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Biomedical subjects

Veronica O'Keane

Publications and source records attributed to Veronica O'Keane.

11 recordsLinked to original sources
PubMed2005

Antipsychotic drugs: a new risk factor for osteoporosis in young women with schizophrenia?

Schizophrenic illness is associated with high rates of osteoporosis, the etiology of which remains obscure, but which may be at least partly explained by the prolactin-raising properties of antipsychotic medication. Conventional antipsychotics all cause hyperprolactinemia, whereas a limited number of atypical antipsychotic drugs do not. To investigate this further, we designed a cross-sectional comparison study between groups taking either prolactin-raising or prolactin-sparing antipsychotic medication. Participants were required to be premenopausal women with a diagnosis of schizophrenia, and to have received exclusively either prolactin-raising (n = 26), or olanzapine (n = 12) antipsychotic medication. Half of the subjects in the prolactin-raising group were being treated with conventional (n = 13), and half with newer "atypical," antipsychotic drugs (n = 13). Subjects had lumbar spine and hip bone mineral density (BMD) evaluated by a dual-energy x-ray absorptiometer (DEXA) scan. A blood sample was taken to measure prolactin and sex hormone axis measures. The results demonstrated that the group taking prolactin-raising medication had higher rates of bone pathology, compared with the olanzapine group. High prolactin levels were related to measures of hypogonadism and low BMD values. Within the prolactin-raising group, those taking newer atypical compounds had higher levels of prolactin, lower levels of sex hormones, and lower BMD values than the group taking conventional antipsychotic medication. These findings suggest that the high rates of osteoporosis associated with schizophrenia may result from hypogonadism secondary to antipsychotic-induced hyperprolactinemia, and that the prolactin-raising profile of antipsychotic drugs should be considered when choosing an antipsychotic drug.

Absorptiometry, Photon↗
PubMed2004

Prevalence of post-stroke depression in an Irish sample and its relationship with disability and outcome following inpatient rehabilitation.

PURPOSE: (1). To examine the prevalence of depressive symptoms and operationally defined depressive disorder (major depression) in an Irish sample of subjects undergoing inpatient rehabilitation following their first stroke. (2). To investigate factors predictive of depression following stroke. (3). To examine the relationship between post-stroke depression and outcome following inpatient rehabilitation. METHODS: Fifty consecutive patients meeting inclusion criteria who were admitted for inpatient rehabilitation to a specialised unit following their first stroke were prospectively studied. INCLUSION CRITERIA: first stroke 3 - 12 months previously, lesion identified on CT or MRI, age 18 - 65 years, at least some sensory/motor impairment, no pre-existing disabling condition and Barthel Index score > 14 prior to stroke. Mood (Center for Epidemiologic Studies Depression scale, Hamilton Depression Rating Scale, DSM-IV diagnostic criteria for Major Depressive Disorder), Cognition (Mini-Mental State Examination) and Disability (Barthel Index, Rankin Disability Scale) were assessed one week after admission (baseline) and again after 2 months of rehabilitation. Outcome was measured as effectiveness of rehabilitation (Shah et al., 1990) and length of inpatient stay (LOS). RESULTS: 10/50 (20%) of the sample met criteria for major depressive disorder on admission. The best predictor of depression was gender, with females having a two-fold higher rate of both subjectively reported and objectively rated depressive symptoms. Depression was unrelated to baseline Barthel Disability, side of lesion or previous psychiatric history. The best predictor of effectiveness of rehabilitation was baseline Barthel Disability score. Depression did not predict either effectiveness or LOS. CONCLUSION: (1). Major depression is common in subjects undergoing rehabilitation following their first stroke. (2). Females appear to be especially at risk, possibly reflecting an increased general risk of depression. (3). Depression in our sample was not related to functional disability following stroke or early functional outcome following rehabilitation.

Adult↗
PubMed2003

Platelet surface glycoprotein expression in post-stroke depression: a preliminary study.

Depression is a significant risk factor for and consequence of both cardiovascular disease and stroke. The pathophysiological processes underlying this association are poorly understood. This study utilised a technique for measurement of whole blood platelet surface glycoproteins involved in early adhesion and aggregation in sample populations of patients with depression and stroke, and healthy controls. We analysed the platelet surface glycoproteins GPIb and GPIIbIIIa using flow cytometry in eight depressed subjects (Hamilton depression score >17), 14 post-stroke subjects (seven depressed and seven non-depressed), and in eight healthy control subjects. The number of GPIb receptors was significantly increased in subjects with depression and in post-stroke subjects compared to control subjects. The number of GPIb receptors from post-stroke subjects was not significantly different from that of depressed subjects. There were no differences between any groups in measures of GPIIbIIIa receptor numbers. No additive effect of co-morbid depression on the surface expression level of either marker could be detected in the post-stroke subjects. Platelet dysfunction may be involved in the pathophysiological process underlying the association between depression and cerebrovascular disease.

Adult↗
PubMed2003

Differing central amine receptor sensitivity in different migraine subtypes? A neuroendocrine study using buspirone.

Despite the importance of the 5HT1A receptor in regulating central serotonergic tone, there is a dearth of research examining its role in migraine. In this study, we examined the hypothesis that there would be altered neuroendocrine responses to a 5HT1A agonist challenge in different migraine subtypes. Prolactin (PRL) responses to the 5HT1A receptor agonist drug buspirone were compared in 30 female subjects with migraine (ten migraine with aura, MA; ten migraine without aura, MO and ten chronic/transformed migraine, CM), and ten healthy controls matched for age, gender and menstrual status. None of the subjects were taking psychotropic medication or migraine prophylactic treatment and those with formal psychiatric disorder were excluded. Endocrine responses were determined by measuring differences between baseline PRL and maximum increases post-buspirone (deltaPRL). There was no difference in baseline PRL between groups. MA subjects did not differ in their PRL responses to buspirone compared to healthy controls. The MO group had a four-fold increase in mean deltaPRL responses compared to healthy controls. Mean deltaPRL was also increased in the CM group compared to controls, but the difference was less exaggerated. This study indicates that there is supersensitive central amine receptor function in MO and CM, but not in MA. These findings support the hypothesis that central 5HT function differs among the migraine subtypes. The results also suggest that migrainous 'transformation' may be associated with adaptive changes in central 5HT receptor sensitivity. The relative contribution of 'state' and 'trait' receptor function to these findings as well as the possible role of dopamine receptors is discussed.

Adult↗
PubMed2003

Factors associated with burden of primary headache in a specialty clinic.

OBJECTIVE: To examine factors associated with social, occupational, and psychological burden of common primary headache (migraine and tension-type headache). BACKGROUND: The personal and social burden of primary headache is high. Health, occupational, social, and psychological factors contributing to burden in people with disabling headache have not been fully unravelled. METHODS: One hundred eighty consecutive patients with either migraine or tension-type headache attending a specialty headache outpatient clinic for the first time were evaluated over a 9-month period. Headache subtype was operationally defined according to International Headache Society criteria. Headache frequency, duration, and severity were recorded. Occupational and social disability were quantified using the Migraine Disability Assessment questionnaire. Psychological burden was quantified using the 28-item General Health Questionnaire, the Beck Depression Inventory, and the State-Trait Anxiety Inventory. Premorbid vulnerability to life stress was quantified using the neuroticism subscale of the Eysenck Personality Inventory. RESULTS: Patients with frequent (chronic) headache scored higher on the Migraine Disability Assessment questionnaire and had higher Beck Depression Inventory and General Health Questionnaire depression scores than those with less frequent (episodic) headache. Frequency of headache, but not pain severity, duration, or diagnosis, predicted both Migraine Disability Assessment total disability and General Health Questionnaire/Beck Depression Inventory depression. Neuroticism was predictive of depression but not disability. Patients with chronic migraine had the highest depression and disability scores. CONCLUSION: The number of days per month with headache is a key determinant of headache-related burden in those attending specialty clinics. Frequent (chronic) headache is associated with significantly higher psychopathology scores and general social impairment, but the direction of this relationship is not clear. Those with migraine and chronicity are the most impaired.

Adolescent↗
PubMed2003

Reduced bone mineral density in patients with schizophrenia receiving prolactin raising anti-psychotic medication.

Patients with schizophrenia frequently develop drug-induced hyperprolactinaemia and consequent hypogonadism. Reduced bone mineral density as a consequence of hyperprolactinaemia-induced hypogonadism has been well documented in medical, but not psychiatric, disorders. Little attention has been given to the potential risk of developing osteoporosis secondary to anti-psychotic-induced hyperprolactinaemia. Three cases are presented that illustrate how this debilitating but silent disease may affect even those young individuals with schizophrenia.

Adult↗
PubMed2002

Prolactin and schizophrenia: clinical consequences of hyperprolactinaemia.

Prolactin is a polypeptide hormone that is synthesized and secreted from specialised cells of the anterior pituitary gland, known as lactotrophs. The hormone was given it's name because extracts from the bovine pituitary gland caused growth of the crop sac and stimulated the elaboration of crop milk in pigeons, and promoted lactation in rabbits. Although prolactin is best known for the multiple effects it exerts on the mammary gland, it has over 300 separate biological activities not represented by its name. It sub serves multiple roles in reproduction other than lactation and is an important modulator of homeostasis in the mammalian organism. Hence Bern and Nicoll suggested renaming it "omnipotin or versatilin". Schizophrenia is a severe psychiatric disorder that affects approximately one percent of the population worldwide. It is well established that traditional typical anti-psychotics elevate prolactin levels. It is also agreed that the serum prolactin concentration is not elevated in patients with schizophrenia who are not receiving anti-psychotic medication. Hyperprolactinaemia has direct effects on the brain and on other organs. Direct consequences include galactorrhoea. Indirect consequences of hyperprolactinaemia include oligomenorrhoea and amenorrhoea, erratic or absent ovulation, sexual dysfunction, reduced bone mineral density and cardiovascular disease. With the advent of prolactin sparing anti-psychotics, ample consideration needs to be given to the physiological consequences of hyperprolactinaemia in schizophrenic patients. In this paper we will examine molecular biology, secretion and physiology of prolactin. The consequences of hyperprolactinaemia in humans including effects on fertility, sexual dysfunction, bone mineral density, cardiovascular disease, changes in psychopathology and movement disorders will be reviewed. The literature on the association between schizophrenia, anti-psychotic medication and hyperprolactinaemia and more specifically on the consequences of this hyperprolactinaemia in schizophrenic patients will also be reviewed.

Humans↗
PubMed2002

The effects of antipsychotic-induced hyperprolactinaemia on the hypothalamic-pituitary-gonadal axis.

Hyperprolactinaemia is commonly induced by antipsychotic medications that have dopamine-blockade as their main mechanism of action. The purpose of this study was to assess the effect of antipsychotic-induced hyperprolactinaemia on hypothalamic-pituitary-gonadal axis (HPG) function.HPG axis function was assessed in 67 consecutive outpatients who were diagnosed with schizophrenia and stabilized for a period of not less than 2 years on typical antipsychotic medication, by means of clinical history, relevant questionnaires and measurement of plasma prolactin, estradiol, progesterone, testosterone, LH, FSH, sex hormone binding globulin, and TSH levels. Normative laboratory data were used to assess whether hormone levels fell within the reference range for a normal population. There was a significant correlation between dose of medication and plasma prolactin levels for the total group (P<0.001). Prolactin levels were significantly negatively associated with sex hormone levels in females (P<0.05). Males taking antipsychotic medication had a mean prolactin level of 404.1m/IU and mean gonadotrophin and sex hormone levels that fell within normal limits. The results of this study indicate that neuroleptic-induced prolactin secretion is a dose-related side effect and, in females, the level of hyperprolactinaemia is correlated with the degree of suppression of the HPG axis. Women taking long-term prolactin-raising antipsychotic medications are likely to be hyperprolactinaemic and have an associated hypogonadal state. In males, prolactin levels remain within normal limits, but at the upper end, with no apparent disturbance of reproductive hormones.

Adult↗
PubMed2002

Acute effects of low-dose interferon-alpha on serum cortisol and plasma interleukin-6.

Major depression is associated with both hypothalamic-pituitary-adrenal (HPA) axis overactivity and immune system activation. Depression is a common occurrence following interferon (IFN)-a treatment. While IFN-alpha is known to stimulate the HPA axis, little is known about the effects of exogenous IFN-a in humans on the proinflammatory cytokine interleukin (IL)-6, a marker of immune system activation. This study examined the acute effects of IFN-alpha on cortisol and IL-6 release, and the time course of any changes in these variables. Serum cortisol and plasma IL-6 were assessed in healthy volunteers over an 8-h period following 3 million units subcutaneous IFN-alpha or placebo using a double-blind, placebo-controlled crossover design. IFN-alpha resulted in a significant increase in both cortisol and IL-6. Regular sampling over 8 h did not delineate any sequential effect of the rise in these variables over time. We conclude that IFN-alpha acutely stimulates both the HPA axis and proinflammatory cytokine release. The hypothesis that the effect of IFN-alpha on the HPA axis is indirect and mediated by IL-6 was not supported by this study. Our findings are nonetheless of relevance to the aetiology of depression following IFN-alpha.

Adult↗
PubMed2000

Sexual dysfunction in depression.

Sexual dysfunction is a well-known symptom of depression. However, it has received little, if any, attention from clinicians and researchers. A review of published literature suggests that sexual dysfunction occurs in the majority of depressed patients. It has a major impact on the quality of life of the patients. The pathophysiology of sexual dysfunction in depression involves a complex interplay of various neurotransmitters and hormones. Clinicians need to be more proactive in enquiring about sexual dysfunction in depressed patients. More information is needed about the nature, prevalence and pathophysiology of sexual dysfunction in depression. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗