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Biomedical subjects

T G Dinan

Publications and source records attributed to T G Dinan.

At least 19 recordsLinked to original sources
PubMed1992

Central serotonin receptors and delayed gastric emptying in non-ulcer dyspepsia.

OBJECTIVE: To determine whether central serotonin receptors are involved in the pathophysiology of non-ulcer dyspepsia. DESIGN: Between subjects study of solid phase gastric emptying and prolactin response to buspirone challenge. SUBJECTS: 12 patients fulfilling criteria for non-ulcer dyspepsia and 12 age and sex matched controls. MAIN OUTCOME MEASURES: Solid phase gastric emptying measured by scintigraphic assessment of the movement of a standard meal labelled with technetium-99m and indium-111; responsiveness of central serotonin 1A receptors measured by the prolactin release following challenge with oral buspirone 60 mg. RESULTS: Solid phase gastric emptying was significantly delayed in the patients with non-ulcer dyspepsia (t 1/2 = 90.6 (SD 14.5) minutes in patients and 54.6 (10.7) minutes in controls; 95% confidence interval 24.7 to 46.7 minutes, p < 0.001). Prolactin release was significantly greater in patients compared with controls (1272.7 (1039.9) mU/l v 292.9 (136.1) mU/l; 352.1 to 1607.5 mU/l, p < 0.01). Gastric emptying and prolactin release were significantly correlated (r = 0.59, p = 0.04) in the patients but not in the controls (r = 0.23). CONCLUSION: Central serotonin 1A receptors may have a role in the pathophysiology of non-ulcer dyspepsia of the dysmotility subtype.

Adult↗
PubMed1992

Possible upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome.

OBJECTIVE: To study the dynamic function of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome. DESIGN: Prospective comparison of patients with postviral fatigue syndrome with two control groups. SETTING: Department of neurology, University of Glasgow, Southern General Hospital; department of psychiatry, St James's Hospital, Dublin. SUBJECTS: 15 patients with postviral fatigue syndrome, 13 age and sex matched healthy subjects, and 13 patients with primary depression. MAIN OUTCOME MEASURES: Serum prolactin concentrations before and one, two, and three hours after administration of buspirone. RESULTS: Because of the effects of sex hormones on prolactin secretion data for men and women were analysed separately. There was no significant difference in baseline prolactin concentrations between patients with postviral fatigue syndrome and healthy subjects or those with primary depression. However, the percentage difference between peak and baseline values was significantly higher in patients with postviral fatigue syndrome than the control groups (one way analysis of variance: women, p = 0.003; men, p = 0.004). CONCLUSIONS: The results suggest upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome but not in those with primary depression. The buspirone challenge test may therefore be useful in distinguishing these two conditions. Larger studies are required to explore the potential value of drugs acting on central 5-hydroxytryptamine receptors in the treatment of patients with the postviral fatigue syndrome.

Adult↗
PubMed1992

D-fenfluramine-induced prolactin and cortisol release in major depression: response to treatment.

In order to test the effects of various biological treatments on serotonergic function in depression, twenty-one patients with a diagnosis of major depression underwent neuroendocrine challenge tests before and after treatment with either ECT, fluoxetine or amitriptyline. The serotonin (5-HT) releasing agent d-fenfluramine was used as a challenge drug and cortisol (CORT) and prolactin (PRL) plasma levels were monitored over a 5-h period. Overall PRL responses were significantly enhanced following pharmacotherapy irrespective of therapeutic outcome. Effective treatment in each case lowered baseline CORT levels but CORT response to d-fenfluramine remained blunted. Hypercortisolaemia may be involved in the impaired pretreatment PRL response as a strong inverse relationship was established, for the combined studies, between basal CORT plasma concentrations and PRL responses.

Adolescent↗
PubMed1992

Pyridostigmine-induced growth hormone responses in healthy and depressed subjects: evidence for cholinergic supersensitivity in depression.

Theorists have extrapolated the cholinergic supersensitivity theory of affective disorder from a convincing and broad spectrum of clinical observation and research. This hypothesis is tested using a neuroendocrine probe approach with the challenge drug pyridostigmine, an indirect cholinergic agent thought to release growth hormone (GH) by decreasing inhibitory somatostatin tone. The consequent increments in plasma GH were considered to reflect central acetylcholine responsivity. Fifty-four volunteers were tested: 27 DSM-III-R major depressives (18 women and 9 men) and 27 age- and sex-matched healthy controls. Subjects were cannulated at 9.00 h following an overnight fast and two baseline samples were taken at 15 min intervals. Pyridostigmine 120 mg was administered orally and thereafter samples were taken at the time points +60, +90, +120 and +180 min. GH responses were significantly greater in depressives than controls and this effect was more marked for men than women. These results support the proposal that muscarinic upregulation and/or supersensitivity is associated with depression.

Acetylcholine↗
PubMed1992

Orofacial dyskinesia and the alcohol dependence syndrome.

A total of 52 patients with a DSM-III-R diagnosis of alcohol dependence syndrome underwent successful detoxification. Two to three weeks later they were examined for the presence of abnormal involuntary movements and rated with the abnormal involuntary movements scale (AIMS). They were also assessed with subtests from the Wechsler Adult Intelligence Scale (WAIS-R), namely, visual reproduction from memory, digit symbols substitution and the vocabulary test. Twenty-nine had evidence of orofacial dyskinesia and the presence of such movements was strongly associated with visuospatial deficits.

Adult↗
PubMed1992

Buspirone induced prolactin responses in obsessive-compulsive disorder (OCD): is OCD a 5-HT2 receptor disorder?

Buspirone (BUSP) is a serotonergic (5-HT) agonist with activity at the 5-HT1A receptor. The BUSP induced prolactin (PRL) response was examined in 10 patients with a DSM IIIR diagnosis of obsessive-compulsive disorder (OCD). The results were compared with PRL responses to BUSP found in 10 age and sex matched healthy controls. The results suggest that the 5-HT1A receptor dysfunction may not be involved in the pathophysiology of OCD. The authors review the literature and consider the hypothesis that in OCD a complex interaction of other 5-HT receptor sub-types may be occurring, possibly with dysfunction primarily of the 5-HT2 receptors.

Adult↗
PubMed1992

Treatment resistance of depression after head injury: a preliminary study of amitriptyline response.

Thirteen patients with depression following minor head injury were matched with 13 functional depressives. Both groups were indistinguishable psychopathologically. Five of the functional group had a family history of affective disorder and none of the head-injury group had such a history. Both groups were treated with amitriptyline, beginning with 100 mg daily, increasing to a maximum of 250 mg/d. There were significant differences in response between the 2 groups, with only 4 of the head-injury patients improving. Our preliminary results suggest that this condition is relatively resistant to tricyclic therapy.

Adult↗
PubMed1992

The desipramine-induced growth hormone response and the dexamethasone suppression test in obsessive-compulsive disorder.

Ten patients with DSM-III-R obsessive-compulsive disorder (OCD) underwent the desipramine (DMI) growth hormone (GH) stimulation test as well as the dexamethasone suppression test (DST). The results were compared with the responses in a group of matched healthy controls. The GH response to DMI did not differ between patients and controls and 9 of 10 patients showed cortisol suppression in response to dexamethasone. The data suggest that neither alpha 2 adrenergic dysfunction nor DST non-suppression are features of primary OCD.

Adult↗
PubMed1992

Effect of metyrapone on the pituitary-adrenal axis in depression: relation to dexamethasone suppressor status.

It has been suggested that the well-documented hypercortisolaemia found in a proportion of patients with severe depression occurs either in response to excessive secretion of corticotrophin-releasing hormone-41 (CRH-41) from the hypothalamus, or as a consequence of up-regulation of pituitary CRH-41 receptors. The attenuation of the normal ACTH response to CRH-41 in these subjects is thought to result from inhibition of corticotrophin secretion by elevated cortisol levels. We tested these hypotheses by examining ACTH responses to metyrapone, an 11 beta-hydroxylase inhibitor which blocks the formation of cortisol, followed by CRH-41 in 15 severely depressed in-patients diagnosed according to DSM-IIIR criteria. Patients were assigned to two groups according to their response to overnight administration of 1 mg dexamethasone: suppressors (8) and nonsuppressors (7). A third group consisted of 6 healthy matched controls. Metyrapone 750 mg was given 4-hourly for 24 h and samples were taken for cortisol and ACTH. Six of the original 15 patients (3 from each group) were given a bolus dose of 100 micrograms human CRH-41 intravenously after 24 h of metyrapone, and ACTH levels were measured over 2 h. Falls in circulating cortisol in response to metyrapone were similar in all three groups. However, we found exaggerated rises in ACTH amongst the nonsuppressors, as compared to the suppressors and the control group, after metyrapone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1992

Blunted prolactin responses to d-fenfluramine in sociopathy. Evidence for subsensitivity of central serotonergic function.

Using a neuroendocrine probe we studied nine male offenders in a forensic hospital, convicted of murder, with a diagnosis of antisocial personality disorder, who had been behaviourally 'quiescent' for varying periods and who had not recently been abusing drugs. Nine healthy age-matched men also participated. All subjects received 30 mg d-fenfluramine (d-FEN), a 5-HT releasing agent, orally, after an overnight fast, and serial samples for prolactin estimation were taken hourly for five hours. Responses were significantly impaired in the patients, suggesting a subsensitivity of certain 5-HT systems in antisocial personality disorder, regardless of recent or ongoing behavioural disturbance.

Adult↗
PubMed1992

Cortisol and prolactin responses to d-fenfluramine in non-depressed patients with obsessive-compulsive disorder: a comparison with depressed and healthy controls.

Cortisol and prolactin responses to d-fenfluramine were measured in 10 drug-free normothymic patients with obsessive-compulsive disorder (OCD). The results were compared with these responses in 10 healthy controls and in 10 major depressives. The endocrine responses in OCD were significantly attenuated when compared to the healthy controls; however, the results were not specific to OCD as the depressives' responses were similarly blunted.

Adult↗
PubMed1992

Sex steroid priming effects on growth hormone response to pyridostigmine throughout the menstrual cycle.

To explore the effect of estradiol and progesterone on the GH response to the indirect cholinergic agonist pyridostigmine nine healthy women were challenged with both active drug and placebo at three time points in two consecutive menstrual cycles: a total of six neuroendocrine tests. A randomized, double-blind, counterbalanced design was used. Subjects were tested in the early follicular, mid-cycle, and luteal phases of the cycle. A cannula was inserted in a forearm vein after an overnight fast and baseline GH, estradiol, and progesterone samples were drawn. After 120 mg oral pyridostigmine or placebo tablets further blood samples for GH analysis were drawn at intervals over 3 h. When expressed as maximum change from baseline (delta GH) mean GH responses to pyridostigmine increased incrementally from early (8.4 +/- 2.7 micrograms/L) through mid (18 +/- 1.3 micrograms/L) to late (22.2 +/- 1.9 micrograms/L) cycle. This represents a significant effect of cycle phase on the GH response to pyridostigmine (P less than 0.001, as assessed by analysis of variance). Responses to placebo did not vary. Plasma estradiol values were significantly correlated with GH responsivity to active drug throughout the cycle (P less than 0.02). Multiple regression analysis also revealed a significant positive correlation between progesterone levels and GH response to pyridostigmine (P less than 0.02). Estrogens augment GH responses to other challenges but a priming effect of progesterone on GH responsivity has not previously been demonstrated. Various mechanisms are discussed including a possible sex steroid priming effect on acetylcholine neurotransmission.

Adult↗
PubMed1991

Effect of fluoxetine on noradrenergic mediated growth hormone release: a double blind, placebo-controlled study.

Twelve patients with DSM-III-R major depressive illness were tested for growth hormone (GH) response to desipramine (DMI), a noradrenergic (NA) reuptake inhibitor. The response is mediated by NA alpha 2 receptors. They were then randomly assigned to treatment under double-blind conditions with either fluoxetine, the highly selective serotonin reuptake inhibitor or placebo. After 4 weeks they were retested. Fluoxetine but not placebo was effective in promoting recovery in four of the six patients treated. Patients treated with fluoxetine showed a significant decrease in DMI-mediated GH release irrespective of therapeutic outcome. This is consistent with marked alteration of NA function and raises questions as to the selectivity of fluoxetine.

Adult↗
PubMed1991

Serum thyrotropin responses to thyrotropin-releasing hormone in alcohol-dependent patients with and without depression.

Forty-one patients with DSM-III alcohol dependence syndrome were studied, as were 30 patients with major depression and 20 healthy controls. Nineteen of the alcohol-dependent patients had depressive symptoms. All subjects underwent a TRH/TSH stimulation test. Fifty percent of the alcohol-dependent patients without depression had a blunted response, while 52% of patients with depression were similarly blunted. The overall rate of blunting in the non-alcoholic major depressives was 26%. Blunting in the alcoholics was not associated with a personal or family history of affective disorder. Furthermore the blunted response in recently detoxified alcoholics was of no prognostic significance.

Adult↗
PubMed1991

Gender and age differences in the growth hormone response to pyridostigmine.

Thirty healthy subjects 12 males and 18 females were given the acetylcholinesterase inhibitor pyridostigmine (120 mg) orally. The growth hormone (GH) response was measured as the maximum GH level post-pyridostigmine relative to baseline. Twenty-six subjects increased their GH level in response to pyridostigmine. Responses in females were considerably greater than those in males and correlated closely with serum oestradiol levels. Overall there was a significant negative correlation between GH response and age.

Adult↗
PubMed1991

A comparison of the mental status, personality profiles and life events of patients with irritable bowel syndrome and peptic ulcer disease.

Forty patients with a diagnosis of irritable bowel syndrome (IBS) and 32 patients with peptic ulcer disease underwent a full psychiatric assessment. All were rated using the Gastrointestinal Symptom Rating Scale (GSRS), the Comprehensive Psychopathological Rating Scale, the Life Experiences Survey and the Eysenck Personality Inventory. The 2 groups were not distinguishable on total GSRS scores or rates of DSM-III diagnosed mental disorder. However, greater trait scores for neuroticism and introversion were found in the IBS group, together with a greater reporting of life events perceived as negative.

Adult↗