scholarly journals Biomarkers of ketamine’s antidepressant effect: a clinical review of genetics, functional connectivity, and neurophysiology

2021 ◽  
Vol 5 ◽  
pp. 247054702110142
Author(s):  
Alexandra A. Alario ◽  
Mark J. Niciu
Keyword(s):  
Treatment Response ◽  
Antidepressant Treatment ◽  
A Priori ◽  
Antidepressant Effect ◽  
Aspartate Receptor ◽  
Neurophysiological Studies ◽  
All Cause Mortality ◽  
Antidepressant Efficacy ◽  
Glutamate Modulators ◽  
Response Biomarkers

Major depressive disorder (MDD) is one of the leading causes of morbidity and all-cause mortality (including suicide) worldwide, and, unfortunately, first-line monoaminergic antidepressants and evidence-based psychotherapies are not effective for all patients. Subanesthetic doses of the N-methyl-D-aspartate receptor antagonists and glutamate modulators ketamine and S-ketamine have rapid and robust antidepressant efficacy in such treatment-resistant depressed patients (TRD). Yet, as with all antidepressant treatments including electroconvulsive therapy (ECT), not all TRD patients adequately respond, and we are presently unable to a priori predict who will respond or not respond to ketamine. Therefore, antidepressant treatment response biomarkers to ketamine have been a major focus of research for over a decade. In this article, we review the evidence in support of treatment response biomarkers, with a particular focus on genetics, functional magnetic resonance imaging, and neurophysiological studies, i.e. electroencephalography and magnetoencephalography. The studies outlined here lay the groundwork for replication and dissemination.

scholarly journals Resting state functional connectivity patterns as biomarkers of treatment response to escitalopram in patients with major depressive disorder

2021 ◽  
Author(s):  
Marieke A. G. Martens ◽  
Nicola Filippini ◽  
Catherine J. Harmer ◽  
Beata R. Godlewska
Keyword(s):  
Functional Connectivity ◽  
Treatment Response ◽  
Resting State ◽  
Rating Scale ◽  
Antidepressant Treatment ◽  
Resting State Functional Connectivity ◽  
The Right ◽  
Treatment Responsivity ◽  
Response Biomarkers

Abstract Rational With no available response biomarkers, matching an appropriate antidepressant to an individual can be a lengthy process. Improving understanding of processes underlying treatment responsivity in depression is crucial for facilitating work on response biomarkers. Objectives To identify differences in patterns of pre-treatment resting-state functional connectivity (rsFC) that may underlie response to antidepressant treatment. Methods After a baseline MRI scan, thirty-four drug-free patients with depression were treated with an SSRI escitalopram 10 mg daily for 6 weeks; response was defined as ≥ 50% decrease in Hamilton Depression Rating Scale (HAMD) score. Thirty-one healthy controls had a baseline clinical assessment and scan. Healthy participants did not receive treatment. Results Twenty-one (62%) of patients responded to escitalopram. Treatment responsivity was associated with enhanced rsFC of the right fronto-parietal network (FPN)—with the posterior DMN, somatomotor network (SMN) and somatosensory association cortex. The lack of treatment response was characterized by reduced rsFC: of the bilateral FPN with the contralateral SMN, of the right FPN with the posterior DMN, and of the extended sensorimotor auditory area with the inferior parietal lobule (IPL) and posterior DMN. Reduced rsFC of the posterior DMN with IPL was seen in treatment responders, although only when compared with HC. Conclusions The study supports the role of resting-state networks in response to antidepressant treatment, and in particular the central role of the frontoparietal and default mode networks.

scholarly journals Treatment Response Biomarkers in Asthma and COPD

Diagnostics ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1668
Author(s):  
Howraman Meteran ◽  
Pradeesh Sivapalan ◽  
Jens-Ulrik Stæhr Jensen
Keyword(s):  
Treatment Response ◽  
Response To Treatment ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Exacerbations ◽  
Copd Patients ◽  
Immunological Mechanisms ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Response Biomarkers

Chronic obstructive pulmonary disease (COPD) and asthma are two of the most common chronic diseases worldwide. Both diseases are heterogenous and complex, and despite their similarities, they differ in terms of pathophysiological and immunological mechanisms. Mounting evidence supports the presence of several phenotypes with various responses to treatment. A systematic and thorough assessment concerning the diagnosis of both asthma and COPD is crucial to the clinical management of the disease. The identification of different biomarkers can facilitate targeted treatment and monitoring. Thanks to the presence of numerous immunological studies, our understanding of asthma phenotypes and mechanisms of disease has increased markedly in the last decade, and several treatments with monoclonal antibodies are available. There are compelling data that link eosinophilia with an increased risk of COPD exacerbations but a greater treatment response and lower all-cause mortality. Eosinophilia can be considered as a treatable trait, and the initiation of inhaled corticosteroid in COPD patients with eosinophilia is supported in many studies. In spite of advances in our understanding of both asthma and COPD in terms pathophysiology, disease mechanisms, biomarkers, and response to treatment, many uncertainties in the management of obstructive airways exist.

scholarly journals Immunoregulation and antidepressant effect of ketamine

2021 ◽  
Vol 12 (1) ◽  
pp. 218-236
Author(s):  
Nan Zhang ◽  
Lihua Yao ◽  
Peilin Wang ◽  
Zhongchun Liu
Keyword(s):  
Disease Burden ◽  
Severe Disease ◽  
Mental Health Disorder ◽  
Antagonistic Effect ◽  
Antidepressant Effect ◽  
Future Research ◽  
Recurrence Rates ◽  
Aspartate Receptor ◽  
Antidepressant Effects ◽  
Common Mental Health Disorder

Abstract Major depressive disorder (MDD) is a common mental health disorder that brings severe disease burden worldwide. Traditional antidepressants are mainly targeted at monoamine neurotransmitters, with low remission rates and high recurrence rates. Ketamine is a noncompetitive glutamate N-methyl-d-aspartate receptor (NMDAR) antagonist, and its rapid and powerful antidepressant effects have come to light. Its antidepressant mechanism is still unclarified. Research found that ketamine had not only antagonistic effect on NMDAR but also strong immunomodulatory effect, both of which were closely related to the pathophysiology of MDD. Although there are many related studies, they are relatively heterogeneous. Therefore, this review mainly describes the immune mechanisms involved in MDD and how ketamine plays an antidepressant role by regulating peripheral and central immune system, including peripheral inflammatory cytokines, central microglia, and astrocytes. This review summarizes the related research, finds out the deficiencies of current research, and provides ideas for future research and the development of novel antidepressants.

scholarly journals Task-Modulated Brain Activity Predicts Antidepressant Responses of Prefrontal Repetitive Transcranial Magnetic Stimulation: A Randomized Sham-Control Study

2021 ◽  
Vol 5 ◽  
pp. 247054702110068
Author(s):  
Cheng-Ta Li ◽  
Chih-Ming Cheng ◽  
Chi-Hung Juan ◽  
Yi-Chun Tsai ◽  
Mu-Hong Chen ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Antidepressant Treatment ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Brain Activity ◽  
Characteristic Curve ◽  
Depression Score ◽  
Double Blind ◽  
Antidepressant Efficacy ◽  
Group B

Background Prolonged intermittent theta-burst stimulation (piTBS) and repetitive transcranial magnetic stimulation (rTMS) are effective antidepressant interventions for major depressive disorder (MDD). Cognition-modulated frontal theta (frontalθ) activity had been identified to predict the antidepressant response to 10-Hz left prefrontal rTMS. However, whether this marker also predicts that of piTBS needs further investigation. Methods The present double-blind randomized trial recruited 105 patients with MDD who showed no response to at least one adequate antidepressant treatment in the current episode. The recruited patients were randomly assigned to one of three groups: group A received piTBS monotherapy; group B received rTMS monotherapy; and group C received sham stimulation. Before a 2-week acute treatment period, electroencephalopgraphy (EEG) and cognition-modulated frontal theta changes (Δfrontalθ) were measured. Depression scores were evaluated at baseline, 1 week, and 2 weeks after the initiation of treatment. Results The Δfrontalθ at baseline was significantly correlated with depression score changes at week 1 (r = −0.383, p = 0.025) and at week 2 for rTMS group (r = −0.419, p = 0.014), but not for the piTBS and sham groups. The area under the receiver operating characteristic curve for Δfrontalθ was 0.800 for the rTMS group (p = 0.003) and was 0.549 for the piTBS group (p = 0.619). Conclusion The predictive value of higher baseline Δfrontalθ for antidepressant efficacy for rTMS not only replicates previous results but also implies that the antidepressant responses to rTMS could be predicted reliably at baseline and both piTBS and rTMS could be effective through different neurobiological mechanisms.

scholarly journals Effect of acute citalopram on self-referential emotional processing and social cognition in healthy volunteers

BJPsych Open ◽  
2020 ◽  
Vol 6 (6) ◽  
Author(s):  
Catherine Hobbs ◽  
Susannah E. Murphy ◽  
Lucy Wright ◽  
James Carson ◽  
Indra Van Assche ◽  
...  
Keyword(s):  
Social Cognition ◽  
Healthy Volunteers ◽  
Antidepressant Treatment ◽  
Affective Learning ◽  
The Self ◽  
Affective Processing ◽  
Antidepressant Effect ◽  
Acute Administration ◽  
Double Blind ◽  
Prosocial Behaviours

Background Depression is characterised by negative views of the self. Antidepressant treatment may remediate negative self-schema through increasing processing of positive information about the self. Changes in affective processing during social interactions may increase expression of prosocial behaviours, improving interpersonal communications. Aims To examine whether acute administration of citalopram is associated with an increase in positive affective learning biases about the self and prosocial behaviour. Method Healthy volunteers (n = 41) were randomised to either an acute 20 mg dose of citalopram or matched placebo in a between-subjects double-blind design. Participants completed computer-based cognitive tasks designed to measure referential affective processing, social cognition and expression of prosocial behaviours. Results Participants administered citalopram made more cooperative choices than those administered placebo in a prisoner's dilemma task (β = 20%, 95% CI: 2%, 37%). Exploratory analyses indicated that participants administered citalopram showed a positive bias when learning social evaluations about a friend (β = 4.06, 95% CI: 0.88, 7.24), but not about the self or a stranger. Similarly, exploratory analyses found evidence of increased recall of positive words and reduced recall of negative words about others (β = 2.41, 95% CI: 0.89, 3.93), but not the self, in the citalopram group. Conclusions Participants administered citalopram showed greater prosocial behaviours, increased positive recall and increased positive learning of social evaluations towards others. The increase in positive affective bias and prosocial behaviours towards others may, at least partially, be a mechanism of antidepressant effect. However, we found no evidence that citalopram influenced self-referential processing.

scholarly journals Macronutrient Quality and All-Cause Mortality in the SUN Cohort

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 972
Author(s):  
Susana Santiago ◽  
Itziar Zazpe ◽  
Cesar I. Fernandez-Lazaro ◽  
Víctor de la de la O ◽  
Maira Bes-Rastrollo ◽  
...  
Keyword(s):  
Quality Index ◽  
Inverse Relationship ◽  
A Priori ◽  
The Sun ◽  
Significant Inverse Relationship ◽  
Carbohydrate Quality ◽  
All Cause Mortality ◽  
Middle Aged Adults ◽  
The Relationship

No previous study has assessed the relationship between overall macronutrient quality and all-cause mortality. We aimed to prospectively examine the association between a multidimensional macronutrient quality index (MQI) and all-cause mortality in the SUN (Seguimiento Universidad de Navarra) (University of Navarra Follow-Up) study, a Mediterranean cohort of middle-aged adults. Dietary intake information was obtained from a validated 136-item semi-quantitative food-frequency questionnaire. We calculated the MQI (categorized in quartiles) based on three quality indexes: the carbohydrate quality index (CQI), the fat quality index (FQI), and the healthy plate protein source quality index (HPPQI). Among 19,083 participants (mean age 38.4, 59.9% female), 440 deaths from all causes were observed during a median follow-up of 12.2 years (IQR, 8.3–14.9). No significant association was found between the MQI and mortality risk with multivariable-adjusted hazard ratio (HR) for the highest vs. the lowest quartile of 0.79 (95% CI, 0.59–1.06; Ptrend = 0.199). The CQI was the only component of the MQI associated with mortality showing a significant inverse relationship, with HR between extreme quartiles of 0.64 (95% CI, 0.45–0.90; Ptrend = 0.021). In this Mediterranean cohort, a new and multidimensional MQI defined a priori was not associated with all-cause mortality. Among its three sub-indexes, only the CQI showed a significant inverse relationship with the risk of all-cause mortality.

Antidepressant Treatment Response in Depressed Hypothyroid Patients

1989 ◽  
Vol 40 (9) ◽  
pp. 954-956
Author(s):  
Mark J. Russ ◽  
Sigurd H. Ackerman
Keyword(s):  
Treatment Response ◽  
Antidepressant Treatment ◽  
Hypothyroid Patients

13. FGF2 Gene is required for Antidepressant Treatment Effects

2018 ◽  
Author(s):  
Jessica MacGregor
Keyword(s):  
Open Field ◽  
Antidepressant Treatment ◽  
Forced Swim Test ◽  
Antidepressant Drugs ◽  
Preference Test ◽  
Antidepressant Effect ◽  
Plus Maze ◽  
Brain Changes ◽  
Carry Over ◽  
Sucrose Preference Test

gene in humans have been shown to predict non-responsiveness to antidepressant drugs; suggesting that FGF2 is required for antidepressants to work. In this study, we hypothesized that antidepressants will not work in rodents that lack the FGF2 gene. Hence, we tested antidepressant treatment in transgenic mice that had the FGF2 gene knocked out. Chronic unpredictable stress (CUS) has been used for several decades to produce a reliable depressive and anxious phenotype in mice. This study followed a CUS paradigm and used fluoxetine (Prozac) as antidepressant treatment. Mice received daily fluoxetine administration beginning on week three of CUS and continued until the end of week five to provide an antidepressant effect and reverse the effects of stress. To test for levels of anxiety and depression, a battery of behavioral tests was conducted which began from the least stressful (i.e. sucrose preference test, open field maze, elevated plus maze) to the most stressful test (forced swim test) to prevent testing carry-over effects. AnyMaze software was used to measure behavior in the open field and elevated plus mazes by recording the amount of time each mouse spent in certain parts of the maze. Future studies will examine brain changes associated with FGF2 gene deletion – particularly in astrocyte cells – which might be necessary for successful antidepressant action. Hopefully, this will elucidate novel therapeutic targets for antidepressant and anti-anxiety medication. 

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