Clinical recording of risk factors in patients with myocardial infarction: relationship between psychiatric history and other risk factors.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
J V Lucey
Publications and source records attributed to J V Lucey.
Intramuscular ziprasidone compared with intramuscular haloperidol in the treatment of acute psychosis. Ziprasidone I.M. Study Group.
BACKGROUND: This 7-day, randomized, open-label, multicenter, international study compared the efficacy and tolerability of intramuscular (i.m.) ziprasidone with haloperidol i.m. and the transition from i.m. to oral treatment in hospitalized patients with acute psychotic agitation (related to DSM-III-R diagnoses). METHOD: Patients received up to 3 days of flexible-dose ziprasidone i.m. (N = 90) or haloperidol i.m. (N = 42) followed by oral treatment to day 7. After an initial ziprasidone i.m. dose of 10 mg, subsequent i.m. doses of 5 to 20 mg could be given every 4 to 6 hours (maximum daily dose = 80 mg) if needed, followed by oral ziprasidone, 80-200 mg/day. Haloperidol i.m. doses of 2.5 to 10 mg were given on entry, followed by 2.5 to 10 mg i.m. every 4 to 6 hours (maximum daily dose = 40 mg) if needed, then by oral haloperidol, 10-80 mg/day. RESULTS: The mean reductions in Brief Psychiatric Rating Scale (BPRS) total, BPRS agitation items, and Clinical Global Impressions-Severity scale scores were statistically significantly greater (p < .05, p < .01, and p < .01, respectively) after ziprasidone i.m. treatment compared with haloperidol i.m. treatment. Further reductions in these scores also occurred in both groups following transition to oral treatment. Ziprasidone was associated with a lower incidence of movement disorders and a reduced requirement for anticholinergic medication during both i.m. and oral treatment compared with haloperidol. Movement disorder scale scores improved with ziprasidone i.m. and oral treatment, but deteriorated with haloperidol. Other adverse events were rare with both treatments. CONCLUSION: Ziprasidone i.m. was significantly more effective in reducing the symptoms of acute psychosis and was better tolerated than haloperidol i.m., particularly in movement disorders. The transition from ziprasidone i.m. to oral ziprasidone was effective and well tolerated.
Acute Disease↗
Risperidone is associated with blunting of D-fenfluramine evoked serotonergic responses in schizophrenia.
The high 5-HT affinity of some atypical antipsychotic agents is thought to contribute to their clinical efficacy. We examined central 5-HT responses in two groups of ten schizophrenic patients by measuring serum prolactin and cortisol responses to the neuroendocrine challenge D-fenfluramine. One group of patients with schizophrenia was tested after a 2-week neuroleptic free period. A similar group were tested after a mean of 12 weeks treatment with the atypical antipsychotic risperidone. A significant elevation of baseline serum prolactin levels, consistent with dopaminergic antagonism was seen after risperidone treatment. Significantly reduced 5-HT mediated serum prolactin responses were seen in risperidone treated patients. D-fenfluramine evoked serum prolactin responses were positively correlated with positive but not negative schizophrenic symptoms for all 20 patients. Risperidone treatment was associated with a significant functional in-vivo 5-HT antagonism similar to clozapine. 5-HT antagonism may contribute to the efficacy of risperidone against positive schizophrenic symptoms.
Adult↗
Neuroendocrine evidence that clozapine's serotonergic antagonism is relevant to its efficacy in treating hallucinations and other positive schizophrenic symptoms.
OBJECTIVE: The authors examined the effect of prolonged clozapine treatment on central serotonergic (5-HT) function in schizophrenia. METHOD: Prolactin responses to the 5-HT releasing agent d-fenfluramine were measured in two groups of 10 schizophrenic subjects. The first group was tested twice, before and after a mean of 10 weeks of clozapine treatment. The second group was tested after a mean of 20 months of clozapine treatment. RESULTS: The prolactin response was significantly blunted in these 20 patients treated with clozapine. There was a significant positive correlation between d-fenfluramine-evoked prolactin release and the overall positive symptom score and the hallucination and delusion subscores of the Scale for the Assessment of Positive Symptoms. CONCLUSIONS: Blunted 5-HT-mediated prolactin responses in schizophrenic patients receiving clozapine monotherapy for up to 20 months were correlated with reductions in positive symptoms. This suggests that 5-HT antagonism is relevant to clozapine's efficacy in alleviating hallucinations and other positive schizophrenic symptoms.
Adult↗
Specificity of the pyridostigmine/growth hormone challenge in the diagnosis of depression.
Acetylcholine is a neurotransmitter that has been implicated in the pathophysiology of major depression. This is supported by the enhanced growth hormone (GH) release in response to pyridostigmine (PYD) challenge in depressed subjects relative to healthy comparison subjects. The aim of this study is to examine the specificity of the PYD/GH challenge in the diagnosis of depression. Pyridostigmine 120 mg orally, was administered to a total of 116 physically healthy subjects. Growth hormone responses were studied in 38 patients with (DSM-III-R) major depression, 13 subjects with panic disorder, 9 subjects with schizophrenia, 10 recently detoxified alcoholics, and a comparison group of 46 healthy volunteers. Mean delta GH (the difference between basal and maximal GH following PYD) was significantly greater than comparison subjects in patients with major depression. Responses observed in patients with schizophrenia and alcohol dependence syndrome did not differ from the comparison group. Those patients with panic disorder and a high Hamilton depression score had an enhanced delta GH. The sensitivity of the PYD/GH test was 63% for major depression. These results indicate that the PYD/GH test may help distinguish depression from schizophrenia, alcohol-dependence syndrome, or panic disorder with a low Hamilton depression score.
Administration, Oral↗
Caudate regional cerebral blood flow in obsessive-compulsive disorder, panic disorder and healthy controls on single photon emission computerised tomography.
We compared regional cerebral blood flow (rCBF) in 15 patients with DSM IIIR obsessive-compulsive disorder (OCD), 15 patients with DSM IIIR panic disorder and 15 healthy controls matched for age, sex and hand preference, using uptake of technetium-99m-D,L-hexamethyl-propylene amine oxime (99mTc HMPAO), on single photon emission computerised tomography (SPECT). Caudate rCBF was significantly reduced in OCD patients compared to healthy subjects and panic disorder patients. When four patients were excluded from each group, right caudate rCBF remained significantly lower in OCD patients than in panic disorder patients or healthy subjects. The data suggest functional involvement of the right caudate nucleus is present in OCD.
Adult↗
Wisconsin Card Sorting Task (WCST) errors and cerebral blood flow in obsessive-compulsive disorder (OCD).
We compared Wisconsin Card Sorting Task (WCST) performance in 19 obsessive-compulsive disorder (OCD) patients and 19 individually matched healthy controls. Measures of intelligence and mood were taken into account for all participants. Within the patient group, factors such as duration and severity of symptoms (as assessed using the Yale-Brown Obsessive-Compulsive Scale, Y-BOCS) were considered. We explored the relationship between OCD WCST errors and regional cerebral blood flow (rCBF) on brain dedicated, high resolution, single photon emission tomography (SPET). We used uptake of 99mTc-hexamethylpropylamine oxime (HMPAO) on SPET to estimate rCBF, and regional values were quantified as ratios of cerebellar blood flow. WCST results confirmed OCD patients were significantly impared when compared with age- and sex-matched healthy volunteers. Patients made significantly more trials, more preseverative errors, and more null-sorts. OCD patients Y-BOCS 'obsessive' subtotal significantly correlated with many WCST errors. Furthermore OCD WCST null-sorts correlated significantly with SPET OCD left inferior frontal cortical rCBF (r(18) = .47, p = .05) and left caudate rCBF (r(18) = .72, p = .01). The implications of these findings are discussed in the context of other studies which examine functional imaging and neuropsychology in OCD.
Adult↗
Correlation between reduced in vivo benzodiazepine receptor binding and severity of psychotic symptoms in schizophrenia.
OBJECTIVE: Although there is evidence from postmortem studies suggestive of deficient inhibitory neurotransmission of gamma-aminobutyric acid (GABA) in schizophrenia, no direct in vivo evidence has been obtained to date. The authors used single photon emission computed tomography (SPECT) with iodine-123-labeled iomazenil ([123I]iomazenil), a radioligand that selectively binds with high affinity to the benzodiazepine subunit of the GABAA receptor complex in the human brain, to investigate the presence of benzodiazepine receptor abnormalities in the cerebral cortex of living subjects with schizophrenia. METHOD: Dynamic [123I]iomazenil SPECT was performed in 15 patients (14 patients with DSM-III-R schizophrenia and one with schizophreniform disorder) and 12 healthy subjects over a period of 2 hours. The time-integral method was used to generate ratios of "specific" to "nonspecific" [123I]iomazenil binding at equilibrium for several cortical regions. RESULTS: No overall between-group differences in benzodiazepine receptor binding were found, but significant correlations emerged between the severity of schizophrenic symptoms and [123I]iomazenil binding in limbic cortical regions: positive symptom scores were negatively correlated with benzodiazepine receptor binding in the left medial temporal region, and negative symptoms were inversely related to receptor binding in the medial frontal region. These correlations were not significant when a Bonferroni correction for multiple comparisons was applied. CONCLUSIONS: These preliminary results are consistent with previous research implicating limbic cortical regions in the pathophysiology of schizophrenia, suggesting that reduced inhibitory GABAergic tone in these areas may contribute to the appearance of schizophrenic symptoms.
Adolescent↗
Enhanced growth hormone responses to pyridostigmine challenge in patients with panic disorder.
BACKGROUND: Panic disorder is associated with neuroendocrinological abnormalities, some of which overlap with those seen in major depression. To date, there has been little assessment of the role of cholinergic mechanisms in this disorder. METHOD: Sixteen patients with DSM-III-R panic disorder and an age and gender-matched comparison group were administered 120 mg of the acetylcholinesterase inhibitor pyridostigmine. Growth hormone (GH) responses over a three-hour period were monitored. RESULTS: Mean delta GH, the difference between basal and the maximum pyridostigmine levels, was significantly greater in patients with panic disorder than in the comparison group. CONCLUSIONS: This may reflect increased cholinergic responsivity in panic disorder.
Adult↗
Brain blood flow in anxiety disorders. OCD, panic disorder with agoraphobia, and post-traumatic stress disorder on 99mTcHMPAO single photon emission tomography (SPET).
BACKGROUND: We compared regional cerebral blood flow (rCBF) in three groups of patients with DSM-III-R anxiety disorders. METHOD: Fifteen patients with obsessive -compulsive disorder (OCD), 15 with panic disorder with agoraphobia (PA), and 16 with post-traumatic stress disorder (PTSD) and a similar group of healthy controls were assessed on brain-dedicated high-resolution SPET. RESULTS: MANOVA revealed significant rCBF differences between diagnostic groups (F = 4.4; d.f. = 3, 57; P = 0.007) and between cerebral regions (F = 6.4; d.f. = 1, 57; P = 0.01) in OCD and PTSD compared with PA and healthy controls, limited to bilateral superior frontal cortices and right caudate nuclei. Whole brain blood flow correlated positively with anxiety (r = 0.24, n = 46, P = 0.05). Beck depression scores correlated significantly negatively with left caudate rCBF (r = -0.24, n = 46, P = 0.05) and right caudate rCBF (r = -0.31, n = 46, P = 0.02). PTSD syndrome severity correlated significantly negatively with the left caudate (r = -0.49, n = 16, P = 0.03) and with right caudate rCBF (r = -0.7, n = 16, P = 0.001). CONCLUSIONS: Functional rCBF differences in anxiety disorders could relate to repetitive, intrusive, distressing mental activity, prominent in both OCD and PTSD.
Adult↗
Serotonin activity in anorexia nervosa after long-term weight restoration: response to D-fenfluramine challenge.
Abnormalities in central serotonin function have been implicated in the pathogenesis of anorexia nervosa. It is difficult, however, to separate neuroendocrine abnormalities induced by weight loss and malnutrition from those related primarily to the disorder itself. To minimize these influences, this study assessed long-term weight restored anorexics. A correlation between persistent eating-related psychopathology, co-morbid illness and serotonin dysfunction was sought. Nine female weight-restored out-patients who had previously fulfilled DSM-III-R criteria for anorexia nervosa and nine healthy controls participated. Following baseline estimation, prolactin and cortisol responses to 30 mg p.o. of D-fenfluramine were measured over a 5 h period. Eating related psychopathology was assessed using the Eating Disorders Inventory and Eating Attitudes Test. Depressive and obsessional symptoms were measured using the Beck Depressive and Maudsley Obsessive-Compulsive Inventories respectively. The Tridimensional Personality Questionnaire assessed impulsivity. The weight-restored anorexic group exhibited persistent eating-related psychopathology and significant co-morbid symptomatology. There was no difference between long-term weight-restored anorexics and controls in their endocrine response to D-fenfluramine. Long-term weight-recovered anorexic subjects continued to exhibit behavioural and attitudinal disturbances characteristic of anorexia nervosa. The results suggest that abnormalities in 5HT activity do not contribute significantly to trait status in anorexia nervosa.
Administration, Oral↗
Schizophrenic auditory hallucinations are associated with increased regional cerebral blood flow during verbal memory activation in a study using single photon emission computed tomography.
Single photon emission tomography with split-dose technetium-99m-d, l-hexamethyl-propylene amine oxime was used to measure regional cerebral blood flow (rCBF) during a memory-activation paradigm in a group of 18 medicated DSM-III-R schizophrenic patients. The relationship between clinical features of schizophrenia and rCBF patterns was examined. Increased blood flow to the left basal ganglia was revealed during activation in patients reporting hallucinations in the previous month, a finding that was not influenced by medication dose or other confounding variables. This result adds to previous functional imaging studies that have related basal ganglia abnormalities to hallucinatory phenomena and suggests that left basal ganglia hyperactivity may be relevant to an internal monitoring deficit responsible for the appearance of those symptoms in schizophrenia.
Adult↗
Effect of clozapine on d-fenfluramine-evoked neuroendocrine responses in schizophrenia and its relationship to clinical improvement.
BACKGROUND: Clozapine is an effective antipsychotic that has high affinity for serotonin type 2 (5-HT2) receptors. The importance of 5-HT antagonism in the overall clinical efficacy of clozapine is unclear. Using a neuroendocrine strategy we tested the hypothesis that clinical response to clozapine is related to alteration in 5-HT function. METHOD: Ten treatment-resistant schizophrenic subjects were treated with clozapine for a mean of 10.3 (s.e. 0.9) weeks; d-fenfluramine (DFEN) challenge tests were performed before and after treatment with concurrent clinical ratings (BPRS, SAPS, SANS) made at the time of testing. RESULTS: All patients showed clinical improvement following treatment with clozapine. In addition, clozapine produced a significant attenuation of prolactin (PRL) and cortisol (CRT) response to DFEN challenge. Change in symptom ratings correlated significantly with reduction in PRL response to DFEN challenge. CONCLUSIONS: These data show that functional alterations occur in the 5-HT system following response to clozapine and lend support to studies suggesting that 5-HT is an important component to the spectrum of action of clozapine.
Adult↗
Regional cerebral blood flow in obsessive-compulsive disordered patients at rest. Differential correlates with obsessive-compulsive and anxious-avoidant dimensions.
BACKGROUND: We tested whether cortical and subcortical regional cerebral blood flow (rCBF) differs between patients with obsessive-compulsive disorder (OCD) and healthy controls. We then explored the relationship between rCBF and OCD mental state. METHOD: Thirty out-patients from the Maudsley Hospital with OCD as defined in DSM-III-R were scanned at rest using brain-dedicated, high-resolution, single photon emission tomography. RCBF was measured as uptake of 99mTc-HMPAO in 15 regions of interest and compared with rCBF data in 30 healthy people matched for age, sex and handedness. Symptom ratings were obtained using standard measures on the scanning day. Principal components factor analysis identified two distinct clinical dimensions: obsessive-compulsive (OC) and anxious-avoidant (AA). These were correlated with patients' rCBF measurements, using Spearman's rank correlation coefficient, and multiple regression coefficients calculated. RESULTS: We found significant reductions in rCBF measurements of OCD patients compared with resting, healthy controls (F = 1.92, P = 0.04) in seven brain regions: the right and left superior frontal cortex, right inferior frontal cortex, left temporal cortex, left parietal cortex, right caudate nucleus and right thalamus. Regional differences were not secondary to generalised reduction in patients' brain perfusion. Reduced blood flow to the right inferior frontal cortex correlated significantly with illness severity (r = 0.37, P = 0.02). There was no relationship with age, age-of-onset, sex, handedness, depression or medication status. OC clinical dimension, concerning obsessions, compulsions and low mood, was significantly negatively correlated with left inferior frontal, medial frontal and right parietal rCBF. AA dimension, concerning anxiety and avoidance, was significantly positively associated with left and right superior frontal, right inferior frontal, medial frontal cortical, and right and left caudate and thalamic rCBF. CONCLUSIONS: rCBF differs significantly between resting OCD patients and healthy controls, and separate clinical dimensions are associated with functionally distinct rCBF patterns.
Adult↗
The growth hormone response to baclofen in obsessive compulsive disorder: does the GABA-B receptor mediate obsessive anxiety?
The growth hormone (GH) response to the gamma amino butyric acid type B (GABA-B) receptor agonist baclofen was measured in 10 Caucasian out-patients with DSM-III-R obsessive compulsive disorder (OCD) and 10 healthy comparison subjects. The patients also underwent a dexamethasone suppression test. The GH response was similar in both groups and there was a low rate of dexamethasone non-suppression in the patients. The data do not suggest that GABA-B receptor dysfunction is a feature of obsessive anxiety.
Adult↗
Central serotonergic hyperresponsivity in late-onset Alzheimer's disease.
The prolactin response to oral d-fenfluramine (30 mg) was measured in nine patients with late-onset Alzheimer's disease and in an elderly comparison group. The serotonin-mediated prolactin response was significantly greater in the patients with Alzheimer's disease than in the comparison group. This finding suggests that central serotonin responsivity is greater in Alzheimer's disease.
Aged↗
The anterior pituitary responds normally to protirelin in obsessive-compulsive disorder: evidence to support a neuroendocrine serotonergic deficit.
The prolactin and thyroid-stimulating hormone (TSH) responses to protirelin and the prolactin and cortisol responses to d-fenfluramine were measured in 8 outpatients with DSM-III-R obsessive-compulsive disorder (OCD). The results were compared to those in 8 age- and sex-matched healthy controls. The responses to d-fenfluramine were significantly attenuated in the OCD patients, but there was no significant difference between the responses to protirelin in OCD patients and healthy controls. The data suggest that, in OCD, blunting of prolactin responses to the serotonin-releasing agent d-fenfluramine is due to a central abnormality and not due to a pituitary deficit.
Adult↗
Elevated growth hormone responses to pyridostigmine in obsessive-compulsive disorder: evidence of cholinergic supersensitivity.
The growth hormone response to the acetylcholinesterase inhibitor pyridostigmine was measured in nine normothymic outpatients who met DSM-III-R criteria for obsessive-compulsive disorder. The responses were significantly elevated when compared to those found in a healthy comparison group (N = 9). The data suggest that cholinergic supersensitivity is present in obsessive-compulsive disorder.
Adult↗