Antidepressant Effects Of Electroconvulsive Therapy Research Articles

The Role of BDNF in the Antidepressant Effects of Electroconvulsive Therapy.

Electroconvulsive therapy (ECT) is an effective treatment method for depression therapy. It produces a number of biological effects, including neurotrophic factors regulation. In the present paper, we investigated the ECT response in depressed rats subjected to the variable frequency ultrasound (20-45 kHz) and examined the contribution of brain-derived neurotrophic factor (BDNF) expression changes to the observed effects. The obtained results reflect the therapeutic potential of ECT for the treatment of depressive-like state in rodents and indicate the role of BDNF in these processes. In future research, it is necessary to investigate the relationship between neurotrophin and structural changes and to study other neurotrophic biomarkers that may be associated with the development of depression-like state and the therapy response.

Long-term effects of electroconvulsive therapy on brain structure in major depression.

Magnetic resonance imaging (MRI) studies on major depressive disorder (MDD) have predominantly found short-term electroconvulsive therapy (ECT)-related gray matter volume (GMV) increases, but research on the long-term stability of such changes is missing. Our aim was to investigate long-term GMV changes over a 2-year period after ECT administration and their associations with clinical outcome. In this nonrandomized longitudinal study, patients with MDD undergoing ECT (n = 17) are assessed three times by structural MRI: Before ECT (t0), after ECT (t1) and 2 years later (t2). A healthy (n = 21) and MDD non-ECT (n = 33) control group are also measured three times within an equivalent time interval. A 3(group) × 3(time) ANOVA on whole-brain level and correlation analyses with clinical outcome variables is performed. Analyses yield a significant group × time interaction (pFWE < 0.001) resulting from significant volume increases from t0 to t1 and decreases from t1 to t2 in the ECT group, e.g., in limbic areas. There are no effects of time in both control groups. Volume increases from t0 to t1 correlate with immediate and delayed symptom increase, while volume decreases from t1 to t2 correlate with long-term depressive outcome (all p ⩽ 0.049). Volume increases induced by ECT appear to be a transient phenomenon as volume strongly decreased 2 years after ECT. Short-term volume increases are associated with less symptom improvement suggesting that the antidepressant effect of ECT is not due to volume changes. Larger volume decreases are associated with poorer long-term outcome highlighting the interplay between disease progression and structural changes.

Etomidate Improves the Antidepressant Effect of Electroconvulsive Therapy by Suppressing Hippocampal Neuronal Ferroptosis via Upregulating BDNF/Nrf2.

Electroconvulsive therapy (ECT) performed under general anesthesia is an effective treatment for severe depression. Etomidate is an intravenous anesthetic that shows beneficial effects on ECT. However, the potential mechanisms have rarely been reported. In this study, male rats were exposed to chronic unpredictable mild stress for 4weeks, followed by ECT for 10days, with or without intervention with ferrostatin-1 (2mg/kg) or all-trans retinoic acid (ATRA, 5mg/kg). Rats subjected to etomidate (20mg/kg) or propofol (120mg/kg) treatment were administered with designated anesthetic before ECT. Compared to depressive rats without ECT, those who received ECT showed increased numbers of hippocampal neurons, increased expression of negative regulators of ferroptosis including glutathione peroxidase 4, ferritin heavy chain 1, and ferroptosis suppressor protein 1, upregulation of brain-derived neurotrophic factor and nuclear factor erythroid 2-related factor, and downregulation of acyl-CoA synthetase long-chain family member 4, a positive regulator of ferroptosis in the hippocampus. Additionally, compared with propofol, etomidate used in ECT resulted in higher upregulation of BDNF/Nrf2 and inhibited neuronal ferroptosis in hippocampus. These results showed etomidate may enhance the antidepressant effect of ECT by protecting hippocampal neurons against ferroptosis.

Longitudinal alterations in mRNA expression of the BDNF neurotrophin signaling cascade in blood correlate with changes in depression scores in patients undergoing electroconvulsive therapy

Electroconvulsive therapy (ECT) appears to be the most effective treatment for severe depression. However, its mechanisms of action are incompletely understood. Evidence suggests ECT enhances neuroplasticity and neurogenesis. While studies on ECT-induced neuroplasticity focused on brain-derived neurotrophic factor (BDNF), other factors of the BDNF/TrkB signaling cascade remain underinvestigated.We assessed longitudinal changes in depression scores, serum BDNF protein levels, and mRNA expression of BDNF/TrkB related genes (BDNF, AKT1, ERK1, CREB), NR3C1 and IGF1 in peripheral blood in 19 treatment-resistant depressed patients undergoing ECT. We also analysed DNA methylation patterns at various timepoints to explore possible epigenetic regulation of mRNA expression.Using multilevel regression, we found a negative association between depression scores and blood-based mRNA expression of BDNF/TrkB related genes and NR3C1. Expression of BDNF, ERK1 and NR3C1 increased significantly over time (BDNF: β = 0.0295, p = 0.003; ERK1: β = 0.0170, p = 0.034; NR3C1: β = 0.0035, p = 0.050). For these three genes changes in mRNA expression were highly correlated (R = 0.59 – 0.88) with changes in DNA methylation for multiple CpG sites in the respective genes. Also, serum BDNF protein levels increased across the study period (β = 0.11, p = 0.001).Our findings show that the antidepressant effects of ECT are associated with changes in expression of BDNF and its signaling molecules and that these molecular markers can be detected in peripheral blood. Alterations in DNA methylation could be a key mechanism whereby ECT influences gene expression.

Volume of hippocampus-amygdala transition area predicts outcomes of electroconvulsive therapy in major depressive disorder: high accuracy validated in two independent cohorts.

Although many previous studies reported structural plasticity of the hippocampus and amygdala induced by electroconvulsive therapy (ECT) in major depressive disorder (MDD), yet the exact roles of both areas for antidepressant effects are still controversial. In the current study, segmentation of amygdala and hippocampal sub-regions was used to investigate the longitudinal changes of volume, the relationship between volume and antidepressant effects, and prediction performances for ECT in MDD patients before and after ECT using two independent datasets. As a result, MDD patients showed selectively and consistently increased volume in the left lateral nucleus, right accessory basal nucleus, bilateral basal nucleus, bilateral corticoamygdaloid transition (CAT), bilateral paralaminar nucleus of the amygdala, and bilateral hippocampus-amygdala transition area (HATA) after ECT in both datasets, whereas marginally significant increase of volume in bilateral granule cell molecular layer of the head of dentate gyrus, the bilateral head of cornu ammonis (CA) 4, and left head of CA 3. Correlation analyses revealed that increased volume of left HATA was significantly associated with antidepressant effects after ECT. Moreover, volumes of HATA in the MDD patients before ECT could be served as potential biomarkers to predict ECT remission with the highest accuracy of 86.95% and 82.92% in two datasets (The predictive models were trained on Dataset 2 and the sensitivity, specificity and accuracy of Dataset 2 were obtained from leave-one-out-cross-validation. Thus, they were not independent and very likely to be inflated). These results not only suggested that ECT could selectively induce structural plasticity of the amygdala and hippocampal sub-regions associated with antidepressant effects of ECT in MDD patients, but also provided potential biomarkers (especially HATA) for effectively and timely interventions for ECT in clinical applications.

Impact of vascular risk factors on clinical outcome in elderly patients with depression receiving electroconvulsive therapy

BackgroundAlthough electroconvulsive therapy (ECT) is a highly effective, safe, and well-tolerated antidepressant treatment for late-life depression (LLD), there is large variability in response rates across individuals. We hypothesized that these variations would be in part explained by the level of vascular risk in this population. We therefore compared response rates to ECT in patients with LLD presenting with or without vascular risk factors (VRF). Methods52 patients with LLD (age > 55) who received a course of ECT were separated into 2 groups according to the presence of VRF (n = 20) or not (n = 32). Framingham score (10-year risk for developing a coronary heart disease) was calculated for each patient. Our primary outcome was the number of responders to ECT in each group (defined as at least 50% decrease of the Montgomery–Åsberg Depression Rating Scale score following ECT course). Scores at the self-rated Beck Depression Inventory are also reported. ResultsPatients with VRF presented significant lower response rates to ECT (12 out of 20; 60%) than patients without VRF (30 out of 32; 94%; p = 0.004). A negative correlation was found between Framingham score and changes in depression scores pre/post ECT (r = -0.42; p = 0.0039). LimitationsOur study was limited by sample size and retrospective design. ConclusionPatients with LLD and VRF showed lower response rates to ECT than those without VRF. The more the VRF increased, the less the antidepressant effect of ECT was observed. Results are discussed in light of the role of apathy in clinical response to ECT.

Volume of hippocampal subregions and clinical improvement following electroconvulsive therapy in patients with depression

It is thought that the hippocampal neurogenesis is an important mediator of the antidepressant effect of electroconvulsive therapy (ECT). However, most previous studies failed to demonstrate the relationship between the increase in the hippocampal volume and the antidepressant effect. We reinvestigated this relationship by looking at distinct hippocampal subregions and applying repeated measures correlation. Using a 3 Tesla MRI-scanner, we scanned 22 severely depressed in-patients at three time points: before the ECT series, after the series, and at six-month follow-up. The depression severity was assessed by the 17-item Hamilton Rating Scale for Depression (HAMD-17). The hippocampus was segmented into subregions using Freesurfer software. The dentate gyrus (DG) was the primary region of interest (ROI), due to the role of this region in neurogenesis. The other major hippocampal subregions were the secondary ROIs (n = 20). The general linear mixed model and the repeated measures correlation were used for statistical analyses. Immediately after the ECT series, a significant volume increase was present in the right DG (Cohen's d = 1.7) and the left DG (Cohen's d = 1.5), as well as 15 out of 20 secondary ROIs. The clinical improvement, i.e., the decrease in HAMD-17 score, was correlated to the increase in the right DG volume (rrm = −0.77, df = 20, p < .001), and the left DG volume (rrm = −0.75, df = 20, p < .001). Similar correlations were observed in 14 out of 20 secondary ROIs. Thus, ECT induces an increase not only in the volume of the DG, but also in the volume of other major hippocampal subregions. The volumetric increases may reflect a neurobiological process that may be related to the ECT's antidepressant effect. Further investigation of the relationship between hippocampal subregions and the antidepressant effect is warranted. A statistical approach taking the repeated measurements into account should be preferred in the analyses.

Effects of Low-Dose Ketamine on the Antidepressant Efficacy and Suicidal Ideations in Patients Undergoing Electroconvulsive Therapy.

It remains controversial whether a subanesthetic dose of ketamine could modulate the antidepressant effect of electroconvulsive therapy (ECT) in patients with major depressive disorder. We investigated the effect of ketamine on accelerating the antidepressant efficacy of ECT. One hundred twenty-seven patients with major depressive disorder were included in this randomized, placebo-controlled, double-blind study. The study group received 0.3 mg/kg ketamine, and the control group received an isovolumetric dose of normal saline before undergoing ECT under propofol anesthesia. The main outcome was the Hamilton Depression Rating Scale score after each ECT session. Suicidal ideation (SI) was also evaluated using the Hamilton Depression Rating Scale. The response, remission, and recurrence rates were analyzed using time-to-event analysis. No significant differences were found in the overall response, remission, and relapse rates between the groups (P > 0.05). The median number of ECT sessions for achieving response was 4.0 ± 0.41 in the study group and 7.0 ± 0.79 in the control group (P < 0.05). The median number of ECT sessions for achieving remission in the study and control groups was 8.0 ± 0.29 and 9.0 ± 0.48, respectively (P < 0.05). The median number of ECT sessions for achieving SI reduction in the study and control groups was 3.0 ± 0.75 and 6.0 ± 1.19, respectively (P < 0.05). Low-dose ketamine (0.3 mg/kg) could modulate the antidepressant efficacy of ECT via accelerating the onset of its effects and reducing the number of ECT sessions required to obtain response, remission, and SI reduction, without influencing the relapse rates in remitting patients after ECT treatment.

Impact of vascular risk factors on clinical outcome in older patients with depression receiving electroconvulsive therapy

Introduction Despite electroconvulsive therapy (ECT) is a highly effective, safe, and well-tolerated antidepressant treatment option for geriatric patients, response rate highly varied across individuals. We hypothesized that, as seen with medication, vascular burden may in part explain those discrepancies. Objective The aim of this study was to compare response rates to ECT in elderly depressed patients presenting or not vascular risk factors (VRF). Method In a retrospective study, 54 elderly patients (age > 55; mean age 60.7 ± 13.6) with moderate to severe MDD (Montgomery–Asberg Depression Rating Scale MADRS score > 20) who received a course of ECT between March 2016 and May 2018 in our specialized unit were separated into 2 groups according to VRF. Patients of the VRF group (n = 21) should presented with at least 2 vascular risk factors among hypercholesterolemia, hypertension, smoking, diabetes mellitus, cardiovascular disease, and cerebral vascular accident/transient ischemic attack. Framingham score (10-year risk for developing a coronary heart disease) was calculated for each included subject. Our primary outcome was the number of responder to ECT (defined as 50% decrease of the MADRS following ECT course) observed between the two groups. As a secondary objective, we investigated the relationship between Framingham score and pre/post ECT MADRS score changes. Results There was no difference between the 2 groups regarding age, gender, cognitive functioning, depression severity, stage of treatment-resistant depression and illness duration. Elderly patients with vascular burden presented a lower rate of response to ECT (58.1%) than patients without vascular burden (86.7%; Chi2 = 5; P = 0.02). A negative correlation was found between Framingham score and pre/post ECT MADRS score changes (r = −0.39; 95% CI − 0.61–0.12; P = 0.01). Conclusion As observed with medication, elderly patient with vascular burden displayed a lower response rate to ECT than elderly patients without vascular burden. The more VRF increased, the less the antidepressant effect of ECT was observed.

Cytokine-mediated cellular immune activation in electroconvulsive therapy: A CSF study in patients with treatment-resistant depression

Objectives: Evidence points towards an important relationship between the antidepressant effects of electroconvulsive therapy (ECT) and the modulation of the immune system. To further elucidate this interplay, we performed a study on the effects of the antidepressant treatment by ECT on 25 cytokines in patients with depression.Methods: We measured 25 different cytokines (interleukin (IL)-1β, IL-1RA, Il-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p40/p70), IL-13, IL-15, IL-17, tumor necrosis factor-α, interferon (IFN)-α, IFN-γ, granulocyte-macrophage colony-stimulating factor, macrophage inflammatory protein (MIP)-1α, MIP-1β, IFN-γ-induced protein 10 (IP-10), monokine induced by IFN-γ, Eotaxin, Rantes and monocyte chemoattractant protein 1) in the cerebrospinal fluid (CSF) and blood of 12 patients with a severe and treatment-resistant depressive episode before and after a course of ECT.Results: CSF levels of IP-10, IL-5 and IL-8 were elevated after ECT and more ECT sessions were associated with the differences of CSF levels before and after ECT of IFN-γ, IL-2RA, Rantes, IL-6 and IL-1β. Responders and/or remitters had a decrease of CSF levels of IL-17, MIP-1α, Rantes and IL-2R during ECT. CSF IP-10 levels increased less during ECT in patients who had a remission.Conclusions: Although the sample size was small, we found different effects of the ECT treatment per se and of the antidepressant action induced by ECT in CSF and blood.

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.

T121. Effect of electroconvulsive therapy and repetitive transcranial magnetic stimulation on corticol excitability in patients with major depression

Repetitive transcranial magnetic stimulation (rTMS) can enhance or depress cortical excitability depending on stimulation frequency and intensity. These features of rTMS may be related to its antidepressant action that has been recently demonstrated. Changes in cortical excitability may also play an important role in the mechanisms of action of other antidepressant treatments, electroconvulsive therapy (ECT) in particular. Twenty-two patients with MD were randomized to receive either ECT + rTMS or ECT + sham rTMS in a double blind design. ECT was given twice weekly and 12 rTMS was applied throughout 3 weeks. rTMS was administered to the right prefrontal cortex with a circular coil. 900 stimuli in each session were delivered at a rate of 1 Hz and at an intensity of 110% of the resting motor threshold (rMT). Severity of depression was assessed by the Hamilton Depression Rating Scale (HDRS). The rMT and the size of motor evoked potential (MEP) were assessed before and after ECT. The MEP/M-wave area ratio was then calculated by dividing the MEP area by the maximal M-wave area obtained after electrical stimulation of the median nerve. For assessment of changes in the intra-cortical inhibition (ICI) and intra-cortical facilitation (ICF), the standard paired-pulse TMS paradigm was used at baseline and after the last ECT. The inter-hemispheric (IHR) ratio was calculated as Rt/Lt for each MEP parameter. 19 out of the 22 patients showed a marked clinical improvement treatments. The left aMT was significantly decreased following 6 ECTs. This was associated with significant change of the rMT inter-hemispheric ratio towards a relative decrease of the left hemisphere rMT indicating enhancement of the excitability in the left hemisphere. Only those patients who improved following ECT or ECT + TMS, had a significant increase of the MEP/M-wave area ratio in the left hemisphere but not in the right hemisphere. Each ECT caused an increase of MEP size in the left hemisphere. The cumulative effect of ECT on the left hemisphere MEP size was significant after 3 ECTs. Paired-pulse TMS paradigm revealed a significant reduction of the intracortical inhibition only in the left hemisphere in patients who clinically improved ECT causes a relative decrease of motor thresholds to TMS in the left hemisphere. The antidepressant effect of ECT is associated with an increase of the MEP size and reduction of the intracortical inhibition in the left hemisphere. These findings suggest that enhancement of left hemispheric excitability may be related to therapeutic effect of ECT. Similar results were obtained in patients who improved in response to antidepressant medication or rTMS. Taken together, this may suggest that an increase of left hemispheric excitability is shared by different antidepressant treatments and might be related to their therapeutic effect. rTMS as applied in our study does not seem to have an additive effect on cortical excitability and does not enhance the therapeutic effect of ECT.

P11 promoter methylation predicts the antidepressant effect of electroconvulsive therapy

Although electroconvulsive therapy (ECT) is among the most effective treatment options for pharmacoresistant major depressive disorder (MDD), some patients still remain refractory to standard ECT practise. Thus, there is a need for markers reliably predicting ECT non/response. In our study, we have taken a novel translational approach for discovering potential biomarkers for the prediction of ECT response. Our hypothesis was that the promoter methylation of p11, a multifunctional protein involved in both depressive-like states and antidepressant treatment responses, is differently regulated in ECT responders vs. nonresponders and thus be a putative biomarker of ECT response. The chronic mild stress model of MDD was adapted with the aim to obtain rats that are resistant to conventional antidepressant drugs (citalopram). Subsequently, electroconvulsive stimulation (ECS) was used to select responders and nonresponders, and compare p11 expression and promoter methylation. In the rat experiments we found that the gene promoter methylation and expression of p11 significantly correlate with the antidepressant effect of ECS. Next, we investigated the predictive properties of p11 promoter methylation in two clinical cohorts of patients with pharmacoresistant MDD. In a proof-of-concept clinical trial in 11 patients with refractory MDD, higher p11 promoter methylation was found in responders to ECT. This finding was replicated in an independent sample of 65 patients with pharmacoresistant MDD. This translational study successfully validated the first biomarker reliably predicting the responsiveness to ECT. Prescreening of this biomarker could help to identify patients eligible for first-line ECT treatment and also help to develop novel antidepressant treatment procedures for depressed patients resistant to all currently approved antidepressant treatments.

Antidepressant efficacy of electroconvulsive therapy is associated with a reduction of the innate cellular immune activity in the cerebrospinal fluid in patients with depression

Objectives: A bidirectional link between the antidepressant effects of electroconvulsive therapy (ECT) and the modulation of the immune system has been proposed. To elucidate the interplay between antidepressant treatment and macrophage/microglia activation in humans, we performed a study on the effects of the antidepressant treatment by ECT on markers of macrophage/microglia activation in patients with depression.Methods: We measured six different markers (IL-6, neopterin, sCD14, sCD163 MIF and MCP1) of macrophage/microglia activation in the cerebrospinal fluid (CSF) and blood of 12 patients with a severe, treatment-resistant depressive episode before and after a course of ECT.Results: Some markers in the CSF of remitters were reduced after the ECT course and differed from non-remitters, but no differences were found before and after ECT independently from the antidepressant efficacy. CSF baseline levels of some markers could predict the reduction of depressive psychopathology during ECT. Higher CSF levels indicating increased macrophage/microglia activation at baseline predicted a better treatment response to ECT.Conclusions: Although the sample size was small, our data suggest that macrophages/microglia are involved in the pathophysiology of major depression and that antidepressant efficacy by ECT might be partly explained by the modulation of the innate immune system within the brain.

Does a single session of electroconvulsive therapy alter the neural response to emotional faces in depression? A randomised sham-controlled functional magnetic resonance imaging study.

Negative neurocognitive bias is a core feature of major depressive disorder that is reversed by pharmacological and psychological treatments. This double-blind functional magnetic resonance imaging study investigated for the first time whether electroconvulsive therapy modulates negative neurocognitive bias in major depressive disorder. Patients with major depressive disorder were randomised to one active ( n=15) or sham electroconvulsive therapy ( n=12). The following day they underwent whole-brain functional magnetic resonance imaging at 3T while viewing emotional faces and performed facial expression recognition and dot-probe tasks. A single electroconvulsive therapy session had no effect on amygdala response to emotional faces. Whole-brain analysis revealed no effects of electroconvulsive therapy versus sham therapy after family-wise error correction at the cluster level, using a cluster-forming threshold of Z>3.1 ( p<0.001) to secure family-wise error <5%. Groups showed no differences in behavioural measures, mood and medication. Exploratory cluster-corrected whole-brain analysis ( Z>2.3; p<0.01) revealed electroconvulsive therapy-induced changes in parahippocampal and superior frontal responses to fearful versus happy faces as well as in fear-specific functional connectivity between amygdala and occipito-temporal regions. Across all patients, greater fear-specific amygdala - occipital coupling correlated with lower fear vigilance. Despite no statistically significant shift in neural response to faces after a single electroconvulsive therapy session, the observed trend changes after a single electroconvulsive therapy session point to an early shift in emotional processing that may contribute to antidepressant effects of electroconvulsive therapy.

Genome-wide meta-analysis of DNA methylation changes associated with antidepressant effects of Electroconvulsive Therapy

Genome-wide meta-analysis of DNA methylation changes associated with antidepressant effects of Electroconvulsive Therapy

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.

Maintained Improvement of Neurocognitive Function in Major Depressive Disorders 6 Months after ECT.

Both impaired and improved cognitive function after electroconvulsive therapy (ECT) in major depressive disorder (MDD) patients may occur. We have previously found improved cognitive function 6 weeks after ECT in this group. The aim of this study was to report 6-month follow-up results from the same prospective project monitoring cognitive effects of ECT. Thirty-one patients with MDD were assessed with the MATRICS Consensus Cognitive Battery (MCCB), the Everyday Memory Questionnaire (EMQ), and the Montgomery–Åsberg Depression Rating Scale prior to, 6 weeks, and 6 months after ECT. Compared to baseline, the speed of processing, attention/vigilance, and reasoning/problem solving test results were significantly improved. The depression score was significantly reduced. There were no changes in subjective memory complaint. There was no significant relationship between the EMQ and the MCCB subtests, but a significant correlation between current depression level and the EMQ. Six months after ECT the cognitive improvement reported at 6-week follow-up was maintained and extended. The corresponding decrease in depressive symptoms and stability in subjectively reported memory complaints suggest that the antidepressant effects of ECT do not occur at the expense of cognitive function.

P.1.i.012 - Regional brain volumes, diffusivity, and metabolite changes after electroconvulsive therapy for severe depression

Objective To investigate the role of hippocampal plasticity in the antidepressant effect of electroconvulsive therapy (ECT). Method We used magnetic resonance (MR) imaging including diffusion tensor imaging (DTI) and proton MR spectroscopy (1H-MRS) to investigate hippocampal volume, diffusivity, and metabolite changes in 19 patients receiving ECT for severe depression. Other regions of interest included the amygdala, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex, and hypothalamus. Patients received a 3T MR scan before ECT (TP1), 1 week (TP2), and 4 weeks (TP3) after ECT. Results Hippocampal and amygdala volume increased significantly at TP2 and continued to be increased at TP3. DLPFC exhibited a transient volume reduction at TP2. DTI revealed a reduced anisotropy and diffusivity of the hippocampus at TP2. We found no significant post-ECT changes in brain metabolite concentrations, and we were unable to identify a spectral signature at ≈1.30 ppm previously suggested to reflect neurogenesis induced by ECT. None of the brain imaging measures correlated to the clinical response. Conclusion Our findings show that ECT causes a remodeling of brain structures involved in affective regulation, but due to their lack of correlation with the antidepressant effect, this remodeling does not appear to be directly underlying the antidepressant action of ECT.

Subgenual cingulate cortical activity predicts the efficacy of electroconvulsive therapy.

Electroconvulsive therapy (ECT) is the most effective treatment for depression, yet its mechanism of action is unknown. Our goal was to investigate the neurobiological underpinnings of ECT response using longitudinally collected resting-state functional magnetic resonance imaging (rs-fMRI) in 16 patients with treatment-resistant depression and 10 healthy controls. Patients received bifrontal ECT 3 times a week under general anesthesia. We acquired rs-fMRI at three time points: at baseline, after the 1st ECT administration and after the course of the ECT treatment; depression was assessed with the Hamilton Depression Rating Scale (HAM-D). The primary measure derived from rs-fMRI was fractional amplitude of low frequency fluctuation (fALFF), which provides an unbiased voxel-wise estimation of brain activity. We also conducted seed-based functional connectivity analysis based on our primary findings. We compared treatment-related changes in HAM-D scores with pre- and post-treatment fALFF and connectivity measures. Subcallosal cingulate cortex (SCC) demonstrated higher BOLD signal fluctuations (fALFF) at baseline in depressed patients, and SCC fALFF decreased over the course of treatment. The baseline level of fALFF of SCC predicted response to ECT. In addition, connectivity of SCC with bilateral hippocampus, bilateral temporal pole, and ventromedial prefrontal cortex was significantly reduced over the course of treatment. These results suggest that the antidepressant effect of ECT may be mediated by downregulation of SCC activity and connectivity. SCC function may serve as an important biomarker of target engagement in the development of novel therapies for depression that is resistant to treatment with standard medications.