Comparative validation of automated presurgical tractography based on constrained spherical deconvolution and diffusion tensor imaging with direct electrical stimulation.

OBJECTIVES: Accurate presurgical brain mapping enables preoperative risk assessment and intraoperative guidance. This cross-sectional study investigated whether constrained spherical deconvolution (CSD) methods were more accurate than diffusion tensor imaging (DTI)-based methods for presurgical white matter mapping using intraoperative direct electrical stimulation (DES) as the ground truth. METHODS: Five different tractography methods were compared (three DTI-based and two CSD-based) in 22 preoperative neurosurgical patients undergoing surgery with DES mapping. The corticospinal tract (CST, N = 20) and arcuate fasciculus (AF, N = 7) bundles were reconstructed, then minimum distances between tractograms and DES coordinates were compared between tractography methods. Receiver-operating characteristic (ROC) curves were used for both bundles. For the CST, binary agreement, linear modeling, and posthoc testing were used to compare tractography methods while correcting for relative lesion and bundle volumes. RESULTS: Distance measures between 154 positive (functional response, pDES) and negative (no response, nDES) coordinates, and 134 tractograms resulted in 860 data points. Higher agreement was found between pDES coordinates and CSD-based compared to DTI-based tractograms. ROC curves showed overall higher sensitivity at shorter distance cutoffs for CSD (8.5 mm) compared to DTI (14.5 mm). CSD-based CST tractograms showed significantly higher agreement with pDES, which was confirmed by linear modeling and posthoc tests (PFWE < .05). CONCLUSIONS: CSD-based CST tractograms were more accurate than DTI-based ones when validated using DES-based assessment of motor and sensory function. This demonstrates the potential benefits of structural mapping using CSD in clinical practice.

Acoustic Stimulation to Improve Slow-Wave Sleep in Alzheimer's Disease: A Multiple Night At-Home Intervention.

OBJECTIVES: To investigate the efficacy of closed-loop acoustic stimulation (CLAS) during slow-wave sleep (SWS) to enhance slow-wave activity (SWA) and SWS in patients with Alzheimer's disease (AD) across multiple nights and to explore associations between stimulation, participant characteristics, and individuals' SWS response. DESIGN: A 2-week, open-label at-home intervention study utilizing the DREEM2 headband to record sleep data and administer CLAS during SWS. SETTING AND PARTICIPANTS: Fifteen older patients with AD (6 women, mean age: 76.27 [SD = 6.06], mean MOCA-score: 16.07 [SD = 6.94]), living at home with their partner, completed the trial. INTERVENTION: Patients first wore the device for two baseline nights, followed by 14 nights during which the device was programmed to randomly either deliver acoustic stimulations of 50 ms pink noise (± 40 dB) targeted to the slow-wave up-phase during SWS or only mark the wave (sham). RESULTS: On a group level, stimulation significantly enhanced SWA and SWS with consistent SWS enhancement throughout the intervention. However, substantial variability existed in individual responses to stimulation. Individuals received more stimulations on nights with increased SWS compared to baseline than on nights with no change or a decrease. In individuals, having lower baseline SWS correlated with receiving fewer stimulations on average during the intervention. CONCLUSION: CLAS during SWS is a promising nonpharmacological method to enhance SWA and SWS in AD. However, patients with lower baseline SWS received fewer stimulations during the intervention, possibly resulting in less SWS enhancement. Individual variability in response to stimulation underscores the need to address personalized stimulation parameters in future research and therapy development.

Late Life Depression is Not Associated With Alzheimer-Type Tau: Preliminary Evidence From a Next-Generation Tau Ligand PET-MR Study.

OBJECTIVE: To investigate whether tau accumulation is higher in late life depression (LLD) compared to non-depressed cognitively unimpaired (CU) older adults. To situate these findings in the neurodegeneration model of LLD by assessing group differences in tau and grey matter volume (GMV) between LLD, non-depressed CU and mild cognitive impairment due to Alzheimer's Disease (MCI). DESIGN: Monocentric, cross-sectional study. SETTING: University Psychiatric hospital, memory clinic and outpatient neurology practice. PARTICIPANTS: A total of 102 adults over age 60, of whom 19 currently depressed participants with LLD, 19 with MCI and 36 non-depressed CU participants completed neuropsychological testing and tau PET-MR imaging. MEASUREMENTS: PET-MRI: 18F-MK-6240 tracer SUVR for tau assessment; 3D T1-weighted structural MRI derived GMV in seven brain regions (temporal, cingulate, prefrontal and parietal regions); amyloid PET to assess amyloid positivity; Neuropsychological test scores: MMSE, RAVLT, GDS, MADRS. ANCOVA and Spearman's rank correlations to investigate group differences in tau and GMV, and correlations with neuropsychological test scores respectively. RESULTS: Compared to non-depressed CU participants, LLD patients showed lower GMV in temporal and anterior cingulate regions but similar tau accumulation and amyloid positivity rate. In contrast, MCI patients had significantly higher tau accumulation in all regions. Tau did not correlate with any neuropsychological test scores in LLD. CONCLUSION: Our findings suggest AD-type tau is not higher in LLD compared to non-depressed, cognitively unimpaired older adults and appears unlikely to contribute to lower gray matter volume in LLD, further underscoring the need to distinguish major depressive disorder from depressive symptoms occurring in early AD.

Electroconvulsive therapy related anxiety in patients with depression: The influence of cognitive coping styles.

INTRODUCTION: Electroconvulsive therapy (ECT) related anxiety (ERA) is a common phenomenon with high individual variability. The way patients cognitively cope with the prospects of receiving ECT could be a mechanism explaining individual differences in ERA. Cognitive coping like monitoring (information seeking, paying attention to consequences) and blunting (seeking distraction and reassurance) has been linked to anxiety in various medical settings, with monitoring leading to more and blunting to less anxiety. How cognitive coping is related to ERA, is unknown. METHODS: The sample consisted of 71 patients with unipolar or bipolar depression referred for ECT. Cognitive coping was assessed at baseline, while ERA was measured each morning before the ECT session. Using a Linear Mixed Model, the influence of cognitive coping styles on ERA was investigated. RESULTS: Blunting was associated with lower levels of ERA (p = 0.037) and monitoring tended to be associated with higher levels of ERA (p = 0.057) throughout the ECT course. Patients with a depression with psychotic features scored significantly higher on monitoring, but even after controlling for monitoring they showed a stronger decline in ERA during treatment compared to patients without psychotic features. CONCLUSION: Cognitive coping style contributes to individual differences in ERA. Blunting is a protective factor, leading to lower levels of ERA throughout the ECT course. On the contrary, patients with a higher monitoring style tend to experience higher levels of ERA. Further insights in these coping mechanisms may help to tailor future treatment to individual patients and reduce ERA before and during ECT treatment.

Associations between childhood adversity, psychiatric symptoms, and self-esteem outcomes in adolescents and young adults: An experience sampling study.

OBJECTIVES: Self-esteem and self-esteem stability are important factors during adolescence and young adulthood that can be negatively impacted by childhood adversity and psychiatric symptoms. We examined whether childhood adversity and psychiatric symptoms are associated with decreased global self-esteem as well as increased self-esteem instability as measured with experience sampling method. In addition, we examined if childhood adversity moderates the association between psychiatric symptoms and self-esteem outcomes. METHODS: Our study consisted of 788 adolescents and young adults who were part of a twin pair. The twin structure was not of interest to the current study. Mean age was 16.8 (SD = 2.38, range: 14-25), 42% was male. We used a multilevel modeling approach to examine our hypotheses to account for the presence of twins in the data set. RESULTS: Childhood adversity and psychiatric symptoms were negatively associated with global self-esteem (respectively standardized ß = -.18, SE = 0.04, p < .0001 and standardized ß = -.45, SE = 0.04, p < .0001), with a larger effect for psychiatric symptoms. Similarly, both were associated with increased self-esteem instability (respectively standardized ß = .076, SE = 0.025, p = .002 and standardized ß = .11, SE = 0.021, p < .0001). In addition, interactions between childhood adversity and psychiatric symptoms on both global self-esteem (standardized ß = .06, SE = 0.01, p < .0001) and self-esteem instability (standardized ß = -.002, SE = 0.0006, p = .001) were found, showing that the negative association of psychiatric symptoms with self-esteem outcomes is less pronounced in young people with higher levels of childhood adversity, or formulated differently, is more pronounced in young people with little or no exposure to childhood adversity. CONCLUSION: Global self-esteem and self-esteem instability in young people are influenced by both current psychiatric symptomatology and exposure to childhood adversity. Those with more psychiatric symptoms show worse self-esteem and higher self-esteem instability, which is moderated by childhood adversity. For young people with high childhood adversity levels lower self-esteem and higher self-esteem instability are less influenced by reductions in psychiatric symptoms.

Mild Motor Signs in Healthy Aging Are Associated with Lower Synaptic Density in the Brain.

OBJECTIVE: To investigate whether mild motor signs (MMS) in old age correlate with synaptic density in the brain. BACKGROUND: Normal aging is associated with a decline in movement quality and quantity, commonly termed "mild parkinsonian signs" or more recently MMS. Whether MMS stem from global brain aging or pathology within motor circuits remains unresolved. The synaptic vesicle glycoprotein 2A positron emission tomography (PET) ligand 11 C-UCB-J allows the investigation of brain-motor associations at the synaptic level in vivo. METHOD: Fifty-eight healthy older adults (≥50 years) were included from two monocentric control cohorts. Brain magnetic resonance imaging and 11 C-UCB-J PET data were available in 54 participants. 11 C-UCB-J PET binding was quantified by standardized uptake value ratio (SUVR) values in grey matter (GM) volumes of interest (VOIs): caudate, putamen, globus pallidus, substantia nigra, thalamus, cerebellum, and the frontal, parietal, temporal, and occipital cortex. Multiple linear regression analyses were performed with Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score measuring MMS as the dependent variable and mean SUVR values in each VOI as the independent variable with age, Fazekas score (white matter lesion [WML] load), VOI and cohort as covariates. RESULTS: Participants (68 ± 7.5 years; 52% female) had an average MDS-UPDRS part III score of 3.3 ± 2.8. The MDS-UPDRS part III score was inversely associated with synaptic density, independently of WML load or GM volume, in the caudate, substantia nigra, thalamus, cerebellum, and parietal, occipital, temporal cortex. Cohen's f2 showed moderate effect sizes for subcortical (range, 0.30-0.35), cortical (0.28-0.35) and cerebellar VOIs (0.31). CONCLUSION: MMS in healthy aging are associated with lower synaptic density throughout the brain. © 2023 International Parkinson and Movement Disorder Society.

Knowledge and Attitudes of First- and Final-Year Medical Students about Electroconvulsive Therapy: The Impact of Media.

OBJECTIVE: The aim of this study is to evaluate medical students' knowledge about and attitudes towards electroconvulsive therapy (ECT) and to assess the impact of information sources (including those within and outside the curriculum) on knowledge and attitudes by comparing first- and final-year medical students. METHODS: Two hundred and ninety-five first-year and one hundred forty-nine final-year medical students of the University of Leuven (KU Leuven) in Belgium responded to an anonymous self-administered survey which consisted of questions about sociodemographic background, self-perceived knowledge about medicine, psychiatry and ECT, interest in psychiatry, experience with psychiatric disorders, information sources of ECT, and knowledge about and attitudes towards ECT. RESULTS: Compared to first-year medical students, final-year students had better knowledge about and more positive attitudes towards ECT, partially explained by differences in information sources. Nevertheless, both student groups showed an average knowledge score below 50%. Whereas freshmen attributed their knowledge to movies or documentaries, senior students gained knowledge mainly at university courses, scientific journals, and attending live ECT sessions. A significant positive correlation was found between knowledge about and positive attitudes towards ECT. CONCLUSIONS: The knowledge of first- and final-year medical students remains limited, potentially due to limited instruction about ECT in medical courses. The use of media as an information source predicted negative attitudes towards ECT. Therefore, the stigma and misinformation provided in the media need to be addressed in the medical curriculum.

Long-term Outcome Following Electroconvulsive Therapy for Late-Life Depression: Five-Year Follow-up Data From the MODECT Study.

OBJECTIVE: Electroconvulsive therapy (ECT) is the most effective treatment for late-life depression (LLD). Research addressing long-term outcome following an acute course of ECT for LLD is limited. We aimed to describe relapse, cognitive impairment and survival 5 years after a treatment with ECT for severe LLD, and assess the association of clinical characteristics with all three outcome measures. METHODS: This cohort study was part of the Mood Disorders in Elderly treated with ECT (MODECT) study, which included patients aged 55 years and older with major depressive disorder. Data regarding clinical course, cognitive impairment and mortality were collected 5 years after the index ECT course. We used multivariable Cox proportional hazards models and logistic regression models to assess the association of clinical characteristics with relapse and survival, and cognitive impairment, respectively. RESULTS: We studied 110 patients with a mean age of 72.9 years. 67.1% of patients who showed response at the end of the index ECT course relapsed, and the included clinical characteristics were not significantly associated with the risk of relapse. 38.8% of patients with available data showed cognitive impairment at five-year follow-up. 27.5% were deceased; higher age and a higher number of previous psychiatric admissions were significantly associated with increased risk of mortality. CONCLUSIONS: Five-year outcome after a course of ECT for severe LLD seems to be in line with long-term outcome following other acute treatments for severe LLD in terms of relapse, cognitive impairment and survival. Additional studies aimed at improving long-term outcome in severe LLD are warranted.

ECT-related anxiety during maintenance ECT: A prospective study.

OBJECTIVE: Despite the established safety of electroconvulsive therapy (ECT), ECT-related anxiety (ERA) remains one of the most distressing complications of ECT. ERA is reported to diminish during an acute course of ECT, but it was never studied during maintenance ECT (M-ECT). Our aim was to study the trajectories of ERA during M-ECT and how they differ from trajectories during the acute course. METHODS: Thirty-nine patients with unipolar or bipolar depression, retained for M-ECT after an acute ECT course, were included. ERA was assessed the morning before each ECT session using the ECT-related Anxiety Questionnaire (ERAQ). RESULTS: ERA remained stable during M-ECT (RC = -0.05 (SE = 0.06), t(8.35) = -0.86, p = 0.42), while ERA declined significantly during the acute course (RC = -0.85 (SE = 0.30), t(33.6) = -2.81, p = 0.0082). During the acute course, patients with a psychotic depression were more anxious at baseline (t(32)= -2.42, p = 0.02), and showed a significant decline in ERAQ scores (RC = -1.65 (SE = 0.46), t(31.6) = -3.56, p = 0.0012), whereas patients with a non-psychotic depression were less anxious at baseline and retained stable ERAQ scores during the acute course (RC = -0.06 (SE = 0.41), t(32.1) = -0.14, p = 0.89). Whereas a correlation (r = 0.48) was noticed between the decline of depression severity and ERA during the acute course, this was not the case during M-ECT. CONCLUSION: ERA runs a stable course during M-ECT, after having decreased during the acute course. During the acute course, ERA trajectories differed significantly between patients with a psychotic and non-psychotic depression. Decline of depression severity and ERA are significantly connected during the acute course of ECT. Both depression severity and ERA remain stable during M-ECT.

Suicidal ideation and ECT, ECT and suicidal ideation: A register study.

OBJECTIVE: Although electroconvulsive therapy (ECT) is anti-suicidal, it is not known whether the presence of suicidal ideation (SI) at baseline predicts response and remission after ECT. The aim of the study was to analyze the impact of baseline SI on response and remission following ECT treatment in a large sample of patients with depression and to assess SI before and after ECT. METHODS: This population-based register study used data from the Swedish National Quality Register for ECT and the Swedish Patient Register. Patients aged 18 years or older who had received ECT for a unipolar or bipolar depressive episode between 2011 and 2018 were included in the study. SI was defined as a score of ≥4 on the last item of the Montgomery-Åsberg Depression Rating Scale - Self Assessment (MADRS-S). Using a logistic regression model, SI at baseline was used to predict response and remission following ECT, while controlling for depression severity, psychotic symptoms, presence of a comorbid personality disorder, age, sex, electrode position, unipolar or bipolar disorder, and number of previous suicide attempts at baseline. RESULTS: In patients who exhibited SI at baseline, 53.7% (N = 632) of cases showed a response to ECT, whereas 68.4% (N = 690) of patients without SI showed a response. In addition, 27.2% (N = 320) of cases with SI achieved remission, whereas 48.5% (N = 489) of cases without SI achieved remission. The odds of achieving response and remission for patients with SI were 0.75 and 0.58 times, respectively, those for patients without SI. Of the 1178 patients with pre-treatment SI, 75.64% (N = 891) exhibited no SI at the end of treatment. Moreover, in this subgroup, the presence of a personality disorder, higher MADRS-S-score, and younger age were associated with persistent SI. CONCLUSION: The presence of SI was associated with lower ECT response and remission rates. Nevertheless, depressive symptoms and SI were reduced in a large proportion of patients across both patient groups. Clinicians should be aware of the lower likelihood of achieving a successful outcome following ECT in younger patients who present with a non-psychotic depressive episode, SI, and (suspected) personality disorders. More research is warranted regarding if these patients can achieve similar or better results with other treatments.

Resilience and quality of life in young adults with a 22q11.2 deletion syndrome: a patient's perspective.

In the transition period between adolescence and young adulthood, individuals with 22q11.2DS are at an increased risk of developing severe psychiatric disorders. Various studies have focused on detecting risk factors, but until now protective factors are still understudied in 22q11.2DS. The current case-control study focuses on the role of resilience and quality of life (QoL) in young adults with 22q11.2DS and behavioural problems, in comparison with persons with an intellectual disability (ID) without a known genetic disorder. Self-report (and caregiver report) standardized questionnaires were used. Predictive general linear models were constructed to compare the resilience and quality of life across both groups (22q11.2DS vs ID-group) and to analyse the association between personal characteristics in both groups. Young adults with a 22q11.2DS show less resilience compared with both the general population norms and young adults with ID. Only a subscale of resilience (Acceptance of self and life) contributes to the reported level of QoL. Reported health problems are not related to resilience, but have an important effect on QoL. Our results suggest different factors are underlying resilience and the relation with QoL in 22q11.2DS and ID in general. These factors deserve more research and are important to take into account in clinical practice.

The Effect of Electroconvulsive Therapy on Positive Affect and Hedonism in Patients With Depression: A Prospective Study.

OBJECTIVES: The outcome of antidepressant treatments is generally assessed with standardized symptom scales such as the Quick Inventory of Depressive Symptomatology-Clinician Rating (QIDS-C). These scales, however, might not reflect patients' expectations for treatment, including a recovery of positive affect (PA) and hedonism. The Leuven Affect and Pleasure Scale (LAPS) was developed to better reflect patients' expectations for treatment. We used the LAPS to investigate changes in PA and hedonism alongside depressive symptoms during electroconvulsive therapy (ECT) and over 12 weeks after treatment. METHODS: Fifty-three patients with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, depressive episode, referred for ECT, were included in this prospective study. The LAPS and QIDS-C were administered before and 1 and 12 weeks after the ECT course. LAPS normative levels were obtained in 149 healthy controls. RESULTS: Pearson correlations revealed only moderate overlap of the QIDS-C with PA and hedonism. Piecewise linear mixed models indicated significant improvements in depressive symptoms (QIDS-C and LAPS negative affect), PA, and hedonism during ECT. In the 12 weeks after ECT treatment, negative affect and QIDS-C further improved, but PA and hedonism plateaued. Exploratory analyses indicated that only fully remitted patients (QIDS-C) attained normative levels on PA and hedonism at 12 weeks after ECT. CONCLUSIONS: Standardized symptom scales (QIDS-C) may incompletely reflect clinical change in ECT treatment for depression. Although ECT improved depressive symptoms, PA, and hedonism in patients with depression, only fully remitted patients attained normative levels of PA and hedonism, due to plateaus in improvement. These plateaus were not observed for depressive symptoms, which further improved after ECT discontinuation.

Transient Cognitive Impairment and White Matter Hyperintensities in Severely Depressed Older Patients Treated With Electroconvulsive Therapy.

BACKGROUND: Although electroconvulsive therapy (ECT) is a safe and effective treatment for patients with severe late life depression (LLD), transient cognitive impairment can be a reason to discontinue the treatment. The aim of the current study was to evaluate the association between structural brain characteristics and general cognitive function during and after ECT. METHODS: A total of 80 patients with LLD from the prospective naturalistic follow-up Mood Disorders in Elderly treated with Electroconvulsive Therapy study were examined. Magnetic resonance imaging scans were acquired before ECT. Overall brain morphology (white and grey matter) was evaluated using visual rating scales. Cognitive functioning before, during, and after ECT was measured using the Mini Mental State Examination (MMSE). A linear mixed-model analysis was performed to analyze the association between structural brain alterations and cognitive functioning over time. RESULTS: Patients with moderate to severe white matter hyperintensities (WMH) showed significantly lower MMSE scores than patients without severe WMH (F(1,75.54) = 5.42, p = 0.02) before, during, and post-ECT, however their trajectory of cognitive functioning was similar as no time × WMH interaction effect was observed (F(4,65.85) = 1.9, p = 0.25). Transient cognitive impairment was not associated with medial temporal or global cortical atrophy (MTA, GCA). CONCLUSION: All patients showed a significant drop in cognitive functioning during ECT, which however recovered above baseline levels post-ECT and remained stable until at least 6 months post-ECT, independently of severity of WMH, GCA, or MTA. Therefore, clinicians should not be reluctant to start or continue ECT in patients with severe structural brain alterations.

Does lithium prevent relapse following successful electroconvulsive therapy for major depression? A systematic review and meta-analysis.

OBJECTIVE: The risk of relapse following successful antidepressant treatment, including electroconvulsive therapy (ECT), is substantial. Lithium has been suggested to effectively prevent relapse, yet data remain limited and inconclusive. We performed a systematic review and meta-analysis to examine the efficacy of continuation treatment with lithium in preventing relapse following a successful acute course of ECT in patients with major depression, in comparison to continuation treatment without lithium. We also assessed the role of several study characteristics, possibly impacting the treatment effect. METHODS: A systematic literature search, using the PubMed, Embase, Web of Science, and Cochrane Library databases (up to June 2020), was conducted for prospective and retrospective studies, including patients with unipolar or bipolar depression, that assessed the efficacy of lithium for post-ECT depressive relapse prevention. RESULTS: Of 2556 records screened, 14 articles reporting on 9748 participants who received continuation treatment either with (N = 1571) or without lithium (N = 8177) were included in the meta-analysis. Patients receiving lithium were less likely to experience depressive relapse after a successful acute course of ECT, compared to patients receiving post-ECT prophylaxis without lithium (weighted odds ratio (OR) = 0.53, 95% confidence interval (CI) = 0.34, 0.82), with a number needed to treat (NNT) of 7 (95% CI = 4, 21). We found some limited evidence that older patients may benefit more from continuation treatment with lithium, compared to younger patients. Using the GRADE criteria, the quality of evidence for our outcome measure (i.e., relapse rate) was rated as very low. CONCLUSION: Continuation treatment with lithium may have superior efficacy in reducing the risk of relapse after a successful acute ECT course for major depression, in comparison to continuation treatment without lithium. High-quality studies are needed to confirm this finding.

Neurocognitive functioning after electroconvulsive therapy in late-life depression: A 4-year prospective study.

OBJECTIVE: Despite the proven efficacy and safety of ECT, there is still concern about the possible cognitive side effects of ECT in older patients. In this study, we aimed to characterize the long-term cognitive effects of ECT in patients with late-life depression (LLD) from before the start until 4 years after the index ECT course. METHODS: Fourty one patients aged 55 years and older with a unipolar depression, referred for ECT, were included. The neuropsychological test battery was assessed prior to ECT, 6 months, 1 year, 2 years, 3 years, and 4 years after the last ECT session. RESULTS: We did not find any statistically significant cognitive changes from before the start to 4 years after ending the ECT course. Although we could not detect cognitive changes at group level, we found clinically important differences on an individual level. CONCLUSION: Cognitive performance in patients with LLD runs a stable course from before the start of ECT until 4 years after the index course. At an individual level, however, both cognitive decline and improvement can be witnessed. Older patients can tolerate ECT and most of them will not experience long-term cognitive side effects.

Relapse after abrupt discontinuation of maintenance electroconvulsive therapy during the COVID-19 pandemic.

OBJECTIVE: Maintenance electroconvulsive therapy (M-ECT) is considered an effective relapse prevention strategy in severe mood and psychotic disorders. How long M-ECT should be continued, and what the outcome is after its discontinuation has not been adequately studied. In our tertiary psychiatric hospital, M-ECT treatments were suspended at the start of the COVID-19 pandemic. We aimed to determine the 6-month relapse rate and time to relapse after abrupt discontinuation of M-ECT and to assess the impact of patient and treatment characteristics on the risk of relapse. METHODS: Eighty-one patients whose M-ECT was discontinued abruptly were followed up prospectively for 6 months, or until relapse (i.e., hospital admission, restart of ECT, change of pharmacotherapy, or suicide (attempt)). We used multivariable Cox proportional hazards models to assess the impact of patient and treatment characteristics on the risk of relapse. RESULTS: Thirty-six patients (44.44%) relapsed within 6 months following abrupt discontinuation of M-ECT. A greater number of previous acute ECT courses, a diagnosis of psychotic disorder (compared with major depressive disorder or bipolar disorder), and a shorter interval between M-ECT treatments at the time of discontinuation were significantly associated with increased risk of relapse. CONCLUSION: Almost half of the patients relapsed, similar to the relapse rate after a successful acute course of ECT. Patients with a shorter interval between M-ECT treatments at the time of discontinuation seem to be at increased risk, as well as patients with a diagnosis of psychotic disorder, compared to patients with mood disorders.

The Leuven late life depression (L3D) study: PET-MRI biomarkers of pathological brain ageing in late-life depression: study protocol.

BACKGROUND: Major depressive disorders rank in the top ten causes of ill health in all but four countries worldwide and are the leading cause of years lived with disability in Europe (WHO). Recent research suggests that neurodegenerative pathology may contribute to the development of late-life depression (LLD) in a sub-group of patients and represent a target for prevention and early diagnosis. In parallel, electroconvulsive therapy (ECT), which is the most effective treatment for severe LLD, has been associated with significant brain structural changes. In both LLD and ECT hippocampal volume change plays a central role; however, the neurobiological mechanism underlying it and its relevance for clinical outcomes remain unresolved. METHODS: This is a monocentric, clinical cohort study with a cross-sectional arm evaluating PET-MR imaging and behavioural measures in 64 patients with LLD compared to 64 healthy controls, and a longitudinal arm evaluating the same imaging and behavioural measures after 10 ECT sessions in 20 patients receiving ECT as part of their normal clinical management. Triple tracer PET-MRI data will be used to measure: hippocampal volume (high resolution MRI), synaptic density using [11C]UCB-J, which targets the Synaptic Vesicle Glycoprotein 2A receptor, tau pathology using [18F]MK-6240, and cerebral amyloid using [18F]-Flutemetamol, which targets beta-amyloid neuritic plaques in the brain. Additional MRI measures and ultrasound will assess cerebral vascular structure and brain connectivity. Formal clinical and neuropsychological assessments will be conducted alongside experience sampling and physiological monitoring to assess mood, stress, cognition and psychomotor function. DISCUSSION: The main aim of the study is to identify the origin and consequences of hippocampal volume differences in LLD by investigating how biomarkers of pathological ageing contribute to medial temporal lobe pathology. Studying how synaptic density, tau, amyloid and vascular pathology relate to neuropsychological, psychomotor function, stress and ECT, will increase our pathophysiological understanding of the in vivo molecular, structural and functional alterations occurring in depression and what effect this has on clinical outcome. It may also lead to improvements in the differential diagnosis of depression and dementia yielding earlier, more optimal, cost-effective clinical management. Finally, it will improve our understanding of the neurobiological mechanism of ECT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03849417 , 21/2/2019.

Monitoring Electroconvulsive Therapy-Related Anxiety: The ECT-Related Anxiety Questionnaire.

OBJECTIVES: A reliable questionnaire designed to measure electroconvulsive therapy (ECT)-related anxiety is currently not available. We report the development and evaluation of the ECT-Related Anxiety Questionnaire (ERAQ), a questionnaire that measures anxiety with respect to ECT in clinical practice. METHODS: Patients 18 years or older who were about to start with or were having an ECT course were asked to complete a self-designed 17-item ECT-related anxiety questionnaire. We investigated the psychometric properties of the ERAQ through the use of an exploratory and confirmatory factor analysis and Item Response Theory analysis. RESULTS: One hundred eighty-three patients were included. From the exploratory factor analysis, we conclude that the scale is unidimensional. The confirmatory factor analysis model did not fit well to the data. The Item Response Theory analysis showed that the slope estimates ranged from 1.23 to 2.95 and that location parameters reflected a sizable underlying anxiety for ECT. CONCLUSIONS: The ERAQ is a questionnaire that assesses ECT-related anxiety. It offers a measure of global severity and differentiates between various topics of anxiety. The ERAQ thus informs the clinician about the specific aspects of an ECT course that could trigger a patient's anxiety and can guide clinicians in how to discuss ECT-related anxieties with patients.

MMSE Changes During and After ECT in Late-Life Depression: A Prospective Study.

OBJECTIVE: There is ongoing concern about the impact of electroconvulsive therapy (ECT) on cognition in patients with late-life depression (LLD), especially in patients for whom pretreatment Mini-Mental State Exam (MMSE) scores are low. Our aim was to examine the evolution of cognitive effects of ECT, using the MMSE in a large group of patients with LLD. METHODS: One hundred nine patients aged 55 years and older with unipolar depression, referred for ECT, were included in our study. The MMSE was assessed before, during, immediately after, and 6 months after ECT. RESULTS: MMSE scores improved significantly during the course of ECT and remained stable during the 6-month period after ending ECT for the total group. In the group of patients with a low MMSE score (<24) at baseline, the MMSE score improved significantly during ECT, whereas in the group of patients with a normal MMSE score (≥24) at baseline, the score did not change significantly during ECT. In both groups, MMSE scores still increased slightly after ECT was discontinued. CONCLUSION: ECT does not cause deleterious cognitive effects, as measured with the MMSE, during and for 6 months after the ECT course in patients with LLD. In the event of a baseline cognitive impairment, MMSE scores tend to improve significantly during and for 6 months after the ECT course. The presence of pretreatment cognitive impairment should not lead clinicians to withhold ECT in older patients with severe depression.

Lateralized Raise in Intraocular Pressure During Electroconvulsive Therapy: A Tonometry Pilot Study.

The aim of this study was to evaluate intraocular pressure (IOP) changes during and after electroconvulsive therapy. In 20 patients, IOP was measured using a handheld iCare tonometer before, during, and up to 15 minutes after the seizure. Electrode placement was either right unilateral (RUL) or bilateral (BL). Statistical analyses were done at baseline, during, and 15 minutes after the seizure. In the RUL group (n = 14), the IOP in the left eye increased from 14.8 mm Hg before the seizure to 27.8 mm Hg during the seizure ( P = 0.0001) and decreased to 14.0 mm Hg after the seizure ( P = 0.0002). The IOP in the right eye increased from 15.4 mm Hg before the seizure to 34.4 mm Hg during the seizure ( P = 0.0001) and decreased to 16.0 mm Hg after the seizure ( P = 0.0002). In the BL group (n = 6), the IOP in the left eye increased from 13.0 mm Hg before the seizure to 26.3 mm Hg during the seizure ( P = 0.1250) and decreased to 14.5 mm Hg after the seizure ( P = 0.250). In the right eye, the IOP increased from 13.3 mm Hg before the seizure to 28.4 mm Hg during the seizure ( P = 0.1250) and decreased to 13.7 mm Hg after the seizure ( P = 0.25). When the results were compared between the 2 electrode placements, the difference in IOP between the right and left eye was higher in the RUL group during (RUL 6.7 mm Hg vs BL 2.0 mm Hg, P = 0.0231) and after (RUL 2.1 mm Hg vs BL −0.8 mm Hg, P = 0.0492) the seizure. RUL stimulation with electroconvulsive therapy causes a rise in IOP that is partially lateralized, ipsilateral to the side of stimulation.