40 research outputs found
Cortical thickness is not associated with current depression in a clinical treatment study
BackgroundReduced cortical thickness is a candidate biological marker of depression, although findings are inconsistent. This could reflect analytic heterogeneity, such as use of regionâwise cortical thickness based on the Freesurfer DesikanâKilliany (DK) atlas or surfaceâbased morphometry (SBM). The Freesurfer Destrieux (DS) atlas (more, smaller regions) has not been utilized in depression studies. This could also reflect differential gender and age effects.MethodsCortical thickness was collected from 170 currently depressed adults and 52 neverâdepressed adults. Visually inspected and approved Freesurferâgenerated surfaces were used to extract cortical thickness estimates according to the DK atlas (68 regions) and DS atlas (148 regions) for regionâwise analysis (216 total regions) and for SBM.ResultsOverall, except for small effects in a few regions, the two regionâwise approaches generally failed to discriminate depressed adults from nondepressed adults or current episode severity. Differential effects by age and gender were also rare and small in magnitude. Using SBM, depressed adults showed a significantly thicker cluster in the left supramarginal gyrus than nondepressed adults (Pâ=â0.047) but there were no associations with current episode severity.ConclusionsThree analytic approaches (i.e., DK atlas, DS atlas, and SBM) converge on the notion that cortical thickness is a relatively weak discriminator of current depression status. Differential age and gender effects do not appear to represent key moderators. Robust associations with demographic factors will likely hinder translation of cortical thickness into a clinically useful biomarker. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc. Hum Brain Mapp 38:4370â4385, 2017. © 2017 Wiley Periodicals, Inc.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138250/1/hbm23664_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138250/2/hbm23664.pd
Testâretest reliability of freesurfer measurements within and between sites: Effects of visual approval process
In the last decade, many studies have used automated processes to analyze magnetic resonance imaging (MRI) data such as cortical thickness, which is one indicator of neuronal health. Due to the convenience of image processing software (e.g., FreeSurfer), standard practice is to rely on automated results without performing visual inspection of intermediate processing. In this work, structural MRIs of 40 healthy controls who were scanned twice were used to determine the testâretest reliability of FreeSurferâderived cortical measures in four groups of subjectsâthose 25 that passed visual inspection (approved), those 15 that failed visual inspection (disapproved), a combined group, and a subset of 10 subjects (Travel) whose test and retest scans occurred at different sites. Testâretest correlation (TRC), intraclass correlation coefficient (ICC), and percent difference (PD) were used to measure the reliability in the Destrieux and DesikanâKilliany (DK) atlases. In the approved subjects, reliability of cortical thickness/surface area/volume (DK atlas only) were: TRC (0.82/0.88/0.88), ICC (0.81/0.87/0.88), PD (0.86/1.19/1.39), which represent a significant improvement over these measures when disapproved subjects are included. Travel subjectsâ results show that cortical thickness reliability is more sensitive to site differences than the cortical surface area and volume. To determine the effect of visual inspection on sample size required for studies of MRIâderived cortical thickness, the number of subjects required to show group differences was calculated. Significant differences observed across imaging sites, between visually approved/disapproved subjects, and across regions with different sizes suggest that these measures should be used with caution. Hum Brain Mapp 36:3472â3485, 2015. © 2015 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113142/1/hbm22856.pd
Demonstrating testâretest reliability of electrophysiological measures for healthy adults in a multisite study of biomarkers of antidepressant treatment response
Growing evidence suggests that loudness dependency of auditory evoked potentials (LDAEP) and resting EEG alpha and theta may be biological markers for predicting response to antidepressants. In spite of this promise, little is known about the joint reliability of these markers, and thus their clinical applicability. New standardized procedures were developed to improve the compatibility of data acquired with different EEG platforms, and used to examine testâretest reliability for the three electrophysiological measures selected for a multisite projectâEstablishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC). Thirtyânine healthy controls across four clinical research sites were tested in two sessions separated by about 1 week. Resting EEG (eyesâopen and eyesâclosed conditions) was recorded and LDAEP measured using binaural tones (1000 Hz, 40 ms) at five intensities (60â100 dB SPL). Principal components analysis of current source density waveforms reduced volume conduction and provided referenceâfree measures of resting EEG alpha and N1 dipole activity to tones from auditory cortex. Lowâresolution electromagnetic tomography (LORETA) extracted resting theta current density measures corresponding to rostral anterior cingulate (rACC), which has been implicated in treatment response. There were no significant differences in posterior alpha, N1 dipole, or rACC theta across sessions. Testâretest reliability was .84 for alpha, .87 for N1 dipole, and .70 for theta rACC current density. The demonstration of goodâtoâexcellent reliability for these measures provides a template for future EEG/ERP studies from multiple testing sites, and an important step for evaluating them as biomarkers for predicting treatment response.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135271/1/psyp12758_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135271/2/psyp12758.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135271/3/psyp12758-sup-0001-suppinfo1.pd
Comprehensive Versus Usual Community Care for First-Episode Psychosis: 2-Year Outcomes From the NIMH RAISE Early Treatment Program
The primary aim was to compare the impact of NAVIGATE, a comprehensive, multidisciplinary, team-based treatment approach for first episode psychosis designed for implementation in the U.S. healthcare system, to Community Care on quality of life
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Test-retest Reliability Of Cerebral Blood Flow In Healthy Individuals Using Arterial Spin Labeling: Findings From The Embarc Study
IntroductionâPrevious investigations of test-retest reliability of cerebral blood flow (CBF) at rest measured with pseudo-continuous Arterial Spin Labeling (pCASL) demonstrated good reliability, but are limited by the use of similar scanner platforms. In the present study we examined test-retest reliability of CBF in regions implicated in emotion and the default mode network
A Comprehensive Examination Of White Matter Tracts And Connectometry In Major Depressive Disorder
Background
Major depressive disorder (MDD) is a debilitating disorder characterized by widespread brain abnormalities. The literature is mixed as to whether or not white matter abnormalities are associated with MDD. This study sought to examine fractional anisotropy (FA) in white matter tracts in individuals with MDD using diffusion tensor imaging (DTI).
Methods
139 participants with MDD and 39 healthy controls (HC) in a multisite study were included. DTI scans were acquired in 64 directions and FA was determined in the brain using four methods: region of interest (ROI), tract-based spatial statistics (TBSS), and diffusion tractography. Diffusion connectometry was used to identify white matter pathways associated with MDD.
Results
There were no significant differences when comparing FA in MDD and HC groups using any method. In the MDD group, there was a significant relationship between depression severity and FA in the right medial orbitofrontal cortex, and between age of onset of MDD and FA in the right caudal anterior cingulate cortex using the ROI method. There was a significant relationship between age of onset and connectivity in the thalamocortical radiation, inferior longitudinal fasciculus, and cerebellar tracts using diffusion connectometry.
Conclusions
The lack of group differences in FA and connectometry analysis may result from the clinically heterogenous nature of MDD. However, the relationship between FA and depression severity may suggest a state biomarker of depression that should be investigated as a potential indicator of response. Age of onset may also be a significant clinical feature to pursue when studying white matter tracts
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A Comparison Of Structural Connectivity In Anxious Depression Versus Non-anxious Depression
Background: Major depressive disorder (MDD) and anxiety disorders are highly co-morbid. Research has shown conïŹicting evidence for white matter alteration and amygdala volume reduction in mood and anxiety disorders. To date, no studies have examined differences in structural connectivity between anxious depressed and non-anxious depressed individuals. This study compared fractional anisotropy (FA) and density of selected white matter tracts and amygdala volume between anxious depressed and non-anxious depressed individuals. Methods: 64- direction DTI and T1 scans were collected from 110 unmedicated subjects with MDD, 39 of whom had a co-morbid anxiety disorder diagnosis. Region of interest (ROI) and tractography methods were performed to calculate amygdala volume and FA in the uncinate fasciculus, respectively. Diffusion connectometry was performed to identify whole brain group differences in white matter health. Correlations were computed between biological and clinical measures. Results: Tractography and ROI analyses showed no signiïŹcant differences between bilateral FA values or bilateral amygdala volumes when comparing the anxious depressed and non-anxious depressed groups. The diffusion connectometry analysis showed no signiïŹcant differences in anisotropy between the groups. Furthermore, there were no signiïŹcant relationships between MRI-based and clinical measures. Conclusion: The lack of group differences could indicate that structural connectivity and amygdalae volumes of those with anxious-depression are not signiïŹcantly altered by a co-morbid anxiety disorder. Improving understanding of anxiety co-morbid with MDD would facilitate development of treatments that more accurately target the underlying networks
Neuroticism And Individual Differences In Neural Function In Unmedicated Major Depression: Findings From The Embarc Study
BACKGROUND: Personality dysfunction represents one of the only predictors of differential response between active treatments for depression to have replicated. We examine whether depressed patients with higher neuroticism scores, a marker of personality dysfunction, show differences compared with depressed patients with lower scores in the functioning of two brain regions associated with treatment response, the anterior cingulate and anterior insula cortices. METHODS: Functional magnetic resonance imaging data during an emotional Stroop task were collected from 135 adults with major depressive disorder at four academic medical centers participating in the EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care) study. Secondary analyses were conducted including a sample of 28 healthy subjects. RESULTS: In whole-brain analyses, higher neuroticism among adults with depression was associated with increased activity in and connectivity with the right anterior insula cortex to incongruent compared with congruent emotional stimuli (all k $ 281, all p , .05 familywise error corrected), covarying for concurrent psychiatric distress. We also observed an unanticipated relationship between neuroticism and reduced activity in the precuneus (k 5 269, p , .05 familywise error corrected). Exploratory analyses including healthy subjects suggested that associations between neuroticism and brain function may be nonlinear over the full range of neuroticism scores. CONCLUSIONS: This study provides convergent evidence for the importance of the right anterior insula cortex as a brain-based marker of clinically meaningful individual differences in neuroticism among adults with depression. This is a critical next step in linking personality dysfunction, a replicated clinical predictor of differential antidepressant treatment response, with differences in underlying brain function
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Cerebral Blood Perfusion Predicts Response To Sertraline Versus Placebo For Major Depressive Disorder In The Embarc Trial
Background: Major Depressive Disorder (MDD) has been associated with brain-related changes. However, biomarkers have yet to be defined that could âaccuratelyâ identify antidepressant-responsive patterns and reduce the trial-and-error process in treatment selection. Cerebral blood perfusion, as measured by Arterial Spin Labeling (ASL), has been used to understand resting-state brain function, detect abnormalities in MDD, and could serve as a marker for treatment selection. As part of a larger trial to identify predictors of treatment outcome, the current investigation aimed to identify perfusion predictors of treatment response in MDD.
Methods: For this secondary analysis, participants include 231 individuals with MDD from the EMBARC study, a randomized, placebo-controlled trial investigating clincal, behavioral, and biological predictors of antidepressant response. Participants received sertraline (n=114) or placebo (n=117) and response was monitored for 8 weeks. Pre-treatment neuroimaging was completed, including ASL. A whole-brain, voxel-wise linear mixed-effects model was conducted to identify brain regions in which perfusion levels differentially predict (moderate) treatment response. Clinical effectiveness of perfusion moderators was investigated by composite moderator analysis and remission rates. Composite moderator analysis combined the effect of individual perfusion moderators and identified which contribute to sertraline or placebo as the âpreferredâ treatment. Remission rates were calculated for participants âaccuratelyâ treated based on the composite moderator (lucky) versus âinaccuratelyâ treated (unlucky).
Findings: Perfusion levels in multiple brain regions differentially predicted improvement with sertraline over placebo. Of these regions, perfusion in the putamen and anterior insula, inferior temporal gyrus, fusiform, parahippocampus, inferior parietal lobule, and orbital frontal gyrus contributed to sertraline response. Remission rates increased from 37% for all those who received sertraline to 53% for those who were lucky to have received it and sertraline was their perfusion-preferred treatment.
Interpretation: This large study showed that perfusion patterns in brain regions involved with reward, salience, affective, and default mode processing moderate treatment response favoring sertraline over placebo. Accurately matching patients with defined perfusion patterns could significantly increase remission rates.
Funding: National Institute of Mental Health, the Hersh Foundation, and the Center for Depression Research and Clinical Care, Peter OâDonnell Brain Institute at UT Southwestern Medical Cente
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Characterizing Anxiety Subtypes And The Relationship To Behavioral Phenotyping In Major Depression: Results From The Embarc Study
The current study aimed to characterize the multifaceted nature of anxiety in patients with major depression by evaluating distinct anxiety factors. We then related these derived anxiety factors to performance on a Flanker Task of cognitive control, in order to further validate these factors. Data were collected from 195 patients with nonpsychotic chronic or recurrent major depression or dysthymic disorder. At baseline, participants completed self-report measures of anxiety, depression, and other related symptoms (mania, suicidality) and clinicians administered a structured diagnostic interview and the Hamilton Rating Scale for Depression, including anxiety/ somatization items. Four discrete factors (State Anxiety, Panic, Neuroticism/Worry, and Restlessness/Agitation) emerged, with high degrees of internal consistency. Discriminant and convergent validity analyses also yielded ïŹndings in the expected direction. Furthermore, the neuroticism/worry factor was associated with Flanker Task interference, such that individuals higher on neuroticism/worry responded more incorrectly (yet faster) to incongruent vs. congruent trials whereas individuals higher on the fear/panic factor responded more slowly, with no accuracy eïŹect, to the Flanker Task stimuli. These results parse anxiety into four distinct factors that encompass physiological, psychological, and cognitive components of anxiety. While state anxiety, panic and neuroticism/worry are related to existing measures of anxiety, the Restlessness/Agitation factor appears to be a unique measure of general anxious arousal. Furthermore, two factors were independently validated through the Flanker Task. These results suggest that these anxiety domains have distinct behavioral proïŹles and could have diïŹerential responses to distinct treatments