Differential role of fusiform gyrus coupling in depressive and anxiety symptoms during emotion perception.

Anxiety and depression co-occur; the neural substrates of shared and unique components of these symptoms are not understood. Given emotional alterations in internalizing disorders, we hypothesized that function of regions associated with emotion processing/regulation, including the anterior cingulate cortex (ACC), amygdala and fusiform gyrus (FG), would differentiate these symptoms. Forty-three adults with depression completed an emotional functional magnetic resonance imaging task and the Hamilton Depression and Anxiety Scales.

Randomized trial of brief interpersonal psychotherapy and cognitive behavioral therapy for depression delivered both in-person and by telehealth.

Background: Expert consensus guidelines recommend Cognitive Behavioral Therapy (CBT) and Interpersonal Psychotherapy (IPT), interventions that were historically delivered face-to-face, as first-line treatments for Major Depressive Disorder (MDD). Despite the ubiquity of telehealth following the COVID-19 pandemic, little is known about differential outcomes with CBT versus IPT delivered in-person (IP) or via telehealth (TH) or whether working alliance is affected.

Methods: Adults meeting DSM-5 criteria for MDD were randomly assigned to either 8 sessions of IPT or CBT (group).

Neural function during emotion regulation and future depressive symptoms in youth at risk for affective disorders.

Affective disorders (AD, including bipolar disorder, BD, and major depressive disorder) are severe recurrent illnesses. Identifying neural markers of processes underlying AD development in at-risk youth can provide objective, "early-warning" signs that may predate onset or worsening of symptoms. Using data (n = 34) from the Bipolar Offspring Study, we examined relationships between neural response in regions supporting executive function, and those supporting self-monitoring, during an emotional n-back task (focusing on the 2-back face distractor versus the 0-back no-face control conditions) and future depressive and hypo/manic symptoms across two groups of youth at familial risk for AD: Offspring of parents with BD (n = 15, age = 14.

Personality and psychopathology: In defense of a practical path toward integrating psychometric and biological approaches to advance a comprehensive model.

Personality and psychopathology each reflect patterns of internal experience and outward behavior that differ between people and affect functioning. Drawing strict distinctions between the two concepts is not only difficult, but it may prove unnecessary for advancing an integrated model of psychological experiences associated with mental illness. We argue that developing such a model will be critical for improving treatment outcomes, and we discuss a practical path forward.

Does the unified protocol really change neuroticism? Results from a randomized trial.

Background: Neuroticism is associated with the onset and maintenance of a number of mental health conditions, as well as a number of deleterious outcomes (e.g. physical health problems, higher divorce rates, lost productivity, and increased treatment seeking); thus, the consideration of whether this trait can be addressed in treatment is warranted.

Functional Disruption of Cerebello-thalamo-cortical Networks in Obsessive-Compulsive Disorder.

Background: Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive, compulsive behaviors. Neuroimaging studies have implicated altered connectivity among the functional networks of the cerebral cortex in the pathophysiology of OCD. However, there has been no comprehensive investigation of the cross-talk between the cerebellum and functional networks in the cerebral cortex.

Assessing Relationships Among Impulsive Sensation Seeking, Reward Circuitry Activity, and Risk for Psychopathology: A Functional Magnetic Resonance Imaging Replication and Extension Study.

Background: High trait impulsive sensation seeking (ISS), the tendency to engage in behavior without forethought and to seek out new or extreme experiences, is a transdiagnostic risk factor for externalizing and mood disorders, particularly bipolar disorder. We published a positive association between trait ISS and reward expectancy-related activity in the left ventrolateral prefrontal cortex (L vlPFC) and the ventral striatum. We aimed to replicate this finding and extend it by testing for mediation effects of ISS on relationships between reward expectancy-related activity and measures denoting hypomania.

Momentary fluctuations in impulsivity domains: Associations with a history of childhood ADHD, heavy alcohol use, and alcohol problems.

Background: The current study examined if fluctuation in in-the-moment impulsivity was more pronounced for adults with, versus without, a childhood history of ADHD and if ADHD group moderated the association between fluctuation in impulsivity and alcohol use behaviors.

Methods: Two hundred and eleven adult drinkers (52% ADHD) completed a 10-day, 6 times/day, momentary assessment of state impulsivity. Self-reported trait impulsivity, alcohol problems, and frequency of 5+ drinks in the past 12 months were also assessed.

Decoupling Personality and Acute Psychiatric Symptoms in a Depressed Sample and a Community Sample.

The association between depression and neuroticism is complex, but due to the difficulty in assessing neuroticism during mood episodes, the mechanisms underlying this relationship remain poorly understood. In this study, we sought to decompose neuroticism into finer-grained elements that were uncorrelated with psychiatric symptoms and to examine the incremental validity of those elements in explaining deficits in interpersonal functioning. A bifactor model with one general factor and six specific factors fit the data well in both a depressed (=807) and a community (=1,284) sample, and the specific factors were relatively independent of acute symptoms.

Reward related ventral striatal activity and differential response to sertraline versus placebo in depressed individuals.

Medications to treat major depressive disorder (MDD) are not equally effective across patients. Given that neural response to rewards is altered in MDD and given that reward-related circuitry is modulated by dopamine and serotonin, we examined, for the first time, whether reward-related neural activity moderated response to sertraline, an antidepressant medication that targets these neurotransmitters. A total of 222 unmedicated adults with MDD randomized to receive sertraline (n = 110) or placebo (n = 112) in the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study completed demographic and clinical assessments, and pretreatment functional magnetic resonance imaging while performing a reward task.

Haste or Speed? Alterations in the Impact of Incentive Cues on Task Performance in Remitted and Depressed Patients With Bipolar Disorder.

A variety of evidence suggests that bipolar disorder is associated with disruptions of reward related processes, although the properties, and scope of these changes are not well understood. In the present study, we aimed to address this question by examining performance of patients with bipolar disorder (30 depressed bipolar; 35 euthymic bipolar) on a motivated choice reaction time task. We compared performance with a group of healthy control individuals ( = 44) and a group of patients with unipolar depression ( = 41), who were matched on several demographic variables.

Personalized prediction of antidepressant v. placebo response: evidence from the EMBARC study.

Background: Major depressive disorder (MDD) is a highly heterogeneous condition in terms of symptom presentation and, likely, underlying pathophysiology. Accordingly, it is possible that only certain individuals with MDD are well-suited to antidepressants. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes of depression, such as neuroticism, anhedonia, and cognitive control deficits.

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. In this study, we examine whether depressed patients with higher neuroticism scores, a marker of personality dysfunction, show differences versus 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 diagnosed with major depressive disorder at four academic medical centers participating in the Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) study.

Test-retest reliability of cerebral blood flow in healthy individuals using arterial spin labeling: Findings from the EMBARC study.

Introduction: Previous 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.

Material And Methods: We measured absolute and relative CBF at rest in thirty-one healthy subjects in two scan sessions, one week apart, at four different sites and three different scan platforms.

Longitudinal relationships among activity in attention redirection neural circuitry and symptom severity in youth.

Background: Changes in neural circuitry function may be associated with longitudinal changes in psychiatric symptom severity. Identification of these relationships may aid in elucidating the neural basis of psychiatric symptom evolution over time. We aimed to distinguish these relationships using data from the Longitudinal Assessment of Manic Symptoms (LAMS) cohort.

Neural correlates of autobiographical problem-solving deficits associated with rumination in depression.

Background: Analytical rumination can be characterized as negative thoughts focused on searching for answers to personal problems. Failure to think concretely during autobiographical problem-solving (APS) is hypothesized to drive the inability of ruminators to generate effective solutions. Clarifying the brain correlates underlying APS deficits in depressed ruminators may identify novel biological targets for treatment.

Within- and Between-Session Changes in Neural Activity During Emotion Processing in Unipolar and Bipolar Depression.

Background: Bipolar disorder (BD) and unipolar depression (UD) can be difficult to distinguish clinically, particularly during episodes of depression. In this study we test for differences between BD, UD, and healthy control (HC) adults regarding within- and between-session changes in BOLD response during implicit emotional processing.

Methods: During fMRI, HC adults (N=19) and depressed adults with UD (N=19) and BD (N=16) performed an implicit emotion-processing task.

Amygdala-prefrontal cortical functional connectivity during implicit emotion processing differentiates youth with bipolar spectrum from youth with externalizing disorders.

Objective: Both bipolar spectrum disorders (BPSD) and attention deficit hyperactivity disorder (ADHD) present with emotion-regulation deficits, but require different clinical management. We examined how the neurobiological underpinnings of emotion regulation might differentiate youth with BPSD versus ADHD (and healthy controls, HCs), specifically assessing functional connectivity (FxC) of amygdala-prefrontal circuitry during an implicit emotion processing task.

Methods: We scanned a subset of the Longitudinal Assessment of Manic Symptoms (LAMS) sample, a clinically recruited cohort with elevated behavioral and emotional dysregulation, and age/sex-ratio matched HCs.

Accounting for Dynamic Fluctuations across Time when Examining fMRI Test-Retest Reliability: Analysis of a Reward Paradigm in the EMBARC Study.

Longitudinal investigation of the neural correlates of reward processing in depression may represent an important step in defining effective biomarkers for antidepressant treatment outcome prediction, but the reliability of reward-related activation is not well understood. Thirty-seven healthy control participants were scanned using fMRI while performing a reward-related guessing task on two occasions, approximately one week apart. Two main contrasts were examined: right ventral striatum (VS) activation fMRI BOLD signal related to signed prediction errors (PE) and reward expectancy (RE).

Psychotherapy and Neuroimaging.

Technological advances in neuroimaging have enabled researchers to examine, , the relationship between psychotherapeutic interventions and markers of brain activity. This review focuses on two kinds of neuroimaging studies in psychotherapy: those that examine the patterns of brain activity associated with response to treatments and those that examine the changes that occur in brain activity during treatment. A general, hypothetical neural model of psychotherapy is presented, and support for the model is evaluated across anxiety disorders and major depression.

Model specification and the reliability of fMRI results: implications for longitudinal neuroimaging studies in psychiatry.

Functional Magnetic Resonance Imagine (fMRI) is an important assessment tool in longitudinal studies of mental illness and its treatment. Understanding the psychometric properties of fMRI-based metrics, and the factors that influence them, will be critical for properly interpreting the results of these efforts. The current study examined whether the choice among alternative model specifications affects estimates of test-retest reliability in key emotion processing regions across a 6-month interval.

Abnormal deactivation of the inferior frontal gyrus during implicit emotion processing in youth with bipolar disorder: attenuated by medication.

Previous neuroimaging studies of youth with bipolar disorder (BD) have identified abnormalities in emotion regulation circuitry. Using data from the Longitudinal Assessment of Manic Symptoms Cohort (a clinical sample recruited for behavioral and emotional dysregulation), we examined the impact of BD and medication on activation in these regions. Functional neuroimaging data were obtained from 15 youth with BD who currently were unmedicated with a mood stabilizer or antipsychotic (U-BD), 19 youth with medicated BD (M-BD), a non-bipolar clinical sample with high rates of disruptive behavioral disorders (non-BD, n = 59), and 29 healthy controls (HC) while they were shown task-irrelevant morphing emotional faces and shapes.

Gains in employment status following antidepressant medication or cognitive therapy for depression.

Background: Depression can adversely affect employment status.

Aims: To examine whether there is a relative advantage of cognitive therapy or antidepressant medication in improving employment status following treatment, using data from a previously reported trial.

Method: Random assignment to cognitive therapy (n = 48) or the selective serotonin reuptake inhibitor paroxetine (n = 93) for 4 months; treatment responders were followed for up to 24 months.

The Personalized Advantage Index: translating research on prediction into individualized treatment recommendations. A demonstration.

Background: Advances in personalized medicine require the identification of variables that predict differential response to treatments as well as the development and refinement of methods to transform predictive information into actionable recommendations.

Objective: To illustrate and test a new method for integrating predictive information to aid in treatment selection, using data from a randomized treatment comparison.

Method: Data from a trial of antidepressant medications (N = 104) versus cognitive behavioral therapy (N = 50) for Major Depressive Disorder were used to produce predictions of post-treatment scores on the Hamilton Rating Scale for Depression (HRSD) in each of the two treatments for each of the 154 patients.