Search

Using desmethylimipramine (DMI) defined and Na+ dependent [3H]imipramine binding, we have examined both 5-HT uptake sites and sites unrelated to 5-HT uptake, in frontal cortex, putamen and substantia nigra of suicides with a firm retrospective diagnosis of depression and matched controls. No differences were seen between antidepressant-free suicides and controls, although [3H]imipramine binding sites were significantly lower in putamen of the subgroup of non-violent suicides. The number of DMI defined [3H]imipramine binding sites was also significantly lower in putamen of antidepressant-treated suicides.

Plasma from healthy subjects inhibited the binding of [3H]imipramine competitively and [3H]paroxetine non-competitively to platelet membranes in a volume-dependent manner. Plasma from 40 depressed patients was more effective at inhibiting [3H]imipramine, but not [3H]paroxetine, binding compared to plasma from matched controls. This difference was not related to recent antidepressant treatment. The results suggest that the concentration of an endogenous modulator of [3H]imipramine binding is increased in depressive illness. The concentration of alpha 1-acid glycoprotein, a proposed endogenous modulator of [3H]imipramine binding, did not differ between depressed patients and controls. Our results suggest that factors other than alpha 1-acid glycoprotein may modulate [3H]imipramine binding.

Saturation binding of [3H]paroxetine was performed in 10 brain regions from a group of suicide victims who had a firm, retrospective diagnosis of depression and who had been prescribed antidepressant drugs, as well as in a group of controls. The number of binding sites did not differ significantly between suicide victims and controls, apart from in putamen, where a lower number of sites was found in the suicide victims. Higher dissociation constant (Kd) values were found in suicide victims dying by antidepressant overdose and also in those dying by other means when compared with controls.

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.

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.

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.

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.

Plasma alpha 1-acid glycoprotein (AGP) levels were measured in 49 subjects with major depressive disorder, 15 subjects with anorexia nervosa and 18 subjects with bulimia nervosa, together with age- and sex-matched controls. AGP levels were elevated in depression and bulimia compared to controls. They were particularly elevated in depressed subjects who proved unresponsive to treatment with a standard course of antidepressants. In the depressed subjects, elevated AGP levels returned to control levels after treatment whether or not treatment was successful. There was a correlation between AGP and post-dexamethasone plasma cortisol levels in depression but not in bulimia and a correlation with age in depressed subjects only. There was no correlation between AGP values and tritiated imipramine binding parameters. Further studies are suggested to explore the issue of whether variations in AGP level are responsible for the abnormalities in platelet 5HT uptake and tritiated imipramine binding that have been reported in depression or for treatment non-response.

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.

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.