scholarly journals Hippocampal and Amygdalar Volume Changes in Major Depressive Disorder: A Targeted Review and Focus on Stress

2020 ◽  
Vol 4 ◽  
pp. 247054702094455
Author(s):  
Mark Nolan ◽  
Elena Roman ◽  
Anurag Nasa ◽  
Kirk J. Levins ◽  
Erik O’Hanlon ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Meta Analysis ◽  
Volume Changes ◽  
Major Depressive ◽  
Cohen’S D ◽  
Left And Right ◽  
Cohen's D

Medial temporal lobe structures have long been implicated in the pathogenesis of major depressive disorder. Although findings of smaller hippocampal and amygdalar volumes are common, inconsistencies remain in the literature. In this targeted review, we examine recent and significant neuroimaging papers examining the volumes of these structures in major depressive disorder. A targeted PubMed/Google Scholar search was undertaken focusing on volumetric neuroimaging studies of the hippocampus and amygdala in major depressive disorder. Where possible, mean volumes and accompanying standard deviations were extracted allowing computation of Cohen’s ds effect sizes. Although not a meta-analysis, this allows a broad comparison of volume changes across studies. Thirty-nine studies in total were assessed. Hippocampal substructures and amygdale substructures were investigated in 11 and 2 studies, respectively. The hippocampus was more consistently smaller than the amygdala across studies, which is reflected in the larger cumulative difference in volume found with the Cohen’s ds calculations. The left and right hippocampi were, respectively, 92% and 91.3% of the volume found in controls, and the left and right amygdalae were, respectively, 94.8% and 92.6% of the volume of controls across all included studies. The role of stress in temporal lobe structure volume reduction in major depressive disorder is discussed.

scholarly journals A Randomized Controlled Trial of Intranasal Neuropeptide Y in Patients With Major Depressive Disorder

2020 ◽  
Vol 23 (12) ◽  
pp. 783-790
Author(s):  
Aleksander A Mathé ◽  
Miranda Michaneck ◽  
Elisabeth Berg ◽  
Dennis S Charney ◽  
James W Murrough
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Neuropeptide Y ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Normal Brain ◽  
Major Depressive ◽  
Cohen’S D ◽  
Group Time ◽  
Cohen's D

Abstract Background Since about one-third of patients with major depressive disorder (MDD) do not respond adequately to available antidepressants, there is a need for treatments based on novel mechanisms of action. Neuropeptide Y (NPY), a normal brain constituent, is reduced in cerebrospinal fluid of patients with MDD and post-traumatic stress disorder and in corresponding rodent models. Moreover, NPY administered centrally or intranasally rescues pathophysiology in these models. Consequently, we conducted the first, to our knowledge, controlled trial of NPY as a treatment for MDD. Methods Thirty MDD patients on a stable dose of a conventional antidepressant insufflated 6.8 mg NPY (n = 12) or placebo (n = 18) in a double blind randomized fashion. Effects were assessed at baseline, +1 hour, +5 hours, +24 hours, and +48 hours. The primary outcome was change in depression severity measured with the Montgomery-Åsberg Depression Rating Scale (MADRS). Results NPY was superior to placebo at +24 hours (change −10.3 [95% CI: −13.8; −6.8]) vs −5.6 (95% CI: −8.4; −2.7); group*time F = 3.26, DF = (1,28), P = .04; Cohen’s d = 0.67). At +5 hours MADRS decreased −7.1 ([95% CI: −10.0; −4.2] vs −3.5 [95% CI: −5.8; −1.2]; group*time F = 2.69, DF = (1,28), P = .05; Cohen’s d = 0.61). MADRS reduction at +48 hours was not significant. Conclusions Since no results regarding the trajectory of NPY effects existed prior to this study we extrapolated from the known NPY biology and predicted the effects will occur 5–48 hours post insufflation. We chose +48 hours as the primary endpoint and +1, +5, and +24 hours as secondary endpoints. The results, the first of their kind, indicate that insufflated NPY is antidepressant, despite not meeting the primary outcome, and call for dose ranging and repeated NPY insufflation trials. Clinical Trial Registration EudraCT Number: 2014-000129-19.

scholarly journals Beneficial and harmful effects of antidepressants versus placebo, ‘active placebo’, or no intervention for adults with major depressive disorder: a protocol for a systematic review of published and unpublished data with meta-analyses and trial sequential analyses

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Sophie Juul ◽  
Faiza Siddiqui ◽  
Marija Barbateskovic ◽  
Caroline Kamp Jørgensen ◽  
Michael Pascal Hengartner ◽  
...  
Keyword(s):  
Systematic Review ◽  
Major Depressive Disorder ◽  
Depressive Symptoms ◽  
Adverse Events ◽  
Depressive Disorder ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Major Depressive ◽  
Serious Adverse Events ◽  
Harmful Effects

Abstract Background Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide. Antidepressants are frequently used to treat major depressive disorder. It has been shown repeatedly that antidepressants seem to reduce depressive symptoms with a statistically significant effect, but the clinical importance of the effect sizes seems questionable. Both beneficial and harmful effects of antidepressants have not previously been sufficiently assessed. The main objective of this review will be to evaluate the beneficial and harmful effects of antidepressants versus placebo, ‘active placebo’, or no intervention for adults with major depressive disorder. Methods/design A systematic review with meta-analysis will be reported as recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), bias will be assessed with the Cochrane Risk of Bias tool-version 2 (ROB2), our eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, Trial Sequential Analysis will be conducted to control for random errors, and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. To identify relevant trials, we will search both for published and unpublished trials in major medical databases from their inception to the present. Clinical study reports will be obtained from regulatory authorities and pharmaceutical companies. Two review authors will independently screen the results of the literature searches, extract data, and perform risk of bias assessment. We will include any published or unpublished randomised clinical trial comparing one or more antidepressants with placebo, ‘active placebo’, or no intervention for adults with major depressive disorder. The following active agents will be included: agomelatine, amineptine, amitriptyline, bupropion, butriptyline, cianopramine, citalopram, clomipramine, dapoxetine, demexiptiline, desipramine, desvenlafaxine, dibenzepin, dosulepin, dothiepin, doxepin, duloxetine, escitalopram, fluoxetine, fluvoxamine, imipramine, iprindole, levomilnacipran, lofepramine, maprotiline, melitracen, metapramine, milnacipran, mirtazapine, nefazodone, nortriptyline, noxiptiline, opipramol, paroxetine, protriptyline, quinupramine, reboxetine, sertraline, trazodone, tianeptine, trimipramine, venlafaxine, vilazodone, and vortioxetine. Primary outcomes will be depressive symptoms, serious adverse events, and quality of life. Secondary outcomes will be suicide or suicide attempt, suicidal ideation, and non-serious adverse events. Discussion As antidepressants are commonly used to treat major depressive disorder in adults, a systematic review evaluating their beneficial and harmful effects is urgently needed. This review will inform best practice in treatment and clinical research of this highly prevalent and burdensome disorder. Systematic review registration PROSPERO CRD42020220279

scholarly journals Investigating regions of shared genetic variation in attention deficit/hyperactivity disorder and major depressive disorder: a GWAS meta-analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Victoria Powell ◽  
Joanna Martin ◽  
Anita Thapar ◽  
Frances Rice ◽  
Richard J. L. Anney
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Genetic Correlation ◽  
Attention Deficit ◽  
Meta Analysis ◽  
Major Depressive ◽  
Hyperactivity Disorder ◽  
High Level ◽  
Genomic Regions

AbstractAttention deficit/hyperactivity disorder (ADHD) demonstrates a high level of comorbidity with major depressive disorder (MDD). One possible contributor to this is that the two disorders show high genetic correlation. However, the specific regions of the genome that may be responsible for this overlap are unclear. To identify variants associated with both ADHD and MDD, we performed a meta-analysis of GWAS of ADHD and MDD. All genome wide significant (p < 5 × 10–8) SNPs in the meta-analysis that were also strongly associated (p < 5 × 10–4) independently with each disorder were followed up. These putatively pleiotropic SNPs were tested for additional associations across a broad range of phenotypes. Fourteen linkage disequilibrium-independent SNPs were associated with each disorder separately (p < 5 × 10–4) and in the cross-disorder meta-analysis (p < 5 × 10–8). Nine of these SNPs had not been highlighted previously in either individual GWAS. Evidence supported nine of the fourteen SNPs acting as eQTL and two as brain eQTL. Index SNPs and their genomic regions demonstrated associations with other mental health phenotypes. Through conducting meta-analysis on ADHD and MDD only, our results build upon the previously observed genetic correlation between ADHD and MDD and reveal novel genomic regions that may be implicated in this overlap.

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