Intra- and Inter-Network connectivity of the default mode network differentiates Treatment-Resistant depression from Treatment-Sensitive depression.

Understanding why some patients with depression remain resistant to antidepressant medication could be elucidated by investigating their associated neural features. Although research has consistently demonstrated abnormalities in the anterior cingulate cortex (ACC) - a region that is part of the default mode network (DMN) - in treatment-resistant depression (TRD), a considerable research gap exists in discerning how these neural networks distinguish TRD from treatment-sensitive depression (TSD). We aimed to evaluate the resting-state functional connectivity (rsFC) of the ACC with other regions of the DMN to better understand the role of this structure in the pathophysiology of TRD. 35 TRD patients, 35 TSD patients, and 38 healthy controls (HC) underwent a resting-state functional MRI protocol. Seed-based functional connectivity analyses were performed, comparing the three groups for the connectivity between two subregions of the ACC (the subgenual ACC (sgACC) and the rostral ACC (rACC)) and the DMN (p < 0.05 FWE corrected). Furthermore, inter-network connectivity of the DMN with other neural networks was explored by independent component (ICA) analyses (p < 0.01, FDR corrected). The results demonstrated hyperconnectivity between the rACC and the posterior cingulate cortex in TRD relative to TSD and HC (F(2,105) = 5.335, p < 0.05). ICA found DMN connectivity to regions of the visual network (TRDTSD), differentiating the two clinical groups. These results provide confirmatory evidence of DMN hyperconnectivity and preliminary evidence for its interactions with other neural networks as key neural mechanisms underlying treatment non-responsiveness.

Continuation or maintenance ECT for schizophrenia: A narrative review of case report data.

OBJECTIVE: This review aimed to address the limited evidence on the efficacy of continuation or maintenance electroconvulsive therapy (C/M-ECT) in schizophrenia, with a focus on international case reports and series due to the scarcity of randomised controlled trials. MATERIALS AND METHODS: Electronic database searches were conducted to identify case reports or series evaluating the efficacy of C/M-ECT in patients with schizophrenia or schizoaffective disorder. RESULTS: C/M-ECT treatment span varied from 3 months to 36 years (Median = 30 months; M = 43.9 months; SD = 63.0) and was effective in maintaining remission for most patients with schizophrenia in combination with antipsychotic medication. Reporting of adverse events including cognitive adverse effects was infrequent. CONCLUSIONS: Collation of case reports and series data indicated that C/M-ECT, when combined with antipsychotics, appears to be a safe and effective strategy for maintaining remission, even over several years. Caution is warranted due to the potential influence of publication bias.

Examining the clinical effectiveness of continuation and maintenance electroconvulsive therapy in schizophrenia.

OBJECTIVE: There are few studies that examine the effectiveness of Continuation/Maintenance Electroconvulsive Therapy (C/M-ECT) in schizophrenia, despite the documented effectiveness of acute ECT treatment. We aimed to investigate the clinical effectiveness of C/M-ECT for in-patients with Schizophrenia in a naturalistic setting. We examined the medical records of 46 in-patients who were diagnosed with Schizophrenia and had received C/M-ECT belonging to non-acute extended care service in a public psychiatry hospital in Sydney, Australia. The focus of analysis was on 138 treatment cycles (71 acute only cycles and 67 acute-continuation/maintenance cycles) across 45 subjects. A linear mixed effects model was used to describe the change in clinical global impression-severity (CGI-S) over time 4 time points viz., pre-post acute and pre-post continuation/maintenance ECT. RESULTS: Acute-only cycles and acute-continuation/maintenance cycles had identical pre- (M = 5, C.I. = 4-6), post-cycle CGI-S scores, and identical CGI-S difference scores (M = 0, C.I. = -1 - 1). Broadly in each continuation/maintenance cycle, we observed an initial sharp decrease in CGI-S scores followed by a logarithmic increase in scores over time, with satisfactory CGI-S score maintenance observed for approximately 6 months. Bitemporal ECT influenced CGI-S across maintenance ECT (p < 0.05) indicating smaller declines in CGI-S scores over time. CONCLUSION: In schizophrenia, C/M ECT preserves effects on illness severity for at least upto 6 months following an acute course of ECT. Bitemporal ECT vis a vis other electrode positions differentiated clinical severity over time.

Abnormal habenula functional connectivity characterizes treatment-resistant depression.

BACKGROUND: A significant proportion of patients with major depressive disorder are resistant to antidepressant medication and psychological treatments. A core symptom of treatment-resistant depression (TRD) is anhedonia, or the inability to feel pleasure, which has been attributed to disrupted habenula function - a component of the reward network. This study aimed to map detailed neural circuitry architecture related to the habenula to identify neural mechanisms of TRD. METHODS: 35 TRD patients, 35 patients with treatment-sensitive depression (TSD), and 38 healthy controls (HC) underwent resting-state functional magnetic resonance imaging. Functional connectivity analyses were performed using the left and right habenula as seed regions of interest, and the three groups were compared using whole-brain voxel-wise comparisons. RESULTS: The TRD group demonstrated hyperconnectivity of the left habenula to the left precuneus cortex and the right precentral gyrus, compared to the TSD group, and to the right precuneus cortex, compared to the TSD and HC groups. In contrast, TSD demonstrated hypoconnectivity than HC for both connectivity measures. These connectivity values were significantly higher in patients with a history of suicidal ideation. CONCLUSIONS: This study provides evidence that, unlike TSD, TRD is characterized by hyperconnectivity of the left habenula particularly with regions of the default mode network. An increased interplay between reward and default mode networks is linked to suicidality and could be a possible mechanism for anhedonia in hard to treat depression.

ECT in the time of the COVID-19 pandemic.

OBJECTIVE: The recent and ongoing COVID-19 pandemic outbreak has placed a huge burden on healthcare systems worldwide. This emergent situation applies invariably to mental health services, and policy makers have issued new directives to adequately deal with this crisis. The COVID-19 outbreak poses special challenges to the administration of electroconvulsive therapy (ECT) since the anaesthetic induction is an aerosol-generating process. The report provides a narrative account of modifications to the ECT practice at a tertiary care psychiatric hospital to mitigate the risk of COVID-19 transmission. CONCLUSION: We emphasise two main modifications: use of personal protective equipment (PPE) during the ECT and modifications in the anaesthetic procedure to mitigate potential transmission.

Naturalistic outcomes of continuation right unilateral ultrabrief ECT in major depression: a retrospective chart review.

OBJECTIVE: Continuation treatment of major depression following an acute course of electroconvulsive treatment (ECT) may be often required to prevent relapse. Data on continuation phase of right unilateral ultrabrief ECT are sparse and there are doubts if it is inherently capable of relapse prevention. METHODS: All consecutive adult patients with major depression who received the first 'run' of continuation phase of right unilateral ultrabrief ECT over a 10-year period were routinely followed up. ECT frequency varied from weekly to up to once every 4 weeks for a maximum period of 6 months. The data were extracted from a retrospective chart review. RESULTS: 20 out of 22 patients persisted with ultrabrief pulses (0.3 ms) with two needing 0.5 ms pulse widths. The median duration of continuation treatment was 51 days (range: 14-460). At the end of 1 month (n = 17), treatment gap in days mean (SD): 10.18 (7.08), widening to mean (SD): 20.11 (16.85) at 4 months (n = 9). Stimulus dose increased throughout the continuation phase: p = 0.026. In 16 out of 22 patients, more than 70% of the visits were charted as being 'in remission'. CONCLUSION: As most patients receiving ultrabrief ECT remained well, this study suggests that ultrabrief ECT can be used effectively in continuation therapy.

Dissociation of identity following left parietal haematoma - a single case report.

OBJECTIVES: Dissociative identity disorder in relation to brain injury has only rarely been reported in literature. This case report, which illustrates a de novo onset of dissociative identity for the first time in an elderly man who had a left parietal haematoma, adds to this scant literature base and supports an integrative view of bridging the dichotomy between organic and functional to explain complex psychiatric phenomena. METHODS: It is a single case report collected through serial semi-structured interviews of the patient and his family over a 12-week period. RESULTS: The patient was an elderly man transiently dissociated into various identities, some of whom seemed to be based upon individuals who had traumatized him in the past. This occurred three weeks after recovery from hemiparesis and delirium following a left parietal haematoma. The dissociations ended after six weeks, which coincided not only with the resolution of the haematoma but also with a faith-healing ritual. A speculative psychobiological formulation was drawn of possible brain origins of dissociation of identity. CONCLUSIONS: This report is a compelling account of temporal correlation between dissociation of identity and left parietal haematoma.

Concomitant Transcranial Direct Current Stimulation With Ultrabrief Electroconvulsive Therapy: A 2-Week Double-Blind Randomized Sham-Controlled Trial.

OBJECTIVE: The feasibility and effectiveness of concomitant use of transcranial direct current stimulation (tDCS) with electroconvulsive therapy (ECT) has not been investigated. The study principally aimed at determining whether tDCS when combined with ECT improved the speed of antidepressant response. Secondarily, the ease of generation of seizures during electroconvulsive therapy and cognitive outcomes were investigated. METHODS: Consecutive patients referred for ECT to treat major depression were randomized to tDCS with dorsolateral prefrontal electrode placements (n = 8) or sham (n = 8) used daily and just before thrice weekly, 6 times threshold, right unilateral ultrabrief (0.3 ms) pulse width ECT. Change of depression severity was determined using the Montgomery Asberg Depression Rating Scale along with cognitive assessments using Montreal Cognitive Assessment and visual memory testing at weeks 1 and 2, which were compared with baseline. RESULTS: Change of depression severity from baseline was similar in tDCS and ECT compared with sham tDCS and ECT at week1 (mean [standard deviation {SD}] = 16.00 [6.78]; 13.75 [7.83]; P = 0.89) and at week 2 (mean [SD] = 23.00 [4.96]; 19.75 [9.85], P = 0.08). No between-group differences were obtained in the cognitive tests at weeks 1 and 2. Combining tDCS with ECT resulted in higher restimulation: 62.5% requiring 3 stimulations to achieve threshold in contrast to 12.5% with sham tDCS and ECT (P = 0.04). The mean suprathreshold dose was higher in the tDCS and ECT group compared with sham tDCS and ECT: mean [SD] = 144.0 [43.54] and mean [SD] = 122.4 [20.36], P = 0.04, respectively. CONCLUSIONS: Concomitant use of tDCS with ultrabrief right unilateral ECT is feasible and safe albeit with higher rates of restimulation when tDCS was combined with ECT. However, there were no statistically significant differences in the speed of antidepressant response or cognitive outcomes at weeks 1 and 2 after the commencement of treatments.

Rapid amelioration of severe manic episodes with right unilateral ultrabrief pulse ECT: a case series of four patients.

OBJECTIVE: The aim of this small case series is to describe four cases of severe mania, where ultrabrief pulse electroconvulsive therapy (ECT) was used as a primary mode of treatment. METHODS: A retrospective file review was undertaken of four patients identified as having received ultrabrief pulse ECT for severe mania. The outcome measures for treatment efficacy were the Young Mania Rating Scale (YMRS) and Clinical Global Impression (CGI). RESULTS: All the patients showed significant clinical improvement. A comparison of pre- and post-treatment YMRS and CGI scores showed a dramatic decrease in all four cases. However, one patient was shifted to brief pulse ECT due to inadequate response. CONCLUSIONS: Ultrabrief pulse ECT may be an effective treatment in cases of severe mania. Due to the very small number of cases in the current case series, no specific conclusions regarding efficacy may be drawn; however, larger, controlled studies would be indicated.

Autobiographical and subjective memory with right unilateral high-dose 0.3-millisecond ultrabrief-pulse and 1-millisecond brief-pulse electroconvulsive therapy: a double-blind, randomized controlled trial.

OBJECTIVE: Shortening the pulse width to 0.3 millisecond holds neurophysiological and clinical promise of making electroconvulsive therapy (ECT) safer by reducing cognitive adverse effects. The exclusive effects of pulse width on autobiographical and subjective memory are largely unstudied. The aim was to principally investigate during the acute ECT course and at 3 months after ECT autobiographical and subjective memory effects of 0.3-millisecond ultrabrief and 1-millisecond brief-pulse ECT. METHODS: Patient with severe depression were randomized to 1-millisecond brief-pulse (n = 20) or 0.3-millisecond ultrabrief-pulse (n = 20) right unilateral ECT, both at 6 times the threshold stimulus dose given thrice weekly. Autobiographical Memory Interview (Kopelman) and Squire Subjective Memory Questionnaire were administered at baseline, after 8 sessions, end of the acute course, and 3 months later. RESULTS: Early adult semantic memory worsened significantly over time with brief-pulse compared with ultrabrief ECT: F3,88 = 2.60, P = 0.05. There was a significant decline in brief-pulse treatment vis-à-vis a significant improvement with ultrabrief-pulse treatment with childhood semantic memory (P = 0.022), early adult semantic (P = 0.03), and recent semantic memory (P = 0.018) only at 24 hours after the eighth ECT treatment. CONCLUSIONS: Clinically meaningful and significant improvement in semantic autobiographical memory occurred in ultrabrief treatment vis-à-vis brief-pulse ECT after 8 treatments. Ultrabrief treatment offered a small but significant advantage over 1-millisecond brief-pulse high-dose right unilateral ECT with early adult semantic autobiographical memory, which persisted up to 3 months.

Acute antidepressant effects of right unilateral ultra-brief ECT: a double-blind randomised controlled trial.

BACKGROUND: Shortening the pulse width to 0.3 ms holds neurophysiological and clinical promise of making ECT safer by limiting cognitive side effects. However, the antidepressant effects of right ultra-brief unilateral ECT are under contention. In an acute ECT course, antidepressant equivalence of ultra-brief right unilateral ECT to the high-dose brief pulse right unilateral ECT was investigated. METHODS: Severely depressed patients were randomised to 1 ms-brief pulse (n=18) or 0.3 ms ultra-brief pulse (n=17) right unilateral ECT, both at high-dose (6 times threshold stimulus dose) given thrice weekly. Depression severity was measured using the Montgomery Asberg Depression Rating Scale at baseline, after 8 treatments and after the acute course of ECT. RESULTS: Depression severity declined equally in both groups: F (1.27,41.97)=0.31, p=0.63. Median time in days to remission (95%CI) was in brief pulse ECT: 26 (18.6-33.4) and ultra-brief pulse ECT:28 (17.9-38.0). LIMITATION: The small sample study in the study increases the likelihood of type 2 error. CONCLUSION: In severe depression, high-dose ultra-brief right unilateral ECT appears to show matching acute antidepressant response to an equally high-dose brief pulse right unilateral ECT.

Comparison of ictal electroencephalogram between ultrabrief- and brief-pulse right unilateral electroconvulsive therapy: a multitaper jackknife analysis.

OBJECTIVE: Characterization of the ictal electroencephalogram (EEG) generated during ultrabrief pulse electroconvulsive therapy (ECT) is important to progress its use in routine ECT practice particularly in indicating treatment efficacy. The study compared 2- to 5-Hz and 5.2- to 13-Hz bands of the ictal EEG signal between brief- and ultrabrief-pulse ECT. METHODS: Twenty-five patients with major depression were randomized to brief- (1 millisecond [ms]) and ultrabrief-pulse (0.3 ms) right unilateral ECT. In sessions 2 to 8, when patients in either group received 6 times threshold ECT, right and left frontal ictal EEG between ultrabrief (n = 60) and brief pulse (n = 63) were compared. Electroencephalographic spectra from 2- to 5-Hz and 5.2- to 13-Hz bands in the mid and postictal phases were subjected to multitaper jackknife analysis of spectral power density (µV/Hz) and its SD or "regularity" (µV/Hz), peak spectral frequency (Hz), and its standard deviation (SD) or regularity (Hz). Linear mixed-effect models were used to compare the outcomes. RESULTS: In ultrabrief ECT, spectral power density and its SD were significantly smaller within the mid seizure of both bands, whereas peak frequency and its SD were similar. Postseizure suppression of spectral power density of both bands was similar in either treatments. CONCLUSION: Lower spectral power densities were noted with ultrabrief-pulse ECT vis-a-vis brief-pulse ECT. However, in ultrabrief pulse ECT, regularity measures and postseizure suppression were comparable to brief-pulse ECT.

Comparison of antidepressant effects between brief and ultrabrief pulse unilateral electroconvulsive therapy: brief report of a randomized double-blind trial.

OBJECTIVE: Electroconvulsive therapy (ECT) treatments with briefer pulse widths have recently shown promise. METHODS: Consenting patients with major depression were randomized in a double-blind protocol into 1-millisecond brief pulse (n = 10) or 0.3-millisecond ultrabrief pulse (n = 12) right unilateral at thrice-weekly, 6 times the threshold dose treatments at identical charge rates. RESULTS: After 8 treatments, the change from baseline in Montgomery-Åsberg Depression Scale was mean = 22.1 (SE, 4.8) for brief pulse and mean = 24.9 (SE, 4.2) for ultrabrief pulse ECT. The mean difference was 2.8 (95% confidence interval = -10.5 to 16.1; P = 0.7). CONCLUSIONS: Although inconclusive because of small sample size (type II error), ultrashort pulse widths appear to be as effective as standard pulse ECT.

Impact of hyperventilation on stimulus efficiency during the early phase of an electroconvulsive therapy course: a randomized double-blind study.

OBJECTIVE: The question whether hyperventilation during electroconvulsive therapy (ECT) can improve stimulus efficiency is as yet unanswered. METHODS: Twenty-five consecutive consenting patients (N = 25) with major depression who were administered ECT entered into the study. Right unilateral ECT at thrice the threshold dose was administered using Mecta spECTrum 5000Q (Mecta Corp, Lake Oswego, Ore), with standard titration procedures and stimulus configurations. At the second ECT session, they were randomly allocated to ECT either with hyperventilation or with no hyperventilation. Hyperventilation was actively administered by an anesthetist just after anesthetic paralysis and before the ECT stimulus during the second, third, and fourth ECT sessions. Assessments were double-blind and performed at baseline and 24 to 48 hours after the fourth ECT session. Time to reorient after ECT was assessed during the first up to the fourth ECT session. Ictal electroencephalogram (EEG) quality was visually assessed using standard scales. RESULTS: There were no significant differences across the 2 groups about depression severity and global cognitive impact. However, the orientation time was 34% longer among those who did not receive hyperventilation. The ratio of orientation time without hyperventilation to that with hyperventilation equals 1.34 (95% confidence interval, 0.94-1.92; P = 0.103). There was a significant increase in threshold over time across both groups (mean difference, 16.4; SE, 5.5; P = 0.006) with no significant main effect for the groups (P = 0.399). There were no significant group differences in the EEG quality. CONCLUSIONS: The addition of hyperventilation during the early phase of the ECT course shows a trend to lessen the impact on immediate orientation without impeding clinical response. This does not seem to be mediated by differential threshold changes or change to the ictal EEG quality.

Impact of depression heterogeneity on attention: an auditory oddball event related potential study.

BACKGROUND: Major depressive disorder is associated with a reduced ability to attend and concentrate, however, the extent to which attentional impairment is dependent on subtype remains to be clarified. METHODS: Event-related potentials (ERPs) associated with a well-validated auditory oddball, selective attention task, were recorded to determine the impact of melancholia (n=57) versus non-melancholia (n=48) relative to controls (n=116). RESULTS: The key findings were an exaggeration of the P200 to both non-target and target stimuli and a reduction in the P300 to targets in patients with melancholia, relative to patients with non-melancholia and controls. In addition, the N200/P300 complex was slowed in latency corresponding to the slowed behavioural responses to targets in melancholia. Stepwise regression analysis also revealed that depression severity, but not psychomotor slowing, contributed to increases in P200 amplitude. LIMITATIONS: This study is cross-sectional and cannot determine whether the observed ERP changes are a state or trait marker, highlighting the need for a longitudinal study of ERP characteristics in different subgroups of depressed patients. CONCLUSIONS: Results point to a difficulty in differentiating significant stimuli in the environment in the depressed individual. The combined disruption of early sensory processing (P200) and subsequent context processing (N200/P300 complex) may provide a potential mechanism for the attentional impairment that is frequently observed in depression, particularly in more severe depression.

Ictal electroencephalographic characteristics during electroconvulsive therapy: a review of determination and clinical relevance.

OBJECTIVE: The usefulness of electroencephalogram (EEG) during electroconvulsive therapy (ECT) is not limited to the duration of seizure. The use of studying its characteristics has gained attention among specialized ECT researchers. This review attempts to put the literature in this area of ictal EEG in ECT into a practical perspective. METHODS: A systematic database search using MEDLINE and EMBASE was performed using the keywords ECT and ictal EEG. RESULTS: Manual, linear, and nonlinear methods have been used to analyze EEG obtained during ECT. Most studies have used spectral or linear methods of analysis. Studies using nonlinear have been sparse. There are 4 overlapping practical applications of analysis of EEG during ECT. First, EEG can discriminate between electrode positions and more controversially different stimulus doses. Second, EEG can predict treatment response. Postictal suppression is the measure most studied from all vantage points. Nonlinear approaches to determine EEG predictors hold promise. Third, changes in the EEG across ECT sessions may indicate threshold changes and aids more optimum dosimetry. Fourth, EEG characteristics have been incorporated into ECT clinical algorithms, but this still remains controversial, and there is a paucity of studies in this area. CONCLUSIONS: The use of ictal EEG extends beyond determining the seizure length. The study of ictal EEG has certain practical uses, which could help individualize ECT treatment if applied in routine ECT practice.