-blinded placebo-controlled trial (SINAPPS2), Trials, Vol: 20, ISSN: 1745-6215
BackgroundEvidence is conflicting about a causal role of inflammation in psychosis and, specifically, regarding antibodies binding to neuronal membrane targets, especially N-methyl-D-aspartate receptors. NMDAR, LGI1 and GABA-A antibodies were found more prevalent in people with psychosis than in healthy controls. We aim to test whether these antibodies are pathogenic and may cause isolated psychosis. The SINAPPS2 phase IIa double-blinded randomised controlled trial will test the efficacy and safety of immunoglobulin and rituximab treatment versus placebo for patients with acute psychosis symptoms as added to psychiatric standard of care.MethodsWe will screen approximately 2500 adult patients with acute psychosis to identify 160 with antibody-positive psychosis without co-existing neurological disease and recruit about 80 eligible participants to the trial in the period from September 2017 to September 2021 across the UK. Eligible patients will be randomised 1:1 either to intravenous immunoglobulin (IVIG) followed by rituximab or to placebo infusions of 1% albumin followed by 0.9% sodium chloride, respectively. To detect a time-to-symptomatic-recovery hazard ratio of 0.322 with a power of 80%, 56 participants are needed to complete the trial, allowing for up to 12 participants to drop out of each group.Eligible patients will be randomised and assessed at baseline within 4 weeks of their eligibility confirmation. The treatment will start with IVIG or 1% albumin placebo infusions over 2–4 consecutive days no later than 7 days from baseline. It will continue 4–5 weeks later with a rituximab or sodium chloride placebo infusion and will end 2–3 weeks after this with another rituximab or placebo infusion. The primary outcome is the time to symptomatic recovery defined as symptomatic remission sustained for at least 6 months on the following Positive and Negative Syndrome Scale items: P1, P2, P3, N1, N4, N6, G5 and G9. Participants will be followed for 12
Yücel M, Oldenhof E, Ahmed SH, et al., 2019, A transdiagnostic dimensional approach towards a neuropsychological assessment for addiction: an international Delphi consensus study, Addiction, Vol: 114, Pages: 1095-1109, ISSN: 0965-2140
BACKGROUND: The US National Institutes of Mental Health Research Domain Criteria (RDoC) seek to stimulate research into biologically validated neuropsychological dimensions across mental illness symptoms and diagnoses. The RDoC framework comprises 39 functional constructs designed to be revised and refined, with the overall goal of improving diagnostic validity and treatments. This study aimed to reach a consensus among experts in the addiction field on the 'primary' RDoC constructs most relevant to substance and behavioural addictions. METHODS: Forty-four addiction experts were recruited from Australia, Asia, Europe and the Americas. The Delphi technique was used to determine a consensus as to the degree of importance of each construct in understanding the essential dimensions underpinning addictive behaviours. Expert opinions were canvassed online over three rounds (97% completion rate), with each consecutive round offering feedback for experts to review their opinions. RESULTS: Seven constructs were endorsed by ≥ 80% of experts as 'primary' to the understanding of addictive behaviour: five from the Positive Valence System (reward valuation, expectancy, action selection, reward learning, habit); one from the Cognitive Control System (response selection/inhibition); and one expert-initiated construct (compulsivity). These constructs were rated to be related differentially to stages of the addiction cycle, with some linked more closely to addiction onset and others more to chronicity. Experts agreed that these neuropsychological dimensions apply across a range of addictions. CONCLUSIONS: The study offers a novel and neuropsychologically informed theoretical framework, as well as a cogent step forward to test transdiagnostic concepts in addiction research, with direct implications for assessment, diagnosis, staging of disorder, and treatment.
Limbrick-Oldfield EH, Cocks IMRE, Flechais RSA, et al., 2019, Impulsivity as a marker of vulnerability to gambling disorder: a study of affected siblings, Publisher: AKADEMIAI KIADO ZRT, Pages: 76-77, ISSN: 2062-5871
Kouimtsidis C, Duka T, Palmer E, et al., 2019, Prehabilitation in alcohol dependence as a treatment model for sustainable outcomes. A narrative review of literature on the risks associated with detoxification, from animal models to human translational research, Frontiers in Psychiatry, Vol: 10, ISSN: 1664-0640
In this review paper, we discuss how the overarching concept of prehabilitation is applicable to alcohol dependence. Central to prehabilitation are the concepts of expected harm, risks, and proactive planning to eliminate the harm or cope with the risks. We review the evidence from animal models, psychological experimental studies, as well as pharmacological studies, on the potential risks and harms associated with medically assisted alcohol detoxification and the current treatment paradigm for alcohol dependence. Animal models provide an approximation mostly of the physical aspect of alcohol withdrawal and detoxification process and make predictions about the development of the phenomena in humans. Despite their limitations, these models provide good evidence that withdrawal from chronic ethanol use induces cognitive impairment, which is worsened by repeated bouts of withdrawal and that these impairments are dependent on the duration of alcohol withdrawal. Initial clinical observations with alcohol-dependent patients confirmed increased incidence of seizures. In recent years, accumulating evidence suggests that patients who have had repeated episodes of withdrawal also show changes in their affect, increased craving, as well as significant deterioration of cognitive abilities, when compared to patients with fewer withdrawals. Alcohol dependence is associated with tolerance and withdrawal, with neuroadaptations in γ-Aminobutyric Acid-A Receptor (GABA-A) and glutamatergic N-methyl-D-aspartate (NMDA) receptors playing key roles. It is suggested that dysregulation of the NMDA receptor system underpins alcohol-related memory impairments. Finally, we discuss the Structured Preparation for Alcohol Detoxification (SPADe) as an example of how prehabilitation has been applied in clinical practice. We discuss the importance of partial control over drinking as an interim step toward abstinence and early introduction of lifestyle changes for both the patient and the immed
Palmer E, Tyacke R, Sastre M, et al., 2019, Alcohol hangover: underlying biochemical, inflammatory and neurochemical mechanisms, Alcohol and Alcoholism, Vol: 54, Pages: 196-203, ISSN: 0735-0414
AIM: To review current alcohol hangover research in animals and humans and evaluate key evidence for contributing biological factors. METHOD: Narrative review with alcohol hangover defined as the state the day after a single episode of heavy drinking, when the alcohol concentration in the blood approaches zero. RESULTS: Many of the human studies of hangover are not well controlled, with subjects consuming different concentrations of alcohol over variable time periods and evaluation not blinded. Also, studies have measured different symptoms and use varying methods of measurement. Animal studies show variations with respect to the route of administration (intragastric or intraperitoneal), the behavioural tests utilised and discrepancy in the timepoint used for hangover onset. Human studies have the advantage over animal models of being able to assess subjective hangover severity and its correlation with specific behaviours and/or biochemical markers. However, animal models provide valuable insight into the neural mechanisms of hangover. Despite such limitations, several hangover models have identified pathological changes which correlate with the hangover state. We review studies examining the contribution of alcohol's metabolites, neurotransmitter changes with particular reference to glutamate, neuroinflammation and ingested congeners to hangover severity. CONCLUSION: Alcohol metabolites, neurotransmitter alterations, inflammatory factors and mitochondrial dysfunction are the most likely factors in hangover pathology. Future research should aim to investigate the relationship between these factors and their causal role.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.