Study of the antidepressant mechanism of electroconvulsive therapy (ECT) is of particular importance because of its: efficacy; uniqueness as a nonchemical centrally-directed treatment; and lack of pharmacokinetic confounding effects. It has been hypothesized on the basis of animal studies showing beta receptor downregulation and 5-HT2 receptor changes (downregulation by antidepressant drugs and upregulation by ECT) that these effects may mediate the antidepressant effect of ECT. However, no such receptor studies have been reported to date in ECT-treated depressed patients. Moreover, we have found an increase in platelet 5-HT2 binding sites and subsensitive beta adrenergic receptor function in depressed patients. The concept that the receptor systems through which ECT exerts its antidepressant effect are the same ones that are altered in depression is an exciting possibility. We will study: 1) lymphocyte beta receptor binding; 2) isoproterenol-sensitive adenylate cyclase response; 3) hormonal regulation of beta receptors by catecholamines and cortisol; 4) acute responses of catecholamines, heart rate, and blood pressure to ECT; 5) 24 hour urinary excretion levels of MHPG and 5-HIAA; 6) platelet 5-HT2 binding; and 7) rise in plasma growth hormone, prolactin, and cortisol after fenfluramine challenge as a measure of central 5-HT function. Patients with a major depressive episode, endogenous subtype will be compared at baseline to controls, and then studied longitudinally during the course of ECT. They will be studied 24 hours after: ECT #1 (effect of 1 ECT); ECT #5 (to distinguish effects specifically correlated with degree of antidepressant response); and after the final ECT. Enduring effects will be assessed by studying patients 5-7 days after the last ECT. These measures may not only have potential as diagnostic tools (state versus trait markers), and monitors of clinical response, but may lead to better understanding of mechanism of action of ECT and thereby to improved chemical antidepressants.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH040695-02
Application #
3378975
Study Section
(TDAB)
Project Start
1986-02-01
Project End
1989-01-31
Budget Start
1987-02-01
Budget End
1988-01-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Type
Schools of Medicine
DUNS #
201373169
City
New York
State
NY
Country
United States
Zip Code
10065
Rizk, Mina M; Rubin-Falcone, Harry; Lin, Xuejing et al. (2018) Gray matter volumetric study of major depression and suicidal behavior. Psychiatry Res Neuroimaging 283:16-23
Daray, Federico M; Mann, J John; Sublette, M Elizabeth (2018) How lipids may affect risk for suicidal behavior. J Psychiatr Res 104:16-23
Pillai, Rajapillai L I; Zhang, Mengru; Yang, Jie et al. (2018) Will imaging individual raphe nuclei in males with major depressive disorder enhance diagnostic sensitivity and specificity? Depress Anxiety 35:411-420
Rubin-Falcone, Harry; Zanderigo, Francesca; Thapa-Chhetry, Binod et al. (2018) Pattern recognition of magnetic resonance imaging-based gray matter volume measurements classifies bipolar disorder and major depressive disorder. J Affect Disord 227:498-505
Coplan, Jeremy D; Gupta, Nishant K; Flynn, Sarah K et al. (2018) Maternal Cerebrospinal Fluid Glutamate in Response to Variable Foraging Demand: Relationship to Cerebrospinal Fluid Serotonin Metabolites in Grown Offspring. Chronic Stress (Thousand Oaks) 2:
Milak, Matthew S; Pantazatos, Spiro; Rashid, Rain et al. (2018) Higher 5-HT1A autoreceptor binding as an endophenotype for major depressive disorder identified in high risk offspring - A pilot study. Psychiatry Res Neuroimaging 276:15-23
Pillai, Rajapillai L I; Malhotra, Ashwin; Rupert, Deborah D et al. (2018) Relations between cortical thickness, serotonin 1A receptor binding, and structural connectivity: A multimodal imaging study. Hum Brain Mapp 39:1043-1055
Rizk, Mina M; Rubin-Falcone, Harry; Keilp, John et al. (2017) White matter correlates of impaired attention control in major depressive disorder and healthy volunteers. J Affect Disord 222:103-111
Iscan, Zafer; Rakesh, Gopalkumar; Rossano, Samantha et al. (2017) A positron emission tomography study of the serotonergic system in relation to anxiety in depression. Eur Neuropsychopharmacol 27:1011-1021
CeƱido, Joshua F; Itin, Boris; Stark, Ruth E et al. (2017) Characterization of lipid rafts in human platelets using nuclear magnetic resonance: A pilot study. Biochem Biophys Rep 10:132-136

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