METHODS: Electroconvulsive therapy (ECT) is a commonly used treatment for severe psychiatric illness in older adults, including in the \'older old\' population aged 80 years and above. However, there can sometimes be a reluctance to treat the 80+ year old age group with ECT due to medical comorbidities, frailty, and concerns about cognition.
UNASSIGNED: This multi-site, longitudinal Australian study aimed to investigate the effectiveness and safety of ECT in older old people compared with younger age groups. Data from 310 people receiving ECT for depression at three participating hospitals was collected in a naturalistic setting, between 2015 and 2022.
METHODS: Clinical ratings were conducted pre-ECT and end-acute ECT using the Montgomery-Åsberg Depression Rating Scale (MADRS). Cognitive outcomes were assessed using the Montreal Cognitive Assessment (MoCA).
RESULTS: Older old adults demonstrated a significant reduction MADRS scores at post-treatment. They were more likely to meet remission criteria compared with the younger age groups. Older old adults were also less likely to show clinically significant cognitive decline post-ECT, and were more likely to show clinically significant cognitive improvement post-ECT compared with younger age groups.
CONCLUSIONS: ECT is highly effective in treating severe psychiatric illness in older old adults. Relative to the younger age groups, the older old group were more likely to remit with ECT and a greater proportion showed cognitive improvement post-ECT. These findings suggest that ECT should be considered as a valuable and safe treatment option for older old individuals with depression.

BACKGROUND: Electroconvulsive therapy (ECT) benefits patients with treatment-resistant depression (TRD), but the underlying biological processes are unclear. We conducted an epigenome-wide association study in 32 TRD patients undergoing ECT to depict ECT-associated methylation changes. Illness severity and ECT outcomes were assessed with the Montgomery-Åsberg Depression Rating Scale at baseline (T0) and 1 month after its end (T1). Methylation was profiled at T0 and T1 with the Illumina Infinium Methylation EPIC BeadChip array.
RESULTS: Longitudinal T0-T1 analyses showed 3 differentially methylated probes (DMPs) with nominal p values ≤ 10-5, with 2 annotated in the genes CYB5B and PVRL4. Including covariates, we found 4 DMPs for symptoms variation, annotated in FAM20C, EPB41, OTUB1 and ADARB1, and 3 DMPs for response status, with 2 annotated in IQCE and FAM20C. Regional analysis revealed 54 differentially methylated regions (DMRs) with nominal p value area ≤ 0.05, with 9 presenting adjusted p-value area ≤ 0.10, annotated in MCF2L, SLC25A24, RUNX3, MIR637, FOXK2, FAM180B, POU6F1, ALS2CL and CCRL2. Considering covariates, we found 21 DMRs for symptoms variation and 26 DMRs for response (nominal p value area ≤ 0.05), with 4 presenting adjusted p-value area ≤ 0.10 for response, annotated in SNORD34, NLRP6, GALNT2 and SFT2D3. None remained significant after false discovery rate correction. Notably, ADARB1 variants are associated with suicide attempt in patients with psychiatric disorders, and SLC25A24 relates to conduct disorder. Several DMPs and DMRs are annotated in genes associated with inflammatory/immune processes. Longitudinal analyses on females (n = 22) revealed statistically significant DMRs (adjusted p value area ≤ 0.05) and trend-significant DMRs (adjusted p value area ≤ 0.07) for symptoms variation and response status, annotated in genes related to psychiatric disorders (ZFP57, POLD4, TRIM10, GAS7, ADORA2A, TOLLIP), trauma exposure (RIPOR2) and inflammatory/immune responses (LAT, DLX4, POLD4, FAM30A, H19). Pathway analysis on females revealed enrichment for transcriptional activity, growth factors, DNA maintenance, and immune pathways including IRF7 and IRF2.
CONCLUSIONS: Although no significant results were found for the whole cohort, the study provides insights into ECT-associated methylation changes, highlighting DMPs and DMRs related to ECT outcomes. Analyses on females revealed significant DMRs and pathways related to psychiatric disorders and inflammatory/immune processes.

The aim of this multicenter study was to evaluate the effectiveness and safety of electrochemotherapy (ECT) for the treatment of mucosal tumors in the head and neck. A total of 71 patients with 84 nodules of different histologies in the oral cavity, pharynx and larynx treated by ECT were evaluated. The data were collected from the InspECT database from 10 participating centers throughout Europe. Primary and recurrent/secondary tumors of different histologies were treated. The overall response rate was 65 %, with a 33 % complete response rate with limited side effects. The response rates of the primary and secondary tumors were not different. However, smaller tumors responded better than tumors larger than 3 cm in diameter. Furthermore, the tumors that were treated with curative intent responded significantly better than those treated with palliative intent. This study demonstrated the feasibility, safety and effectiveness of ECT in a larger cohort of patients with mucosal lesions in the head and neck region. Based on the available data, ECT can be used for the treatment of recurrent and, in some cases, primary mucosal tumors located in the oral cavity, larynx, and pharynx. A better response was obtained in patients with smaller primary tumors treated with curative intent.

BACKGROUND: Rapid cycling bipolar disorder (RCBD), characterized by four or more episodes per year, is a complex subtype of bipolar disorder (BD) with poorly understood characteristics.
METHODS: This multicenter, observational, longitudinal cohort study enrolled 520 BD patients across seven psychiatric institutions in China from January 2013 to January 2014. Participants were divided into RCBD and non-RCBD (NRCBD) groups based on the frequency of mood episodes in the preceding year. Data collection utilized a standardized form, supplemented by a medical record review, focusing on sociodemographic, clinical, and treatment characteristics. Statistical analysis involved independent samples t-tests, Kruskal-Wallis H tests, Chi-square or Fisher\'s exact tests, with Bonferroni correction applied to account for multiple comparisons, and multivariable logistic regression to identify characteristics associated with RCBD.
RESULTS: Among the BD cohort, 9.4% were identified as current RCBD. Compared to NRCBD, RCBD patients had a shorter duration from the first psychiatric consultation to the diagnosis of BD, a reduced duration of their longest period of euthymia, a lower proportion of lifetime hospitalization history due to BD, and less use of electroconvulsive therapy (ECT) within the last 12 months. Additionally, they presented higher baseline scores on the Mood Disorder Questionnaire (MDQ) and the Brief 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). However, after applying the Bonferroni correction, these differences were not statistically significant. Multivariable logistic regression analysis identified three factors that were independently associated with RCBD: time from first psychiatric consultation to BD diagnosis (Odds Ratio [OR] = 0.512, P = 0.0416), lifetime hospitalization history due to BD (OR = 0.516, P = 0.0476), and ECT treatment within the past 12 months (OR = 0.293, P = 0.0472).
CONCLUSIONS: This study revealed that the duration from first psychiatric consultation to BD diagnosis, lifetime hospitalization history due to BD, and ECT treatment in the past year were associated with RCBD. Recognizing these factors could contribute to enhance the early identification and clinical outcomes of RCBD. Trial Registration Number Registry ClinicalTrials.gov NCT01770704. Date of Registration: First posted on January 18, 2013.

Electroconvulsive therapy (ECT) is an efficient and rapid-acting treatment indicated for severe depressive disorders. While ECT is commonly accompanied by transient memory decline, the brain mechanisms underlying these side effects remain unclear.
In this exploratory functional magnetic resonance (fMRI) study, we aimed to compare effects of ECT versus pharmacological treatment on neural response during episodic memory encoding in patients with affective disorders.
This study included 32 ECT-treated patients (major depressive disorder (MDD), n = 23; bipolar depression, n = 9) and 40 partially remitted patients in pharmacological treatment (MDD, n = 24; bipolar disorder, n = 16). Participants underwent neuropsychological assessment, a strategic picture encoding fMRI scan paradigm, and mood rating. The ECT group was assessed before ECT (pre-ECT) and 3 days after their eighth ECT session (post-ECT).
Groups were comparable on age, gender, and educational years (ps ⩾ 0.05). Within-group analyses revealed a selective reduction in verbal learning and episodic memory pre- to post-ECT (p = 0.012) but no decline in global cognitive performance (p = 0.3). Functional magnetic resonance imaging analyses adjusted for mood symptoms revealed greater activity in ECT-treated patients than pharmacologically treated No-ECT patients across left precentral gyrus (PCG), right dorsomedial prefrontal cortex (dmPFC), and left middle frontal gyrus (MFG). In ECT-treated patients, greater decline in verbal learning and memory performance from pre- to post-ECT correlated with higher PCG response (r = -0.46, p = 0.008), but not with dmPFC or MFG activity (ps ⩾ 0.1), post-ECT.
Episodic memory decline was related to greater neural activity in the left PCG, but unrelated to increased dmPFC and MFG activity, immediately after ECT.

There is no established treatment for patients with clozapine-resistant schizophrenia (CRS). Clozapine augmentation strategies with antipsychotics or others substances are effective in comparison with placebo while and Electroconvulsive therapy (ECT) showed to be effective in comparison with treatment as usual (TAU) but not with placebo (sham-ECT). In the present double- blind randomized controlled trial, we compared 40 outpatients who received 20 sessions of ECT (n = 21) or sham-ECT (n = 19) (age = 37.40 ± 9.62, males = 77.5 %, illness duration = 14.95 ± 8.32 years, mean total Positive and Negative Syndrome Scale (PANSS) = 101.10 ± 24.91) who fulfilled well-defined CRS criteria including baseline clozapine plasma levels ≥350 ng/mL. The primary outcome was the ≥50 % PANSS Total Score reduction; secondary outcomes were the scores of the PANSS subscales, PANSS five-factor dimensions, PANSS-6 and the Calgary Depression Rating Scale (CDRS). Treatment response was analyzed by percentage reduction, Linear Mixed Models and effect sizes. At baseline both groups showed no differences except for years of school education (included as a covariate). At endpoint, only 1/19 of the completers (5.26 %) in the ECT group and 0/17 in the sham-ECT group showed a ≥50 % total PANSS score reduction. Both groups showed no significant differences of the total PANSS score (F = 0.12; p = 0.73), Positive (F = 0.27, p = 0.61), Negative (F = 0.25, p = 0.62), and General Psychopathology scores (F = 0.01, p = 0.94) as well for all PANSS five factors, the PANSS-6 and CDRS. Thus, the present study found no evidence that ECT is better than Sham-ECT in patients with CRS. Future sham-ECT controlled studies with larger sample sizes are warranted to test the efficacy of ECT for patients with CRS.

Electroconvulsive therapy (ECT) is one of the most effective and rapid-acting treatment for severe depression but is associated with cognitive side-effects. Identification of add-on treatments that counteract these side-effects would be very helpful. This randomized, double-blinded, placebo-controlled, parallel-group study investigated the effects of four add-on erythropoietin (EPO; 40,000 IU/ml) or saline (placebo) infusions over 2.5 weeks of ECT (eight ECT sessions) in severely depressed patients with unipolar or bipolar depression. Neuropsychological assessments were conducted pre-ECT, three days after the eighth ECT (week 4), and at a 3-month follow-up. Further, functional magnetic resonance imaging (fMRI) was conducted after the eighth ECT. The primary outcome was change from pre- to post-ECT in a \'speed of complex cognitive processing\' composite. Secondary outcomes were verbal and autobiographical memory. Of sixty randomized patients, one dropped out before baseline. Data were thus analysed for 59 patients (EPO, n = 33; saline, n = 26), of whom 28 had fMRI data. No ECT-related decline occurred in the primary global cognition measure (ps≥0.1), and no effect of EPO versus saline was observed on this outcome (ps≥0.3). However post-ECT, EPO-treated patients exhibited faster autobiographical memory recall than saline-treated patients (p = 0.02), which was accompanied by lower memory-related parietal cortex activity. The absence of global cognition changes with ECT and EPO, coupled with the specific impact of EPO on autobiographical memory recall speed and memory-related parietal cortex activity, suggests that assessing autobiographical memory may provide increased sensitivity in evaluating and potentially preventing cognitive side-effects of ECT. TRIAL REGISTRATIONS: ClinicalTrials.gov: NCT03339596, EudraCT no.: 2016-002326-36.

UNASSIGNED: Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, but the biological changes induced by ECT remain poorly understood.
UNASSIGNED: This study investigated alterations in blood serum proteins in 309 patients receiving ECT for a major depressive episode. We analyzed 201 proteins in samples collected at 3 time points (T): just before the first ECT treatment session (T0), within 30 minutes after the first ECT session (T1), and just before the sixth ECT session (T2).
UNASSIGNED: Using statistical models to account for repeated sampling, we identified 152 and 70 significantly (<5% false discovery rate) altered proteins at T1 and T2, respectively. The most pronounced alterations at T1 were transiently increased levels of prolactin, myoglobin, and kallikrein-6. However, most proteins had decreased levels at T1, with the largest effects observed for pro-epidermal growth factor, proto-oncogene tyrosine-protein kinase Src, tumor necrosis factor ligand superfamily member 14, sulfotransferase 1A1, early activation antigen CD69, and CD40 ligand. The change of several acutely altered proteins correlated with electric current and pulse frequency in a dose-response-like manner. Over a 5-session course of ECT, some acutely altered levels were sustained while others increased, e.g., serine protease 8 and chitinase-3-like protein 1. None of the studied protein biomarkers were associated with clinical response to ECT.
UNASSIGNED: We report experimental data on alterations in the circulating proteome triggered by ECT in a clinical setting. The findings implicate hormonal signaling, immune response, apoptotic processes, and more. None of the findings were associated with clinical response to ECT.

UNASSIGNED: Electroconvulsive therapy (ECT) is effective for treatment-resistant and psychotic depression. One previously reported side effect of ECT is the disruption of memory reconsolidation. This study examines whether this disruption induced by ECT can be detected in routine neuropsychological assessments.
UNASSIGNED: In this retrospective study, the Autobiographical Memory Interview (AMI) was applied before and after ECT. Memories of the same events and facts were tested pre and post ECT treatments. 38 patients, receiving ECT for the treatment of unipolar or bipolar depression, were matched for age, sex, and stimulus intensity and divided into two groups: Group A was tested on the day before the first ECT treatment, whereas group B two or more days before.
UNASSIGNED: Patients who were tested by AMI on the day before ECT and thus reactivated memorie shortly before the first ECT treatment deteriorated in AMI score. Patients who had at least two days between memory activation and treatment improved regarding the number of recalled memories. Memory impairment was not associated with depression severity.
UNASSIGNED: This finding suggests that ECT might be capable of impairing reconsolidation. The study demonstrates that memories of personal events can potentially be affected by ECT within a time interval of 24 h of memory vulnerability after reactivation. Implications for practice and future research are discussed.

The induction of electroconvulsive seizures (ECS) in rodents induces sex- and age-specific disparities in antidepressant-like responses, with females and young age being the most unresponsive ones. Since the electrical charge needed to induce an effective convulsion is also altered by these variables, our aim was to compare different dose-intensities of ECS exclusively in female rats, since there is a lack of preclinical data characterizing this particular sex, while also evaluating efficacy during distinctive age periods of treatment (adolescence vs. adulthood).
Adolescent and adult female Sprague-Dawley rats were exposed to an intensity dose-response study (55, 75 or 95 mA; 0.6 s, 100 Hz, 1 session/day, 5 days). The particular characteristics of the induced convulsions (tonic, clonic, recovery times) were monitored during treatment. Antidepressant-like responses were evaluated under the stress of the forced-swim test 1-, 3-, and 7-days post-treatment (i.e., improved immobility time as an indicative of an antidepressant-like response), and brains were collected 24 h later (8 days post-treatment) to evaluate potential changes in hippocampal neurogenesis (Ki-67 and NeuroD) by immunohistochemistry.
The lowest intensities tested of ECS (55 and 75 mA) induced an antidepressant-like effect in adult female rats, but rendered insufficient in adolescence. The lack of efficacy observed in adolescent rats paralleled differences in the characteristics of the seizures induced by ECS as compared to adulthood. In line with prior results, different dose-intensities of ECS modulated hippocampal neurogenesis in a comparable fashion with age (i.e., increased survival of neural progenitors 8 days post-treatment).
In conjunction, these results reinforce the importance of fine-tuning the parameters of ECS that might render efficacious while considering sex and age as essential variables for treatment response, and suggest that other molecular mechanisms, beside the partial role of hippocampal neurogenesis, might be participating in the antidepressant-like effects induced by ECS.
Although the induction of electroconvulsive seizures (ECS) is a safe therapeutical option for treatment-resistant depression, there are important differences in treatment response driven by biological sex and age that require further characterization for ensuring optimal outcomes. In fact, most of the preclinical literature is centered in adult male rodents, with almost no prior studies characterizing ECS\' response in adolescent female rodents. In this context, the present study compared the antidepressant-like responses induced by different intensity doses of ECS (55, 75 or 95 mA; 0.6 s, 100 Hz, 1 session/day, 5 days), exclusively in female rats (adolescent and adult). The results showed that the lowest doses tested (55 or 75 mA) induced an antidepressant-like response in adult female rats, while no dose was capable of inducing efficacy in adolescent female rats. These results replicated prior data from our group showing the inefficacy of the 95-mA dose at both ages, while demonstrating that lowering the dose is sufficient to exert efficacy in female adult rats. Further studies should center in adjusting the parameters to elicit efficacy in females during adolescence.