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Biomedical subjects

D Nutt

Publications and source records attributed to D Nutt.

At least 19 recordsLinked to original sources
PubMed2004

Acute carbon dioxide exposure in healthy adults: evaluation of a novel means of investigating the stress response.

Acute hypercapnia was studied to assess its potential as a noninvasive and simple test for evoking neuroendocrine, cardiovascular and psychological responses to stress in man. A single breath of four concentrations of carbon dioxide (CO(2)), 5%, 25%, 35% and 50%, was administered to nine healthy volunteers in a randomized, single-blind fashion. Although no adverse effects occurred, most subjects were unable to take a full inspired vital capacity breath of 50% CO(2). In response to the remaining exposures, subjective and somatic symptoms of anxiety increased in a dose-dependent manner. Unlike 5% and 25% CO(2), 35% CO(2) stimulated significant adrenocorticotropic hormone and noradrenaline release at 2 min and cortisol and prolactin release at 15 min following inhalation. This same dose also provoked a significant bradycardia that was followed by an acute pressor response. No significant habituation of psychological, hypothalamic-pituitary-adrenal (HPA) or cardiovascular responses following 35% CO(2) was seen when this dose was repeated after 1 week. A single breath of 35% CO(2) safely and reliably produced sympathetic and HPA axis activation and should prove a useful addition to currently available laboratory tests of the human stress response.

Adaptation, Physiological↗
PubMed2003

Future directions in substance dependence research.

Substance dependence is a major health problem but increasing understanding of its neurobiology is likely to lead to improved prevention and treatment. Fundamental aspects of dependence include tolerance and withdrawal and the fact that the drug becomes the centre of the addict's world. Neuroimaging has been key in defining underlying neurobiological mechanisms. The activity in particular brain regions has been shown to be altered in addiction. These include the anterior cingulate which is involved in emotional salience and the orbitofrontal cortex, involved in impulse control. Dopamine is the key neurotransmitter since most abused drugs increase its levels, and many pharmacotherapies have targeted this system. The opiate system is also key in mediating the pleasurable effects of some drugs such as alcohol by increasing dopamine levels. The GABA and glutamate systems mediate many of the other effects of alcohol. As the neurobiology of different components of addiction become evident, pharmacological approaches involve exploiting our new understanding which will likely lead to improved treatments.

Brain Chemistry↗
PubMed2001

Effects of contextual priming on reactions to craving and withdrawal stimuli in alcohol-dependent participants.

The researchers investigated craving for alcohol using a computerized contextual priming task involving alcohol-related or alcohol-unrelated words and nonwords under 2 priming conditions in 3 groups of alcohol-dependent participants who had abstained from alcohol for 3 to 14 days, 15 days to 6 months, or more than 6 months. Results indicated that participants who had abstained up to 14 days reacted more slowly to alcohol-related words that followed sentences describing avoidance of withdrawal than did control participants. Furthermore, the first 2 groups of participants reacted more slowly to alcohol-related words that followed craving sentences, compared with neutral words following neutral sentences. The results give preliminary support to the withdrawal and craving models of addiction rather than models that separate craving and withdrawal in early abstinence. Results are discussed in light of current cognitive approaches to alcohol dependence.

Adult↗
PubMed2001

Tryptophan depletion and its implications for psychiatry.

BACKGROUND: Over the past 10 years the technique of tryptophan depletion has been used increasingly as a tool for studying brain serotonergic systems. AIMS: To review the technique of tryptophan depletion and its current status as a tool for investigating psychiatric disorders. METHOD: Systematic review of preclinical and clinical studies. RESULTS: Tryptophan depletion produces a marked reduction in plasma tryptophan and consequently brain serotonin (5-HT) synthesis and release. In healthy volunteers the effects of tryptophan depletion are influenced by the characteristics of the subjects and include some mood lowering, some memory impairment and an increase in aggression. In patients with depression tryptophan depletion tends to result in no worsening of depression in untreated subjects but a relapse in those who have responded to antidepressants (particularly serotonergic agents). In panic disorder the results are similar. CONCLUSIONS: The findings that tryptophan depletion produces a relapse of symptoms in patients with depression and panic disorder who have responded to treatment with antidepressants suggests that enhanced 5-HT function is important in maintaining response in these conditions.

Anxiety Disorders↗
PubMed2000

Impulsiveness and the prolactin response to d-fenfluramine.

RATIONALE: A number of studies have reported abnormalities of serotonin function in aggressive and impulsive behaviours in psychiatric and forensic populations. It is unknown whether this is because serotonin function plays a part in determining the dimension of trait impulsiveness in the general population or whether this is restricted to these behaviourally extreme groups. METHOD: The prolactin response to d-fenfluramine was measured in subjects scoring high and low on a scale of impulsiveness selected from a panel of healthy volunteers screened for impulsiveness. Measures included the 17 impulsiveness scale, State Trait Anger Expression Inventory (STAngXI) and the Tridimensional Personality Questionnaire (TPQ). Plasma cortisol was also determined along with fenfluramine and its metabolite norfenfluramine. RESULTS: The high impulsive group had reduced AUC (PRL) compared with the low impulsive group; this remained significant after adjusting for baseline prolactin, cortisol and drug levels. There was no significant association between impulsiveness, the harm avoidance subscale of the TPQ or trait anger (STAngXI) and prolactin rise. Repeated serum prolactin measures were not significantly different between the two groups. CONCLUSIONS: This study provides some support to the hypothesis that reduced serotonin function contributes to high trait impulsiveness and is not restricted to behaviourally extreme populations.

Adult↗
PubMed2000

Treatment of depression and concomitant anxiety.

The prevalence of depression and concomitant anxiety is high in the community. Patients with depression and concomitant anxiety experience increased functional disability, increased disruption to social, work and family life, and frequently report more symptoms. Treatment needs to be primarily efficacious for depression and secondly for anxiety; both sets of symptoms require prompt and effective treatment. Although benzodiazepines are still prescribed for depression and associated anxiety, they are essentially ineffective in treating depression and therefore are inappropriate. The anxiolytic effect of tricyclic antidepressants (TCAs) takes longer to develop than their antidepressant effect and their adverse tolerability profile can hinder treatment compliance. Selective serotonin re-uptake inhibitors (SSRIs) are a newer class of antidepressants that are as effective as TCAs in treating depression and are well tolerated in the long term and have demonstrated efficacy in the treatment of anxiety. This paper will provide evidence to demonstrate the short- and long-term efficacy of SSRIs in the treatment of depression and comorbid anxiety, with most clinical evidence supporting the anxiolytic profile of the SSRI paroxetine.

Anti-Anxiety Agents↗
PubMed2000

Impulsiveness, serotonin genes and repetition of deliberate self-harm (DSH).

BACKGROUND: Few studies have investigated independent associations of psychological, biological and social variables with repeated deliberate self-harm (DSH). Serotonin function has been linked to impulsive and suicidal behaviour and genetic polymorphisms have been identified within the serotonin system that could account for this link. This study tested hypotheses linking impulsiveness, genetic polymorphisms of tryptophan hydroxylase (TPH) and the 5-HT2c receptor and repeated DSH. METHODS: Individuals presenting after DSH were interviewed, completed personality questionnaires and gave venous blood samples. Genotypes were determined for TPH intron7 and 5-HT2c (cys-ser) polymorphisms. Follow-up to identify repetition of DSH was for 1 year. RESULTS: Males with the 5-HT2c serine variant were more impulsive than those with the cysteine variant (039 standardized units, P = 0.041, 95% CI 0.017 to 0.076). There was no association between impulsiveness and the TPH intron7 polymorphism overall but a weak association with the L allele in men (0.41 standardized units, P = 0.05, 95 % CI 0.001 to 0.82). Impulsiveness, although high in the group as a whole, did not distinguish those who repeated DSH. CONCLUSIONS: The personality trait of impulsiveness may in part be related to genotypes of the 5-HT2c receptor and TPH gene in men. Impulsiveness does not differ between those who do and do not repeat DSH.

Adult↗
PubMed1999

Assessment of GABA(A)benzodiazepine receptor (GBzR) sensitivity in patients on benzodiazepines.

OBJECTIVES: To measure GABA(A) benzodiazepine receptor sensitivity in patients taking benzodiazepines and compare with matched controls. METHODS: Seven patients who were on prescribed benzodiazepines for an anxiety disorder or insomnia were recruited from general practice and an adult mental health service outpatient clinic. They were matched with seven volunteers. All subjects received an intravenous injection of midazolam 50 microgram/kg in 10 ml normal saline over 10 min. Objective responses to midazolam were assessed using saccadic eye movement velocity slowing and subjective assessments using visual analogue scales. Measurements were recorded for 120 min and plasma midazolam concentrations obtained at 15-min intervals post-infusion to 120 min. Ratios of pharmacodynamic/pharmacokinetic effects were obtained for each individual to estimate GABA(A) benzodiazepine receptor sensitivity. RESULTS: Patients had an attenuated response to midazolam on both subjective and objective measures. GABA(A) benzodiazepine receptor sensitivity was significantly reduced in the patient group. CONCLUSIONS: Chronic treatment with benzodiazepines was associated with reduced effects of midazolam. Saccadic eye movement velocity was especially sensitive as a measure of attenuated response.

Adult↗
PubMed1999

Alcohol and the brain. Pharmacological insights for psychiatrists.

BACKGROUND: Alcohol misuse, as well as being a major form of psychiatric morbidity, is also commonly associated with other psychiatric disorders. A greater understanding of the brain mechanisms underlying the adverse effects of alcohol is now possible, thanks to significant research advances made over the past decade. AIMS: To elucidate for psychiatrists the growing knowledge of the importance of specific neurotransmitter interactions in the effects of alcohol. METHOD: A survey of the literature, extracting current knowledge of interest to psychiatrists. RESULTS: There is good evidence that the acute effects of alcohol are mediated through interactions with amino acid neurotransmitters plus parallel changes in amines such as noradrenaline, dopamine and serotonin. Neuroadaptive responses at amino acid receptors probably underlie significant components of the withdrawal syndrome and probably also contribute to neuronal death found in chronic alcoholism. CONCLUSIONS: An understanding of the pharmacology of alcohol use may lead to greater ability to treat psychiatric consequences of alcoholism, and may also prevent some of the secondary psychiatric comorbidity and later brain damage.

Alcohol-Related Disorders↗
PubMed1999

Paroxetine and its uses in psychiatry.

Paroxetine is one of the specific serotonin-reuptake inhibitor antidepressants which is used in a variety of psychiatric disorders. It has recently gained considerable publicity because of its use in social anxiety disorder and its subsequent labelling by the media as a 'lifestyle drug'. This review summarizes current indications for paroxetine and outlines doses and duration of treatment for each condition.

Antidepressive Agents, Second-Generation↗
PubMed1997

Imagery of craving in opiate addicts undergoing detoxification.

Craving is a significant factor in opiate addiction that is associated with drug-dependence and in relapse to drug use after treatment. In order to better understand the psychological and physiological mechanisms of craving for opiates, we have developed an imagery-based procedure using personal verbal descriptions of craving in abstinent opiate addicts. Thirteen opiate addicts in detoxification were required to imagine and describe their craving experiences while autonomic measures of heart rate and arterial pressure were taken. Subjects displayed a significant increase in systolic blood pressure and heart rate while describing drug craving compared with neutral descriptions. Furthermore, an increase in systolic blood pressure during imagery of craving descriptions compared with neutral descriptions was observed. These results provide preliminary evidence that imagery is powerful in eliciting craving for opiates, as indicated by subjective ratings and autonomic measures. The implications of the results of this paper for the cue-exposure paradigm and contemporary models of addiction are being discussed.

Adult↗
PubMed1997

Mirtazapine: pharmacology in relation to adverse effects.

Mirtazapine is a new antidepressant that falls into the general class of receptor-blocking drugs rather than being an uptake or enzyme inhibitor. It can be described as a noradrenergic and specific serotonergic antidepressant (NaSSA). The unique pharmacology of mirtazapine means that it has a very different side effect profile from the tricyclic antidepressants, producing less alpha 1 adrenergic and muscarinic blockade, and the selective serotonin reuptake inhibitors (SSRIs) and the serotonin-noradrenaline reuptake inhibitors (SNRIs), causing much less nausea and sexual dysfunction by virtue of its blockade of 5-HT2 and 5-HT3 receptors.

Adrenergic alpha-Antagonists↗