Clinical and sociodemographic features of the Texas resilience against depression (T-RAD) study: Findings from the initial cohort.

Objective: The burden of major depressive disorder is compounded by a limited understanding of its risk factors, the limited efficacy of treatments, and the lack of precision approaches to guide treatment selection. The Texas Resilience Against Depression (T-RAD) study was designed to explore the etiology of depression by collecting comprehensive socio-demographic, clinical, behavioral, neurophysiological/neuroimaging, and biological data from depressed individuals (D2K) and youth at risk for depression (RAD).

Methods: This report details the baseline sociodemographic, clinical, and functional features from the initial cohort (D2K N = 1040, RAD N = 365).

Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo.

Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw MRI data were shared from international samples ( = 1,384) of medication-free individuals with first-episode and recurrent MDD ( = 685) in a current depressive episode of at least moderate severity, but not treatment-resistant depression, as well as healthy controls ( = 699).

Brain ventricle and choroid plexus morphology as predictor of treatment response in major depression: Findings from the EMBARC study.

Recent observations suggest a role of the volume of the cerebral ventricle volume, corpus callosum (CC) segment volume, in particular that of the central-anterior part, and choroid plexus (CP) volume for treatment resistance of major depressive disorder (MDD). An increased CP volume has been associated with increased inflammatory activity and changes in the structure of the ventricles and corpus callosum. We attempt to replicate and confirm that these imaging markers are associated with clinical outcome in subjects from the EMBARC study, as implied by a recent pilot study.

Features of immunometabolic depression as predictors of antidepressant treatment outcomes: pooled analysis of four clinical trials.

Background: Profiling patients on a proposed 'immunometabolic depression' (IMD) dimension, described as a cluster of atypical depressive symptoms related to energy regulation and immunometabolic dysregulations, may optimise personalised treatment.

Aims: To test the hypothesis that baseline IMD features predict poorer treatment outcomes with antidepressants.

Method: Data on 2551 individuals with depression across the iSPOT-D ( = 967), CO-MED ( = 665), GENDEP ( = 773) and EMBARC ( = 146) clinical trials were used.

Reward Behavior Disengagement, a Neuroeconomic Model-Based Objective Measure of Reward Pathology in Depression: Findings from the EMBARC Trial.

The probabilistic reward task (PRT) has identified reward learning impairments in those with major depressive disorder (MDD), as well as anhedonia-specific reward learning impairments. However, attempts to validate the anhedonia-specific impairments have produced inconsistent findings. Thus, we seek to determine whether the Reward Behavior Disengagement (RBD), our proposed economic augmentation of PRT, differs between MDD participants and controls, and whether there is a level at which RBD is high enough for depressed participants to be considered objectively disengaged.

Immune Dysregulation in Treatment-Resistant Depression: Precision Approaches to Treatment Selection and Development of Novel Treatments.

Owing to the link between immune dysfunction and treatment-resistant depression (TRD) and the overwhelming evidence that the immune dysregulation and major depressive disorder (MDD) are associated with each other, using immune profiles to identify the biological distinct subgroup may be the step forward to understanding MDD and TRD. This report aims to briefly review the role of inflammation in the pathophysiology of depression (and TRD in particular), the role of immune dysfunction to guide precision medicine, tools used to understand immune function, and novel statistical techniques.

Brain Ventricle and Choroid Plexus Morphology as Predictor of Treatment Response: Findings from the EMBARC Study.

Recent observations suggest a role of the choroid plexus (CP) and cerebral ventricle volume (CV), to identify treatment resistance of major depressive disorder (MDD). We tested the hypothesis that these markers are associated with clinical improvement in subjects from the EMBARC study, as implied by a recent pilot study. The EMBARC study characterized biological markers in a randomized placebo-controlled trial of sertraline vs.

AI-based dimensional neuroimaging system for characterizing heterogeneity in brain structure and function in major depressive disorder: COORDINATE-MDD consortium design and rationale.

Background: Efforts to develop neuroimaging-based biomarkers in major depressive disorder (MDD), at the individual level, have been limited to date. As diagnostic criteria are currently symptom-based, MDD is conceptualized as a disorder rather than a disease with a known etiology; further, neural measures are often confounded by medication status and heterogeneous symptom states.

Methods: We describe a consortium to quantify neuroanatomical and neurofunctional heterogeneity via the dimensions of novel multivariate coordinate system (COORDINATE-MDD).

Accelerated Brain Aging in Adults With Major Depressive Disorder Predicts Poorer Outcome With Sertraline: Findings From the EMBARC Study.

Background: Major depressive disorder (MDD) may be associated with accelerated brain aging (higher brain age than chronological age). This report evaluated whether brain age is a clinically useful biomarker by checking its test-retest reliability using magnetic resonance imaging scans acquired 1 week apart and by evaluating the association of accelerated brain aging with symptom severity and antidepressant treatment outcomes.

Methods: Brain age was estimated in participants of the EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care) study using T1-weighted structural magnetic resonance imaging (MDD n = 290; female n = 192; healthy control participants n = 39; female n = 24).

Accelerated brain aging in individuals with diabetes: Association with poor glycemic control and increased all-cause mortality.

Background: Diabetes has been linked to accelerated brain aging, i.e., neuroimaging-predicted age of brain is higher than chronological age.

Neural substrates of emotional conflict with anxiety in major depressive disorder: Findings from the Establishing Moderators and biosignatures of Antidepressant Response in Clinical Care (EMBARC) randomized controlled trial.

Background: The brain circuitry of depression and anxiety/fear is well-established, involving regions such as the limbic system and prefrontal cortex. We expand prior literature by examining the extent to which four discrete factors of anxiety (immediate state anxiety, physiological/panic, neuroticism/worry, and agitation/restlessness) among depressed outpatients are associated with differential responses during reactivity to and regulation of emotional conflict.

Methods: A total of 172 subjects diagnosed with major depressive disorder underwent functional magnetic resonance imaging while performing an Emotional Stroop Task.

Patterns of Pretreatment Reward Task Brain Activation Predict Individual Antidepressant Response: Key Results From the EMBARC Randomized Clinical Trial.

Background: The lack of biomarkers to inform antidepressant selection is a key challenge in personalized depression treatment. This work identifies candidate biomarkers by building deep learning predictors of individual treatment outcomes using reward processing measures from functional magnetic resonance imaging, clinical assessments, and demographics.

Methods: Participants in the EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care) study (n = 222) underwent reward processing task-based functional magnetic resonance imaging at baseline and were randomized to 8 weeks of sertraline (n = 106) or placebo (n = 116).

Comparison of inflammatory markers as moderators of depression outcomes: A CO-MED study.

Background: Prior work suggests some individual immunomarkers may be useful moderators of treatment response between antidepressant medications. The relative moderating effect of individual immunomarkers remains unclear. It is also unknown whether combinations of immunomarkers have a superior moderating effect compared to any individual immunomarker.

Impact of the COVID-19 pandemic on adults with current and prior depression: initial findings from the longitudinal Texas RAD study.

Background: Emerging work has suggested worsening mental health in the general population during the COVID-19 pandemic, but there is minimal data on individuals with a prior history of depression.

Methods: Data regarding depression, anxiety and quality of life in adult participants with a history of a depressive disorder (n = 308) were collected before and during the COVID-19 pandemic. Mixed effects regression models were fit for these outcomes over the period May - August 2020, controlling for pre-pandemic depressive groups (none, mild, moderate-to-severe), demographic characteristics, and early COVID-19 related experiences (such as disruptions in routines, mental health treatment, and social supports).

Smoking status links habenular volume to glycated hemoglobin: Findings from the Human Connectome Project-Young Adult.

Background: The habenula-pancreas axis regulates the stimulatory effects of nicotine on blood glucose levels and may participate in the emergence of type 2 diabetes in human tobacco smokers. This secondary analysis of young adults from the Human Connectome Project (HCP-YA) evaluated whether smoking status links the relationship between habenular volume and glycated hemoglobin (HbA1c), a marker of long-term glycemic control.

Methods: Habenula segmentation was performed using a fully-automated myelin content-based approach in HCP-YA participants and the results were inspected visually (n = 693; aged 22-37 years).

Cross-Sectional Associations Among Symptoms of Pain, Irritability, and Depression and How These Symptoms Relate to Social Functioning and Quality of Life: Findings From the EMBARC and STRIDE Studies and the VitalSign6 Project.

Objective: The aim of this report was to evaluate the psychometric properties of the Pain Frequency, Intensity, and Burden Scale (P-FIBS), a brief measure of pain, as well as the association of pain with irritability and depression and how these symptoms relate to functional impairments.

Methods: Participants of 2 randomized controlled trials (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care [EMBARC; n = 251 with DSM-IV diagnosis of major depressive disorder; study duration: August 2011-December 2015] and STimulant Reduction Intervention Using Dosed Exercise [STRIDE; n = 302 with DSM-IV diagnosis of stimulant abuse or dependence; study-duration: July 2010-February 2013]) and treatment-seeking patients in primary care clinics from an ongoing quality-improvement project (VitalSign; n = 4,370; project duration: August 2014-July 2019) were included. Psychometric properties of the P-FIBS were evaluated with confirmatory factor and item response theory analyses in EMBARC and VitalSign.

Anatomically-Informed Data Augmentation for Functional MRI with Applications to Deep Learning.

The application of deep learning to build accurate predictive models from functional neuroimaging data is often hindered by limited dataset sizes. Though data augmentation can help mitigate such training obstacles, most data augmentation methods have been developed for natural images as in computer vision tasks such as CIFAR, not for medical images. This work helps to fills in this gap by proposing a method for generating new functional Magnetic Resonance Images (fMRI) with realistic brain morphology.