Electroconvulsive Stimulation Research Articles

Neurogenesis-independent mechanisms of MRI-detectable hippocampal volume increase following electroconvulsive stimulation

Electroconvulsive therapy (ECT) is one of the most effective psychiatric treatments but the underlying mechanisms are still unclear. In vivo human magnetic resonance imaging (MRI) studies have consistently reported ECT-induced transient hippocampal volume increases, and an animal model of ECT (electroconvulsive stimulation: ECS) was shown to increase neurogenesis. However, a causal relationship between neurogenesis and MRI-detectable hippocampal volume increases following ECT has not been verified. In this study, mice were randomly allocated into four groups, each undergoing a different number of ECS sessions (e.g., 0, 3, 6, 9). T2-weighted images were acquired using 11.7-tesla MRI. A whole brain voxel-based morphometry analysis was conducted to identify any ECS-induced brain volume changes. Additionally, a histological examination with super-resolution microscopy was conducted to investigate microstructural changes in the brain regions that showed volume changes following ECS. Furthermore, parallel experiments were performed on X-ray-irradiated mice to investigate the causal relationship between neurogenesis and ECS-related volume changes. As a result, we revealed for the first time that ECS induced MRI-detectable, dose-dependent hippocampal volume increase in mice. Furthermore, increased hippocampal volumes following ECS were seen even in mice lacking neurogenesis, suggesting that neurogenesis is not required for the increase. The comprehensive histological analyses identified an increase in excitatory synaptic density in the ventral CA1 as the major contributor to the observed hippocampal volume increase following ECS. Our findings demonstrate that modification of synaptic structures rather than neurogenesis may be the underlying biological mechanism of ECT/ECS-induced hippocampal volume increase.

Identification of the antidepressant effect of electroconvulsive stimulation-related genes in hippocampal astrocyte

Major depressive disorder (MDD) remains a significant global health concern, with limited and slow efficacy of existing antidepressants. Electroconvulsive therapy (ECT) has superior and immediate efficacy for MDD, but its action mechanism remains elusive. Therefore, the elucidation of the action mechanism of ECT is expected to lead to the development of novel antidepressants with superior and immediate efficacy. Recent studies suggest a potential role of hippocampal astrocyte in MDD and ECT. Hence, we investigated antidepressant effect of electroconvulsive stimulation (ECS), an animal model of ECT, -related genes in hippocampal astrocyte with a mouse model of MDD, in which corticosterone (CORT)-induced depression-like behaviors were recovered by ECS. In this model, both of CORT-induced depression-like behaviors and the reduction of hippocampal astrocyte were recovered by ECS. Following it, astrocytes were isolated from the hippocampus of this model and RNA-seq was performed with these isolated astrocytes. Interestingly, gene expression patterns altered by CORT were reversed by ECS. Additionally, cell proliferation-related signaling pathways were inhibited by CORT and recovered by ECS. Finally, serum and glucocorticoid kinase-1 (SGK1), a multi-functional protein kinase, was identified as a candidate gene reciprocally regulated by CORT and ECS in hippocampal astrocyte. Our findings suggest a potential role of SGK1 in the antidepressant effect of ECS via the regulation of the proliferation of astrocyte and provide new insights into the involvement of hippocampal astrocyte in MDD and ECT. Targeting SGK1 may offer a novel approach to the development of new antidepressants which can replicate superior and immediate efficacy of ECT.

Blood-brain barrier permeability and electroconvulsive therapy: a systematic review.

The cause of cognitive side effects after electroconvulsive therapy (ECT) is largely unknown. Alterations in the blood-brain barrier (BBB) have been considered in several recent ECT studies. We therefore found it worthwhile to perform a systematic review of the literature to examine if electrically induced seizures affect the permeability of the BBB. PubMed/MEDLINE and Embase were searched 16 November 2022. Studies with a direct measurement of BBB permeability in animals treated with modified electroconvulsive stimulation (ECS) and in humans treated with ECT were included. Synthesis of results was narrative due to the low number of studies and differences in study designs. Four animal and two human (31 participants) studies were included. In animals, two studies found increased BBB permeability to some smaller molecules after modified ECS, while the two other studies found marginally increased or unchanged permeability to albumin after treatment. In contrast, the human studies did not find increased BBB permeability to smaller molecules or albumin after ECT. Animal but not human studies support increased BBB permeability to some smaller molecules after electrically induced seizures. However, this conclusion is confined by the low number of studies and the lack of studies applying state-of-the-art methods. More studies using modern approaches to measuring of BBB permeability are warranted. The study was founded by Mental Health Services in the Capital Region of Denmark (grant number 61151-05) and was registered on PROSPERO before data extraction was initiated (CRD42022331385).

Electroconvulsive Stimulation in Rats Induces Alterations in the Hippocampal miRNome: Translational Implications for Depression.

MicroRNAs (miRNAs) may contribute to the development of depression and its treatment. Here, we used the hypothesis-neutral approach of next-generation sequencing (NGS) to gain comprehensive understanding of the effects of a course of electroconvulsive stimulation (ECS), the animal model equivalent of electroconvulsive therapy (ECT), on rat hippocampal miRNAs. Significant differential expression (p < 0.001) of six hippocampal miRNAs was noted following NGS, after correcting for multiple comparisons. Three of these miRNAs were upregulated (miR-132, miR-212, miR-331) and three downregulated (miR-204, miR-483, miR-301a). qRT-PCR confirmed significant changes in four of the six miRNAs (miR-132, miR-212, miR-204, miR-483). miR-483 was also significantly reduced in frontal cortex, though no other significant alterations were noted in frontal cortex, cerebellum, or whole blood. Assessing the translatability of the results, miR-132 and miR-483 were significantly reduced in whole blood samples from medicated patients with depression (n = 50) compared to healthy controls (n = 45), though ECT had no impact on miRNA levels. Notably, pre-ECT miR-204 levels moderately positively correlated with depression severity at baseline and moderately negatively correlated with mood score reduction post-ECT. miRNAs were also examined in cerebrospinal fluid and serum from a separate cohort of patients (n = 8) treated with ECT; no significant changes were noted post-treatment. However, there was a large positive correlation between changes in miR-212 and mood score post-ECT in serum. Though replication studies using larger sample sizes are required, alterations in miRNA expression may be informative about the mechanism of action of ECS/ECT and in turn might give insight into the neurobiology of depression.

Combination of electroconvulsive stimulation with ketamine or escitalopram protects the brain against inflammation and oxidative stress induced by maternal deprivation and is critical for associated behaviors in male and female rats.

This study aimed at evaluating the treatment effects with ketamine, electroconvulsive stimulation (ECS), escitalopram, alone or in combination in adult rats of both sexes, subjected to the animal model of maternal deprivation (MD). All groups were subjected to the forced swimming test (FST), splash and open field tests. The prefrontal cortex (PFC), hippocampus and serum were collected to analyze oxidative stress and inflammatory parameters. MD induced depressive-like behavior in the FST test in males and reduced grooming time in male and female rats. The treatments alone or combined reversed depressive and anhedonic behavior in females. In males, all treatments increased grooming time, except for ECS + escitalopram + ketamine. MD increased lipid peroxidation and protein carbonylation, nitrite/nitrate concentration and myeloperoxidase activity in the PFC and hippocampus of males and females. However, the treatment's response was sex dependent. Catalase activity decreased in the PFC of males and the PFC and hippocampus of females, and most treatments were not able to reverse it. MD increased the inflammation biomarkers levels in the PFC and hippocampus of males and females, and most treatments were able to reverse this increase. In all groups, a reduction in the interleukin-10 levels in the PFC and hippocampus of female and male rats was observed. Our study shows different responses between the sexes in the patterns evaluated and reinforces the use of the gender variable as a biological factor in MDD related to early stress and in the response of the therapeutic strategies used.

Distinct Aging-Vulnerable and -Resilient Trajectories of Specific Motor Circuit Functions in Oxidation- and Temperature-Stressed Drosophila.

In Drosophila, molecular pathways affecting longevity have been extensively studied. However, corresponding neurophysiological changes underlying aging-related functional and behavioral deteriorations remain to be fully explored. We examined different motor circuits in Drosophila across the life span and uncovered distinctive age-resilient and age-vulnerable trajectories in their established functional properties. In the giant fiber (GF) and downstream circuit elements responsible for the jump-and-flight escape reflex, we observed relatively mild deterioration toward the end of the life span. In contrast, more substantial age-dependent modifications were seen in the plasticity of GF afferent processing, specifically in use dependence and habituation properties. In addition, there were profound changes in different afferent circuits that drive flight motoneuron activities, including flight pattern generation and seizure spike discharges evoked by electroconvulsive stimulation. Importantly, in high-temperature (HT)-reared flies (29°C), the general trends in these age-dependent trajectories were largely maintained, albeit over a compressed time scale, lending support for the common practice of HT rearing for expediting Drosophila aging studies. We discovered that shortened life spans in Cu/Zn superoxide dismutase (Sod) mutant flies were accompanied by altered aging trajectories in motor circuit properties distinct from those in HT-reared flies, highlighting differential effects of oxidative versus temperature stressors. This work helps to identify several age-vulnerable neurophysiological parameters that may serve as quantitative indicators for assessing genetic and environmental influences on aging progression in Drosophila.

Risk Assessment of Electroconvulsive Therapy in Clinical Routine: A 3-Year Analysis of Life-Threatening Events in More Than 3,000 Treatment Sessions.

Background: Extensive research has reported that electroconvulsive therapy (ECT) can be highly effective in approximately 80% of patients suffering from depression. Its clinical use is mainly limited by historical objections and the concern about unwanted adverse effects (AEs), including serious and potentially life-threatening adverse events (pLTAEs), induced either by ECT or by anesthesia. Objective risk estimation is, therefore, a decisive factor in determining an indication for ECT.Methods: This paper presents a retrospective analysis of 3-year safety protocols and patient files of 157 patients who received a total of 3,106 ECT applications in a psychiatric inpatient setting at a psychiatric community hospital. This patient group comprises 5.3% of inpatients admitted with comparable diagnoses. Adverse events were analyzed from standardized safety protocols and patient files with a focus on pLTAEs.Results: Adverse events were reported for 30 (19.1%) of the 157 participants during 39 (6.1%) of 641 hospital stays. Serious pLTAEs occurred during three electroconvulsive stimulations in three patients, who needed action through the administration of medication or mechanical respiration. No patient suffered permanent damage to health, and no patient died. The incidence of these and other AEs was independent of sex, age, and diagnosis of patients, and anesthesia medication. Minor AEs occurred more often with higher stimulus doses and an increasing number of treatments.Conclusion: The low incidence rate of 0.097% of serious pLTAEs that require medical action may allow the conclusion that ECT is a rather safe treatment when performed in a controlled setting. The beneficial risk profile of ECT performed in the standard care of psychiatric hospitals suggests a more generous indication of this treatment method. We recommend that ECT facilities collect individual safety data to allow a reliable judgment of their institutional ECT risk profile.

Microglia and their LAG3 checkpoint underlie the antidepressant and neurogenesis-enhancing effects of electroconvulsive stimulation.

Despite evidence implicating microglia in the etiology and pathophysiology of major depression, there is paucity of information regarding the contribution of microglia-dependent molecular pathways to antidepressant procedures. In this study, we investigated the role of microglia in a mouse model of depression (chronic unpredictable stress-CUS) and its reversal by electroconvulsive stimulation (ECS), by examining the effects of microglia depletion with the colony stimulating factor-1 antagonist PLX5622. Microglia depletion did not change basal behavioral measures or the responsiveness to CUS, but it completely abrogated the therapeutic effects of ECS on depressive-like behavior and neurogenesis impairment. Treatment with the microglia inhibitor minocycline concurrently with ECS also diminished the antidepressant and pro-neurogenesis effects of ECS. Hippocampal RNA-Seq analysis revealed that ECS significantly increased the expression of genes related to neurogenesis and dopamine signaling, while reducing the expression of several immune checkpoint genes, particularly lymphocyte-activating gene-3 (Lag3), which was the only microglial transcript significantly altered by ECS. None of these molecular changes occurred in microglia-depleted mice. Immunohistochemical analyses showed that ECS reversed the CUS-induced changes in microglial morphology and elevation in microglial LAG3 receptor expression. Consistently, either acute or chronic systemic administration of a LAG3 monoclonal antibody, which readily penetrated into the brain parenchyma and was found to serve as a direct checkpoint blocker in BV2 microglia cultures, rapidly rescued the CUS-induced microglial alterations, depressive-like symptoms, and neurogenesis impairment. These findings suggest that brain microglial LAG3 represents a promising target for novel antidepressant therapeutics.

Shape and volume changes of the superior lateral ventricle after electroconvulsive therapy measured with ultra-high field MRI

The subventricular zone (SVZ) of the lateral ventricles harbors neuronal stem cells in adult mammals. Rodent studies report neurogenic effects in the SVZ of electroconvulsive stimulation. We hypothesize that if this finding translates to depressed patients undergoing electroconvulsive therapy (ECT), this would be reflected in shape changes at the SVZ.Using T1-weighted MR images acquired at ultra-high field strength (7T), the shape and volume of the ventricles were compared from pre to post ECT after 10 ECT sessions (in patients twice weekly) or 5 weeks apart (controls) using linear mixed models with age and gender as covariates.Ventricle shape significantly changed and volume significantly decreased over time in patients for the left ventricle, but not in controls. The decrease in volume of the ventricles was associated to a decrease in depression scores, and an increase in the left dentate gyrus,However, the shape changes of the ventricles were not restricted to the neurogenic niche in the lateral walls of the ventricles, providing no clear evidence for neurogenesis as sole explanation of volume changes in the ventricles after ECT.

The Potential Synergistic Activity of Zolmitriptan Combined in New Self-Nanoemulsifying Drug Delivery Systems: ATR-FTIR Real-Time Fast Dissolution Monitoring and Pharmacodynamic Assessment.

PurposeThe current work aimed to overcome the poor permeability and undesirable adverse effects of Zolmitriptan (ZMT) and to increase its efficacy in the treatment of acute migraine by exploiting the synergistic effect of the essential oil, lavender, to fabricate ZMT self-nanoemulsifying drug delivery systems (ZMT-SNEDDS).MethodsZMT-SNEDDS were fabricated based on full factorial design (32) to statistically assess the impact of oil and surfactant concentrations on the nanoemulsion globule size, zeta potential and percentage drug dissolution efficiency. An ATR-FTIR method was developed and validated for continuous real-time monitoring of ZMT dissolution and permeation. The dose of the optimized ZMT-SNEDDS used in the efficacy study was selected according to the acute toxicity study. The efficacy study was performed on migraineous rats induced by nitroglycerin and was evaluated by the activity cage and thermal tests, electroencephalogram, electroconvulsive stimulation, and biochemical analysis of brain tissue. Finally, histopathological and immunohistochemical examinations of the cerebra were carried out.ResultsUpon dilution, the optimized ZMT-SNEDDS (F5) exhibited nanosized spherical droplets of 19.59±0.17 nm with narrow size distribution, zeta potential (−23.5±1.17mV) and rapid emulsification characteristics. ATR-FTIR spectra elucidated the complete time course of dissolution and permeation, confirming F5 superior performance. Moreover, ZMT-SNEDDS (F5) showed safety in an acute toxicity study. ZMT concentration in rat brain tissues derived from F5 was lower compared to that of ZMT solution, yet its effect was better on the psychological state, algesia, as well as maintaining normal brain electrical activity and delayed convulsions. It counteracted the cerebral biochemical alternations induced by nitroglycerin, which was confirmed by histopathological examination.ConclusionIn a nutshell, these findings corroborated the remarkable synergistic efficacy and the high potency of lavender oil-based ZMT-SNEDDS in migraine management compared to the traditional zolmitriptan solution.

A qualitative study of key stakeholders’ perceived risks and benefits of psychiatric electroceutical interventions

Amid a renewed interest in alternatives to psychotherapy and medication to treat depression, there is limited data as to how different stakeholders perceive of the risks and benefits of psychiatric electroceutical interventions (PEIs), including electroconvulsive therapy (ECT) and deep brain stimulation (DBS). To address this gap, we conducted 48 semi-structured interviews, including 16 psychiatrists, 16 persons diagnosed with depression, and 16 members of the general public. To provide a basis of comparison, we asked participants to also compare each modality to front-line therapies for depression and to neurosurgical procedures used for non-psychiatric conditions. Across all stakeholder groups, perceived memory loss was the most frequently mentioned potential risk with ECT. The most discussed benefits across all stakeholder groups were efficacy and quick response. Psychiatrists most often referenced effectiveness when discussing ECT, while patients and the public did so when discussing DBS. Taken as a whole, these data highlight stakeholders’ contrasting perspectives on the risks and benefits of electroceuticals.

The effect of electroconvulsive therapy on neuroinflammation, behavior and amyloid plaques in the 5xFAD mouse model of Alzheimer\u2019s disease

Microglial cells are affected in Alzheimer’s disease (AD) and interact with amyloid-beta (Aβ) plaques. Apart from memory loss, depression is common in patients with AD. Electroconvulsive therapy (ECT) is an anti-depressive treatment that may stimulate microglia, induce neuroinflammation and alter the levels of soluble Aβ, but the effects of ECT on microglia and Aβ aggregation in AD are not known. We investigated the short- and long-term effects of ECT on neuroinflammation and Aβ accumulation. 5xFAD mice received either electroconvulsive stimulation (ECS n = 26) or sham treatment (n = 25) for 3 weeks. Microglia and Aβ were analyzed in samples collected 24 h, 5 weeks, or 9 weeks after the last treatment. Aβ plaques and microglia were quantified using immunohistochemistry. The concentration of soluble Aβ and cytokines was quantified using ELISA and levels of Aβ aggregates were measured with Western Blot. Microglial phagocytosis of Aβ in the hippocampus was evaluated by flow cytometry in Methoxy-X04 injected mice 24 h following the last ECS treatment. Y-maze and Elevated plus maze were performed to study behavior after 5 weeks. We could not detect any significant short- or long-term effects of ECS on Aβ pathology or neuroinflammation, but ECS reduced abnormal behavior in the Elevated Plus maze.

Treatment Approach and Modalities for Management of Depression in Older People.

Depression is common in older people, and while the approach to treatment is similar to a younger population, there are several additional treatment considerations to make based on comorbidities and cognitive impairment. Evidence-based psychotherapies such as cognitive behavioral therapy, interpersonal psychotherapy, and problem-solving therapy are recommended for mild-moderate depression in older people; however, the efficacy of these are limited in very old patients (older than 75 years of age) and those with cognitive impairment. Additionally, neuromodulation treatments such as electroconvulsive therapy and transcranial magnetic stimulation could prove beneficial for specific older people with depression. Use of pharmacotherapy that has demonstrated to be safe in older adults, as well as agents with adequate clinical experience in this population, should be considered based on patient-specific characteristics. Because of generally more complex medication regimens, risks of pharmacotherapy should be minimized with careful dosing strategies and special attention to avoid significant drug-drug interactions. While some data are available, antidepressant combination or augmentation strategies are less well studied in older people who fail to achieve remission or those with treatment-resistant depression, compared with younger populations.

Treatment Approach and Modalities for Management of Depression in Older People

Depression is common in older people, and while the approach to treatment is similar to a younger population, there are several additional treatment considerations to make based on comorbidities and cognitive impairment. Evidence-based psychotherapies such as cognitive behavioral therapy, interpersonal psychotherapy, and problem-solving therapy are recommended for mild-moderate depression in older people; however, the efficacy of these are limited in very old patients (older than 75 years of age) and those with cognitive impairment. Additionally, neuromodulation treatments such as electroconvulsive therapy and transcranial magnetic stimulation could prove beneficial for specific older people with depression. Use of pharmacotherapy that has demonstrated to be safe in older adults, as well as agents with adequate clinical experience in this population, should be considered based on patient-specific characteristics. Because of generally more complex medication regimens, risks of pharmacotherapy should be minimized with careful dosing strategies and special attention to avoid significant drug-drug interactions. While some data are available, antidepressant combination or augmentation strategies are less well studied in older people who fail to achieve remission or those with treatment-resistant depression, compared with younger populations.

The Effects of Ultrasound, Infrasound, and Electroconvulsive Stimulations on Depression-like Behavior in Mice

Abstract Introduction: In the present study, the effects of ultrasound, infrasound, and electroconvulsive stimulation on depression-like behavior was assessed in animal models. Method: For carrying out this study, 60 male BALB/c mice (mean age of 60 days, weight range of 25 – 30 g) were randomly selected. Depression was induced using reserpine 0.1 mg/kg i.p. for 30 days. They were allocated to three groups of experimental (ultrasound, infrasound, and electroconvulsive stimulation) and one group of control animals, each including 15 mice. Experimental animals received ultra- or infrasound 0.5 hours or 1 electroconvulsive pulse, daily for 10 days. Finally the Forced Swim Test was carried out. Results: There was a statistically significant difference between the groups regarding the duration of immobility posture [F(3,54) = 99.54, P = 0.001]. Mean immobility time was significantly longer in the control group compared to the other groups. Also, immobility was significantly longer for electroconvulsive compared to the ultra- and infrasound groups. Group ultrasound showed longer immobility than group infrasound; however, the difference was not significant. Conclusion: Ultrasound and infrasound stimulations are capable of decreasing depression-like behavior in mice. The results of this study were also compatible with the application of electroconvulsive therapy. However, a more successful response can be exploited with ultra- and infrasound stimulations.

Assessment of Behavioral Phenotypes After Chronic Social Defeat Stress and Electroconvulsive Stimulation in Mice Using Lasso Regression

Chronic social defeat stress (CSDS) is a method for modeling depressive- and anxiety-like phenotypes in rodents. There is limited report examining the effects of electroconvulsive stimulation (ECS) on mouse behavior after CSDS. Additionally, some rodent results can be difficult to translate to humans. We have used a regression model to create a probability of defeat score (PoDS) for each mouse to better analyze effects of ECS on post-CSDS behaviors.

Sox11 is an Activity-Regulated Gene with Dentate-Gyrus-Specific Expression Upon General Neural Activation.

Neuronal activity initiates transcriptional programs that shape long-term changes in plasticity. Although neuron subtypes differ in their plasticity response, most activity-dependent transcription factors (TFs) are broadly expressed across neuron subtypes and brain regions. Thus, how region- and neuronal subtype-specific plasticity are established on the transcriptional level remains poorly understood. We report that in young adult (i.e., 6-8weeks old) mice, the developmental TF SOX11 is induced in neurons within 6h either by electroconvulsive stimulation or by exploration of a novel environment. Strikingly, SOX11 induction was restricted to the dentate gyrus (DG) of the hippocampus. In the novel environment paradigm, SOX11 was observed in a subset of c-FOS expressing neurons (ca. 15%); whereas around 75% of SOX11+ DG granule neurons were c-FOS+, indicating that SOX11 was induced in an activity-dependent fashion in a subset of neurons. Environmental enrichment or virus-mediated overexpression of SOX11 enhanced the excitability of DG granule cells and downregulated the expression of different potassium channel subunits, whereas conditional Sox11/4 knock-out mice presented the opposite phenotype. We propose that Sox11 is regulated in an activity-dependent fashion, which is specific to the DG, and speculate that activity-dependent Sox11 expression may participate in the modulation of DG neuron plasticity.

Current clinical practice of electroconvulsive therapy and repetitive transcranial magnetic stimulation in psychiatry, a German sample

The purpose of the study was to evaluate the current clinical practice of Electroconvulsive Therapy and Repetitive Transcranial Magnetic Stimulation in German psychiatry. Case-based data (> 1.000.000 cases) were collected according to §21 of the German hospital remuneration law from January 2015 to December 2017. The study cohort comprises approximately 35–40% of the annual psychiatric cases and hospitals in Germany. Frequency of ECT and rTMS cases were investigated considering main diagnoses according to ICD-10 and treatment settings (inpatient vs. day-care). ECT cases with short-term hospitalization (≤ 4 days) were supposed to be maintenance ECT cases. A linear regression analysis was conducted to estimate trends in the use of ECT and rTMS. Different groups were compared using Chi-square tests. ECT and rTMS cases appear to increase in total during the observation period possibly due to facilities newly introducing ECT and rTMS but also to increased frequency of treatments. Both treatments were rarely performed in day-care settings (0.89% and 11.25%). ECT was performed in 1.72% of all cases with affective disorders and in 1.48% with major depressions, respectively. Age ≥ 65 years, females, severe and psychotic depression were significantly associated with a higher rate of ECT cases. > 40% of all ECT cases were possibly maintenance ECT cases. Only 0.60% of these were performed in day- care settings. rTMS was primarily performed in major depression (86,7% of all rTMS cases). This study suggests a growing demand for ECT and rTMS. Nevertheless, the use of ECT is still low compared to the high prevalence of treatment resistant depression. The use of rTMS is even lower and seems to be restricted to specialized institutions. Maintenance ECT is frequently carried out in an inpatient setting. Limitations of this study are the case- and group-based analysis, missing data on outpatient services and treatment sessions per case. Therefore, the database is not necessarily representative for the entire German healthcare system. Further studies are needed to verify the presented findings and should address the feasibility of ambulatory and day-care ECT services.

P.403 Brain volumetric correlates of electroconvulsive therapy versus transcranial magnetic stimulation for depression

P.403 Brain volumetric correlates of electroconvulsive therapy versus transcranial magnetic stimulation for depression

The effect of erythropoietin on electroconvulsive stimulation induced cognitive impairment in rats

Electroconvulsive therapy (ECT) is the most effective and fast-acting treatment for severe depression but associated with troublesome cognitive side-effects. Systemically administered erythropoietin (EPO) crosses the blood-brain-barrier and is a promising treatment for cognitive dysfunction in a wide array of neuropsychiatric and neurological disorders. In this study we trained rats to locate a submerged platform in a water maze and then subjected them to electroconvulsive stimulations (ECS, the rodent equivalent to ECT) and EPO treatment. We then analysed their ability to remember and relearn the location of the platform. In addition, we examined “wall-clinging” (thigmotaxis), a behavioural indicator of stress. ECS caused significant deficit in a probe trial administered after three weeks (nine stimulations) as well as one week (six stimulations) of treatment, indicative of induction of retrograde amnesia. ECS had no effect on relearning of the water maze task or performance in a subsequent probe trial. EPO treatment did not ameliorate the ECS-induced retrograde amnesia, but after nine ECS stimulations the animals that had received EPO relearned the position of the hidden platform faster than the animals that had not. We also found EPO to decrease “wall-clinging” behaviour, suggesting an effect of EPO on the stress response in rats. Thus, we establish the Morris Water Maze as a suitable model for ECS-induced memory loss in rats and provide some evidence for potential beneficial effects of EPO.