scholarly journals A double-blind placebo-controlled trial of minocycline on translocator protein distribution volume in treatment-resistant major depressive disorder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sophia Attwells ◽  
Elaine Setiawan ◽  
Pablo M. Rusjan ◽  
Cynthia Xu ◽  
Stephen J. Kish ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Distribution Volume ◽  
Anterior Cingulate ◽  
Translocator Protein ◽  
Protein Distribution ◽  
Treatment Resistant ◽  
Major Depressive ◽  
Neuropsychiatric Diseases ◽  
Significant Difference

AbstractGliosis is implicated in the pathophysiology of many neuropsychiatric diseases, including treatment-resistant major depressive disorder (TRD). Translocator protein total distribution volume (TSPO VT), a brain marker mainly reflective of gliosis in disease, can be measured using positron emission tomography (PET). Minocycline reduces gliosis and translocator protein binding in rodents, but this is not established in humans. Here, the ability of oral minocycline to reduce TSPO VT was assessed in TRD. To determine whether oral minocycline, as compared to placebo, can reduce prefrontal cortex (PFC), anterior cingulate cortex (ACC), and insula TSPO VT in TRD, twenty-one TRD participants underwent two [18F]FEPPA PET scans to measure TSPO VT. These were completed before and after either oral minocycline 100 mg bid or placebo which was administered in a randomized double-blinded fashion for 8 weeks. There was no significant difference between the minocycline and placebo groups on change in TSPO VT within the PFC, ACC, and insula (repeated measures ANOVA, effect of group interaction, PFC: F1,19 = 0.28, P = 0.60; ACC: F1,19 = 0.54, P = 0.47; insula F1,19 = 1.6, P = 0.22). Oral minocycline had no significant effect on TSPO VT which suggests that this dosage is insufficient to reduce gliosis in TRD. To target gliosis in TRD either alternative therapeutics or intravenous formulations of minocycline should be investigated. These results also suggest that across neuropsychiatric diseases in humans, it should be assumed that oral minocycline will not reduce TSPO VT or gliosis unless empirically demonstrated.

scholarly journals Theta burst stimulation for the acute treatment of major depressive disorder: A systematic review and meta-analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jeffrey D. Voigt ◽  
Andrew F. Leuchter ◽  
Linda L. Carpenter
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Rating Scale ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
High Frequency Stimulation ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Major Depressive ◽  
Significant Difference ◽  
Theta Burst

AbstractPatients with major depressive disorder (MDD) may be refractory to or have contraindications that preclude treatment with antidepressant pharmacotherapies. Alternative therapies such as repetitive transcranial magnetic stimulation (rTMS) continue to evolve, and include theta burst stimulation (TBS), which has advantages over conventional rTMS. The aim of this study was to identify and meta-analyze efficacy data from all randomized controlled trials (RCTs) investigating TBS as a treatment for MDD. Published reports of RCTs (January 1, 2010 to October 23, 2020) were identified via systematic searches in computerized databases, followed by review of individual reports for inclusion. Inclusion criteria included primary diagnosis of MDD ≥ 1 week duration of therapy with ≥10 sessions, and treatment with any form of TBS. The Cochrane GRADE methodology and PRISMA criteria were used for evaluation of individual trials. Data from ten RCTs were included, representing 667 patients. Of these, 8 RCTs compared TBS to sham treatment and one compared TBS to standard rTMS (i.e., high frequency stimulation over left dorsolateral prefrontal cortex [HFL]). Quality of evidence assessment yielded high confidence in the finding of TBS being superior to sham on response measured by the Hamilton Depression Rating Scale (HRSD) (RR = 2.4; 95% CI: 1.27 to 4.55; P = 0.007; I2 = 40%). Comparison of HRSD response rates for TBS versus rTMS produced no statistically significant difference (RR = 1.02; 95% CI: 0.85 to 1.23; P = 0.80; I2 = 0%). The incidence of adverse events between TBS and rTMS was not statistically different. The findings of a positive effect of TBS vs. sham, and noninferiority of TBS vs. standard HFL rTMS support the continued development of TBS to treat depression.

Increased pregenual anterior cingulate glucose and lactate concentrations in major depressive disorder

2016 ◽  
Vol 22 (1) ◽  
pp. 113-119 ◽  
Author(s):  
J Ernst ◽  
A Hock ◽  
A Henning ◽  
E Seifritz ◽  
H Boeker ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Anterior Cingulate ◽  
Major Depressive

Prefrontal cortex function in remitted major depressive disorder

2012 ◽  
Vol 43 (6) ◽  
pp. 1219-1230 ◽  
Author(s):  
N. L. Nixon ◽  
P. F. Liddle ◽  
G. Worwood ◽  
M. Liotti ◽  
E. Nixon
Keyword(s):  
Major Depressive Disorder ◽  
Prefrontal Cortex ◽  
Depressive Disorder ◽  
Negative Feedback ◽  
Affective State ◽  
Recurrence Risk ◽  
Anterior Cingulate ◽  
Major Depressive ◽  
Negative Experience

BackgroundRecent models of major depressive disorder (MDD) have proposed the rostral anterior cingulate (rACC) and dorsomedial prefrontal cortex (dmPFC) as nexus sites in the dysfunctional regulation of cognitive-affective state. Limited evidence from remitted-state MDD supports these theories by suggesting that aberrant neural activity proximal to the rACC and the dmPFC may play a role in vulnerability to recurrence/relapse within this disorder. Here we present a targeted analysis assessing functional activity within these two regions of interest (ROIs) for groups with identified vulnerability to MDD: first, remitted, high predicted recurrence-risk patients; and second, patients suffering observed 1-year recurrence.MethodBaseline T2* images sensitive to blood oxygen level-dependent (BOLD) contrast were acquired from patients and controls during a Go/No-Go (GNG) task incorporating negative feedback, with 1-year patient follow-up to identify recurrence. BOLD contrast data for error commission (EC) and visual negative feedback (VNF) were used in an ROI analysis based on rACC and dmPFC coordinates from the literature, comparing patientsversuscontrols and recurrenceversusnon-recurrenceversuscontrol groups.ResultsAnalysis of patients (n = 20)versuscontrols (n = 20) showed significant right dmPFC [Brodmann area (BA) 9] hypoactivity within the patient group, co-localized during EC and VNF, with additional significant rACC (BA 32) hypoactivity during EC. The results from the follow-up analysis were undermined by small groups and potential confounders but suggested persistent right dmPFC (BA 9) hypoactivity associated with 1-year recurrence.ConclusionsConvergent hypoactive right dmPFC (BA 9) processing of VNF and EC, possibly impairing adaptive reappraisal of negative experience, was associated most clearly with clinically predicted vulnerability to MDD.

Augmentation strategies in the treatment of major depressive disorder

2016 ◽  
Vol 33 (S1) ◽  
pp. S407-S407
Author(s):  
S. Bise ◽  
B. Kurtovic ◽  
D. Begic ◽  
O. Cemalovic
Keyword(s):  
Major Depressive Disorder ◽  
Combination Therapy ◽  
Depressive Disorder ◽  
Mood Stabilizers ◽  
Augmentation Therapy ◽  
Major Depressive ◽  
Augmentation Strategies ◽  
Significant Difference ◽  
Augmentation Strategy ◽  
Competing Interest

Augmentation strategies for the treatment of Major depressive disorder (MDD) are needed when patients with MDD have a partial, or not responded to antidepressant monotherapy. The focus of augmentation therapy has been combining an antidepressant (AD) medication with another AD. Atypical antipsychotics (AAP) are becoming commonly used to augment antidepressants. Beyond AD and AAP, alternative augmentation strategies include mood stabilizers (MS).AimTo analyze the characteristics of therapy in patients with diagnosis of MDD and to investigate the frequency of augmentation therapy.MethodStudy included 28 patients hospitalized during one year with MDD diagnosis. Statistical analysis was performed with x2 and t-test.ResultAmong patients with MDD there were 18 (64.28%) women with an average age 57.5 and 10 (35.71%) men with an average age 53.5. Of the 28 patients with MDD, 25 (89.28%) were treated with a combination therapy, and monotherapy in the remaining 3 patients (10.71%). Of 25 patients with augmentation strategy treatment, 22 (88%) used two medications and the remaining 3 (12%) tree psychotropic medications (AAP, AD, MS). The most frequent combinations were a combination of AD and AAP (17 patients, 68%). Beyond that frequent combination were AD and MS (6 patients, 24%). Two patients used combination two AAP, and one patient with two AD and one patients used AAP and MS.ConclusionAugmentation strategy is often used in patients with MDD. There is no significant difference in the use combination therapy based on gender and age.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Alteration of Transthyretin and Thyroxine-Binding Globulin in Major Depressive Disorder: Multiple Reaction Monitoring-Based Proteomic Analysis

2020 ◽  
Author(s):  
Hye In Woo ◽  
Jisook Park ◽  
Shinn-Won Lim ◽  
Doh Kwan Kim ◽  
Soo-Youn Lee
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Proteomic Analysis ◽  
Antidepressant Treatment ◽  
Multiple Reaction Monitoring ◽  
Reaction Monitoring ◽  
Healthy Individuals ◽  
Major Depressive ◽  
Thyroxine Binding Globulin ◽  
Significant Difference

Abstract Background: Major depressive disorder (MDD), common mental disorder, lacks objective diagnostic and prognosis biomarkers. The objective of this study was to perform proteomic analysis to identify proteins with changed expression levels after antidepressant treatment and investigate differences in protein expression between MDD patients and healthy individuals.Methods: A total of 111 proteins obtained from literature review were subjected to multiple reaction monitoring (MRM)-based protein quantitation. Finally, seven proteins were quantified for plasma specimens of 10 healthy controls and 78 MDD patients (those at baseline and at 6 weeks after antidepressant treatment of either selective serotonin reuptake inhibitors (SSRIs) or mirtazapine). Results: Among 78 MDD patients, 35 patients were treated with SSRIs and 43 patients were treated with mirtazapine. Nineteen (54.3%) and 16 (37.2%) patients responded to SSRIs and mirtazapine, respectively. Comparing MDD patients with healthy individuals, alteration of transthyretin was observed in MDD (p = 0.026). There was no significant difference in protein levels related to SSRIs treatment. Plasma thyroxine-binding globulin (TBG) was different between before and after mirtazapine treatment only in responders (p = 0.007).Conclusions: In proteomic analysis of plasma specimens from MDD patients, transthyretin and TBG levels were altered in MDD and changed after antidepressant treatment.

Sign in / Sign up

Export Citation Format

Share Document