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Biomedical subjects

A H Young

Publications and source records attributed to A H Young.

At least 19 recordsLinked to original sources
PubMed2005

Prevalence of obesity, glucose homeostasis disorders and metabolic syndrome in psychiatric patients taking typical or atypical antipsychotic drugs: a cross-sectional study.

AIMS/HYPOTHESIS: Atypical antipsychotic drugs may be associated with obesity and other components of the metabolic syndrome, but this relationship is controversial. We investigated the hypothesis that atypical antipsychotics are associated with a greater degree of metabolic dysfunction than typical agents. METHODS: Metabolic parameters were measured in 103 diagnostically heterogeneous psychiatric out-patients. Patients had been taking typical or atypical antipsychotic drugs for a minimum of six months. RESULTS: Sixty-nine patients were taking atypical agents, 20 typical agents and 14 a combination. Mean values (+/-SD) for the whole group were: age 43.8 years (11.4); BMI 29.1 kg/m(2) (5.1); W:H ratio 0.88 (0.09). Metabolic parameters, including beta cell function and insulin sensitivity, measured by HOMA, did not differ with regard to the prescribed antipsychotic drug. Six patients had undiagnosed diabetes, six patients had impaired fasting glucose, and eight fulfilled criteria for the metabolic syndrome, all of whom were taking atypical agents (p=0.07 vs typical agents). Subgroup analyses of those taking atypical agents revealed differences in BMI (mean, +/-SD) between olanzapine (27.3 kg/m(2)+/-5.1) and quetiapine (31.9 kg/m(2)+/-5.1), p=0.01, and HbA(1c) (olanzapine, 5.1%+/-0.6 vs quetiapine, 5.6%+/-0.6; p=0.03). Other atypical agents were intermediate with regard to these parameters. CONCLUSIONS: Obesity, dyslipidaemia and abnormalities of glucose homeostasis are prevalent in this group. Patients taking atypical agents showed a trend towards abnormalities of glucose homeostasis. Prospective studies are needed to explore the precise relationship between antipsychotic drugs, glucose homeostasis, obesity and the metabolic syndrome.

Adult↗
PubMed2005

Hypothalamic-pituitary-adrenal axis and bipolar disorder.

There is robust evidence demonstrating abnormalities of the HPA axis in bipolar disorder. Hypercortisolism may be central to the pathogenesis of depressive symptoms and cognitive deficits, which may in turn result from neurocytotoxic effects of raised cortisol levels. Manic episodes may be preceded by increased ACTH and cortisol levels, leading to cognitive problems and functional impairments. Identification and effective treatment of mood and cognitive symptoms of mood disorders are clinical goals, but currently available treatments may fall short of this ideal. Manipulation of the HPA axis has been shown to have therapeutic effects in preclinical and clinical studies, and recent data suggest that direct antagonism of GRs maybe a future therapeutic strategy in the treatment of mood disorders.

Antimanic Agents↗
PubMed2005

Aripiprazole in schizophrenia: consensus guidelines.

Schizophrenia is a chronic disabling disease which in the majority of cases requires long-term treatment with antipsychotic medication. Before the development of atypical antipsychotics, treatment choice was restricted to conventional (or typical) antipsychotics, which are known to cause a range of side effects including extrapyramidal symptoms. Although atypical agents provide a favourable alternative (advocated by the National Institute of Clinical Excellence in the UK), they are associated with side effects. These differ between agents, but can include weight gain, sedation and hyperprolactinaemia. Aripiprazole is a newly available atypical antipsychotic for the treatment of schizophrenia. With the apparent imitations of currently available medications, aripiprazole provides clinicians with another treatment option. The purpose of these guidelines is to outline the consensus reached by the Schizophrenia Innovation Working Group on best practice in prescribing and appropriate use of aripiprazole in the UK.

Antipsychotic Agents↗
PubMed2005

Cannabinoids in bipolar affective disorder: a review and discussion of their therapeutic potential.

Bipolar affective disorder is often poorly controlled by prescribed drugs. Cannabis use is common in patients with this disorder and anecdotal reports suggest that some patients take it to alleviate symptoms of both mania and depression. We undertook a literature review of cannabis use by patients with bipolar disorder and of the neuropharmacological properties of cannabinoids suggesting possible therapeutic effects in this condition. No systematic studies of cannabinoids in bipolar disorder were found to exist, although some patients claim that cannabis relieves symptoms of mania and/or depression. The cannabinoids Delta(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) may exert sedative, hypnotic, anxiolytic, antidepressant, antipsychotic and anticonvulsant effects. Pure synthetic cannabinoids, such as dronabinol and nabilone and specific plant extracts containing THC, CBD, or a mixture of the two in known concentrations, are available and can be delivered sublingually. Controlled trials of these cannabinoids as adjunctive medication in bipolar disorder are now indicated.

Arachidonic Acids↗
PubMed2004

Effects of the menstrual cycle on mood, neurocognitive and neuroendocrine function in healthy premenopausal women.

BACKGROUND: Neurocognitive functioning may be impaired in the luteal phase of the menstrual cycle due to associated changes in hypothalamic-pituitary adrenal (HPA) axis function. This study examines the relationship between changes in neurocognition and HPA axis function in different phases of the menstrual cycle. METHOD: Fifteen female volunteers, free from psychiatric history and hormonal medication were tested twice, during mid-follicular and late-luteal phases in a randomized, crossover design. Mood, neurocognitive function, and basal cortisol and dehydroepiandrosterone (DHEA) were profiled. RESULTS: Relative to the follicular phase, verbal fluency was impaired in the luteal phase and reaction times speeded on a continuous performance task, without affecting overall accuracy. 'Hedonic' scores on the UWIST-MACL scale were decreased in the luteal phase. There was also evidence of changes in the function of the HPA axis, with 24 h urinary cortisol concentrations and salivary DHEA levels being significantly lower during the luteal phase. CONCLUSIONS: These data suggest that luteal phase HPA axis function is lower than in the follicular phase in premenopausal healthy women. This putative biological difference may be important for our understanding of the aetiopathogenesis of menstrually related mood change and neurocognitive disturbance.

Adolescent↗
PubMed2003

Altered glucocorticoid rhythm attenuates the ability of a chronic SSRI to elevate forebrain 5-HT: implications for the treatment of depression.

Both glucocorticoids and selective serotonin reuptake inhibitors (SSRIs) alter aspects of 5-HT function including somatodendritic 5-HT1A autoreceptor sensitivity. Many depressed patients prescribed SSRIs have pre-existing flattened diurnal gluococorticoid rhythm. In these patients, interactions between flattened glucocorticoid rhythm and chronic SSRIs, which impact on the SSRI's ability to elevate forebrain 5-HT, may alter clinical efficacy. To address this issue rats underwent implantation of slow-release corticosterone (75 mg pellet s.c.) (to flatten the glucocorticoid rhythm) or sham surgery, and injection of fluoxetine (10 mg/kg/day i.p., 12 days) or vehicle. Using microdialysis in the frontal cortex we found that (21 h after the last injection) extracellular 5-HT was elevated in fluoxetine- or corticosterone-treated animals, but not in those treated with corticosterone plus fluoxetine. In fluoxetine-treated animals, blockade of terminal reuptake by local perfusion of fluoxetine increased 5-HT to the same level as it did in controls, suggesting normal terminal 5-HT release after chronic fluoxetine. However, 5-HT levels following local reuptake blockade in both the corticosterone and corticosterone plus fluoxetine groups were lower than controls, suggesting a corticosterone-induced decrease in terminal release. Finally in fluoxetine, corticosterone, and corticosterone plus fluoxetine groups, there was marked 5-HT1A receptor desensitization, evidenced by attenuation of the decrease in 5-HT release following systemic fluoxetine injection. The data indicate that, despite desensitization of 5-HT1A autoreceptors, concurrent flattened glucocorticoid rhythm compromises the ability of SSRIs to elevate forebrain 5-HT. These findings suggest a potential mechanism for the reduced antidepressant efficacy of SSRIs in those patients with pre-existing glucocorticoid abnormalities.

Analysis of Variance↗
PubMed2002

Hypothalamic-pituitary-adrenal axis function in patients with chronic depression.

BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) axis function in patients with chronic depression has previously been shown to be normal when measured using the dexamethasone suppression test (DST). We examined patients with chronic depression using the sensitive dexamethasone/corticotropin releasing hormone (dex/CRH) test and the dexamethasone suppression test (DST) to establish whether HPA axis abnormalities are present in this group. We also compared the sensitivity of the two tests and compared the results with previous studies in depression that have not specifically selected chronic patients. METHOD: Twenty-nine patients with the chronic subtype of major depressive disorder and 28 matched controls underwent examination of HPA axis function. RESULTS: Neither the cortisol response to the DST or the dex/CRH test differed significantly between the patient and control groups. There was a trend in favour of more patients than controls having an abnormal response to the dex/CRH test (P = 0.052). Neither the patients with an abnormally enhanced response, nor the magnitude of response could be predicted by any illness or demographic variable. CONCLUSION: The HPA axis is not overtly abnormal in chronic depression. This contrasts with previous findings in acute depression and bipolar disorder and may suggest that the HPA axis abnormalities present in acute depression resolve, but are not accompanied by symptom resolution. Alternatively, a subgroup of depressives with less HPA dysfunction may progress to chronicity. This has implications for treatment and prognosis. The dex/CRH is a more sensitive test of HPA axis function than the DST in patients with chronic depression.

Adult↗
PubMed2002

A systematic review of the use of atypical antipsychotics in autism.

Conventional antipsychotic medication is commonly prescribed to patients with autistic spectrum disorder. However, a high incidence of severe adverse reactions highlights the need to find more favourable treatments. Atypical antipsychotics may combine efficacy in ameliorating some autistic symptoms with a lower incidence of some adverse reactions. This article reviews the use of atypical antipsychotics in autistic disorder, with particular focus on behaviour, cognition and physical well-being. Thirteen studies using risperidone, three using olanzapine, one using clozapine, one using amisulpride and one using quetiapine were identified. Few firm conclusions can be drawn due to the limitations of the studies; however, there is an indication that risperidone may be effective in reducing hyperactivity, aggression and repetitive behaviours, often without inducing severe adverse reactions. Olanzapine and clozapine may also be effective; however, there is little evidence for using amisulpride or quetiapine in this population. Randomized trials are required to clarify the effectiveness of these agents.

Antipsychotic Agents↗
PubMed2001

PET measurement of the influence of corticosteroids on serotonin-1A receptor number.

BACKGROUND: The hypothalamic-pituitary-adrenal (HPA) axis and serotonergic system interact functionally. The modulatory effect of corticosteroids on 5-HT(1A) receptor number and function has been repeatedly demonstrated in preclinical studies suggesting that raised corticosteroid levels decrease 5-HT(1A) receptor number and function in the hippocampus. METHODS: We used positron emission tomography (PET) to quantify the number of 5-HT(1A) receptors in two studies, the first in normal subjects given a single dose of hydrocortisone using a random-order, double-blind, placebo-controlled design and second in patients treated long-term with corticosteroids. RESULTS: We did not find that exposure to elevated levels of corticosteroids in either the short or long term alters 5-HT(1A) receptor binding in the hippocampus or other brain regions examined. CONCLUSIONS: This study does not support the hypothesis that corticosteroids exert a major inhibitory regulatory control over the 5-HT(1A) receptor binding in the human brain.

Adult↗
PubMed2001

Basal activity of the hypothalamic-pituitary-adrenal axis in patients with depersonalization disorder.

Depersonalisation disorder may occur during severe anxiety or following a traumatic event, suggesting a possible role of stress hormones. This study investigated basal activity of the hypothalamic-pituitary-adrenal (HPA) axis in patients with depersonalisation disorder. Salivary cortisol levels were measured at four time points over 12 h in patients with depersonalisation disorder (N=13), major depressive disorder (MDD, N=14) and healthy controls (N=13). Beck Depression Inventory scores were significantly higher in depersonalised subjects than controls, while MDD subjects demonstrated higher scores than both groups. Basal cortisol levels of depersonalised subjects were significantly lower than those of MDD subjects but not healthy controls. These results point to reduced basal activity of the HPA axis in depersonalisation disorder. This pilot study supports the distinction between depersonalisation disorder and major depressive disorder which should be examined in a larger sample.

Adult↗
PubMed2001

Acute tryptophan depletion in schizophrenia.

BACKGROUND: Brain 5-hydroxytryptamine (5-HT) function is implicated in the pathophysiology of schizophrenia and the action of new generation antipsychotic drugs. By the method of acute tryptophan depletion (ATD) 5-HT can be selectively manipulated. The aim of this study was to examine the effects of ATD on symptoms, mood and cognition in schizophrenic patients. METHODS: Twenty-eight schizophrenic patients participated in a within subject, double-blind, placebo-controlled counterbalanced cross-over study. Patients with a concurrent DSM-IV axis I diagnosis were excluded. Symptoms, mood and cognitive function were evaluated following ATD or ingestion of a control drink. RESULTS: The depleting drink significantly reduced plasma total and free tryptophan. Tryptophan/LNAA ratios did not alter with the administration of the control drink, but differed significantly with ATD; however there was no significant change in tyrosine/LNAA ratio. ATD led to impairment in executive function that was dependent upon the order of administration. Tests of sustained attention, speed of processing, and everyday memory were not affected. No effects were observed on subjective mood ratings, movement disorders or PANSS scores. CONCLUSIONS: Acute tryptophan depletion selectively alters cognition in schizophrenia, but has no effect on symptoms, mood ratings or movement disorders.

Administration, Oral↗
PubMed2001

Corticosterone selectively attenuates 8-OH-DPAT-mediated hypothermia in mice.

The 5-HT1A agonist 8-OH-DPAT produces a hypothermia in mice mediated by somatodendritic 5-HT1A receptors, that is attenuated by antidepressants and corticosterone. The present study investigated if the effect of corticosterone is specific to the serotonergic system or a non-specific effect on thermoregulation. Administration of corticosterone for 3 d had no effect on dopaminergic (apomorphine) or adrenergic (clonidine) hypothermic challenges. However in addition to 8-OH-DPAT, nicotine-induced hypothermia was attenuated by corticosterone. Administration of the selective nicotinic antagonist mecamylamine had no effect on 8-OH-DPAT-induced hypothermia, although nicotine-induced hypothermia was attenuated by the selective 5-HT1A antagonist WAY-100635. This demonstrates a serotonergic-nicotinic interaction in the generation of hypothermia in mice and is consistent with corticosterone selectively attenuating somatodendritic 5-HT1A receptor function.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2001

Raised levels of plasma interleukin-1beta in major and postviral depression.

OBJECTIVE: Interleukin-1beta (IL-1beta) is released as part of the acute phase immune response and can directly stimulate the release of corticotrophin-releasing hormone and thus induce hypothalamic pituitary adrenal axis hyperactivity. Major depression has been shown to be accompanied by both an acute phase immune response, including raised IL-1beta production and hypothalamic pituitary adrenal axis hyperactivity. In this study the possible role of IL-1beta in major depression and postviral depression was investigated. METHOD: Plasma IL-1beta levels were measured in four groups; patients suffering from postviral depression (n= 17), patients with major depression (n = 20), subjects who were postviral and euthymic (n= 12) and normal controls (n = 20). RESULTS: IL-1beta serum concentrations were significantly elevated in both groups of depressed patients compared to controls. The serum concentrations of IL-1beta were higher in the postviral group than in the major depression group; this difference was not significant. CONCLUSION: These data confirm previous suggestions of elevated IL-1beta levels in major depression and postviral depression. IL-1beta is known to induce depressive symptoms as well as sickness behaviour and may contribute to the hypothalamic pituitary adrenal axis hyperactivity found in mood disorders.

Major Depressive Disorder↗