Publications
30 results found
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.
Kalafatakis K, Russell GM, Harmer CJ, et al., 2018, Ultradian rhythmicity of plasma cortisol is necessary for normal emotional and cognitive responses in man, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 115, Pages: E4091-E4100, ISSN: 0027-8424
Hart EC, Ratcliffe LEK, Narkiewicz K, et al., 2016, Unilateral carotid body resection in patients with resistant hypertension: a safety and feasibility trial, FASEB JOURNAL, Vol: 30, ISSN: 0892-6638
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- Citations: 2
Nahar LK, Cordero R, Nutt D, et al., 2016, Validated method for the quantification of baclofen in human plasma using solid-phase extraction and liquid chromatography–tandem mass spectrometry, Journal of Analytical Toxicology, Vol: 40, Pages: 117-123, ISSN: 0146-4760
A highly sensitive and fully validated method was developed for the quantification of baclofen in human plasma. After adjusting the pH of the plasma samples using a phosphate buffer solution (pH 4), baclofen was purified using mixed mode (C8/cation exchange) solid-phase extraction (SPE) cartridges. Endogenous water-soluble compounds and lipids were removed from the cartridges before the samples were eluted and concentrated. The samples were analyzed using triple-quadrupoleliquid chromatography–tandem mass spectrometry (LC–MS-MS) with triggered dynamic multiple reaction monitoring mode for simultaneous quantification and confirmation. The assay was linear from 25 to 1,000 ng/mL (r2 > 0.999; n = 6). Intraday (n = 6) and interday (n = 15) imprecisions (% relative standard deviation) were <5%, and the average recovery was 30%. The limit of detection of the method was 5 ng/mL, and the limit of quantification was 25 ng/mL. Plasma samples from healthymale volunteers (n = 9, median age: 22) given two single oral doses of baclofen (10 and 60 mg) on nonconsecutive days were analyzed to demonstrate method applicability.
Kalafatakis K, Russell GM, Harmer CJ, et al., 2016, Effects of the pattern of glucocorticoid replacement on neural processing, emotional reactivity and well-being in healthy male individuals: study protocol for a randomised controlled trial, Trials, Vol: 17, ISSN: 1745-6215
BACKGROUND: Deviation from the physiological glucocorticoid dynamics (circadian and underlying ultradian rhythmicity) is a common characteristic of various neuropsychiatric and endocrine disorders as well as glucocorticoid-based therapeutics. These states may be accompanied by neuropsychiatric symptomatology, suggesting continuous dynamic glucocorticoid equilibrium is essential for brain homeostasis. METHODS/DESIGN: The study consists of two parts. The preliminary stage of the study aims to validate (technically and pharmacologically) and optimise three different patterns of systemic cortisol administration in man. These patterns are based on the combinatory administration of metyrapone, to suppress endogenous cortisol production, and concurrent hydrocortisone replacement. The second, subsequent, core part of the study is a randomised, double-blinded, placebo-controlled, crossover study, where participants (healthy male individuals aged 18-60 years) will undergo all three hydrocortisone replacement schemes. During these infusion regimes, we plan a number of neurobehavioural tests and imaging of the brain to assess neural processing, emotional reactivity and perception, mood and self-perceived well-being. The psychological tests include: ecological momentary assessment, P1vital Oxford Emotional Test Battery and Emotional Potentiated Startle Test, Leeds Sleep Evaluation Questionnaire and the visual working memory task (n-back). The neuroimaging protocol combines magnetic resonance sequences that capture data related to the functional and perfusion status of the brain. DISCUSSION: Results of this clinical trial are designed to evaluate the impact (with possible mechanistic insights) of different patterns of daily glucocorticoid dynamics on neural processing and reactivity related to emotional perception and mood. This evidence should contribute to the optimisation of the clinical application of glucocorticoid-based therapeutics. TRIAL REGISTRATION: UK Clinical Research
Hellmich C, Durant C, Jones MW, et al., 2015, Genetics, sleep and memory: a recall-by-genotype study of ZNF804A variants and sleep neurophysiology, BMC Medical Genetics, Vol: 16, ISSN: 1471-2350
BACKGROUND: Schizophrenia is a complex, polygenic disorder for which over 100 genetic variants have been identified that correlate with diagnosis. However, the biological mechanisms underpinning the different symptom clusters remain undefined. The rs1344706 single nucleotide polymorphism within ZNF804A was among the first genetic variants found to be associated with schizophrenia. Previously, neuroimaging and cognitive studies have revealed several associations between rs1344706 and brain structure and function. The aim of this study is to use a recall-by-genotype (RBG) design to investigate the biological basis for the association of ZNF804A variants with schizophrenia. A RBG study, implemented in a population cohort, will be used to evaluate the impact of genetic variation at rs1344706 on sleep neurophysiology and procedural memory consolidation in healthy participants. METHODS/DESIGN: Participants will be recruited from the Avon Longitudinal Study of Parents and Children (ALSPAC) on the basis of genotype at rs1344706 (n = 24). Each participant will be asked to take part in two nights of in-depth sleep monitoring (polysomnography) allowing collection of neurophysiological sleep data in a manner not amenable to large-scale study. Sleep questionnaires will be used to assess general sleep quality and subjective sleep experience after each in-house recording. A motor sequencing task (MST) will be performed before and after the second night of polysomnography. In order to gather additional data about habitual sleep behaviour participants will be asked to wear a wrist worn activity monitor (actiwatch) and complete a sleep diary for two weeks. DISCUSSION: This study will explore the biological function of ZNF804A genotype (rs1344706) in healthy volunteers by examining detailed features of sleep architecture and physiology in relation to motor learning. Using a RBG approach will enable us to collect precise and detailed phenotypic data whilst achieving an informative biol
Turton S, Durant C, Wilson S, et al., 2015, GABA-B receptor function in healthy volunteers, a pharmacokinetic and pharmacodynamic study of two doses of baclofen compared to placebo
AIMS AND HYPOTHESISTo assess the subjective and objective effects of baclofen on brain function in healthy volunteers. BACKGROUNDRecent evidence suggests baclofen, a γ-aminobutyric acid type B (GABA-B) receptor agonist, reduces alcohol consumption and craving and promotes abstinence in alcoholics. However, characterisation of the GABA-B receptor system in clinical addiction is limited, and it is unclear why some patients require, or tolerate, higher doses to treat alcoholism. This study assesses the effects of baclofen on brain function in healthy volunteers to inform future studies investigating the sensitivity of GABA-B receptors in alcohol addiction. METHODSEight healthy male volunteers completed a double blind randomised 3-way cross over study, receiving oral placebo (vitamin C 100mg), 10mg and 60mg baclofen. Subjective and objective measurements were taken at baseline (before medication) and at +30mins, 1, 2, 3, 4 and 6 hours after dosing. Objective measures included blood plasma samples, heart rate and blood pressure. Subjective measures included; the Subjective High Assessment Questionnaire (SHAS), visual analogue scales for sleepy, relaxed, tense and alert and a motor coordination task (zig-zag task). Pharmacokinetic data was obtained using liquid chromatography mass-spectrometry (LC-MS) to measure plasma baclofen concentrations.RESULTS60mg Baclofen showed changes in subjective measures peaking at 2 hours post dosing compared with placebo, including a significant increase (p<0.05) in total SHAS scores with individual items, including feeling ‘drunk or intoxicated’, effects of alcohol and ‘muddled or confused’ particular affected.. Systolic blood pressure was significantly increased (p<0.05) at the 2 hours post 60mg dose. For both 10mg and 60mg baclofen, peak plasma concentration was achieved 60 minutes post dose. Pharmacokinetic data will be presented. There were no significant changes in these measures between 10mg Baclof
Harrison L, Durant C, Wilson S, et al., 2015, The effects of sleep disruption on central pain modulation: A polysomnographic study in healthy volunteers, ECNP Workshop for Junior Scientists in Europe, Publisher: ELSEVIER SCIENCE BV, Pages: S89-S89, ISSN: 0924-977X
Russell GM, Durant C, Ataya A, et al., 2014, Subcutaneous pulsatile glucocorticoid replacement therapy, CLINICAL ENDOCRINOLOGY, Vol: 81, Pages: 289-293, ISSN: 0300-0664
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- Citations: 28
Russell GM, Durant C, Ataya A, et al., 2014, Pulsed Glucocorticoid Replacement Therapy - a Novel Treatment Modality, Publisher: ENDOCRINE SOC, ISSN: 0163-769X
Malizia AL, Rich AS, Durant CM, et al., 2013, DEEP BRAIN STIMULATION OF NUCLEUS ACCUMBENS AND POSTERIOR SUBGENUAL CINGULATE DO NOT RESULT IN LASTING BENEFITS FOR PATIENTS WITH CHRONIC AND SEVERE TREATMENT RESISTANT DEPRESSION, Publisher: ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, ISSN: 0924-9338
Durant CF, Wilson SJ, Lightman S, et 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
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- Citations: 1
Bould H, Panicker V, Kessler D, et al., 2012, Investigation of thyroid dysfunction is more likely in patients with high psychological morbidity, FAMILY PRACTICE, Vol: 29, Pages: 163-167, ISSN: 0263-2136
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- Citations: 14
Durant CF, Wilson SJ, Lightman S, et 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
Wilson SJ, Paterson LM, Durant CF, et 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
Tyacke RJ, Durant CF, Paterson LM, et 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
Budd M, Tyacke RJ, Wilson SJ, et al., 2010, SUBJECTIVE AND OBSERVED MOOD CHANGES WITH ACUTE DEEP BRAIN STIMULATION OF THE SUBGENUAL CINGULATE (SGC), OF THE VENTRAL CAPSULE OR OF THE NUCLEUS ACCUMBENS (VACNAC): PRELIMINARY RESULTS FROM A DOUBLE BLIND CROSSOVER STUDY, Summer Meeting of the British-Association-for-Psychopharmacology, Publisher: SAGE PUBLICATIONS LTD, Pages: A82-A82, ISSN: 0269-8811
Durant C, Malizia AL, Paterson L, et al., 2010, Acute deep brain stimulation in the subgenual cingulate alters REM sleep in patients with treatment resistant depression, 23rd Congress Meeting of European-College-of-Neuropsychopharmacology, Publisher: ELSEVIER SCIENCE BV, Pages: S343-S343, ISSN: 0924-977X
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- Citations: 1
Durant CF, Malizia AL, Paterson LM, et al., 2010, DEEP BRAIN STIMULATION IN THE SUBGENUAL CINGULATE ALTERS REM SLEEP IN PATIENTS WITH TREATMENT RESISTANT DEPRESSION, Summer Meeting of the British-Association-for-Psychopharmacology, Publisher: SAGE PUBLICATIONS LTD, Pages: A54-A54, ISSN: 0269-8811
Harrison L, Griffith L, Koukouni E, et al., 2010, NEUROPSYCHOLOGICAL CHARACTERISTICS OF PATIENTS UNDERGOING DEEP BRAIN STIMULATION FOR TREATMENT RESISTANT DEPRESSION: BASELINE MEASURES AND SINGLE CASE REPORT, Summer Meeting of the British-Association-for-Psychopharmacology, Publisher: SAGE PUBLICATIONS LTD, Pages: A53-A53, ISSN: 0269-8811
Rich AS, Srivastava S, Durant CF, et al., 2010, THE CLINICAL CHARACTERISTICS OF PATIENTS WITH TREATMENT RESISTANT DEPRESSION REFERRED FOR DEEP BRAIN STIMULATION, Summer Meeting of the British-Association-for-Psychopharmacology, Publisher: SAGE PUBLICATIONS LTD, Pages: A53-A53, ISSN: 0269-8811
Diaper AM, Holmes RB, Talbot PS, et al., 2010, BLOOD FLOW CHANGES DURING DEEP BRAIN STIMULATION FOR TREATMENT RESISTANT DEPRESSION: A PET STUDY, Summer Meeting of the British-Association-for-Psychopharmacology, Publisher: SAGE PUBLICATIONS LTD, Pages: A53-A53, ISSN: 0269-8811
Durant C, Malizia AL, Paterson L, et al., 2010, Acute deep brain stimulation in the subgenual cingulate alters REM sleep in patients with treatment resistant depression, 23rd Congress Meeting of European-College-of-Neuropsychopharmacology, Publisher: ELSEVIER SCIENCE BV, Pages: S343-S343, ISSN: 0924-977X
Durant CF, Christmas D, Nutt DJ, 2010, The Pharmacology of Anxiety, Behavioral Neurobiology of Anxiety and Its Treatment, Editors: Stein, Steckler, Publisher: Springer Verlag, Pages: 303-330, ISBN: 9783642029110
The book aims to cover a broad range of topics related to anxiety disorders, including symptomatology, etiology, epidemiology, diagnostic features, comorbidity, clinical neuroscience, genetics, neuroanatomy, neuroendocrinology, ...
Paterson LM, Nutt DJ, Durant C, et al., 2009, Efficacy of trazodone in primary insomnia; a double-blind randomised placebo controlled polysomnographic study, 22nd Congress of the European-College-of-Neuropsychopharmacology, Publisher: ELSEVIER SCIENCE BV, Pages: S385-S386, ISSN: 0924-977X
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- Citations: 2
Durant C, Wilson S, Paterson L, et al., 2009, Sleep changes during deep brain stimulation for treatment resistant depression: preliminary findings from a case study, European-College-of-Neuropsychopharmacology Workshop on Neuropsychopharmacology for Young Scientists in Europe, Publisher: ELSEVIER SCIENCE BV, Pages: S67-S68, ISSN: 0924-977X
Durant CF, Wilson SJ, Paterson LM, et al., 2008, Sleep changes associated with mood improvement during acute deep brain stimulation of two different brain targets for treatment resistant depression, 19th Congress of the European-Sleep-Research-Society, Publisher: WILEY-BLACKWELL PUBLISHING, INC, Pages: 259-260, ISSN: 0962-1105
Panicker V, Cluett C, Shields B, et al., 2008, A common variation in deiodinase 1 gene DIO1 is associated with the relative levels of free thyroxine and triiodothyronine, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 93, Pages: 3075-3081, ISSN: 0021-972X
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- Citations: 96
Luyt K, Slade TP, Dorward JJ, et al., 2007, Developing oligodendrocytes express functional GABA(B) receptors that stimulate cell proliferation and migration, JOURNAL OF NEUROCHEMISTRY, Vol: 100, Pages: 822-840, ISSN: 0022-3042
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- Citations: 71
Luyt K, Varadi A, Durant CF, et al., 2006, Oligodendroglial metabotropic glutamate receptors are developmentally regulated and involved in the prevention of apoptosis, JOURNAL OF NEUROCHEMISTRY, Vol: 99, Pages: 641-656, ISSN: 0022-3042
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- Citations: 50
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