Therapeutic Effect Of Electroconvulsive Therapy Research Articles

Amygdala and hippocampal substructure volumes and their association with improvement in mood symptoms in patients with mood disorders undergoing electroconvulsive therapy

Electroconvulsive therapy (ECT) demonstrates favorable outcomes in the management of severe depressive disorders. ECT has been consistently associated with volumetric increases in the amygdala and hippocampus. However, the underlying mechanisms of these structural changes and their association to clinical improvement remains unclear. In this cross-sectional structural MRI study, we assessed the difference in amygdala subnuclei and hippocampus subfields in n = 37 patients with either unipolar or bipolar disorder immediately after eighth ECT sessions compared to (n = 40) demographically matched patients in partial remission who did not receive ECT (NoECT group). Relative to NoECT, the ECT group showed significantly larger bilateral amygdala volumes post-treatment, with the effect originating from the lateral, basal, and paralaminar nuclei and the left corticoamydaloid transition area. No significant group differences were observed for the hippocampal or cortical volumes. ECT was associated with a significant decrease in depressive symptoms. However, there were no significant correlations between amygdala subnuclei volumes and symptom improvement. Our study corroborates previous reports on increased amygdalae volumes following ECT and further identifies the subnuclei driving this effect. However, the therapeutic effect of ECT does not seem to be directly related to structural changes in the amygdala.

Comparative efficacy and tolerability of different anesthetics in electroconvulsive therapy for major depressive disorder: A systematic review and network meta-analysis

Electroconvulsive therapy (ECT) is one of the most effective treatments for major depressive disorder. Modern ECT is conducted with anesthesia, however, the optimal anesthetic agent for ECT is yet to be understood. This study is aimed to compare the effects of different anesthetic agents on antidepressant efficacy and tolerability in depressed individuals undergoing ECT. We searched MEDLINE, EMBASE, the CENTRAL and PsycINFO for randomized controlled trials from database inception until Nov 13, 2022 (PROSPERO: CRD42022375407). Global and local inconsistencies, heterogeneity and publication bias were assessed. Rankings were calculated with the surface under the cumulative ranking curve. A total of 33 studies involving 1898 patients were enrolled. Remission rates were higher for ketamine anesthesia as compared to adjunctive ketamine and propofol. In terms of ranking, ketamine was found to be first in terms of response/remission rates and depressive scores after the 1st, 3rd and 6th ECT and at the end of ECT session, while a higher incidence of adverse events was also observed. No significant advantage of any anesthetic was revealed for the cognitive function after ECT. In summary, based on current evidence, no specific anesthetic is recommended for ECT anesthesia. However, despite more side effects, ketamine monoanesthesia seems to reveal a potential benefit in improving antidepressant efficacy of ECT, and further studies are needed to investigate the relationship between anesthetic agents and the therapeutic effect of ECT.

Information flow and dynamic functional connectivity during electroconvulsive therapy in patients with depression

BackgroundElectroconvulsive therapy is effectively used for treatment-resistant depression; however, its neural mechanism is largely unknown. Resting-state functional magnetic resonance imaging is promising for monitoring outcomes of electroconvulsive therapy for depression. This study aimed to explore the imaging correlates of the electroconvulsive therapy effects on depression using Granger causality analysis and dynamic functional connectivity analyses. MethodsWe performed advanced analyses of resting-state functional magnetic resonance imaging data at the beginning and intermediate stages and end of the therapeutic course to identify neural markers that reflect or predict the therapeutic effects of electroconvulsive therapy on depression. ResultsWe demonstrated that information flow between the functional networks analyzed by Granger causality changes during electroconvulsive therapy, and this change was correlated with the therapeutic outcome. Information flow and the dwell time (an index reflecting the temporal stability of functional connectivity) before electroconvulsive therapy are correlated with depressive symptoms during and after treatment. LimitationsFirst, the sample size was small. A larger group is needed to confirm our findings. Second, the influence of concomitant pharmacotherapy on our results was not fully addressed, although we expected it to be minimal because only minor changes in pharmacotherapy occurred during electroconvulsive therapy. Third, different scanners were used the groups, although the acquisition parameters were the same; a direct comparison between patient and healthy participant data was not possible. Thus, we presented the data of the healthy participants separately from that of the patients as a reference. ConclusionsThese results show the specific properties of functional brain connectivity.

The Therapeutic Effect of Electroconvulsive Therapy in Patients With Obsessive-compulsive Disorder: A Quasi-experimental Study.

Electroconvulsive therapy (ECT) is an effective treatment for some psychiatric disorders. It is postulated that ECT should primarily be considered for patients with treatment-resistant obsessive-compulsive disorder (OCD) in the context of major depression. Therefore, we aimed to evaluate the efficacy of ECT in OCD patients without comorbid psychiatric disorders. This quasi-experimental study was conducted on 12 adult patients with severe OCD (Yale-Brown test score above 25) and no comorbid psychiatric disorders referred to a tertiary care hospital for psychiatric disorders. Treatment was administered three times a week for up to three to four weeks (a minimum of 8 sessions and a maximum of 12 sessions). We completed the Yale-Brown test for all patients before ECT, on the day after applying ECT, and two months after the final ECT session to evaluate the effect of therapy. Yale-Brown patients' Mean±SD significantly decreased after the ECT sessions from 28.08±2.50 to 17.17±3.78 (P=0.043). After treatment, the severity of OCD decreased in all patients and turned to mild and moderate levels in 4 patients (33.3%) and 8 (66.7%), respectively. After two months, the Mean±SD Yale-Brown score slightly increased to 18.08±1.62 (P=0.125), and the severity of OCD in all 12 patients (100%) became moderate. Nevertheless, in none of them, the Yale-Brown score increased and returned to the baseline value in this period. None of the patients developed significant side effects during or after ECT sessions. ECT was a safe and effective therapeutic strategy for patients with treatment-resistant OCD with no comorbid psychiatric disorders. However, further randomized controlled trials are required to validate the efficacy of ECT for OCD treatment before implementing it in the routine clinical practice.

Changes in Tryptophan-Kynurenine Metabolism in Patients with Depression Undergoing ECT-A Systematic Review.

The kynurenine pathway of tryptophan (Trp) metabolism generates multiple biologically active metabolites (kynurenines) that have been implicated in neuropsychiatric disorders. It has been suggested that modulation of kynurenine metabolism could be involved in the therapeutic effect of electroconvulsive therapy (ECT). We performed a systematic review with aims of summarizing changes in Trp and/or kynurenines after ECT and assessing methodological issues. The inclusion criterium was measures of Trp and/or kynurenines before and after ECT. Animal studies and studies using Trp administration or Trp depletion were excluded. Embase, MEDLINE, PsycInfo and PubMed were searched, most recently in July 2022. Outcomes were levels of Trp, kynurenines and ratios before and after ECT. Data on factors affecting Trp metabolism and ECT were collected for interpretation and discussion of the reported changes. We included 17 studies with repeated measures for a total of 386 patients and 27 controls. Synthesis using vote counting based on the direction of effect found no evidence of effect of ECT on any outcome variable. There were considerable variations in design, patient characteristics and reported items. We suggest that future studies should include larger samples, assess important covariates and determine between- and within-subject variability. PROSPERO (CRD42020187003).

Cerebral oxygen saturation in the prefrontal cortex during electroconvulsive therapy and its relation with the postictal reorientation time

The therapeutic effect of Electroconvulsive Therapy (ECT) has been attributed to generalised seizure. Although patients are well oxygenated prior to and during treatment, critics have associated ECT with brain tissue hypoxemia. In this study, the regional oxygen saturation (rSO2) was measured continuously during ECT in the prefrontal cortex (PFC) of both hemispheres using 2-channel Near Infrared Spectroscopy (NIRS). Additionally, the postictal reorientation time (PRT) was determined and related to the rSO2 course. We evaluated 72 ECT treatments in 22 adult patients who were treated for a therapy-resistant depressive syndrome. The therapy was performed according to our standard clinical procedures deploying right unilateral (RUL) and left anterior versus right temporal (LART) electrode placements. According to our results, the rSO2 courses showed an increase during hyperventilation, a sharp drop immediately after the stimulus, and a long recovery period with values far exceeding the baseline. In 55,6% of treatments the rSO2 course stayed above the baseline. In the others, the drop fell below it for an average of 12.6 s. According to a cardio surgical standard no signs of hypoxemia occurred during ECT treatments. The rSO2 drop at seizure onset was the only parameter of the oxygen course related to the PRT in the multivariate analysis and might therefore be a characteristic feature of the seizure. It could reflect its physiological intensity and thereby be involved in the mechanism of action of ECT. NIRS seems to be an interesting non-invasive tool for monitoring and studying ECT.

Using EEG to Predict Clinical Response to Electroconvulsive Therapy in Patients With Major Depression: A Comprehensive Review

Introduction: An important approach to improve the therapeutic effect of electroconvulsive therapy (ECT) may be to early characterize patients who are more likely to respond. Our objective was to explore whether baseline electroencephalography (EEG) settings before the beginning of ECT treatment can predict future clinical response to ECT in patients with depressive disorder.Methods: We conducted a systematic search in the MEDLINE, EMBASE, PsycINFO, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases to identify studies using EEG in adults with depressive disorder treated by ECT. To investigate the predictive value of baseline EEG on clinical outcomes of ECT, we extracted from the retrieved studies and qualitatively described the association between the baseline EEG markers characteristics and the rates of future responders and/or remitters to ECT.Results: The primary search yielded 2,531 potentially relevant citations, and 12 articles were selected according to inclusion criteria. Most of the studies were prospective studies with small sample size. Sociodemographic and clinical characteristics of patients, ECT settings, EEG settings, and outcomes were heterogeneous. Event-related potential (ERP) paradigms were used in three studies, polysomnography was used in three studies, and the six other studies used EEG to measure cerebral connectivity and activity.Conclusions: P300 amplitude, coherence, and connectivity measures were correlated with remission in patients with depression treated by ECT. Sleep EEG recordings seemed not to be correlated with remission after ECT. Further prospective studies with large sample size are needed to determine optimal EEG parameters associated with clinical response to ECT in depressive disorder.Systematic Review Registration: PROSPERO CRD42020181978.

Movement, mood and cognition: Preliminary insights into the therapeutic effects of electroconvulsive therapy for depression through a resting-state connectivity analysis

Background: Electroconvulsive therapy (ECT) is a highly effective treatment for depression but how it achieves its clinical effects remains unclear.Methods: We set out to study the brain's response to ECT from a large-scale brain-network perspective. Using a voxelwise analysis, we looked at resting-state functional connectivity before and after a course of ECT at the whole-brain and the between- and within-network levels in 17 patients with a depressive episode. Using a group-independent component analysis approach, we focused on four networks known to be affected in depression: the salience network (SN), the default mode network (DMN), the cognitive executive network (CEN), and a subcortical network (SCN). Our clinical measures included mood, cognition, and psychomotor symptoms.Results: We found ECT to have increased the connectivity of the left CEN with the left angular gyrus and left middle frontal gyrus as well as its within-network connectivity. Both the right CEN and the SCN showed increased connectivity with the precuneus and the anterior DMN with the left amygdala. Finally, improvement of psychomotor retardation was positively correlated with an increase of within-posterior DMN connectivity.Limitations: The limitations of our study include its small sample size and the lack of a control dataset to confirm our findings.Conclusion: Our voxelwise data demonstrate that ECT induces a significant increase of connectivity across the whole brain and at the within-network level. Furthermore, we provide the first evidence on the association between an increase of within-posterior DMN connectivity and an improvement of psychomotor retardation, a core symptom of depression.

In Response.

We thank the editor for giving us the opportunity to respond to Dr Ansari et al,1 who claim that the association of exposure to general anesthesia for cesarean delivery with elevated risk of severe postpartum depression (PPD) might be due to residual confounding and that our conclusion implies a causality.1,2 Dr Ansari et al1 misread our study, and their concerns are unfounded. We discussed extensively in our article the limitations of our study, its proof-of-concept nature, and the need for confirmatory studies. More importantly, we explicitly stated that “[T]he reported association between exposure to general anesthesia and the risk of PPD and suicidality does not necessarily represent a causal relationship,” and “confounding by indication and residual confounding could explain the observed association between general anesthesia and postpartum mood disorders.”2 We also used the E value to evaluate the potential bias from residual confounding and acknowledged that “the exact indication for general anesthesia cannot be accurately identified in administrative data and the propensity score used to estimate the odds of receiving general anesthesia includes only known confounders or available confounders.”2 Dr Ansari et al1 assert that “General anesthesia is not generally performed without a clinical rationale…As such, women who do receive general anesthesia are likely to have had a more complicated peripartum course than women receiving regional anesthesia.” They attempted to back up this assertion by using the results from a quick chart review of 100 cesarean deliveries under general anesthesia performed in a single academic medical center. Based on a convenience sample, their result is not peer reviewed and cannot be taken as evidence to refute our findings. Our recent study in New York State indicates that about 40% of cesarean deliveries performed under general anesthesia did not have such a clinical rationale and could have been potentially avoided.3 Although postoperative depressive disorders are an understudied area in anesthesia outcomes research, there is emerging experimental and epidemiologic evidence linking general anesthesia to increased risk of postoperative depression, as alluded to in our study. Recent research in nonobstetric patients suggests that exposure to surgery under general anesthesia is associated with the development of newly onset postoperative depressive disorders and the acceleration of preexisting depressive symptoms.4 Studies in obstetric patients indicate that exposure to general anesthesia is partially responsible for heightened risk of postpartum depression. Acute or persistent postoperative pain, delayed first interaction with the newborn, and delayed breastfeeding have all been associated with the development of postpartum depression and are more frequent when general anesthesia is used for cesarean delivery.2,5,6 The antidepressant effect of ketamine does not necessarily contradict our findings, because the prophylactic administration of ketamine to surgical patients does not decrease the risk of newly onset postoperative depressive symptoms or the acceleration of preexisting depressive symptoms.4 Similarly, the therapeutic effect of electroconvulsive therapy on severe depressive disorders is due to the electrical current applied to the brain rather than the general anesthetic used for performing this traumatic procedure. Our preliminary findings should be viewed as positive signals that exposure to general anesthesia for cesarean delivery is a partially modifiable risk factor for PPD. More rigorous research is warranted to better establish the relationship between exposure to general anesthesia and PPD, assess the causative nature of this relationship, and elicit the mechanisms underlying this relationship. Jean Guglielminotti, MD, PhDDepartment of AnesthesiologyColumbia University Vagelos College of Physicians and SurgeonsNew York, New York[email protected] Guohua Li, MD, Dr PHDepartment of AnesthesiologyColumbia University Vagelos College of Physicians and SurgeonsNew York, New YorkDepartment of EpidemiologyColumbia University Mailman School of Public HealthNew York, New York

How does ECT work? A new explanatory model and suggestions for non-convulsive applications

In this article a new hypothesis is presented concerning the causal mechanism underlying electroconvulsive therapy (ECT). According to this model the antidepressant effect is caused by a change in sleep architecture triggered by the ictal events induced by ECT. This change in sleep architecture – a profound change in the neurophysiological and neurochemical state of the organism – is what causes the therapeutic effects of ECT and not any simple change in the release of neurotransmitters, neurotrophic factors and/or hormones. This realization also means that a comparable antidepressant effect could be achieved without the need of inducing seizures, but with the help of behavioral interventions that explicitly take aim at changing sleep architecture. The article presents and discusses evidence in favor of this thesis and also puts forth two simple, non-convulsive, applications of the theory.

Knowledge and attitudes of older psychiatric patients and their caregivers towards electroconvulsive therapy.

Electroconvulsive therapy (ECT) is an effective treatment for older patients with severe psychiatric disorders, but their knowledge and attitudes regarding ECT have not been well studied. This study examined the knowledge and attitudes of older Chinese patients and their caregivers towards ECT. A total of 216 participants comprising older patients treated with ECT (n = 108) and their caregivers (n = 108) were recruited. Their knowledge and attitudes regarding ECT were assessed using self-reported questionnaires. Most caregivers received sufficient information on the therapeutic effects of ECT, but inadequate information about the ECT process, its adverse effects, and risks was provided to caregivers and patients before treatment. Although ECT was generally viewed as beneficial, effective, and safe, around two-thirds of patients and caregivers believed that ECT should be used only for critically ill patients. Over half of the patients reported adverse effects caused by ECT, with memory impairment being the most commonly reported. Clinicians in Chinese psychiatric hospitals need to provide sufficient information on ECT to older patients and their caregivers before treatment, particularly regarding the treatment process and adverse effects.

As ECT Marks 80th Birthday, Experts Reflect on Its Future

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessAs ECT Marks 80th Birthday, Experts Reflect on Its FutureNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:3 Jul 2018https://doi.org/10.1176/appi.pn.2018.6b24AbstractResearchers are using neuroimaging to determine additional ways to make this proven treatment for treatment-resistant depression even safer and more effective.It has been 80 years since electroconvulsive therapy (ECT) was first used on a human patient. A group of ECT researchers and practitioners marked the anniversary during a session at APA’s 2018 Annual Meeting in May, where they reflected on the past, present, and future of the first member of the neuromodulation family. Sarah Lisanby, M.D., notes that ECT has evolved greatly since it was first used clinically in 1938, and today is a safe, personalized procedure that remains effective at alleviating treatment-resistant depression.“ECT has come far,” said session chair Sarah Lisanby, M.D., the director of the Division of Translational Research at the National Institute of Mental Health (NIMH). The procedure used to be a one-size-fits-all approach, during which patients received a standard seizure-inducing dose of current. Today, ECT involves a brief electrical stimulation to targeted regions of the brain while the patient is under anesthesia and has been given a muscle relaxant. Despite the proven effectiveness of ECT, Lisanby acknowledged that the therapy remains underused largely because of ongoing misperceptions and stigma. With newer techniques such as transcranial magnetic stimulation (TMS) now available, ECT must continue to evolve to remain relevant, she said.Modern neuroscience can assist this evolution by elucidating how ECT exerts its therapeutic effect, Chris Abbot, M.D., medical director of the ECT program at the University of New Mexico, told the audience. Researchers still don’t know whether the therapeutic effects of ECT are due to the seizure caused by ECT or the electric current, Abbot explained. He noted that studies have shown that administering the seizure-inducing chemical fluorothyll to patients with depression can improve depressive symptoms; similar findings have been seen in patients who received nonconvulsive electrotherapy.Researchers are using functional MRI to better understand how the brain changes following ECT sessions. Studies by Abbot and others have shown that ECT is associated with an increased volume in several brain regions, including the hippocampus (which regulates memory), and more connections between these regions. This work has also suggested that people with smaller hippocampal volumes prior to treatment are more likely to benefit from ECT.“If we can show that in addition to not damaging the brain, ECT even restores some brain function, it may change how people see this treatment and reduce stigma associated with ECT,” he said.It’s also possible that imaging combined with clinical measures could soon be used to identify depression subtypes that respond well to ECT, Abbot said. Studies have shown that neuroimaging can be used to determine subtypes of depression that respond differently to TMS.Other researchers are focused on ways to make ECT more precise, NIMH research fellow Zhi Deng, Ph.D., said during the session. He noted that while modern ECT offers different options for electric wavelengths, the current intensity, or amplitude, is fixed. Because people have anatomical differences, such as hair type or skull thickness, this can impact how big of an electric field they receive from ECT.“Why not make amplitude a variable in treatment, too?” Deng asked. Deng is currently using computer simulations to generate theoretical models showing which brain regions are stimulated when amplitudes are adjusted. ECT typically involves the placement of two electrodes, one on each side of the head, though there is some flexibility in the exact positioning. “But there are no hard rules that say ECT can only use two electrodes,” Deng said. By using multiple small electrodes—like those used for EEG tests—instead of the large steel disks currently used for ECT, Deng thinks that ECT can become more focalized and target specific brain regions, potentially making the technology safer but still highly effective. Patients with treatment-resistant depression could also benefit from an emerging technology known as magnetic seizure therapy (MST), which uses magnetic fields instead of electric current to induce seizures, explained Jeff Daskalakis M.D., Ph.D., a professor of psychiatry at the University of Toronto. Daskalakis recently completed an open-label, eight-week study of MST on 100 patients with treatment-resistant depression. The study tested three different frequencies of magnetic fields (low, medium, and high) and the results showed that at the high frequency almost 40 percent experienced a remission of their symptoms. That rate is higher than what TMS has achieved in clinical trials (about 30 percent of patients achieved remission), though it was not as high as the 50 percent remission rates following ECT. However, Daskalakis said that MST requires less anesthesia than ECT, which patients may find more favorable. ■ ISSUES NewArchived

Anesthesia for Electroconvulsive Therapy: an Update

The purpose of this review is to discuss the safety and therapeutic effects of electroconvulsive therapy (ECT), research advances in neurobiology of depression and antidepressant mechanisms of general anesthetics, and make recommendations applicable to anesthesia practice in the ECT suite. Recent epidemiological studies reported 0.08–0.75% 30-day mortality after ECT, with falls and cardiopulmonary complications as the most frequent adverse events. Advanced age (65 years and older) and ischemic heart disease are risk factors for adverse events after ECT. Animal and human research proposed two novel hypotheses of depression: a neurotrophic one and one of impaired connectivity. Studies utilizing biomarkers and functional imaging suggest that the antidepressant effect of ECT and ketamine is a result of the improved neuroplasticity in the brain via stimulation of brain-derived neurotrophic factor. Recent randomized controlled studies evaluating various doses of ketamine for anesthesia for ECT are inconclusive. One well-designed study did not demonstrate the beneficial effect of ketamine on depression and cognition. Ketamine as a sole anesthetic in ECT seems to be safe, but its effect on long-term outcomes after ECT is unclear. Risks and benefits of ECT should be carefully considered, particularly in patients older than 65 years, and with ischemic heart disease. Anesthesia should be adjusted to assure a good- quality seizure during ECT. Along with previously recommended methohexital and etomidate, ketamine may be also safely used for anesthesia in ECT.

Differential plastic changes in synthesis and binding in the mouse somatostatin system after electroconvulsive stimulation.

Electroconvulsive therapy (ECT) is regularly used to treat patients with severe major depression, but the mechanisms underlying the beneficial effects remain uncertain. Electroconvulsive stimulation (ECS) regulates diverse neurotransmitter systems and induces anticonvulsant effects, properties implicated in mediating therapeutic effects of ECT. Somatostatin (SST) is a candidate for mediating these effects because it is upregulated by ECS and exerts seizure-suppressant effects. However, little is known about how ECS might affect the SST receptor system. The present study examined effects of single and repeated ECS on the synthesis of SST receptors (SSTR1-4) and SST, and SST receptor binding ([125I]LTT-SST28) in mouse hippocampal regions and piriform/parietal cortices. A complex pattern of plastic changes was observed. In the dentate gyrus, SST and SSTR1 expression and the number of hilar SST immunoreactive cells were significantly increased at 1 week after repeated ECS while SSTR2 expression was downregulated by single ECS, and SSTR3 mRNA and SST binding were elevated 24 h after repeated ECS. In hippocampal CA1 and parietal/piriform cortices, we found elevated SST mRNA levels 1 week after repeated ECS and elevated SST binding after single ECS and 24 h after repeated ECS. In hippocampal CA3, repeated ECS increased SST expression 1 week after and SST binding 24 h after. In the parietal cortex, SSTR2 mRNA expression was downregulated after single ECS while SSTR4 mRNA expression was upregulated 24 h after repeated ECS. Considering the known anticonvulsant effects of SST, it is likely that these ECS-induced neuroplastic changes in the SST system could participate in modulating neuronal excitability and potentially contribute to therapeutic effects of ECT.

Frontal and temporal cortical functional recovery after electroconvulsive therapy for depression: A longitudinal functional near-infrared spectroscopy study

While the efficacy and tolerability of electroconvulsive therapy (ECT) for depression has been well established, the acute effects of ECT on brain function remain unclear. Particularly, although cognitive dysfunction has been consistently observed after ECT, little is known about the extent and time course of ECT-induced brain functional changes, as observed during cognitive tasks. Considering the acute antidepressant effects of ECT on depression, aberrant brain functional responses during cognitive tasks in patients with depression may improve immediately after this treatment. To clarify changes in cortical functional responses to cognitive tasks following ECT, we used task-related functional near-infrared spectroscopy (NIRS) to assess 30 patients with major depressive disorder or bipolar depression before and after an ECT series, as well as 108 healthy controls. Prior to ECT, patients exhibited significantly smaller [oxy-Hb] values in the bilateral frontal cortex during a letter verbal fluency task (VFT) compared with healthy controls. We found a significant increase in [oxy-Hb] values in the bilateral frontal cortex during the VFT after ECT in the patient group. A decrease in depression severity was significantly correlated with an increase in [oxy-Hb] values in the right ventrolateral prefrontal cortex following ECT. This is the first NIRS study to evaluate brain functional changes before vs. after ECT. Impaired functional responses, observed during the cognitive task in depressed patients, were normalized after ECT. Thus, recovery from abnormal functional responses to cognitive tasks in the frontal brain regions may be associated with the acute therapeutic effects of ECT for depression.

Electroconvulsive shock attenuated microgliosis and astrogliosis in the hippocampus and ameliorated schizophrenia-like behavior of Gunn rat

BackgroundAlthough electroconvulsive therapy (ECT) is regarded as one of the efficient treatments for intractable psychiatric disorders, the mechanism of therapeutic action remains unclear. Recently, many studies indicate that ECT affects the immune-related cells, such as microglia, astrocytes, and lymphocytes. Moreover, microglial activation and astrocytic activation have been implicated in the postmortem brains of schizophrenia patients. We previously demonstrated that Gunn rats showed schizophrenia-like behavior and microglial activation in their brains. The present study examined the effects of electroconvulsive shock (ECS), an animal counterpart of ECT, on schizophrenia-like behavior, microgliosis, and astrogliosis in the brain of Gunn rats.MethodsThe rats were divided into four groups, i.e., Wistar sham, Wistar ECS, Gunn sham, and Gunn ECS. ECS groups received ECS once daily for six consecutive days. Subsequently, prepulse inhibition (PPI) test was performed, and immunohistochemistry analysis was carried out to determine the activation degree of microglia and astrocytes in the hippocampus by using anti-CD11b and anti-glial fibrillary acidic protein (GFAP) antibody, respectively.ResultsWe found PPI deficit in Gunn rats compared to Wistar rats, and it was significantly improved by ECS. Immunohistochemistry analysis revealed that immunoreactivity of CD11b and GFAP was significantly increased in Gunn rats compared to Wistar rats. ECS significantly attenuated the immunoreactivity of both CD11b and GFAP in Gunn rats.ConclusionsECS ameliorated schizophrenia-like behavior of Gunn rats and attenuated microgliosis and astrogliosis in the hippocampus of Gunn rats. Accordingly, therapeutic effects of ECT may be exerted, at least in part, by inhibition of glial activation. These results may provide crucial information to elucidate the role of activated glia in the pathogenesis of schizophrenia and to determine whether future therapeutic interventions should attempt to up-regulate or down-regulate glial functions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0688-2) contains supplementary material, which is available to authorized users.

Abstract # 1774 Microglia mediate the anti-depressive effects of electroconvulsive shock therapy in mice exposed to chronic unpredictable stress

Electroconvulsive therapy (ECT) is one of the most effective treatments for depression. Although it has been used for decades, particularly for treatment of major depression patients with drug resistance, the mechanisms underlying ECT’s action are still elusive. Recent studies in our laboratory demonstrated that decline in the number and activation status of hippocampal microglia underlies the development of depressive-like symptoms in chronic unpredictable stress (CUS)-exposed mice. Here, we investigated whether the therapeutic effects of ECT are mediated via modulation of microglial status. We specifically assessed whether microglial inhibition (by minocycline administration), or depletion (by chronic treatment with the selective CSF1 receptor kinase inhibitor PLX5622), interferes with the therapeutic effects of ECT in CUS-exposed mice. ECT (3 sessions/week for 2.5 weeks) reversed the CUS-induced reductions in sucrose preference (anhedonia) and social exploration. These effects were microglia-dependent, evidenced by blockade of these therapeutic effects by minocycline, or by the mere absence of brain microglia. ECT-induced increases in hippocampal neurogenesis were also reduced by minocycline. Furthermore, ECT reversed the CUS-induced decrease in the total length of hippocampal microglial processes, but not the reduction in microglial number. Consistent with these morphological changes, ECT significantly altered microglia-related gene transcripts including Csfr1, P2y12r, and P2x7. In conclusion, we show that the anti-depressive therapeutic effects of ECT are dependent on the presence and activity level of microglia in the hippocampus.

Antidepressant Effects of Electroconvulsive Therapy Correlate With Subgenual Anterior Cingulate Activity and Connectivity in Depression

The mechanisms underlying the effects of electroconvulsive therapy (ECT) in major depressive disorder (MDD) are not fully understood. Resting-state functional magnetic resonance imaging (rs-fMRI) is a new tool to study the effects of brain stimulation interventions, particularly ECT. The authors aim to investigate the mechanisms of ECT in MDD by rs-fMRI.They used rs-fMRI to measure functional changes in the brain of first-episode, treatment-naive MDD patients (n = 23) immediately before and then following 8 ECT sessions (brief-pulse square-wave apparatus, bitemporal). They also computed voxel-wise amplitude of low-frequency fluctuation (ALFF) as a measure of regional brain activity and selected the left subgenual anterior cingulate cortex (sgACC) to evaluate functional connectivity between the sgACC and other brain regions.Increased regional brain activity measured by ALFF mainly in the left sgACC following ECT. Functional connectivity of the left sgACC increased in the ipsilateral parahippocampal gyrus, pregenual ACC, contralateral middle temporal pole, and orbitofrontal cortex. Importantly, reduction in depressive symptoms were negatively correlated with increased ALFF in the left sgACC and left hippocampus, and with distant functional connectivity between the left sgACC and contralateral middle temporal pole. That is, across subjects, as depression improved, regional brain activity in sgACC and its functional connectivity increased in the brain.Eight ECT sessions in MDD patients modulated activity in the sgACC and its networks. The antidepressant effects of ECT were negatively correlated with sgACC brain activity and connectivity. These findings suggest that sgACC-associated prefrontal-limbic structures are associated with the therapeutic effects of ECT in MDD.

Are morphological changes necessary to mediate the therapeutic effects of electroconvulsive therapy?

The neurotrophic hypothesis has become the favorite model to explain the antidepressant properties of electroconvulsive therapy (ECT). It is based on the assumption that a restoration of previously defective neural networks drives therapeutic effects. Recent data in rather young patients suggest that neurotrophic effects of ECT might be detectable by diffusion tensor imaging. We here aimed to investigate whether the therapeutic response to ECT necessarily goes along with mesoscopic effects in gray matter (GM) or white matter (WM) in our patients in advanced age. Patients (n=21, 15 males and 7 females) suffering from major depressive disorder were treated with ECT. Before the start of treatment and after the completion of the index series, they underwent magnetic resonance imaging, including a diffusion-weighed sequence. We used voxel-based morphometry to assess GM changes and tract-based spatial statistics and an SPM-based whole-brain analysis to detect WM changes in the course of treatment. Patients significantly improved clinically during the course of ECT. This was, however, not accompanied by GM or WM changes. This result challenges the notion that mesoscopic brain structure changes are an obligatory prerequisite for the antidepressant effects of ECT.

The Efficiency Of Electroconvulsive Therapy In The Treatment Of Depression In The Elderly

The Electroconvulsive Therapy (ECT) is a safe and effective treatment of depression in the elderly. With a high rate of remission may be t he treatment of choice in cases of psychotic depression or when antidepressant treatment fails. Although its mechanism of action is unknown the therapeutic effects of ECT may be related to changes in cerebral blood flw. Studies confim differences in the effects of ECT according to patient age. There are side effects related to cognitive function. ECT is as safe for elderly patients and for young patients.