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Biomedical subjects

R W Horton

Publications and source records attributed to R W Horton.

At least 37 records · Page 2Linked to original sources
PubMed1994

Platelet 5-HT uptake sites, labelled with [3H] paroxetine, in controls and depressed patients before and after treatment with fluoxetine or lofepramine.

Platelet [3H] paroxetine binding was measured in 73 depressed patients and in 64 healthy volunteers. No differences were found in Bmax or Kd either overall, or when the 61 depressed subjects who had never received psychotropic drugs were analysed separately. Within the depressed group, no differences in Bmax or Kd were found between subgroups divided on the basis of endogenicity, suicidal thoughts or severity of depression. None of the subgroups differed significantly from controls. Forty of the depressed subjects were retested after 6 weeks' treatment with fluoxetine (n = 22) or lofepramine (n = 18). Treatment was not associated with any change in Bmax but a similar and significant increase in Kd was noted following treatment with either antidepressant. Neither pre- nor post-treatment platelet binding parameters appeared to relate to clinical response to treatment.

Adolescent↗
PubMed1993

NMDA glutamatergic receptors, labelled with [3H]MK-801, in brain samples from drug-free depressed suicides.

Glutamate receptors of the NMDA-subtype were quantitated by binding of [3H]dizocilpine maleate (MK-801) in nine brain regions from 22 suicide victims (20-60 yr), with a firm retrospective diagnosis of depression, who had not recently received antidepressant drugs, and 20 age- and sex-matched controls. [3H]MK-801-binding did not differ between suicides and controls in any region studied. Suicides who died violently did not differ from non-violent suicides and controls. A significative negative correlation was found between age and NMDA receptor-binding in the frontal cortex of suicide victims, but not in controls. This preliminary study provides little evidence for an important role of NMDA-binding sites in the pathophysiology of depression.

Adult↗
PubMed1993

Platelet 5-HT uptake sites in depression: three concurrent measures using [3H] imipramine and [3H] paroxetine.

Platelet 5-HT uptake sites were measured in 40 depressed patients and 40 controls using [3H] imipramine binding, defined with desmethylimipramine (DMI) and Na+ dependence, and [3H] paroxetine binding. In control subjects the Bmax of DMI defined [3H] imipramine binding was significantly higher than both Na+ dependent [3H] imipramine (by 30%) and [3H] paroxetine binding (by 22%). The Bmax of Na+ dependent [3H] imipramine and [3H] paroxetine binding did not differ significantly. The Kd of Na+ dependent [3H] imipramine binding was significantly lower than the Kd of DMI defined [3H] imipramine binding. The binding of DMI defined and Na+ dependent [3H] imipramine and [3H] paroxetine did not differ significantly between depressed patients and controls in the total group, in those depressed patients and controls in the total group, in those depressed patients who had never taken antidepressants or in those depressed patients who had been recently withdrawn from antidepressants. This study provides no support for the view that the number of platelet 5-HT uptake sites are reduced in depression.

Adult↗
PubMed1993

Growth hormone and physiological responses to clonidine in depression.

Clonidine (1.3 micrograms/kg) was administered to 62 control and 55 depressed patients free of psychoactive drugs for at least 7 days and fasted overnight. Growth hormone (GH), pulse, blood pressure and sedation were measured every 15 min for 1 h before and 2 h after clonidine infusion. GH response did not differ significantly between control and depressed subjects overall or when divided by sex. The systolic hypotensive and sedative responses were blunted in depressed subjects compared with controls; these effects appeared to be secondary to residual antidepressant drugs since the differences were only significant for those depressed subjects with short drug-free intervals. No differences between depressed subjects and controls were seen in diastolic hypotensive or bradycardic responses and no differences in GH, cardiovascular or sedative responses were found between endogenous and non-endogenous depressed subjects.

Adult↗
PubMed1992

The distribution of 5-HT1D and 5-HT1E binding sites in human brain.

Total 5-HT1, 5-HT1D and 5-HT1E binding sites were measured in homogenates of human frontal cortex, hippocampus, amygdala, globus pallidus, caudate and putamen. Combined 5-HT1D/1E sites were the predominant 5-HT1 subtype (66-95% of total 5-HT1 sites in all regions except hippocampus (38% of total 5-HT1 sites). Globus pallidus contained the highest density and the highest proportion of 5HT1D sites (74% of total 5-HT1 sites). 5HT1D sites in the other brain areas accounted for 19-27% of the total 5-HT1 sites. The highest densities and the highest proportions of 5-HT1E sites were in caudate (72%) and putamen (64%) and the lowest density and lowest proportion in hippocampus (16%).

Adult↗
PubMed1992

Social isolation does not alter brain regional benzodiazepine binding site numbers, affinity and coupling in the rat.

Male Sprague-Dawley rats were differentially housed for 21 days immediately after weaning. Isolated animals showed a selective suppression of exploration of the light side of a two compartment box; spending significantly less time in the light, and making fewer transitions between the light and dark compartments compared to socially reared controls. However, both basal and GABA-stimulated [3H] flunitrazepam binding was unaltered in the frontal cortex, hippocampus, amygdala and cerebellum following social isolation. These results are discussed in relation to other studies on central benzodiazepine receptor changes following a variety of experimental stressors.

Animals↗
PubMed1992

beta-adrenoceptors in brain and pineal from depressed suicide victims.

beta-Adrenoceptors were measured by saturation binding of [3H]CGP 12177 in nine brain regions and pineal from suicides, with a firm retrospective diagnosis of depression, and age and sex matched controls. Twenty one suicides had not recently received antidepressant drugs, 17 had been receiving drugs prior to death. In antidepressant drug-free suicides, the number of total beta-adrenoceptors was significant lower in temporal cortex (Brodmann area 38) and beta 1-adrenoceptors (Brodmann areas 21/22) was significant lower than matched controls. Suicides who died by violent means had significantly lower numbers of total beta- and beta 1-adrenoceptors in the frontal cortex and lower numbers of beta 1-adrenoceptors in temporal cortex (Brodmann areas 21/22) than matched controls. Suicides who died by non-violent means had lower numbers of total beta-adrenoceptors in occipital cortex controls and lower numbers of total beta- and beta 1-adrenoceptors in temporal cortex (Brodmann area 38) than matched controls. In antidepressant drug-treated suicides, significantly lower number of beta-adrenoceptor binding sites were found in temporal cortex (Brodmann area 38) and thalamus compared to matched controls. The lower number of beta-adrenoceptors binding sites in the thalamus appeared to be related to drug treatment. There were no differences in beta-adrenoceptor binding in the pineal gland between antidepressant-free and antidepressant-treated suicides and controls, although there were apparent differences between suicides and controls related to the time of death and season of death.

Adrenergic beta-Antagonists↗
PubMed1991

Brain beta-adrenoceptor binding sites in depressed suicide victims: effects of antidepressant treatment.

beta-Adrenoceptor binding sites were measured by saturation binding of [3H]CGP 12177 in nine brain regions from 13 suicides, with a firm retrospective diagnosis of depression, who had been receiving antidepressant drugs, and 11 matched controls. Significantly lower numbers of beta-adrenoceptor binding sites were found in thalamus and temporal cortex (Brodmann area 38), but not in other brain regions, of antidepressant-treated suicides compared to controls. The lower number of beta-adrenoceptor binding sites in thalamus appeared to be related to drug treatment, whereas lower numbers of beta-adrenoceptors in temporal cortex were also found in antidepressant-free suicides.

Adolescent↗
PubMed1991

Platelet alpha 2-adrenoceptors, defined with agonist and antagonist ligands, in depressed patients, prior to and following treatment.

Saturation binding of the alpha 2-adrenoceptor antagonist, 3H-yohimbine, and displacement of 3H-yohimbine with the alpha 2-adrenoceptor agonist, UK-14,304, were performed concurrently in platelet membranes obtained from drug-free depressed patients and healthy volunteers. Where possible platelet binding was repeated in depressed patients following treatment. The number and affinity of 3H-yohimbine binding sites did not differ between controls and depressed patients, or when depressed patients were divided on the basis of endogenicity (Newcastle or RDC criteria) or dexamethasone test result. The proportion of alpha 2-adrenoceptor binding sites with high affinity for UK-14,304 and KD values for the two states of the receptor did not differ in the total sample of depressed patients compared to controls. The KD for both states of the receptor and the proportion of sites with high affinity for UK-14,304 was lower in RDC non-endogenous patients than RDC endogenous patients. Treatment did not alter the total number of alpha 2-adrenoceptors or the proportion of sites with high affinity for UK-14,304, but reduced the KD for 3H-yohimbine and the KD of UK-14,304 for the low affinity state of the alpha 2-adrenoceptor.

Adrenergic alpha-Agonists↗
PubMed1991

Platelet [3H]imipramine and alpha 2-adrenoceptor binding in normal subjects during desipramine administration and withdrawal.

The effect of desipramine 150 mg daily on platelet [3H]imipramine and alpha 2-adrenoceptor binding sites was studied over a 6-week period and for 6 weeks after withdrawal. Modest (10%) increases in [3H]imipramine binding site densities during treatment were noted with a decrease between 1 and 4 weeks after withdrawal. No effect was found on alpha 2-adrenoceptors. Time of day appeared to have some effect on the results found. None of the [3H]imipramine binding site effects of desipramine, on treatment or following withdrawal, was comparable in magnitude to trait differences that were also found between subjects.

Adult↗
PubMed1990

Brain 5-HT uptake sites, labelled with [3H]paroxetine, in antidepressant-free depressed suicides.

Brain serotonin (5-HT) uptake sites were quantitated, by saturation binding of [3H]paroxetine, in 10 brain regions from 22 suicide victims and 20 control subjects. Suicide victims were restricted to those subjects in whom a firm retrospective diagnosis of depression was established and who had not recently been prescribed antidepressant drugs. The Kd and Bmax of [3H]paroxetine did not differ significantly between controls and depressed suicides in any of the brain regions. In putamen, Bmax values of suicides who died non-violently were lower than controls, whereas those who died by violent methods did not differ from controls. No significant differences between violent or non-violent suicides and their matched controls were found in other brain areas. These results offer little support for the view that suicide/depression is associated with an abnormality in 5-HT uptake.

Brain Chemistry↗
PubMed1990

Brain beta-adrenoceptor binding sites in antidepressant-free depressed suicide victims.

beta-Adrenoceptor binding sites were quantitated by saturation binding of [3H]CGP 12177 in 9 brain regions from 21 suicide victims, with a firm retrospective diagnosis of depression, who had not recently received antidepressant drugs, and 20 age- and sex-matched controls. In depressed suicides the number of total beta-adrenoceptors was significantly lower in temporal cortex (Brodmann area 38, by 19%) and beta 1-adrenoceptors (Brodmann area 21/22, by 17%) compared to controls. Suicides who died by violent means had significantly lower numbers of total beta- and beta 1-adrenoceptors in frontal cortex than matched controls (by 23 and 25%, respectively) and than non-violent suicides (by 20 and 22%, respectively) and lower numbers of beta 1-adrenoceptors in temporal cortex (Brodmann area 21/22) than matched controls (by 16%). Depressed suicides who died by non-violent means had lower numbers of total beta-adrenoceptors in occipital cortex than matched controls (by 24%) and than violent suicides (by 18%), and lower numbers of total beta- and beta 1-adrenoceptors in temporal cortex (Brodmann area 38) than matched controls (by 27 and 24%, respectively). Depression in suicide victims is associated with deficits in beta-adrenoceptor binding sites, largely restricted to cortical areas.

Adult↗
PubMed1990

Brain 5-HT1 binding sites in depressed suicides.

5-HT1 and 5-HT1A binding sites were measured in brain tissue obtained at postmortem from 19 suicides, with definite evidence of depression, and 19 sex and age-matched controls. Thirteen of the depressed suicides had not been prescribed psychoactive drugs recently (drug-free suicides); six had been receiving antidepressant drugs, alone or in combination with other drugs (antidepressant-treated suicides). No significant differences were found in the number or affinity of 5-HT1 and 5-HT1A binding sites in frontal or temporal cortex between drug-free suicides and controls. The number of 5-HT1 sites was significantly lower (by 20%), affinity unaltered, in hippocampus and the affinity significantly lower (by 33%), number unaltered, in amygdala of drug-free suicides than controls. The number of 5-HT1 binding sites tended to be higher and the affinity lower in the antidepressant-treated compared to drug-free suicides, and significantly so in hippocampus. The present results, together with our previous studies, provide no evidence of altered cortical 5-HT markers in depressed suicides, but further emphasise abnormalities in the hippocampus.

Adult↗
PubMed1990

3H-imipramine binding to previously frozen platelet membranes from depressed patients, before and after treatment.

3H-imipramine binding in 39 drug-free patients with major depression and 44 healthy controls did not differ significantly between the two groups, in male or female subjects or in subgroups of depressed patients divided by endogenicity or dexamethasone suppression test result. 3H-imipramine binding in depressed patients drug-free for less than three weeks did not differ from those drug-free for longer intervals or from controls. A significant seasonal variation of 3H-imipramine Bmax was found, with lower values in summer and autumn. Treatment of depressed patients with imipramine or lofepramine for six weeks increased KD and Bmax. Methodological modification (in preparation and storage of platelets) does not explain the major differences in results between this study (using frozen platelets), a previous one (using freshly prepared platelets) and others in general, although it might contribute to the range of values reported.

Adult↗
PubMed1989

Serotonin concentrations and turnover in brains of depressed suicides.

5-Hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations and 5-HT turnover (5-HIAA/5-HT) were determined in 6 brain regions from 19 suicide victims in whom a retrospective diagnosis of depression was established, and 19 age- and sex-matched control subjects. Thirteen of the suicides were free of psychoactive drugs at the time of death; 5 were receiving antidepressant drugs. 5-HT, 5-HIAA and 5-HT turnover did not differ significantly between the total, drug-free and antidepressant-treated suicides and controls in frontal and temporal cortex, caudate and hippocampus. 5-HIAA concentration was significantly higher in amygdala of drug-free suicides than controls, whereas 5-HT and 5-HT turnover did not differ. 5-HT concentration was significantly lower in putamen of the total and antidepressant-treated suicides and a similar reduction was also apparent in the drug-free suicides. 5-HT turnover in putamen was significantly higher in the total and drug-free suicides compared to controls. 5-HT and 5-HIAA concentrations in putamen were significantly lower in drug-free suicides who died by non-violent means than in those who died by violent means. Differences between controls and suicides could not be attributed to age, sex or postmortem delay. These results offer no support for the view that 5-HT turnover is reduced in depressed subjects who commit suicide.

Adolescent↗