Filip Bouckaert

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.

Speed of remission in elderly patients with depression: electroconvulsive therapy v. medication

BACKGROUND Severe depression can be a life-threatening disorder, especially in elderly patients. A fast-acting treatment is crucial for this group. Electroconvulsive therapy (ECT) may work faster than medication. AIMS To compare the speed of remission using ECT v. medication in elderly in-patients. METHOD The speed of remission in in-patients with a DSM-IV diagnosis of major depression (baseline MADRS score ≥20) was compared between 47 participants (mean age 74.0 years, s.d. = 7.4) from an ECT randomised controlled trial (RCT) and 81 participants (mean age 72.2 years, s.d. = 7.6) from a medication RCT (nortriptyline v. venlafaxine). RESULTS Mean time to remission was 3.1 weeks (s.d. = 1.1) for the ECT group and 4.0 weeks (s.d. = 1.0) for the medication group; the adjusted hazard ratio for remission within 5 weeks (ECT v. medication) was 3.4 (95% CI 1.9-6.2). CONCLUSIONS Considering the substantially higher speed of remission, ECT deserves a more prominent position in the treatment of elderly patients with severe depression.

Efficacy and Cognitive Side Effects After Brief Pulse and Ultrabrief Pulse Right Unilateral Electroconvulsive Therapy for Major Depression: A Randomized, Double-Blind, Controlled Study

OBJECTIVE To compare the efficacy and cognitive side effects of high-dose unilateral brief pulse electroconvulsive therapy (ECT) with those of high-dose unilateral ultrabrief pulse ECT in the treatment of major depression. METHOD From April 2007 until March 2011, we conducted a prospective, double-blind, randomized multicenter trial in 3 tertiary psychiatric hospitals. All patients with a depressive disorder according to DSM-IV criteria were eligible. Depression severity was assessed with the Montgomery-Asberg Depression Rating Scale; primary efficacy outcomes were response, defined as a score decrease ≥ 60% from baseline, and remission, defined as a score < 10 at 2 consecutive weekly assessments. Total scores on the Autobiographical Memory Interview and Amsterdam Media Questionnaire were the primary outcome measures for retrograde amnesia. Other cognitive domains included category fluency (semantic memory) and letter fluency (lexical memory). Patients received twice-weekly unilateral brief pulse (1.0 millisecond) or ultrabrief pulse (0.3-0.4 millisecond) ECT 8 times seizure threshold until remission, for a maximum of 6 weeks. RESULTS Of the 116 patients, 75% (n = 87) completed the study. Among completers, 68.4% (26/58) of those in the brief pulse group achieved remission versus 49.0% (24/49) of those in the ultrabrief pulse group (P = .019), and the brief pulse group needed fewer treatment sessions to achieve remission: mean (SD) of 7.1 (2.6) versus 9.2 (2.3) sessions (P = .008). No significant group differences were found in the evaluation of the cognitive assessments. CONCLUSIONS The efficacy and speed of remission seen with high-dose brief pulse right unilateral ECT twice weekly were superior to those seen with high-dose ultrabrief pulse right unilateral ECT, with equal cognitive side effects as defined by retrograde amnesia, semantic memory, and lexical memory. TRIAL REGISTRATION Netherlands National Trial Register number: NTR1304.

Personality disorders in older adults: emerging research issues.

Empirical research focusing on personality disorders (PDs) among older adults is mainly limited to studies on psychometric properties of age-specific personality tests, the age neutrality of specific items/scales, and validation of personality inventories for older adults. We identified only two treatment studies—one on dialectical behavior therapy and one on schema therapy—both with promising results among older patients despite small and heterogeneous populations. More rigorous studies incorporating age-specific adaptations are needed. Furthermore, in contrast to increasing numbers of psychometric studies, the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 pays little attention to the characteristics of older adults with PDs. Moreover, the constructs “personality change due to another medical condition” and “late-onset personality disorder” warrant further research among older adults. These needs will become even more pressing given the aging society worldwide.

Dual task performance of working memory and postural control in major depressive disorder

OBJECTIVE Previous studies with patients diagnosed with Major Depressive Disorder (MDD) revealed deficits in working memory and executive functions. In the present study we investigated whether patients with MDD have the ability to allocate cognitive resources in dual task performance of a highly challenging cognitive task (working memory) and a task that is seemingly automatic in nature (postural control). METHOD Fifteen young (18-35 years old) patients with MDD and 24 healthy age-matched controls performed a working memory task and two postural control tasks (standing on a stable or on a moving platform) both separately (single task) and concurrently (dual task). RESULTS Postural stability under single task conditions was similar in the two groups, and in line with earlier studies, MDD patients recalled fewer working memory items than controls. To equate working memory challenges for patients and controls, task difficulty (number of items presented) in dual task was individually adjusted such that accuracy of working memory performance was similar for the two groups under single task conditions. Patients showed greater postural instability in dual task performance on the stable platform, and more importantly when posture task difficulty increased (moving platform) they showed deficits in both working memory accuracy and postural stability compared with healthy controls. CONCLUSIONS We interpret our results as evidence for executive control deficits in MDD patients that affect their task coordination. In multitasking, these deficits affect not only cognitive but also sensorimotor task performance.

Psychomotor Retardation in Elderly Untreated Depressed Patients

Background: Psychomotor retardation (PR) is one of the core features in depression according to DSM V (1), but also aging in itself causes cognitive and psychomotor slowing. This is the first study investigating PR in relation to cognitive functioning and to the concomitant effect of depression and aging in a geriatric population ruling out contending effects of psychotropic medication. Methods: A group of 28 non-demented depressed elderly is compared to a matched control group of 20 healthy elderly. All participants underwent a test battery containing clinical depression measures, cognitive measures of processing speed, executive function and memory, clinical ratings of PR, and objective computerized fine motor skill-tests. Statistical analysis consisted of a General Linear Method multivariate analysis of variance to compare the clinical, cognitive, and psychomotor outcomes of the two groups. Results: Patients performed worse on all clinical, cognitive, and PR measures. Both groups showed an effect of cognitive load on fine motor function but the influence was significantly larger for patients than for healthy elderly except for the initiation time. Limitations: Due to the restrictive inclusion criteria, only a relatively limited sample size could be obtained. Conclusion: With a medication free sample, an additive effect of depression and aging on cognition and PR in geriatric patients was found. As this effect was independent of demand of effort (by varying the cognitive load), it was apparently not a motivational slowing effect of depression.

Relationship Between Hippocampal Volume, Serum BDNF, and Depression Severity Following Electroconvulsive Therapy in Late-Life Depression

Recent structural imaging studies have described hippocampal volume changes following electroconvulsive therapy (ECT). It has been proposed that serum brain-derived neurotrophic factor (sBDNF)-mediated neuroplasticity contributes critically to brain changes following antidepressant treatment. To date no studies have investigated the relationship between changes in hippocampal volume, mood, and sBDNF following ECT. Here, we combine these measurements in a longitudinal study of severe late-life unipolar depression (LLD). We treated 88 elderly patients with severe LLD twice weekly until remission (Montgomery–Åsberg Depression Rating Scale (MADRS) <10). sBDNF and MADRS were obtained before ECT (T0), after the sixth ECT (T1), 1 week after the last ECT (T2), 4 weeks after the last ECT (T3), and 6 months after the last ECT (T4). Hippocampal volumes were quantified by manual segmentation of 3T structural magnetic resonance images in 66 patients at T0 and T2 and in 23 patients at T0, T2, and T4. Linear mixed models (LMM) were used to examine the evolution of MADRS, sBDNF, and hippocampal volume over time. Following ECT, there was a significant decrease in MADRS scores and a significant increase in hippocampal volume. Hippocampal volume decreased back to baseline values at T4. Compared with T0, sBDNF levels remained unchanged at T1, T2, and T3. There was no coevolution between changes in MADRS scores, hippocampal volume, and sBDNF. Hippocampal volume increase following ECT is an independent neurobiological effect unrelated to sBDNF and depressive symptomatology, suggesting a complex mechanism of action of ECT in LLD.

Short seizures in continuation electroconvulsive therapy: an indication for remifentanil anesthesia?

To the Editor: During electroconvulsive therapy (ECT), the clinician is occasionally faced with the problem of shortened seizures or the inability to elicit seizures, even at maximum device capacity. Because seizure duration and seizure quality may diminish as the course of ECT progresses, this problem is encountered more frequently in continuation and maintenance ECT. Although there have been some reports on an inverse relation between stimulus dose and seizure duration, increasing the stimulus dose is the preferred method to ensure seizures of adequate duration. When patients fail to seize at maximum electrical dosage, there are only few strategies to follow. Several authors have recommended the use of caffeine or theophylline to lengthen seizures, but the use of these agents has been discarded. Changing methohexital to etomidate, which is said to have neutral or slightly proconvulsive effects, may also be a reasonable choice, although in some studies a comparison of methohexital and etomidate revealed no significant difference in seizure duration. There are some preliminary reports on the use of remifentanil in combination with methohexital to increase the duration of seizure activity in patients undergoing ECT. Remifentanil is a potent short-acting opioid analgesic. It has no proor anticonvulsant effect on the duration of motor or EEG seizure activity. The addition of remifentanil to the anesthetic regimen, however, can make it possible to reduce the dosage of methohexital by 30–40% and can produce a 40% increase in the duration of ECTinduced seizure activity. Remifentanil anesthesia also decreases the electrical requirement for induction of seizures compared with methohexital while providing an enhanced motor and EEG seizure in patients refractory to ECT induction using standard methohexital anesthesia. Moreover, remifentanil has been found to reduce blood pressure and heart rate when administered as an adjuvant during general anesthesia and attenuates the acute hemodynamic response to ECT under methohexital anesthesia. In a recent study, however, peak heart rate after ECT was significantly higher when remifentanil (1 μg/kg IV) was coadministered.

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.