RESUMO
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.
RESUMO
BACKGROUND: Increased gray matter volume (GMV) following electroconvulsive therapy (ECT) has been well-documented, with limited studies reporting a subsequent decrease in GMV afterwards. OBJECTIVE: This study characterized the reversion pattern of GMV after ECT and its association with clinical depression outcome, using multi-site triple time-point data from the Global ECT-MRI Research Collaboration (GEMRIC). METHODS: 86 subjects from the GEMRIC database were included, and GMV in 84 regions-of-interest (ROI) was obtained from automatic segmentation of T1 MRI images at three timepoints: pre-ECT (T0), within one-week post-ECT (T1), and one to six months post-ECT (T2). RM-ANOVAs were used to assess longitudinal changes and LMM analyses explored associations between GMV changes and demographical and clinical characteristics. RESULTS: 63 of the 84 ROIs showed a significant increase-and-decrease pattern (RM-ANOVA, Bonferroni corrected p < 0.00059). Post hoc tests indicated a consistent pattern in each of these 63 ROIs: significant increase from T0 to T1inGMV, followed by significant decrease from T1 to T2 and no difference between T0 and T2, except for both amygdalae, right hippocampus and pars triangularis, which showed the same increase and decrease but GMV at T2 remained higher compared to T0. No consistent relationship was found between GMV change pattern and clinical status. CONCLUSION: The GEMRIC cohort confirmed a rapid increase of GMV after ECT followed by reversion of GMV one to six months thereafter. The lack of association between the GMV change pattern and depression outcome scores implies a transient neurobiological effect of ECT unrelated to clinical improvement.
RESUMO
The Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT) is a rare but concerning neurological complication resulting from lithium intoxication. Despite being reported since the 1960s, SILENT remains poorly understood and previous reviews on this topic commonly have been narrative. We therefore conducted a scoping review to assess the nature and scope of the research literature on the long-term neurological sequelae of lithium toxicity and determine the current knowledge of SILENT. A comprehensive and systematic literature search, using the MEDLINE, Embase, and Web of Science databases (from inception to July 2023), was conducted for English and Dutch articles, assessing the long-term neurological sequelae of lithium intoxication. Key information concerning clinical manifestations, risk factors, therapeutic approaches, or preventive measurements was extracted. We reviewed 91 articles, extracting information from 117 cases of SILENT. The prevailing outcome observed was persistent cerebellar dysfunction (77% of cases), often in combination with other sequelae. Other common sequelae included cognitive problems, parkinsonism, choreoathetosis, tardive dyskinesia, and peripheral neuropathy. The most common (61.4%) acute neurological symptom in the development of SILENT is an altered level of consciousness ranging from confusion to comatose states. Cerebellar sequelae were mentioned in 77% of cases as most common persistent sequelae. Antipsychotic use was mentioned in 59% of cases and fever was reported in 37.6% of cases. Scientific knowledge about this phenomenon has not advanced much since its initial reports in the 1960s and 1970s. While the use of lithium has become much more stringent than it had been in years past, and the occurrence of SILENT is rather exceptional, raising awareness about SILENT nevertheless remains crucial to avoid deleterious neurological consequences. Comprehensive, high-quality research in a systematic and standardized manner is therefore urgently needed to better understand this phenomenon.
Assuntos
Eletroconvulsoterapia , Tomografia por Emissão de Pósitrons , Humanos , Projetos Piloto , Idoso , Estudos Longitudinais , Feminino , Masculino , Imageamento por Ressonância Magnética , Sinapses/fisiologia , Pessoa de Meia-Idade , Encéfalo/diagnóstico por imagem , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Maior/diagnóstico por imagemRESUMO
Late-life depression has been consistently associated with lower gray matter volume, the origin of which remains largely unexplained. Recent in-vivo PET findings in early-onset depression and Alzheimer's Disease suggest that synaptic deficits contribute to the pathophysiology of these disorders and may therefore contribute to lower gray matter volume in late-life depression. Here, we investigate synaptic density in vivo for the first time in late-life depression using the synaptic vesicle glycoprotein 2A receptor radioligand 11C-UCB-J. We included 24 currently depressed adults with late-life depression (73.0 ± 6.2 years, 16 female, geriatric depression scale = 19.5 ± 6.8) and 36 age- and gender-matched healthy controls (70.4 ± 6.2 years, 21 female, geriatric depression scale = 2.7 ± 2.9) that underwent simultaneous 11C-UCB-J positron emission tomography (PET) and 3D T1- and T2-FLAIR weighted magnetic resonance (MR) imaging on a 3-tesla PET-MR scanner. We used analyses of variance to test for 11C-UCB-J binding and gray matter volumes differences in regions implicated in depression. The late-life depression group showed a trend in lower gray matter volumes in the hippocampus (p = 0.04), mesial temporal (p = 0.02) and prefrontal cortex (p = 0.02) compared to healthy control group without surviving correction for multiple comparison. However, no group differences in 11C-UCB-J binding were found in these regions nor were any associations between 11C-UCB-J and depressive symptoms. Our data suggests that, in contrast to Alzheimer's Disease, lower gray matter volume in late-life depression is not associated with synaptic density changes. From a therapeutic standpoint, preserved synaptic density in late-life depression may be an encouraging finding.
Assuntos
Doença de Alzheimer , Depressão , Humanos , Feminino , Idoso , Depressão/diagnóstico por imagem , Doença de Alzheimer/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Hipocampo/diagnóstico por imagem , Córtex Pré-FrontalRESUMO
Neurostimulation is a mainstream treatment option for major depression. Neuromodulation techniques apply repetitive magnetic or electrical stimulation to some neural target but significantly differ in their invasiveness, spatial selectivity, mechanism of action, and efficacy. Despite these differences, recent analyses of transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS)-treated individuals converged on a common neural network that might have a causal role in treatment response. We set out to investigate if the neuronal underpinnings of electroconvulsive therapy (ECT) are similarly associated with this causal depression network (CDN). Our aim here is to provide a comprehensive analysis in three cohorts of patients segregated by electrode placement (N = 246 with right unilateral, 79 with bitemporal, and 61 with mixed) who underwent ECT. We conducted a data-driven, unsupervised multivariate neuroimaging analysis Principal Component Analysis (PCA) of the cortical and subcortical volume changes and electric field (EF) distribution to explore changes within the CDN associated with antidepressant outcomes. Despite the different treatment modalities (ECT vs TMS and DBS) and methodological approaches (structural vs functional networks), we found a highly similar pattern of change within the CDN in the three cohorts of patients (spatial similarity across 85 regions: r = 0.65, 0.58, 0.40, df = 83). Most importantly, the expression of this pattern correlated with clinical outcomes (t = -2.35, p = 0.019). This evidence further supports that treatment interventions converge on a CDN in depression. Optimizing modulation of this network could serve to improve the outcome of neurostimulation in depression.
RESUMO
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.
Assuntos
Envelhecimento Saudável , Transtornos dos Movimentos , Humanos , Feminino , Idoso , Masculino , Encéfalo/patologia , Substância Cinzenta/diagnóstico por imagem , Envelhecimento/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Transtornos dos Movimentos/patologiaRESUMO
Neurostimulation is a mainstream treatment option for major depression. Neuromodulation techniques apply repetitive magnetic or electrical stimulation to some neural target but significantly differ in their invasiveness, spatial selectivity, mechanism of action, and efficacy. Despite these differences, recent analyses of transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS)-treated individuals converged on a common neural network that might have a causal role in treatment response. We set out to investigate if the neuronal underpinnings of electroconvulsive therapy (ECT) are similarly associated with this common causal network (CCN). Our aim here is to provide a comprehensive analysis in three cohorts of patients segregated by electrode placement (N = 246 with right unilateral, 79 with bitemporal, and 61 with mixed) who underwent ECT. We conducted a data-driven, unsupervised multivariate neuroimaging analysis (Principal Component Analysis, PCA) of the cortical and subcortical volume changes and electric field (EF) distribution to explore changes within the CCN associated with antidepressant outcomes. Despite the different treatment modalities (ECT vs TMS and DBS) and methodological approaches (structural vs functional networks), we found a highly similar pattern of change within the CCN in the three cohorts of patients (spatial similarity across 85 regions: r = 0.65, 0.58, 0.40, df = 83). Most importantly, the expression of this pattern correlated with clinical outcomes. This evidence further supports that treatment interventions converge on a CCN in depression. Optimizing modulation of this network could serve to improve the outcome of neurostimulation in depression.
RESUMO
OBJECTIVE: To test whether the cortisol awakening response (CAR) could be a biomarker for cognitive decline during electroconvulsive therapy (ECT). METHODS: We studied 50 older patients with depression who were treated with ECT from the MODECT cohort. We used linear regression analyses to examine the association between CAR and cognitive change, assessed by the change in Mini Mental State Examination scores between baseline and 1 week after ECT course. CAR was assessed by the area under the curve of cortisol levels, according to Pruessner's-formula. Associations were adjusted for putative confounders, based on previous literature and availability. RESULTS: We found no significant associations between the CAR and cognitive change during the ECT course in (un)adjusted models. CONCLUSION: Our results indicate that the CAR is not usable as a biomarker for ECT-induced cognitive decline during ECT course. Further research in cohorts with larger samples is needed.
RESUMO
The risk of relapse following successful acute-phase treatment of late-life depression (LLD), including electroconvulsive therapy (ECT), is substantial. In order to improve reliable prediction of individuals' risk of relapse, we assessed the association between individual residual symptoms following a successful acute course of ECT for LLD and relapse at six-month follow-up. This prospective cohort study was part of the MODECT study, which included 110 patients aged 55 years and older with major depressive disorder. Participants who showed response to the index ECT course were monitored for relapse for six months. We used multivariable stepwise logistic regression models to assess the association between the scores on the 10 individual Montgomery-Åsberg Depression Rating Scale (MADRS) items at the end of the acute ECT course and relapse at six-month follow-up. Of the 80 responders with available six-month follow-up data (58.75% of which had psychotic features at baseline), 36.25% had relapsed. Higher scores on the MADRS items 'reduced sleep' (odds ratio (OR) = 2.03, 95% confidence interval (CI) = 1.11-3.69, p = 0.0214) and 'lassitude' (OR = 1.62, 95% CI = 1.00-2.62, p = 0.0497) at the end of the acute ECT course were significantly associated with increased risk of relapse at six-month follow-up. In conclusion, some residual depressive symptoms, including sleep disturbance and lassitude, may help better identify patients vulnerable to relapse following a successful acute course of ECT for LLD. If these findings can be replicated, studies assessing interventions that target specific residual symptoms may further reduce post-ECT depressive relapse rates.
Assuntos
Transtorno Depressivo Maior , Eletroconvulsoterapia , Depressão/terapia , Transtorno Depressivo Maior/terapia , Progressão da Doença , Humanos , Estudos Prospectivos , Recidiva , Resultado do TratamentoRESUMO
Objective: Electroconvulsive therapy (ECT) is a safe and effective treatment, especially in psychotic late-life depression (LLD). However, it is not yet clear whether the greater efficacy seen in psychotic LLD is because of a shorter index episode duration. The first aim of this study was to substantiate the superior ECT remission rates in patients with psychotic LLD, as compared to patients with nonpsychotic LLD, and a second aim was to investigate whether this association is independent of the index duration.Methods: 186 patients with LLD treated with ECT were included in the study: 76 from the Valerius cohort (data collection from 2001 to 2006) and 110 from the Mood Disorders Treated with Electroconvulsive Therapy (MODECT) cohort (data collection from 2011 to 2013). The Montgomery-Asberg Depression Rating Scale (MADRS) was used to evaluate depression severity, with remission defined as 2 consecutive MADRS scores < 10. Diagnosis of depression was based on DSM-IV (Valerius) and DSM-IV-TR (MODECT) criteria. A stepwise logistic regression model was built to assess the association between psychotic symptoms, index duration, and remission.Results: Patients with psychotic LLD showed significantly higher remission rates compared to patients with nonpsychotic LLD (68.9% vs 51.0%), independent of index duration, additionally corrected for age, sex, and baseline depression severity (OR = 2.10 [95% CI, 1.07-4.10], P = .03).Conclusions: Patients with psychotic LLD treated with ECT show higher remission rates compared to patients with nonpsychotic LLD. The high remission rates in patients with psychotic LLD are not explained by a shorter index duration. Future studies focusing on neurobiological differences in psychotic versus nonpsychotic depression may indicate why this subtype of depression is very responsive to ECT.Trial Registration: ClinicalTrials.gov identifier: NCT02667353.
Assuntos
Transtorno Depressivo Maior , Eletroconvulsoterapia , Transtornos Psicóticos , Depressão , Transtorno Depressivo Maior/terapia , Eletroconvulsoterapia/efeitos adversos , Humanos , Transtornos Psicóticos/terapia , Resultado do TratamentoRESUMO
Background: Cognitive side-effects are an important reason for the limited use of electroconvulsive therapy (ECT). Cognitive side-effects are heterogeneous and occur frequently in older persons. To date, insight into these side-effects is hampered due to inconsistencies in study designs and small sample sizes. Among all cognitive side-effects, confusion and delirious states are especially troublesome for patients, relatives and clinicians. In particular inter-ictal delirium-like states are worrisome, since they may lead to premature treatment discontinuation. Besides a need for further insight into determinants of cognitive side-effects of ECT, there is a great need for treatment options. Methods and design: The Rivastigmine for ECT-induced Cognitive Adverse effects in Late Life depression (RECALL) study combines a multicenter, prospective cohort study on older patients with depression, treated with ECT, with an embedded randomized, placebo-controlled cross-over trial to examine the effect of rivastigmine on inter-ictal delirium. Patients are recruited in four centers across the Netherlands and Belgium. We aim to include 150 patients into the cohort study, in order to be able to subsequently include 30 patients into the trial. Patients are included in the trial when inter-ictal delirium, assessed by the Confusion Assessment method (CAM), or a drop in Mini Mental State Examination (MMSE) score of ≥4 during ECT, develops. In the cohort study, comprehensive measurements of ECT-related cognitive side-effects-and their putative determinants-are done at baseline and during the ECT-course. The primary outcome of the clinical trial is the effectiveness of rivastigmine on inter-ictal delirium-severity, assessed with a change in the Delirium Rating Scale-Revised-98. Secondary outcomes of the clinical trial are several ECT-characteristics and side-effects of rivastigmine. Discussion: This study is the first clinical trial with a focus on ECT-induced, inter-ictal delirium. The cohort provides the basis for recruitment of patients for the cross-over trial and additionally provides an excellent opportunity to unravel cognitive side-effects of ECT and identify putative determinants. This paper describes the rationale and study protocol. Clinical trial registration: EudraCT 2014-003385-24.
RESUMO
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.
Assuntos
Transtorno Depressivo Maior , Eletroconvulsoterapia , Idoso , Humanos , Eletroconvulsoterapia/efeitos adversos , Transtorno Depressivo Maior/terapia , Estudos de Coortes , Depressão/terapia , Seguimentos , Resultado do Tratamento , RecidivaRESUMO
Amyloid positron emission tomography (PET) and hippocampal volume derived from magnetic resonance imaging may be useful clinical biomarkers for differentiating between geriatric depression and Alzheimer's disease (AD). Here we investigated the incremental value of using hippocampal volume and 18F-flutemetmol amyloid PET measures in tandem and sequentially to improve discrimination in unclassified participants. Two approaches were compared in 41 participants with geriatric depression and 27 participants with probable AD: (1) amyloid and hippocampal volume combined in one model and (2) classification based on hippocampal volume first and then subsequent stratification using standardized uptake value ratio (SUVR)-determined amyloid positivity. Hippocampal volume and amyloid SUVR were significant diagnostic predictors of depression (sensitivity: 95%, specificity: 89%). 51% of participants were correctly classified according to clinical diagnosis based on hippocampal volume alone, increasing to 87% when adding amyloid data (sensitivity: 94%, specificity: 78%). Our results suggest that hippocampal volume may be a useful gatekeeper for identifying depressed individuals at risk for AD who would benefit from additional amyloid biomarkers when available.
Assuntos
Doença de Alzheimer , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Compostos de Anilina , Protocolos Clínicos , Depressão/diagnóstico por imagem , Diagnóstico Diferencial , Humanos , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodosRESUMO
Psychotic major depression (PMD) is hypothesized to be a distinct clinical entity from nonpsychotic major depression (NPMD). However, neurobiological evidence supporting this notion is scarce. The aim of this study is to identify gray matter volume (GMV) differences between PMD and NPMD and their longitudinal change following electroconvulsive therapy (ECT). Structural magnetic resonance imaging (MRI) data from 8 independent sites in the Global ECT-MRI Research Collaboration (GEMRIC) database (n = 108; 56 PMD and 52 NPMD; mean age 71.7 in PMD and 70.2 in NPMD) were analyzed. All participants underwent MRI before and after ECT. First, cross-sectional whole-brain voxel-wise GMV comparisons between PMD and NPMD were conducted at both time points. Second, in a flexible factorial model, a main effect of time and a group-by-time interaction were examined to identify longitudinal effects of ECT on GMV and longitudinal differential effects of ECT between PMD and NPMD, respectively. Compared with NPMD, PMD showed lower GMV in the prefrontal, temporal and parietal cortex before ECT; PMD showed lower GMV in the medial prefrontal cortex (MPFC) after ECT. Although there was a significant main effect of time on GMV in several brain regions in both PMD and NPMD, there was no significant group-by-time interaction. Lower GMV in the MPFC was consistently identified in PMD, suggesting this may be a trait-like neural substrate of PMD. Longitudinal effect of ECT on GMV may not explain superior ECT response in PMD, and further investigation is needed.
Assuntos
Depressão/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Espessura Cortical do Cérebro , Eletroconvulsoterapia/métodos , Eletroconvulsoterapia/estatística & dados numéricos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/estatística & dados numéricos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Should we treat older, patients with depression with white matter hyperintensities (WMH) with electroconvulsive therapy (ECT)? WMH, inflammation, depression and cognitive functioning are suggested to be intertwined. Hence, this study investigates whether the association between inflammation and cognition is different in patients with depression with or without WMH. METHODS: Cognitive functioning was assessed using the Mini-Mental State Examination during and after a course of ECT in 77 older patients with depression. Serum samples (C-reactive protein [CRP], interleukin-6 [IL-6], interleukin-10 [IL-10] and tumour necrosis factor-alpha [TNF-α]) and 3T magnetic resonance imaging were obtained prior to ECT. RESULTS: An interaction effect was found for IL-10, but not for CRP, IL-6 or TNF-α. CONCLUSION: In general, the association between inflammatory markers and cognition in patients with depression treated with ECT is not different in patients with WMH compared to patients without WMH.
Assuntos
Eletroconvulsoterapia , Substância Branca , Idoso , Cognição , Depressão/complicações , Depressão/patologia , Depressão/terapia , Eletroconvulsoterapia/efeitos adversos , Eletroconvulsoterapia/métodos , Humanos , Inflamação , Imageamento por Ressonância Magnética , Substância Branca/diagnóstico por imagem , Substância Branca/patologiaRESUMO
BACKGROUND: Electroconvulsive therapy (ECT) is the most effective treatment for severe late-life depression (LLD), and several hypotheses on the precise working mechanism have been proposed. Preclinical evidence suggests that ECT induces changes in neurotrophin and inflammatory signaling and that these neurotrophic and inflammatory systems affect each other. We examine the relation, interaction, and ratio between the neurotrophic brain-derived neurotrophic factor (BDNF) and the proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α), and depression severity during ECT. METHODS: In this naturalistic longitudinal study, linear mixed models were used to analyze the relation between BDNF, IL-6, TNF-α, and depression severity (determined by the Montgomery-Åsberg Depression Rating Scale; MADRS) in 99 patients with severe LLD before ECT (T0), three weeks after the first ECT (T1), and one week after the last ECT (T2). RESULTS: No significant association was found between BDNF, IL-6 and TNF-α, and MADRS scores at any time point. However, a significant interaction between TNF-α and BDNF in relation to MADRS was established (p â= â.020) at all time points. With higher levels of TNF-α, the relation between BDNF and MADRS becomes more negative. Furthermore, a higher ratio of TNF-α/BDNF was associated with a higher score on the MADRS (p â= â.007). CONCLUSION: A possible explanation for the absence of a significant coevolution between the proinflammatory cytokines and BDNF could be that the study design was unable to determine parameters shortly after ECT sessions. However, the TNF-α/BDNF ratio was positively associated with depression severity, and the association of BDNF-level and depression severity depended on the level of TNF-α. This suggests that the interaction and balance between neurotrophin and immune signaling, specifically BDNF and TNF-α, could be relevant in LLD. This could be a focus in future research regarding treatment and the working mechanism of ECT.
RESUMO
Objective: Despite the effectiveness of electroconvulsive therapy (ECT), patients and practitioners are often reluctant to start it due to the risk of transient cognitive side effects, particularly in older patients. Inflammatory processes may be associated with the occurrence of these effects. This study assessed whether inflammatory markers prior to ECT are associated with cognitive functioning in depressed patients treated with ECT.Methods: Between 2011 and 2013, 97 older patients (mean [SD] age = 73.1 [8.1] years) with severe unipolar depression (according to DSM-IV) referred for ECT were included. Mini-Mental State Examination (MMSE) scores were used to determine cognitive functioning prior to, weekly during, and in the first week after a course of ECT. Serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) were assessed prior to ECT.Results: In fully adjusted models, there was an association between TNF-α and cognitive functioning (ß = -1.05; 95% CI, -2.04 to -0.06; f2 = 0.06). An association was also found between baseline levels of IL-10 and TNF-α and lower MMSE scores during ECT (IL-10: ß = -2.08; 95% CI, -3.22 to -0.95; TNF-α: ß = -0.65; 95% CI, -1.07 to -0.22). In addition, an association was found between baseline CRP and lower MMSE scores directly after a course of ECT (ß = -0.51; 95% CI, -0.93 to -0.09; f2 = 0.10). Associations with IL-6 did not reach significance.Conclusions: This study suggests that inflammatory processes are associated with lower cognitive functioning prior to ECT and predispose for further cognitive dysfunction during and after a course of ECT.Trial registration: ClinicalTrials.gov identifier: NCT02667353.
Assuntos
Cognição , Disfunção Cognitiva/etiologia , Eletroconvulsoterapia/efeitos adversos , Inflamação/etiologia , Idoso , Biomarcadores/sangue , Proteína C-Reativa/análise , Depressão/terapia , Feminino , Humanos , Inflamação/sangue , Interleucina-10/sangue , Interleucina-6/sangue , Masculino , Testes de Estado Mental e Demência , Estudos Prospectivos , Fator de Necrose Tumoral alfa/sangueRESUMO
Late-life depression (LLD) is associated with a risk of developing Alzheimer's disease (AD). However, the role of AD-pathophysiology in LLD, and its association with clinical symptoms and cognitive function are elusive. In this study, one hundred subjects underwent amyloid positron emission tomography (PET) imaging with [18F]-flutemetamol and structural MRI: 48 severely depressed elderly subjects (age 74.1 ± 7.5 years, 33 female) and 52 age-/gender-matched healthy controls (72.4 ± 6.4 years, 37 female). The Geriatric Depression Scale (GDS) and Rey Auditory Verbal Learning Test (RAVLT) were used to assess the severity of depressive symptoms and episodic memory function respectively. Amyloid deposition was quantified using the standardized uptake value ratio. Whole-brain voxel-wise comparisons of amyloid deposition and gray matter volume (GMV) between LLD and controls were performed. Multivariate analysis of covariance was conducted to investigate the association of regional differences in amyloid deposition and GMV with clinical factors, including GDS and RAVLT. As a result, there were no significant group differences in amyloid deposition. In contrast, LLD showed significant lower GMV in the left temporal and parietal region. GMV reduction in the left temporal region was associated with episodic memory dysfunction, but not with depression severity. Regional GMV reduction was not associated with amyloid deposition. LLD is associated with lower GMV in regions that overlap with AD-pathophysiology, and which are associated with episodic memory function. The lack of corresponding associations with amyloid suggests that lower GMV driven by non-amyloid pathology may play a central role in the neurobiology of LLD presenting as a psychiatric disorder.Trial registration: European Union Drug Regulating Authorities Clinical Trials identifier: EudraCT 2009-018064-95.