ABSTRACT
We conducted a series of experiments to evaluate possible molecular mechanisms by which electroconvulsive therapy, a commonly used treatment for depression, may exert its adverse effects such as amnesia. We assessed the effects of repeated electroconvulsive shocks (ECS) alone and in combination with low-level radiograph irradiation on DNA single-strand breaks in cells in the rat brain, using a sensitive alkaline microgel electrophoresis assay method. Our results show that ECS, when administered alone, had no significant effects on DNA single-strand breaks in cells in either the hippocampus or the rest of the brain. However, repeated ECS when combined with a low-level radiograph irradiation produced a small but significant increase in DNA single-strand breaks in rat brain cells.
Subject(s)
Brain Chemistry , DNA Damage , DNA, Single-Stranded/metabolism , Electroconvulsive Therapy/adverse effects , Animals , Brain/cytology , Brain/radiation effects , Brain Chemistry/radiation effects , DNA, Single-Stranded/chemistry , DNA, Single-Stranded/radiation effects , Electrophoresis , Hippocampus/cytology , Hippocampus/metabolism , Hippocampus/radiation effects , Male , Rats , Rats, Sprague-DawleyABSTRACT
A low dose (0.5 mg) of thyrotropin-releasing hormone (TRH), a short-acting tripeptide with known analeptic properties, was administered to eight depressed patients 5 minutes after ECT session 3 or 4 in a double-blind, placebo-controlled crossover design. After TRH infusion the patients displayed selectively better performance on a battery of neuropsychological tests than they did after placebo infusion. Further exploration with pharmacological probes to mitigate ECT postictal cognitive deficits is warranted.
Subject(s)
Cognition Disorders/prevention & control , Depressive Disorder/therapy , Electroconvulsive Therapy , Thyrotropin-Releasing Hormone/administration & dosage , Adult , Blood Pressure/drug effects , Cognition Disorders/etiology , Cross-Over Studies , Dose-Response Relationship, Drug , Double-Blind Method , Electroconvulsive Therapy/adverse effects , Female , Heart Rate/drug effects , Humans , Infusions, Intravenous , Male , Middle Aged , Neuropsychological Tests , Placebos , Thyrotropin-Releasing Hormone/therapeutic useABSTRACT
Rats given five consecutive daily electroconvulsive shock (ECS) treatments and trained to run in the Morris water maze, starting three days posttreatment, showed deficits in learning and memory functions. Treatment before each training session with the thyrotropin-releasing hormone (TRH) analog NS-3 [(CG-3703), (3R),(6R)-6-methyl-5-oxo-3-thiomorphorinyl-l-histidyl-l-prolinamid e tetrahydrate] reversed these behavioral deficits. The possible use of TRH and its analogs as therapeutic treatment for the cognitive dysfunctions resulting from electroconvulsive shock treatment for depression and the possible involvement of central cholinergic systems in the cognitive dysfunctions are discussed.
Subject(s)
Electroshock , Learning/drug effects , Thyrotropin-Releasing Hormone/analogs & derivatives , Animals , Male , Memory/drug effects , Rats , Rats, Sprague-Dawley , Thyrotropin-Releasing Hormone/pharmacologyABSTRACT
1. A systematic review of the literature revealed twelve clinical trials that evaluated nine different drugs, and used three different conceptual models to prevent, restore or treat ECT-induced cognitive deficits. 2. This review indicated inconclusive results regarding clinical utility of any of the drugs. 3. Major factors discussed include the complexities involved in the evaluation of ECT-induced cognitive deficits, and the techniques of evaluating changes in cognitive functions. 4. Our conclusion is that future research should emphasize understanding the neural mechanisms related to ECT-induced cognitive deficits. We suggest several areas for future exploration.
Subject(s)
Cognition Disorders/drug therapy , Electroconvulsive Therapy/adverse effects , Cognition Disorders/etiology , HumansABSTRACT
Modern ECT practice has evolved far from its beginnings more than 50 years ago. ECT is effective, safe, and rewarding in the clinical setting. This discussion complements the 1990 APA Task Force report and elaborates on some of the clinical and scientific factors that could not be fully addressed by the report. The future of ECT lies in understanding the mechanisms by which it relieves depressive symptoms and causes amnesia and related cognitive deficits.
Subject(s)
Depressive Disorder/therapy , Electroconvulsive Therapy/methods , Combined Modality Therapy/adverse effects , Depressive Disorder/psychology , Electroconvulsive Therapy/adverse effects , Humans , Psychotropic Drugs/adverse effects , Psychotropic Drugs/therapeutic useABSTRACT
The cognitive effects of a low dose of thyrotropin-releasing hormone (TRH) (2.0 mg, IV) were evaluated in 18 chronic alcoholic patients who exhibited memory dysfunction secondary to chronic alcohol abuse. The study used a double-blind crossover design that compared cognitive functions in patients with 2.0 mg of TRH IV as compared with a placebo. TRH was chosen because of its ability to enhance cholinergic transmission. Only minimal effects were seen with TRH. Patients with a shorter duration of alcohol use (mean of 16 years) performed significantly better with TRH as compared with placebo on a test involving verbal learning and memory. Those with a more chronic history of alcohol abuse (mean of 27 years) did not show such a response. All of the subjects showed cardiovascular response to TRH. Factors that may have contributed to the results of our study are discussed. It is our impression that future studies evaluating the cognitive effects of TRH in chronic alcoholics need to include an evaluation of the functional activity of TRH in the brain.
Subject(s)
Alcohol Amnestic Disorder/rehabilitation , Alcoholism/rehabilitation , Thyrotropin-Releasing Hormone/administration & dosage , Adult , Alcohol Amnestic Disorder/psychology , Alcoholism/psychology , Arousal/drug effects , Cholinergic Fibers/drug effects , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Neuropsychological Tests , Synaptic Transmission/drug effectsABSTRACT
Up to 15% of elderly women may suffer from depression. Patients with this disorder present with change in mood or diminished interest or pleasure in usual activities, as well as a variety of other neurovegetative symptoms. Depression is amenable to treatment, and a wide range of drug and nonpharmacologic modalities may be useful. The mere action of seeking professional help signals that the depressed patient has begun to take control of the situation and serves as a promising sign for recovery. The tricyclic antidepressants have a long history of use for the treatment of depression and are probably the most widely used agents for this indication, despite numerous adverse effects. Bupropion and the new selective serotonin reuptake inhibitors are effective in treating depression and are better tolerated than the tricyclics. For this reason, they may be particularly useful for treating depression in the elderly.
Subject(s)
Antidepressive Agents/administration & dosage , Depressive Disorder/drug therapy , Suicide/psychology , Aged , Antidepressive Agents/adverse effects , Depressive Disorder/diagnosis , Depressive Disorder/physiopathology , Drug Administration Schedule , Female , Humans , Risk FactorsABSTRACT
In this paper we describe the findings from two preliminary experiments, a human and an animal study, investigating whether thyrotropin-releasing hormone (TRH) can mitigate electroconvulsive therapy (ECT)-induced cognitive deficits. Our results suggest further explorations of TRH and its analogs as possible therapeutic agents for these deficits. We speculate that the major cause of the ECT-induced cognitive deficits is a decrease in cholinergic transmission in the central nervous system. Treatments such as TRH, which enhance cholinergic activity, can reverse the cognitive deficits.
