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.

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.

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).

Differential response to SSRI versus Placebo and distinct neural signatures among data-driven subgroups of patients with major depressive disorder.

Objective: To identify data-driven subgroups in Major Depressive Disorder (MDD) in order to elucidate underlying neural correlates and determine if these subgroups have utility in predicting response to antidepressant versus placebo.

Methods: Using 27 clinical measures at baseline of Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC) study, participants with MDD (n=244) were sub grouped using principal component (PC) analysis. Baseline-to-week-8 changes in depression severity with sertraline versus placebo were compared in these subgroups.

Sex-specific differences in the association between body mass index and brain aging in young adults: Findings from the human connectome project.

Background: This report evaluated sex-specific differences in the association between brain aging and body mass index (BMI) in young adults using the publicly available data from the Human Connectome Project (HCP).

Methods: Participants of HCP with available structural imaging and BMI data were included [n = 1112; mean age = 28.80 (SD = 3.

Dorsolateral Prefrontal Cortex and Subcallosal Cingulate Connectivity Show Preferential Antidepressant Response in Major Depressive Disorder.

Background: Major depressive disorder is associated with abnormal connectivity across emotion and reward circuits as well as other established circuits that may negatively impact treatment response. The goal of this study was to perform an exploratory reanalysis of archival data from a clinical trial to identify moderators of treatment outcome of sertraline over placebo.

Methods: EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care) study participants completed magnetic resonance imaging before randomization to either sertraline or placebo for 8 weeks (n = 279).

Pretreatment Reward Sensitivity and Frontostriatal Resting-State Functional Connectivity Are Associated With Response to Bupropion After Sertraline Nonresponse.

Background: Standard guidelines recommend selective serotonin reuptake inhibitors as first-line antidepressants for adults with major depressive disorder, but success is limited and patients who fail to benefit are often switched to non-selective serotonin reuptake inhibitor agents. This study investigated whether brain- and behavior-based markers of reward processing might be associated with response to bupropion after sertraline nonresponse.

Methods: In a two-stage, double-blinded clinical trial, 296 participants were randomized to receive 8 weeks of sertraline or placebo in stage 1.

Comprehensive phenotyping of depression disease trajectory and risk: Rationale and design of Texas Resilience Against Depression study (T-RAD).

Depression has a chronic and recurrent course often with early onset and is the leading cause of disability worldwide. In contrast to diagnoses for other conditions which rely on precise medical tests, the diagnosis of depression still focuses exclusively on symptom reports. As a result, heterogeneous patient groups are included under broad categories.

Effect of Intrinsic Patterns of Functional Brain Connectivity in Moderating Antidepressant Treatment Response in Major Depression.

Objective: Major depressive disorder is associated with aberrant resting-state functional connectivity across multiple brain networks supporting emotion processing, executive function, and reward processing. The purpose of this study was to determine whether patterns of resting-state connectivity between brain regions predict differential outcome to antidepressant medication (sertraline) compared with placebo.

Methods: Participants in the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study underwent structural and resting-state functional MRI at baseline.

Discovery and replication of cerebral blood flow differences in major depressive disorder.

Major depressive disorder (MDD) is a serious, heterogeneous disorder accompanied by brain-related changes, many of which are still to be discovered or refined. Arterial spin labeling (ASL) is a neuroimaging technique used to measure cerebral blood flow (CBF; perfusion) to understand brain function and detect differences among groups. CBF differences have been detected in MDD, and may reveal biosignatures of disease-state.

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 "accurately" identify antidepressant-responsive patterns and reduce the trial-and-error process in treatment selection. Cerebral blood perfusion, as measured by Arterial Spin Labelling (ASL), has been used to understand resting-state brain function, detect abnormalities in MDD, and could serve as a marker for treatment selection.