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Biomedical subjects

T Dinan

Publications and source records attributed to T Dinan.

7 recordsLinked to original sources
PubMed2003

Central 5-HT receptor hypersensitivity in migraine without aura.

Serotonin has long been implicated as a key neurotransmitter in migraine. There is a dearth of research specifically examining 5-HT1A receptor sensitivity in migraine despite the importance of this receptor in regulating central serotonergic tone. In this study we examined the hypothesis that migraine without aura is associated with hypersensitivity of central 5-HT1A receptors, using a 5-HT1A neuroendocrine challenge drug and comparing serum prolactin responses between a test group with migraine and a matched group of healthy controls. Twelve female subjects fulfilling International Headache Society (IHS) criteria for migraine without aura were evaluated. Following an overnight fast, subjects presented for testing at 9am. An intravenous canula was inserted and serum prolactin was assessed at baseline and every 30 min for 3 h following a single dose of 30 mg oral buspirone, a 5-HT1A-receptor agonist. Subjects were assessed during the first 5 days of the menstrual cycle. No subjects were taking psychotropic medication or migraine prophylactic treatment. Patients with current or previous psychiatric disorder, daily headache or analgesic overuse were excluded. 16 healthy female volunteers matched for age and menstrual status were also evaluated and served as controls. There was no difference in baseline prolactin between groups. There was a significant rise in prolactin following buspirone in both groups. Subjects with migraine had a significantly increased prolactin response to buspirone (delta max) compared to controls (P < 0.001). This study supports the hypothesis that migraine without aura is associated with a relative hypersensitivity of central 5-HT1A receptors. This is of relevance given the role of the 5-HT1A receptor in controlling raphe 5-HT tone and in the possible association between migraine and anxiety and depression.

Administration, Oral↗
PubMed2000

A preliminary study of dehydroepiandrosterone response to low-dose ACTH in chronic fatigue syndrome and in healthy subjects.

Abnormalities of the production of dehydroepiandrosterone (DHEA), the adrenal androgen, have been linked with disorders such as obesity and psychological disorders such as major depression. Adrenocorticotropin (ACTH) is the primary stimulant of DHEA, and cortisol, from the adrenal. We chose to examine the DHEA and DHEA/cortisol response to the novel low-dose ACTH test in healthy subjects and a cohort with chronic fatigue syndrome (CFS): this test is useful in assessing subtle irregularities of pituitary-adrenal activity. Nineteen CFS subjects (diagnosed by CDC criteria) and 10 healthy subjects were examined. We demonstrated that 1 microg ACTH significantly elevates DHEA levels, with no difference in output between CFS and healthy subjects. The DHEA/cortisol ratio decreased in response to ACTH stimulation in healthy subjects but not in the CFS cohort. We suggest this divergence of response between the two groups represents an imbalance in the relative synthetic pathways of the CFS group which, if present chronically and if comparable to daily stressors, may manifest itself as an inappropriate response to stress. This difference may be important in either the genesis or propagation of the syndrome.

Adrenocorticotropic Hormone↗
PubMed1994

Changes in immunoglobulin, complement and acute phase protein levels in the depressed patients and normal controls.

Recently, several authors have reported that immunoglobulin IgM, complement C3c, complement C4, and positive acute phase proteins (e.g., haptoglobin, alpha 1-acid glycoprotein and alpha 1-antitrypsin) were significantly increased, while negative acute phase proteins (e.g., albumin and transferrin), were decreased in depressed patients. In the present study, the levels of the immunoglobulin IgM, complement C3c, C4, alpha 1-antitrypsin and haptoglobin were found to be significantly increased in 20 unipolar depressed patients compared to healthy controls. The concentrations of total protein and albumin were significantly reduced in these patients. The concentrations of alpha 1-protein, (which is related to alpha 1-antitrypsin), and alpha 2-protein (which related to haptoglobin), were also significantly elevated in unipolar depressed patients. The results suggest that unipolar depression is associated with an acute phase response, which is possibly caused by changes in cytokines and corticosteroid secretion in depressed patients.

Acute-Phase Proteins↗
PubMed1994

Selective serotonin reuptake inhibitors: meta-analysis of discontinuation rates.

A meta-analysis was carried out of 42 published randomized controlled studies comparing the selective serotonin reuptake inhibitors (SSRIs) with the tricyclic antidepressants (TCAs) that measured discontinuation rates for side effects and lack of efficacy by treatment group in order to compare the discontinuation rates for side effects and lack of efficacy. These discontinuation rates were pooled to produce the main outcome measure. Seven studies were placebo controlled and the discontinuation rates in these studies were also pooled in a separate analysis. Significantly fewer patients receiving SSRIs discontinued treatment because of side effects (14.9%) compared with those receiving TCAs (19%) (p < 0.01). There was also a significant difference in discontinuation rates due to side effects in the placebo- and TCA-controlled studies analysed separately, SSRIs (19%) compared with TCAs (27%) (p < 0.01). In both analyses a similar proportion of patients discontinued for lack of efficacy on SSRIs and TCAs. There is a significant and clinically important advantage for the SSRIs compared with the TCAs in the acceptability of treatment measured by the number of discontinuations due to side effects reported in published studies. The risk-benefit calculation favours the SSRIs since there were similar levels of efficacy but more discontinuations with the TCAs. The selection of an antidepressant for first-line treatment requires critical evaluation of the full risk-benefit equation.

Antidepressive Agents, Tricyclic↗
PubMed1991

d-fenfluramine/prolactin response throughout the menstrual cycle: evidence for an oestrogen-induced alteration.

The prolactin (PRL) response to fenfluramine (FEN), a serotonin (5-HT) releasing agent, is used as an index of 5-HT sensitivity in studying disorders associated with central 5-HT abnormality. Plasma oestrogen levels are known to augment PRL responses to a variety of stimuli. In order to examine the effect that ovarian steroids have on this response nine, healthy women were tested twice at three time points in the menstrual cycle: early follicular, mid-cycle and late luteal phase with either d-FEN, a more specific 5-HT agent than the racemic mixture, or placebo. Responses to d-FEN were maximal at mid-cycle, lowest during the early follicular phase, with responses premenstrually being intermediate between the two. Responses to placebo did not vary. Plasma oestradiol levels fluctuated in parallel with neuroendocrine responses to d-FEN. The possible mechanisms are discussed, including an effect that oestradiol may exert at central serotonin sites.

Adult↗
PubMed1984

Cortically projecting nucleus basalis neurons in rat are physiologically heterogeneous.

Cortically projecting, putatively cholinergic neurons in the area of globus pallidus (corresponding to nucleus basalis) were identified by antidromic activation from frontal cortex in anesthetized rats. These cells exhibited heterogeneous physiological properties, yielding spontaneous discharge rates of 0-40 Hz, a variety of impulse amplitudes and waveforms, and a wide range of conduction latencies from frontal cortex (1-13 ms). In addition, many cells were found to be antidromically activated from neighboring cortical sites 1-2 mm apart.

Afferent Pathways↗