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3H-imipramine binding to freshly prepared platelet membranes in depression
A E Theodorou1, C L Katona, S L Davies
1Department of Pharmacology, St. George's Hospital Medical School, London, U.K.
Abstract:
3H-Imipramine binding was measured in freshly prepared platelet membranes from 47 drug-free major depressives and 46 healthy controls. Where possible, platelet binding in depressed subjects was repeated following treatment. A significant negative correlation was found between Bmax and assay protein concentration and Bmax values were corrected for this effect. Adjusted Bmax was significantly lower (by 14%) in female depressed patients than in female control subjects, and the difference was of similar magnitude premenopausally and postmenopausally. No such difference was found in males. Kd did not differ significantly between depressed and control subjects. Multiple regression analysis confirmed significant effects on Bmax of presence of depressive illness, age (positive correlation), and season (higher in summer). Within the depressed sample, Bmax was significantly lower in those subjects with obsessional features. Endogenicity (Research Diagnostic Criteria or Newcastle), dexamethasone suppression test result, drug-free interval, family history of depression, depressive psychosis, suicidal ideation, and past history of suicide attempts were not significantly related to Bmax. Paired comparisons revealed no significant effect on Bmax of 6 weeks' treatment with imipramine, maprotiline, or BRL 14342 or of a course of electroconvulsive therapy.
Insights
Major depressive disorder is associated with lower platelet imipramine binding (Bmax) in females, but not males. Treatment and other clinical factors did not significantly alter Bmax levels in depressed patients.
Area of Science:
- Neuroscience
- Psychiatry
- Biochemistry
Background:
- Platelet imipramine binding, a marker for serotonin transporter availability, has been investigated as a potential biomarker for depression.
- Previous studies have yielded conflicting results regarding imipramine binding in depressed individuals.
Purpose of the Study:
- To investigate differences in 3H-imipramine binding to platelet membranes between drug-free major depressive patients and healthy controls.
- To examine the influence of depressive illness, gender, age, season, and clinical features on imipramine binding.
- To assess the effect of antidepressant treatment and electroconvulsive therapy on imipramine binding.
Main Methods:
- 3H-imipramine binding assays were performed on platelet membranes from 47 major depressives and 46 controls.
- Bmax values were corrected for protein concentration.
- Multiple regression analysis and paired comparisons were used to analyze the data.
Main Results:
- Adjusted Bmax was significantly lower (14%) in female depressed patients compared to female controls, irrespective of menopausal status.
- No significant difference in Bmax was observed between male depressed patients and male controls.
- Bmax was positively correlated with age and season (higher in summer), and negatively with depressive illness.
- Lower Bmax was associated with obsessional features in depressed subjects.
- Treatment with imipramine, maprotiline, BRL 14342, or electroconvulsive therapy did not significantly alter Bmax.
Conclusions:
- Reduced platelet imipramine binding in major depressive disorder is primarily observed in females.
- Bmax is influenced by demographic and seasonal factors, as well as the presence of obsessional features.
- Short-term antidepressant treatments and ECT do not appear to normalize platelet imipramine binding levels.