Test–retest 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 test–retest reliability of FreeSurfer‐derived cortical measures in four groups of subjects—those 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. Test–retest correlation (TRC), intraclass correlation coefficient (ICC), and percent difference (PD) were used to measure the reliability in the Destrieux and Desikan–Killiany (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 subjects’ 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 MRI‐derived 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 36:3472–3485, 2015. © 2015 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113142/1/hbm22856.pd

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

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

The Bidirectional Relationship of Depression and Inflammation: Double Trouble

Depression represents the number one cause of disability worldwide and is often fatal. Inflammatory processes have been implicated in the pathophysiology of depression. It is now well established that dysregulation of both the innate and adaptive immune systems occur in depressed patients and hinder favorable prognosis, including antidepressant responses. In this review, we describe how the immune system regulates mood and the potential causes of the dysregulated inflammatory responses in depressed patients. However, the proportion of never-treated major depressive disorder (MDD) patients who exhibit inflammation remains to be clarified, as the heterogeneity in inflammation findings may stem in part from examining MDD patients with varied interventions. Inflammation is likely a critical disease modifier, promoting susceptibility to depression. Controlling inflammation might provide an overall therapeutic benefit, regardless of whether it is secondary to early life trauma, a more acute stress response, microbiome alterations, a genetic diathesis, or a combination of these and other factors. In at least a subset of patients, depression is associated with dysregulated innate and adaptive immune response. Beurel et al. discuss how inflammation contributes to the pathophysiology of depression, acting as a disease modifier, hindering favorable prognosis and antidepressant response

Kynurenine pathway metabolites selectively associate with impaired associative memory function in depression

Activation of the kynurenine pathway (KP), an important downstream effect of inflammation, is a driver of depression and neurodegeneration. Damage from the end product of KP activation, quinolinic acid, may be responsible specifically for impairment in hippocampally mediated memory function, among its effects. We hypothesized that associative memory – the ability to recall relationships between items – would be sensitive to KP activation because it is heavily dependent on the hippocampus. We tested a sample of N ​= ​80 adults with unmedicated depression using a face-name task which assesses the ability to recognize, as well as to recall correct pairings, of faces and names. Plasma samples were analyzed for KP metabolites – tryptophan (TRP), kynurenine (KYN), quinolinic acid (QUIN) and kynurenic acid (KYNA). Using linear models we examined whether the KYN/TRP and QUIN/KYNA ratios predicted performance of recognition memory and associative memory, accounting for item type and the number of learning exposures to items (1 vs. 3). We found that for rearranged items viewed three times, associative memory performance was inversely related to the QUIN/KYNA ratio (p ​= ​0.01, p ​= ​0.001 adjusted for age, gender and race/ethnicity). Recognition memory was not associated with KP activation. The results support our hypothesis that KP activation most sensitively impacts hippocampally mediated memory function

Do menopausal status and use of hormone therapy affect antidepressant treatment response? Findings from the sequenced treatment alternatives to relieve depression (STAR*D) study

10.1089/jwh.2012.3479Journal of Women's Health222121-131JWHO

Test-retest Reliability Of Freesurfer Measurements Within And Between Sites: Effects Of Visual Approval Process: Test-retest Reliability Of Freesurfer Measurements

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 test–retest reliability of FreeSurfer-derived cortical measures in four groups of subjects—those 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. Test–retest correlation (TRC), intraclass correlation coefficient (ICC), and percent difference (PD) were used to measure the reliability in the Destrieux and Desikan–Killiany (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 subjects’ 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 MRI-derived 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