scholarly journals Methylome-wide change associated with response to electroconvulsive therapy in depressed patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lea Sirignano ◽  
Josef Frank ◽  
Laura Kranaster ◽  
Stephanie H. Witt ◽  
Fabian Streit ◽  
...  
Keyword(s):  
Electroconvulsive Therapy ◽  
Rating Scale ◽  
Antidepressant Treatment ◽  
Cpg Sites ◽  
Cpg Site ◽  
Depressed Patients ◽  
Resistant Depression ◽  
Functional Pathway ◽  
Regional Analyses ◽  
The Relationship

AbstractElectroconvulsive therapy (ECT) is a quick-acting and powerful antidepressant treatment considered to be effective in treating severe and pharmacotherapy-resistant forms of depression. Recent studies have suggested that epigenetic mechanisms can mediate treatment response and investigations about the relationship between the effects of ECT and DNA methylation have so far largely taken candidate approaches. In the present study, we examined the effects of ECT on the methylome associated with response in depressed patients (n = 34), testing for differentially methylated CpG sites before the first and after the last ECT treatment. We identified one differentially methylated CpG site associated with the effect of ECT response (defined as >50% decrease in Hamilton Depression Rating Scale score, HDRS), TNKS (q < 0.05; p = 7.15 × 10−8). When defining response continuously (ΔHDRS), the top suggestive differentially methylated CpG site was in FKBP5 (p = 3.94 × 10−7). Regional analyses identified two differentially methylated regions on chromosomes 8 (Šídák’s p = 0.0031) and 20 (Šídák’s p = 4.2 × 10−5) associated with ΔHDRS. Functional pathway analysis did not identify any significant pathways. A confirmatory look at candidates previously proposed to be involved in ECT mechanisms found CpG sites associated with response only at the nominally significant level (p < 0.05). Despite the limited sample size, the present study was able to identify epigenetic change associated with ECT response suggesting that this approach, especially when involving larger samples, has the potential to inform the study of mechanisms involved in ECT and severe and treatment-resistant depression.

scholarly journals Electroconvulsive Therapy and Age: Effectiveness, Safety and Tolerability in the Treatment of Major Depression among Patients under and over 65 Years of Age

2021 ◽  
Vol 14 (6) ◽  
pp. 582
Author(s):  
Monika Dominiak ◽  
Anna Z. Antosik-Wójcińska ◽  
Marcin Wojnar ◽  
Paweł Mierzejewski
Keyword(s):  
Major Depression ◽  
Autobiographical Memory ◽  
Electroconvulsive Therapy ◽  
Cognitive Functions ◽  
Rating Scale ◽  
Short Form ◽  
Serious Adverse Events ◽  
Before And After ◽  
Trail Making ◽  
Resistant Depression

Electroconvulsive therapy (ECT) remains the most effective therapy in treatment-resistant depression. However, the safety of ECT has been consistently questioned, particularly among elderly patients. We assessed the efficacy and safety of ECT in patients before and after 65 years old. The study was conducted between 2015 and 2018 and included 91 patients (61 under and 29 over 65 years old) with major depression undergoing ECT. The Hamilton Depression Rating Scale was used to evaluate efficacy. Cognitive functions were assessed using: MMSE, RAVLT, Trail Making Test, Stroop Test and Autobiographical Memory Interview-Short Form. ECT was more effective in older patients as compared to younger (p < 0.001). No serious adverse events were observed in either group. Increased blood pressure and arrhythmias were more common in the older compared to the younger group (p = 0.044 and p = 0.047, respectively), while disturbances of consciousness did not differ between groups (p = 0.820). Most of the cognitive functions remained unchanged compared to baseline, whereas the outcomes of MMSE, RAVLT and Stroop tests showed greater improvements in the older compared to the younger group (all p < 0.05). The decline in the retrieval consistency of autobiographical memory was more pronounced in the younger group (p = 0.024). ECT is a highly effective, safe and well-tolerated method of treating depression regardless of age.

Placebo-Controlled Trial of Lithium Augmentation of Fluoxetine and Lofepramine

1995 ◽  
Vol 166 (1) ◽  
pp. 80-86 ◽  
Author(s):  
Cornelius L. E. Katona ◽  
Mohammed T. Abou-Saleh ◽  
Deborah A. Harrison ◽  
Bertrand A. Nairac ◽  
Denzil R. L. Edwards ◽  
...  
Keyword(s):  
Rating Scale ◽  
Antidepressant Treatment ◽  
Controlled Trial ◽  
Depressive Illness ◽  
Controlled Trials ◽  
Major Depressive ◽  
Double Blind ◽  
Primary Care Settings ◽  
Resistant Depression ◽  
Lithium Augmentation

BackgroundThis study was designed to establish whether (as suggested in a number of open and relatively small controlled trials) lithium augmentation is more effective than continued antidepressant alone, where response to a standard course of antidepressant treatment has been absent or partial.MethodLithium or placebo was added on a double-blind basis for six weeks to the drug regime of 62 patients with major depressive illness (in both hospital and primary care settings) who had failed to respond to a controlled trial of fluoxetine or lofepramine. Response was defined as a final Hamilton Depression Rating Scale (HDRS) score of < 10.ResultsResponse was seen more frequently in patients taking lithium (15/29) than in those remaining on antidepressant alone (8/32; P < 0.05). Rapid response to lithium augmentation (LA) was not consistently observed in this cohort. Mean HDRS scores after six weeks were significantly lower (P < 0.01) in the lithium group after excluding those who had not achieved significant exposure to lithium (arbitrarily defined as two or more lithium levels ≥ 0.4 mmol/1). No differences in the efficacy of LA were apparent between fluoxetine and lofepramine.ConclusionsOur results confirm that LA is a useful strategy in the treatment of antidepressant-resistant depression. Partial response was, however, frequently observed with continued antidepressant treatment alone, and the superiority of LA appears to depend on achieving adequate serum lithium levels.

Is There a Delay in the Onset of the Antidepressant Effect of Electroconvulsive Therapy?

1994 ◽  
Vol 164 (1) ◽  
pp. 106-109 ◽  
Author(s):  
Colin R. Rodger ◽  
Allan I. F. Scott ◽  
Lawrence J. Whalley
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Electroconvulsive Therapy ◽  
Rating Scale ◽  
Antidepressant Effect ◽  
Major Depressive ◽  
Depressed Patients ◽  
Severity Of Depression ◽  
Drug Free ◽  
Hamilton Rating Scale

The severity of depression in 11 drug-free unipolar patients diagnosed with definite major depressive disorder was assessed using the Hamilton Rating Scale for Depression during a course (5–10 treatments) of bilateral electroconvulsive therapy (ECT). The degree of improvement after three treatments of ECT was six times greater than the improvement that occurred over the remainder of the course. Although depressed patients who recover with ECT require repeated treatments, the treatments early in a course of ECT can have marked antidepressant effect.

scholarly journals Hippocampal-subregion functional alterations associated with antidepressant effects and cognitive impairments of electroconvulsive therapy

2018 ◽  
Vol 49 (08) ◽  
pp. 1357-1364 ◽  
Author(s):  
Tongjian Bai ◽  
Qiang Wei ◽  
Wen Xie ◽  
Anzhen Wang ◽  
Jiaojian Wang ◽  
...  
Keyword(s):  
Electroconvulsive Therapy ◽  
Rating Scale ◽  
Cognitive Impairments ◽  
Structural Connectivity ◽  
Angular Gyrus ◽  
Resting State Functional Connectivity ◽  
Antidepressant Effects ◽  
Emotion And Memory ◽  
Middle Occipital Gyrus ◽  
The Relationship

AbstractBackgroundElectroconvulsive therapy (ECT), an effective antidepressive treatment, is frequently accompanied by cognitive impairment (predominantly memory), usually transient and self-limited. The hippocampus is a key region involved in memory and emotion processing, and in particular, the anterior-posterior hippocampal subregions has been shown to be associated with emotion and memory. However, less is known about the relationship between hippocampal-subregion alterations following ECT and antidepressant effects or cognitive impairments.MethodsResting-state functional connectivity (RSFC) based on the seeds of hippocampal subregions were investigated in 45 pre- and post-ECT depressed patients. Structural connectivity between hippocampal subregions and corresponding functionally abnormal regions was also conducted using probabilistic tractography. Antidepressant effects and cognitive impairments were measured by the Hamilton Depressive Rating Scale (HDRS) and the Category Verbal Fluency Test (CVFT), respectively. Their relationships with hippocampal-subregions alterations were examined.ResultsAfter ECT, patients showed increased RSFC in the hippocampal emotional subregion (HIPe) with the left middle occipital gyrus (LMOG) and right medial temporal gyrus (RMTG). Decreased HDRS was associated with increased HIPe-RMTG RSFC (r = −0.316, p = 0.035) significantly and increased HIPe-LMOG RSFC at trend level (r = −0.283, p = 0.060). In contrast, the hippocampal cognitive subregion showed decreased RSFC with the bilateral angular gyrus, and was correlated with decreased CVFT (r = 0.418, p = 0.015 for left; r = 0.356, p = 0.042 for right). No significant changes were found in structural connectivity.ConclusionThe hippocampal-subregions functional alterations may be specially associated with the antidepressant and cognitive effects of ECT.

scholarly journals DNA methylation partially mediates the relationship between childhood adversity and depressive symptoms in adolescence

2021 ◽  
Author(s):  
Brooke J. Smith ◽  
Alexandre A Lussier ◽  
Janine Cerutti ◽  
Daniel J. Schaid ◽  
Andrew J. Simpkin ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Depressive Symptoms ◽  
Life Course ◽  
Adolescent Depression ◽  
Childhood Adversity ◽  
Depression Symptoms ◽  
Cpg Sites ◽  
Cpg Site ◽  
Sensitive Periods ◽  
The Relationship

Background: Exposure to adversity during childhood is estimated to at least double the risk of depression later in life. Some evidence suggests childhood adversity may have a greater impact on depression risk, if experienced during specific windows of development called sensitive periods. During these sensitive periods, there is evidence that adversity may leave behind biological memories, including changes in DNA methylation (DNAm). Here we ask if those changes play a role in the link between adversity and later adolescent depressive symptoms. Methods: We applied a method for high-dimensional mediation analysis using data from a subsample (n=627-675) of the Avon Longitudinal Study of Parents and Children. We first assessed the possibility of time-dependent relationships between seven types of childhood adversity (caregiver abuse, physical/sexual abuse, maternal psychopathology, one-adult household, family instability, financial stress, neighborhood disadvantage), measured on at least four occasions between ages 0-7 years, and adolescent depression at mean age 10.6. Specifically, we considered three types of life course hypotheses (sensitive periods, accumulation, and recency), and then evaluated which of these hypotheses had the strongest association in each adversity-adolescent depression relationship using the structured life course modeling approach (SLCMA; pronounced slick-mah). To conduct the mediation analyses, we used a combination of pruning and sure independence screening (a dimension reduction method) to reduce the number of methylated CpG sites under consideration to a viable subset for our sample size. We then applied a sparse group lasso penalized model to identify the top mediating loci from that subset using the combined strength of the coefficient measuring the relationship between the childhood adversity and a CpG site (α) and of the coefficient measuring the relationship between the CpG site and depressive symptoms (β) as a metric. Using a Monte Carlo method for assessing mediation (MCMAM), we assigned a significance level and confidence interval to each identified mediator. Results: Across all seven adversities, we identified a total of 70 CpG sites that showed evidence of mediating the relationship between adversity and adolescent depression symptoms. Of these 70 mediators, 37 were significant at the p < 0.05 level when applying the MCMAM, a method tailored to estimating the significance of SEM-derived mediation effects. These sites exhibited four different mediating patterns, differentiated by the direction of α and β. These patterns had signals that were: (1) both positive (19 loci), (2) both negative (18 loci), (3) positive α and negative β (23 loci) or (4) negative α and positive β (10 loci). Conclusion: Our results suggest that DNAm partially mediates the relationship between different types of childhood adversity and depressive symptoms in adolescence. These findings provide insight into the biological mechanisms that link childhood adversity to depression, which will ultimately help develop treatments to prevent depression in more vulnerable populations.

scholarly journals Efficacy of repetitive transcranial magnetic stimulation in treatment-resistant depression: the evidence thus far

2019 ◽  
Vol 32 (4) ◽  
pp. e100074 ◽  
Author(s):  
Aditya Somani ◽  
Sujita Kumar Kar
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Electroconvulsive Therapy ◽  
Magnetic Stimulation ◽  
Antidepressant Treatment ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Common Mental Disorder ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Number Of Patients ◽  
Resistant Depression

Depression is a common mental disorder, which attributes to significant morbidity, disability and burden of care. A significant number of patients with depression still remain symptomatic after adequate trials of antidepressant treatment as well as psychotherapy, which is often referred to as treatment-resistant depression. Neuromodulation techniques—like electroconvulsive therapy, vagus nerve stimulation, transcranial magnetic stimulation (TMS) and transcranial direct current stimulation, may be useful augmenting techniques in depression, mostly recommended for treatment-resistant cases. Robust evidence exists regarding the efficacy of electroconvulsive therapy in the management of treatment-resistant depression; however, other techniques are understudied. TMS has been increasingly studied in various psychiatric disorders including depression. It has been approved by the US Food and Drug Administration for use in major depressive disorder. Over the past two decades, TMS has been studied in diverse groups of the population with depression using several research designs. This article gives an overview of the efficacy of repetitive TMS in treatment-resistant depression with the recent evidence.

Biochemical Aspects of Therapy-Resistant Depression

1988 ◽  
Vol 152 (4) ◽  
pp. 453-459 ◽  
Author(s):  
B. E. Leonard
Keyword(s):  
Affective Disorders ◽  
Clinical Evidence ◽  
Antidepressant Treatment ◽  
Depressed Patients ◽  
High Incidence ◽  
Resistant Depression ◽  
Serotonergic Function ◽  
Definition Of ◽  
Therapy Resistant Depression

Despite the relatively high incidence of therapy-resistant depression, there is little clinical evidence to suggest that there are significant biochemical differences between therapy-resistant and therapy-responsive patients. A major problem for investigators is the lack of an internationally recognised definition of resistant depression. Also, it is possible that depressed patients with delusional symptoms or rapidly cycling affective disorders form subgroups that are more likely to be resistant to tricylic antidepressant treatment and are therefore classified as therapy-resistant. Evidence is presented to show that an abnormality in serotonergic function may characterise some therapy-resistant depressed patients.

scholarly journals Cognitive improvement after treatment of depressive symptoms in the acute phase of stroke

2006 ◽  
Vol 64 (2b) ◽  
pp. 412-417 ◽  
Author(s):  
Samuel Simis ◽  
Ricardo Nitrini
Keyword(s):  
Depressive Symptoms ◽  
Acute Phase ◽  
Rating Scale ◽  
Antidepressant Treatment ◽  
Controlled Study ◽  
Attention And Memory ◽  
Memory And Attention ◽  
Cognitive Improvement ◽  
Depressed Patients

The outcome of antidepressant treatment for depressive symptoms and cognitive impairment at the acute phase of stroke is controversial. We investigated 93 patients, treating with citalopram 36 with severe depressive symptoms (HAM-D: Hamilton Depression Rating Scale >18), whilst 19 patients with mild depressive symptoms, and 38 non-depressed patients, remained untreated. At baseline (two weeks after stroke), patients with severe depressive symptoms had lower scores in total Dementia Rating Scale (DRS) and in the attention and memory DRS subscales, than the non-depressed patients (p<0.001). At the end of the three-month follow-up period, these differences had disappeared, but patients initially with mild depressive symptoms had higher HAM-D scores than the non-depressed patients (p=0.015), and lower scores in DRS attention and memory subscales (p<0.01), than the patients treated with citalopram. Treatment was associated with improved mood, memory and attention, and a placebo-controlled study on the treatment of mild depressive symptoms is warranted.

CSF monoamine metabolites and neuropeptides in depressed patients before and after electroconvulsive therapy

2008 ◽  
Vol 23 (5) ◽  
pp. 356-359 ◽  
Author(s):  
Georg Nikisch ◽  
Aleksander A. Mathé
Keyword(s):  
Electroconvulsive Therapy ◽  
Antidepressant Treatment ◽  
Antidepressant Drugs ◽  
Treatment Modalities ◽  
Depressed Patients ◽  
Human Cerebrospinal Fluid ◽  
Rodent Brain ◽  
Before And After ◽  
Hydroxyindoleacetic Acid ◽  
The Common

AbstractAntidepressant drugs affect monoamines and neuropeptides in human cerebrospinal fluid (CSF) and in rodent brain. The purpose of this study was to investigate if also electroconvulsive therapy (ECT) affects these compounds in a similar manner in the CSF of depressed patients. Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and corticotropin-releasing hormone (CRH)-like immunoreactivity (-LI) and neuropeptide Y (NPY)-LI were determined in CSF in six drug resistant patients with major depression. Lumbar puncture was performed at baseline and after completion of eight ECTs. ECT was associated with an increase in NPY-LI (p = 0.009) and a decrease in CRH-LI (p ≤ 0.001). HVA (p = 0.003) and 5-HIAA (p = 0.002) were significantly increased after the ECT. Findings of NPY increase and CRH decrease were similar to those following chronic treatment with citalopram, indicating that these changes might constitute one of the common underpinnings of antidepressant treatment modalities.

scholarly journals Is Interleukin 17 (IL-17) Expression A Common Point in the Pathogenesis of Depression and Obesity?

2020 ◽  
Vol 9 (12) ◽  
pp. 4018
Author(s):  
Katarzyna Bliźniewska-Kowalska ◽  
Bernadeta Szewczyk ◽  
Małgorzata Gałecka ◽  
Kuan-Pin Su ◽  
Michael Maes ◽  
...  
Keyword(s):  
Depressive Disorders ◽  
Rating Scale ◽  
Enzyme Linked Immunosorbent Assay ◽  
Interleukin 17 ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Depressed Patients ◽  
Level 3 ◽  
Polymerase Chain ◽  
The Relationship

(1) Background: Activated immune-inflammatory pathways play an important role in the pathogenesis of depression and pathological obesity. Obesity might promote production of cytokine interleukin 17, which plays a significant role in neuro-immune reactions. The study aimed at assessing the relationship between Body Mass Index (BMI) and IL-17 expression, taking into account the clinical psychiatric variables in patients with depression. (2) Methods: A total of 125 participants took part in the study (95 depressed patients, 30 healthy controls). Data concerning the course of depressive disorders and BMI were collected. The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). Reverse transcription polymerase chain reaction (RT-PCR) was used to assess IL-17 gene expression at the mRNA levels, while enzyme-linked immunosorbent assay (ELISA) was used to assess IL-17 expression at the protein level. (3) Results: Patients with more hospitalizations showed significantly higher IL-17 mRNA expression levels and higher BMI. However, no correlation between BMI and IL-17 expression was found in depressed patients. (4) Conclusions: Our study revealed that BMI does not affect IL-17 expression in patients with depression. However, further studies should be conducted to evaluate the effects of IL-17 inhibition on adipose tissue and vice versa.

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