- Antidepressant electroconvulsive therapy: mechanism of action, recent advances and limitations. (2009). Merkl A, Heuser I, Bajbouj M. Experimental Neurology. 219, 20-26.
The authors acknowledge that ECT has stood the test of time even with the introduction of other physical therapies. The article contains sections on history and reviews of possible mechanism of action, efficacy data and adverse effects as well as anaesthetic concerns and possible interactions with prescribed medication.
- Neurophysiological mechanisms of electroconvulsive therapy for depression. (2009). Nobuo Kato. Neuroscience Research. 64, 3-11.
A study of the Homer 1a scaffold protein present in neural circuits and induced by electroconvulsive stimulation (ECS). The resultant effect is a reduction in neuronal excitability and presumed modification of the synaptic plasticity. The author postulates that this may tie in with the GABAergic dysfunction hypothesis of depression which features increased excitability of the cerebral cortex in depressed patients.
- Chronic treatment with electroconvulsive shock may modulate the immune function of macrophages. (December 2008) Roman A, Nawrat D, Nalepa I. J of ECT; 24;260-267.
The theory being postulated is that an increased number or increased activity of macrophages and their metabolites compared to normal response in the immune system results in depressive illness. Repeated electroconvulsive stimulation (ECS) was shown to change the biological properties of macrophages, reducing their tendency to cause inflammation without damaging their strucure.
- Neurobiological correlates of the cognitive side effects of electroconvulsive therapy. March 2008. Nobler M & Sackeim H. J of ECT; 24:40-45.
This review highlights some of the biochemical, electrophysiological and neuroimaging correlates of amnesic effects of ECT. Brain regions associated with the therapeutic effects of ECT overlap with regions critical for cognitive side effects. The data suggest: [1] the neurophysiological alterations associated with retrograde and anterograde amnesia are distinct, [2] altered function in the prefrontal cortex may be associated with retrograde amnesia cf medial temporal lobe, [3] short term cerebral physiological changes as measured by PET scans may predict longer term retrograde amnesia.
- Pharmacological attenuation of electroconvulsive therapy-induced cognitive deficits: theoretical background and clinical findings. March 2008. Pigot M, Andrade C, Loo C. J of ECT, 24:57-67.
Evidence now exists for the involvement of glutaminergic, cholinergic and glucocorticoid mechanisms in the genesis of cognitive side effects at ECT. Other systems have also been considered eg calcium channels, thyroid hormones, nitric oxide, opioid transmission and the hypertensive surge. As such there lies the potential for the development of neuroprotective strategies, as yet none emerge as superior.
- Change in seizure threshold during electroconvulsive therapy. June 2008. Fink M et al. J of ECT; 24:114-116
This was a naturalistic study of 80 subjects entered for maintenance ECT after remission using bilateral treatment at 1.5 times seizure threshold. Retitration of the seizure threshold after remission showed no increase in 70% compared to that prior to treatment and a decrease in 9%. This study does not support the view that ECT exerts its benefit via anticonvulsant effects.
- Electroconvulsive therapy, brain-derived neurotrophic factor, and possible neurorestorative benefit of the clinical application of electroconvulsive therapy. June 2008, Taylor S. J of ECT; 24:160-165.
This article describes the association of brain derived neurotrophic factor (BDNF) with hippocampal size and function, both low in treatment resistant depression. ECT results in an increase in BDNF and so may have a positive effect in restoring hippocampal grey matter.
- The effects of electroconvulsive therapy on GABAergic function in major depressive patients. September 2008. Esel E et al. J of ECT; 24:224-228.
GABA levels were measured before and after ECT in 25 depressed patients compared to matched controls. Depressed patients had lower GABA at the outset and ECT caused a significant increase in levels post treatment although not to the level of healthy controls. ECT also appeared to potentiate growth hormone release to a baclofen challenge, a measure of GABAb receptor activity in the hypothalamus.
- Metabolic correlates of antidepressant and antipsychotic response in patients with psychotic depression undergoing electroconvulsive therapy. McCormick L et al. December 2007. J of ECT;23:265-273.
Positron emission tomography was used to assess cerebral glucose metabolism in ten subjects before and after a course of ECT. Antidepressant efficacy was associated with increased metabolism in the left subgenual anterior cingulated cortex and the hippocampus. Reduction in antipsychotic symptoms was associated with increased metabolism in the left hippocampal region.
- CREB binding and activity in brain: regional specificity and induction by electroconvulsive seizure. Tanis K, Duman R, Newton S. 2008, Biological Psychiatry (in press)
The group looked at cyclic AMP response element binding (CREB) receptor sites in the rat brain and conclude that CREB is an important mediator of the biological responses to electroconvulsive therapy seizure. Also that such studies play an important role in understanding psychiatric and cognitive function.
- Long-term follow up in depressed patients treated with electroconvulsive therapy. Johanson et al. J of ECT 2005;21(4):214-220.
This was a study of ten patients who underwent neurophysiological measurements with regional cerebral blood flow and EEG before the first ECT, 6 months later and after approximately 1 year. The authors found a lower, but not significant, bilateral cerebral frontal flow compared to controls at one year follow up. Eight patients had a normal EEG.
- Electroconvulsive seizures induce angiogenesis in adult rat hippocampus. Hellsten et al. Biological Psychiatry 2005;58:871-878.
This paper describes animal model experiments using convulsive stimulations. The authors postulate that the beneficial effects of ECT result from increased vascularisation of the hippocampus.
- Non convulsive seizures in electroconvulsive therapy: further evidence of differential neurophysiological aspects of bitemporal versus bifrontal electrode placement. Teman P et al. J of ECT 2006; 22(1):46-48.
This article discusses the possible reasons for the different rates of non-convulsive seizures seen with different types of ECT and postulates that bifrontal ECT is more likely to generate non-convulsive seizures localised to the frontal lobes.
- Effects of right unilateral electroconvulsive therapy on motor cortical excitability in depressive patients. Bajbouj M et al. J of Psychiatric Research 2005 (in press)
The reduction in seizure duration in the course of ECT was associated with clinical improvement and an increase in intracortical inhibition. The authors postulate GABA-ergic neurotransmission involvement and refer to similar studies.
- Metabolic Changes within the Left Dorsolateral Prefrontal Cortex occurring with Electroconvulsive Therapy in patients with Treatment Resistant Unipolar Depression. Michael N et al; Psychological Medicine. October 2003. 33(7):11277-1284.
Proton STEAM Spectroscopy was used to study metabolic changes in the dorsolateral prefrontal cortex (DLPFC) pre and post ECT in 12 severely depressed patients. The DLPFC glutamate/glutamine levels correlated negatively with severity of depression. Successful ECT resulted in an increase in the level of glutamate/glutamine to that of the control group.
- Raised Plasma levels of Tumour Necrosis Factor (alpha) in Patients with Depression. Hestad K et al; Journal of ECT. December 2003. 19:183-188.
Tumour Necrosis Factor (TNF) is an indication of inflammation and was found to be high in the fifteen patients studied, returning to normal after successful ECT. Factors such as concomitant medication were controlled for and patients excluded if other sources on inflammation detected. The TNF of those depressed patients not receiving ECT remained high.
- Increased Cortical GABA Concentrations in depressed Patients Receiving ECT. Sancora G et al. Am J of Psychiatry March 2003, 160: 577-579.
Occipital cortex GABA concentrations in eight depressed patients were measured before and after a course of ECT. A significant increase in GABA was seen following treatment. Treatment was terminated solely on the basis of clinical judgement and outcome was measured by a fall in the Hamilton Rating Scale for Depression.
- Relationship between Prolactin Responses to ECT and Dopaminergic and Serotonergic Responsivity in Depressed Patients. Markianos et al. European Archives of Psychiatry & Clinical Neuroscience, 2002, Vol 252 Issue 4, p166-172.
This study on 15 male depressed patients matched with 15 male controls concludes that the rise in prolactin levels seen at ECT is a reflection of a decrease in the dopamine mediated inhibitory hypothalamo-pituitary system.
- Electroconvulsive Stimuli Alter the Regional Concentrations of Nerve Growth Factor, Brain-Derived Neurotrophic Factor in Adult Rat Brain. Angelucci F et al. Journal of ECT. 18(3):138-143.
This research on rat brains indicate that neurotrophic factors play a role in the mechanism of action of ECS and, by extrapolation, may play a role in the mechanism of ECT.
- Magnetic and seizure thresholds before and after six electroconvulsive therapy treatments. Amiaz R et al. Journal of ECT. September 2001, 17(3): 195-197.
This study was designed to determine if there was a common mechanism for the effectiveness of ECT and TMS in terms of their effect on seizure and magnetic threshold. It concluded that there was not but of interest is the fact that the seizure threshold rose on average by a factor of x5.
- The effects of electroconvulsive therapy on melatonin. Krahn et al. December 2000, J of ECT, 16(4):391-398.
Results from a study of 14 patients suggesting an association between therapeutic response and a decrease in endogenous melatonin production post ECT.
- Electrophysiological correlates of the adverse cognitive effects of electroconvulsive therapy. Sakeim H et al. June 2000, J of ECT 16(2):110-120.
Further evidence to support the observation that post-ictal disorientation is related to post-ECT retrograde amnesia. These may share a common mechanism detectable by EEG.
- Quantitative EEG during seizures induced by electroconvulsive therapy: relations to treatment modality and clinical features; I global analyses. Nobler MS et al, September 2000, Journal of ECT, Vol 16, no3, 211-228.
The authors conclude that manipulations of ECT technique strongly determine the magnitude of seizure expression, but relations with clinical outcome are weak thereby casting doubt on the analysis of EEG features to determine machine settings.
- Quantitative EEG during seizures induced by electroconvulsive therapy: relations to treatment modality and clinical features; II topographical analyses. Luber et al. September 2000, Journal of ECT, Vol 16, no3, 229-243.
The companion study looking for EEG supports for the mechanisms of ECT. The authors report evidence for
i) transcortical EEG changes and superior clinical outcome (small effect size)
ii) superior clinical outcome associated with more intense seizure expression in the prefrontal regions.
but no evidence for efficacy in relation to stimulation of the deep brain structures.
- Electroconvulsive therapy and the alpha-2 noradrenergic receptor: implications of treatment schedule effects. Andrade C & Sudha S. September 2000, J of ECT, 16(3):268-278.
Six animal studies designed to look at the noradrenergic system concluded that ECS produces time dependent downregulation of the alpha-2 receptor. Maintenance ECS produced sustained downregulation.
- Bolwig T, Woldbye D, Mikkelsen J, (1999), Electroconvulsive therapy as an anticonvulsant: a possible role of neuropeptide Y. Journal of ECT, 15(1):93-101.
- Duman R & Vaidya V, (1998), Molecular and cellular actions of chronic electroconvulsive seizures. Journal of ECT, 14(3):181-193
- Hiroi N, Marek G, Brown J et al., (1998), Essential role of the fosB gene in molecular, cellular and behavioural actions of chronic electroconvulsive therapy seizures. Journal of neuroscience, 18(17):6952-6962.
- Krystal AD, Weiner RD, (1999), EEG correlates of the response to ECT: A possible antidepressant role of brain-derived neurotrophic factor. Journal of ECT. 15(1):27-38.
- Mann J, (1998), Neurobiological correlates of the antidepressant action of electroconvulsive therapy. Journal of ECT, 14(3):172-180
- Mathe A (1999), Neuropeptides and electroconvulsive treatment. Journal of ECT, 15(1):60-75.
- Newman M, Gur E et al. (1998), Neurochemical mechanisms of the action of ECS: evidence from in vivo studies. Journal of ECT, 14(3):153-171
- Sackeim H, (1999), The anticonvulsant hypothesis of the mechanisms of action of ECT: current status. Journal of ECT, 15(1):5-26
- Sattin A, (19990 The role of TRH and related peptides in the mechanism of action of ECT. Journal of ECT, 15(1):76-92.
