Jasmien Obbels

ECT: its brain enabling effects. A review of electroconvulsive therapy-induced structural brain plasticity

Background Since the past 2 decades, new evidence for brain plasticity has caused a shift in both preclinical and clinical ECT research from falsifying the “brain damage hypothesis” toward exploring ECT’s enabling brain (neuro)plasticity effects. Methods By reviewing the available animal and human literature, we examined the theory that seizure-induced structural changes are crucial for the therapeutic efficacy of ECT. Results Both animal and human studies suggest electroconvulsive stimulation/electroconvulsive therapy (ECT)-related neuroplasticity (neurogenesis, synaptogenesis, angiogenesis, or gliogenesis). Conclusion It remains unclear whether structural changes might explain the therapeutic efficacy and/or be related to the (transient) learning and memory impairment after ECT. Methods to assess in vivo brain plasticity of patients treated with ECT will be of particular importance for future longitudinal studies to give support to the currently available correlational data.

No Association of Lower Hippocampal Volume With Alzheimer’s Disease Pathology in Late-Life Depression

OBJECTIVE Hippocampal volume is commonly decreased in late-life depression. According to the depression-as-late-life-neuropsychiatric-disorder model, lower hippocampal volume in late-life depression is associated with neurodegenerative changes. The purpose of this prospective study was to examine whether lower hippocampal volume in late-life depression is associated with Alzheimers disease pathology. METHOD Of 108 subjects who participated, complete, good-quality data sets were available for 100: 48 currently depressed older adults and 52 age- and gender-matched healthy comparison subjects who underwent structural MRI, [18F]flutemetamol amyloid positron emission tomography imaging, apolipoprotein E genotyping, and neuropsychological assessment. Hippocampal volumes were defined manually and normalized for total intracranial volume. Amyloid binding was quantified using the standardized uptake value ratio in one cortical composite volume of interest. The authors investigated group differences in hippocampal volume (both including and excluding amyloid-positive participants), group differences in amyloid uptake and in the proportion of positive amyloid scans, and the association between hippocampal volume and cortical amyloid uptake. RESULTS A significant difference was observed in mean normalized total hippocampal volume between patients and comparison subjects, but there were no group differences in cortical amyloid uptake or proportion of amyloid-positive subjects. The difference in hippocampal volume remained significant after the amyloid-positive subjects were excluded. There was no association between hippocampal volume and amyloid uptake in either patients or comparison subjects. CONCLUSIONS Lower hippocampal volume was not related to amyloid pathology in this sample of patients with late-life depression. These data counter the common belief that changes in hippocampal volume in late-life depression are due to prodromal Alzheimers disease.

Early- and Late-Onset Depression in Late Life: A Prospective Study on Clinical and Structural Brain Characteristics and Response to Electroconvulsive Therapy

OBJECTIVE The clinical profile of late-life depression (LLD) is frequently associated with cognitive impairment, aging-related brain changes, and somatic comorbidity. This two-site naturalistic longitudinal study aimed to explore differences in clinical and brain characteristics and response to electroconvulsive therapy (ECT) in early- (EOD) versus late-onset (LOD) late-life depression (respectively onset <55 and ≥55 years). METHODS Between January 2011 and December 2013, 110 patients aged 55 years and older with ECT-treated unipolar depression were included in The Mood Disorders in Elderly treated with ECT study. Clinical profile and somatic health were assessed. Magnetic resonance imaging (MRI) scans were performed before the first ECT and visually rated. RESULTS Response rate was 78.2% and similar between the two sites but significantly higher in LOD compared with EOD (86.9 versus 67.3%). Clinical, somatic, and brain characteristics were not different between EOD and LOD. Response to ECT was associated with late age at onset and presence of psychotic symptoms and not with structural MRI characteristics. In EOD only, the odds for a higher response were associated with a shorter index episode. CONCLUSION The clinical profile, somatic comorbidities, and brain characteristics in LLD were similar in EOD and LOD. Nevertheless, patients with LOD showed a superior response to ECT compared with patients with EOD. Our results indicate that ECT is very effective in LLD, even in vascular burdened patients.

ECT-Related Anxiety A Systematic Review

Background A significant proportion of electroconvulsive therapy (ECT)–treated patients experience anxiety anticipating the treatment, often to such an extent that they refuse or discontinue a much-needed treatment. Despite its great impact on treatment adherence, anxiety in patients receiving ECT is underexposed in the scientific literature. Objectives We aimed to review the prevalence and specific subjects of ECT-related anxiety and therapeutic interventions to reduce it. Methods We performed a computerized search (EMBASE, MEDLINE, and PsycINFO) for articles meeting the following inclusion criteria: (1) qualitative (interview) studies, quantitative (questionnaire) studies, or experimental (interventional) studies that (2) report on anxiety that is related to a planned, ongoing, or past ECT treatment. Results Of 1160 search results, 31 articles were included. Electroconvulsive therapy–related anxiety is estimated to be present in 14% to 75% of patients and is most often linked to worries about memory impairment or brain damage. Only a few interventions (chlorpromazine, meprobamate, propofol, a talking-through technique, an information leaflet, and animal-assisted therapy) have been proposed to reduce patients’ ECT-related anxiety. Conclusions Electroconvulsive therapy–related anxiety is a highly prevalent phenomenon, and the literature provides little guidance for its clinical management. Most studies are of a low methodological quality and suffer from significant limitations, thereby hampering generalized conclusions. Given the clinical importance of ECT-related anxiety, further study on its nature and evolution through the course of treatment and on anxiety-reducing interventions is warranted.

Long-term neurocognitive functioning after electroconvulsive therapy in patients with late-life depression

There is ongoing concern about the possible negative impact of ECT on neurocognitive functioning in older patients. In this study, we aimed to characterize the long‐term cognitive effects of ECT in patients with late‐life depression, using an extensive neuropsychological battery.

The Clinical Practice of Assessing Cognitive Function in Adults Receiving Electroconvulsive Therapy: Whom Are We Missing?

Background Cognition can be affected by electroconvulsive therapy (ECT). Good clinical practice includes neuropsychological assessment, although this is seldom a part of routine clinical practice. It looks like a substantial part of patients fail to complete cognitive assessments. This constitutes a problem in the generalizability of published clinical research on cognitive side effects. Most studies of ECT-related cognitive adverse effects do not discuss this important issue of so-called cognitive test nonparticipants. Recent findings suggest that cognitive test nonparticipants are more severely ill, and probably more vulnerable to cognitive side effects. Objectives To examine the feasibility of a neuropsychological test battery in daily clinical practice, in an adult population referred for ECT. Methods We reviewed the clinical records of 84 patients referred for ECT. Demographic and clinical characteristics of those patients who were able to complete our routine cognitive testing at baseline are compared with those who could not complete the assessment. Results From 84 ECT patients, 60 (71%) completed a pre-ECT cognitive assessment, whereas 24 (29%) did not. Patients with a unipolar depression, with psychotic symptoms, who started their treatment with a bitemporal electrode placement were more likely to be test noncompleters than test completers. Conclusions Patients with a unipolar depression, with psychotic features, who are treated with a bitemporal electrode placement, have a higher likelihood of not completing a pre-ECT cognitive assessment. These patients probably represent a subgroup more vulnerable to cognitive side effects.

How Do Age-related White Matter Changes Such as MRI Hyperintensities and Amyloid Deposition Relate to ECT Outcome in Late Life Depression?

The treatment of late-life depression (LLD) using electroconvulsive therapy (ECT) in the elderly is complicated by the presence of age-related brain structural changes that may affect the underlying biophysical mechanisms of the treatment. For example, previous research has shown that the presence of medial temporal lobe atrophy (MTA) and white matter hyperintensities (WMH) on MRI is associated with poor ECT response and increased transient cognitive impairment following ECT. Recent advances in neuroimaging methods allow more precise quantification of regional brain volumes, white matter (WM) micro- and macrostructure and WM lesion load, as well as in vivo detection of Alzheimer’s disease pathology using amyloid PET imaging. Such measurements may have predictive potential for stratifying patients with respect to the efficacy of ECT and its potential cognitive side effects. In this presentation we review strategies for investigating WM changes associated with ECT in the elderly, and present findings from our longitudinal, multimodal, neuroimaging research employing quantitative structural MRI morphometry and 18F-Flutemetamol PET (an amyloid imaging technique), to investigate how quantitative measurements of WM lesion volume, WM macrostructure, hippocampal volume and amyloid deposition relate to clinical assessments of ECT response in a large cohort of treatment resistant LLD patients.