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Meta-Analysis of 89 Structural MRI Studies in Posttraumatic Stress Disorder and Comparison With Major Depressive Disorder.

ABSTRACT: OBJECTIVE:The authors conducted a comprehensive meta-analysis of MRI region-of-interest and voxel-based morphometry (VBM) studies in posttraumatic stress disorder (PTSD). Because patients have high rates of comorbid depression, an additional objective was to compare the findings to a meta-analysis of MRI studies in depression. METHOD:The MEDLINE database was searched for studies from 1985 through 2016. A total of 113 studies met inclusion criteria and were included in an online database. Of these, 66 were selected for the region-of-interest meta-analysis and 13 for the VBM meta-analysis. The region-of-interest meta-analysis was conducted and compared with a meta-analysis of major depressive disorder. Within the region-of-interest meta-analysis, three subanalyses were conducted that included control groups with and without trauma. RESULTS:In the region-of-interest meta-analysis, patients with PTSD compared with all control subjects were found to have reduced brain volume, intracranial volume, and volumes of the hippocampus, insula, and anterior cingulate. PTSD patients compared with nontraumatized or traumatized control subjects showed similar changes. Traumatized compared with nontraumatized control subjects showed smaller volumes of the hippocampus bilaterally. For all regions, pooled effect sizes (Hedges' g) varied from -0.84 to 0.43, and number of studies from three to 41. The VBM meta-analysis revealed prominent volumetric reductions in the medial prefrontal cortex, including the anterior cingulate. Compared with region-of-interest data from patients with major depressive disorder, those with PTSD had reduced total brain volume, and both disorders were associated with reduced hippocampal volume. CONCLUSIONS:The meta-analyses revealed structural brain abnormalities associated with PTSD and trauma and suggest that global brain volume reductions distinguish PTSD from major depression.

SUBMITTER: Bromis K

PROVIDER: S-EPMC6169727 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Meta-Analysis of 89 Structural MRI Studies in Posttraumatic Stress Disorder and Comparison With Major Depressive Disorder.

Bromis Konstantinos K Calem Maria M Reinders Antje A T S AATS Williams Steven C R SCR Kempton Matthew J MJ

The American journal of psychiatry 20180719 10

<h4>Objective</h4>The authors conducted a comprehensive meta-analysis of MRI region-of-interest and voxel-based morphometry (VBM) studies in posttraumatic stress disorder (PTSD). Because patients have high rates of comorbid depression, an additional objective was to compare the findings to a meta-analysis of MRI studies in depression.<h4>Method</h4>The MEDLINE database was searched for studies from 1985 through 2016. A total of 113 studies met inclusion criteria and were included in an online da ...[more]

PMID: 30021460

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Project description:BackgroundDecisions under risk and with outcomes that are delayed in time are ubiquitous in real life and can have a significant impact on the health and wealth of the decision-maker. Despite its potential relevance for real-world choices, the degree of aberrant risky and intertemporal decision-making in patients suffering from major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) has received little attention to date.MethodWe used a case-control design to compare decision-making in healthy control subjects (N=16) versus untreated depressed subjects in a current major depressive episode (N=20). In order to examine how major depressive disorder (MDD) may impact decision-making, subjects made decisions over (1) risky outcomes and (2) delayed outcomes in the domain of gains and losses using choice paradigms from neuroeconomics. In a pre-planned analysis, depressed subjects were subdivided into those with primary PTSD along with comorbid MDD (MDD+PTSD) versus those with primary MDD without PTSD (MDD-only). Choice behavior was modeled via a standard econometric model of intertemporal choice, a quasi-hyperbolic temporal discounting function, which was estimated for each subject group separately.ResultsUnder conditions of potential gain, depressed subjects demonstrated greater discounting for gains across all time frames compared to controls. In the realm of losses, both subgroups of depressed subjects discounted more steeply than controls for short time frames. However, for delayed losses ranging from >1-10 years, MDD+PTSD subjects showed shallower discounting rates relative to MDD-only subjects, who continued to discount future losses steeply. Risk attitudes did not contribute to differences in intertemporal choice.ConclusionsDepressed patients make choices that minimize current pain and maximize current reward, despite severe later consequences or lost opportunities. Anxiety associated with PTSD may serve as a partially protective factor in decision-making about long-term potential losses compared to MDD patients without PTSD.

Project description:BackgroundRepetitive transcranial magnetic stimulation (TMS) therapy can modulate pathological neural network functional connectivity in major depressive disorder (MDD). Posttraumatic stress disorder is often comorbid with MDD, and symptoms of both disorders can be alleviated with TMS therapy. This is the first study to evaluate TMS-associated changes in connectivity in patients with comorbid posttraumatic stress disorder and MDD.MethodsResting-state functional connectivity magnetic resonance imaging was acquired before and after TMS therapy in 33 adult outpatients in a prospective open trial. TMS at 5 Hz was delivered, in up to 40 daily sessions, to the left dorsolateral prefrontal cortex. Analyses used a priori seeds relevant to TMS, posttraumatic stress disorder, or MDD (subgenual anterior cingulate cortex [sgACC], left dorsolateral prefrontal cortex, hippocampus, and basolateral amygdala) to identify imaging predictors of response and to evaluate clinically relevant changes in connectivity after TMS, followed by leave-one-out cross-validation. Imaging results were explored using data-driven multivoxel pattern activation.ResultsMore negative pretreatment connectivity between the sgACC and the default mode network predicted clinical improvement, as did more positive amygdala-to-ventromedial prefrontal cortex connectivity. After TMS, symptom reduction was associated with reduced connectivity between the sgACC and the default mode network, left dorsolateral prefrontal cortex, and insula, and reduced connectivity between the hippocampus and the salience network. Multivoxel pattern activation confirmed seed-based predictors and correlates of treatment outcomes.ConclusionsThese results highlight the central role of the sgACC, default mode network, and salience network as predictors of TMS response and suggest their involvement in mechanisms of action. Furthermore, this work indicates that there may be network-based biomarkers of clinical response relevant to these commonly comorbid disorders.

Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

Dataset Information

Meta-Analysis of 89 Structural MRI Studies in Posttraumatic Stress Disorder and Comparison With Major Depressive Disorder.

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Meta-Analysis of 89 Structural MRI Studies in Posttraumatic Stress Disorder and Comparison With Major Depressive Disorder.

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