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IntroductionInteroception refers to awareness, interpretation, and integration of sensations in the body. While interoceptive accuracy has long been regarded as a core component of emotional experience, less is known about the relationship of interoceptive accuracy and related facets of interoception to emotion regulation deficits. This study explores how interoceptive accuracy and interoceptive sensibility relate to emotion regulation in a non-clinical sample.MethodsUndergraduate participants completed a heartbeat perception task and the Multidimensional Assessment of Interoceptive Awareness (Noticing and Body Listening sub-scales), and rated their confidence in performance on the heartbeat perception task. Participants also completed self-report measures of emotional awareness and regulation (Profile of Emotional Competence, intrapersonal emotion identification and emotion regulation sub-scales), and rated their use of different coping strategies (Brief COPE).ResultsNoticing predicted emotion identification, emotion regulation, and the use of adaptive but not maladaptive coping strategies. Heartbeat perception accuracy did not significantly contribute to the prediction of any outcome variables.DiscussionFuture work is needed to extend these findings to clinical populations. The results from this study support the use of interoceptive training interventions to promote emotional wellbeing.

Mind-wandering is an essential cognitive process in which people engage for 30–50% of their waking day and is highly associated with neuroticism. The current study identified the factor structure of retrospective self-report items related to mind-wandering and perseverative cognition content and explored these associations with neuroticism. In an adult community sample ( N = 309), items from the NYC Cognition Questionnaire, the Penn State Worry Questionnaire Short Form, and the Rumination Responses Brooding Subscale were entered into factor analyses to test the optimal factor structure of these items. We employed a structural model to investigate associations of mind-wandering facets with neuroticism. A correlated three factor solution best fit the data (CFI = .94, TLI = .93, SRMR = .07, RMSEA = .07). Bifactor models failed to provide evidence for a general mind-wandering construct above and beyond variance explained by mind-wandering and perseverative cognition facets. The structural model revealed differential associations of each facet with neuroticism. A wandering mind is not always an unhappy mind. Whereas worry and rumination are associated with higher levels of neuroticism, mind-wandering has other components that relate to positively valenced cognition and lower neuroticism. Adaptive and maladaptive mind-wandering should be tested together in future studies of personality and psychopathology.

Major depressive disorder (MDD) is characterized by abnormal resting-state functional connectivity (RSFC), especially in medial prefrontal cortical (MPFC) regions of the default network. However, prior research in MDD has not examined dynamic changes in functional connectivity as networks form, interact, and dissolve over time. We compared unmedicated individuals with MDD (n=100) to control participants (n=109) on dynamic RSFC (operationalized as SD in RSFC over a series of sliding windows) of an MPFC seed region during a resting-state functional magnetic resonance imaging scan. Among participants with MDD, we also investigated the relationship between symptom severity and RSFC. Secondary analyses probed the association between dynamic RSFC and rumination. Results showed that individuals with MDD were characterized by decreased dynamic (less variable) RSFC between MPFC and regions of parahippocampal gyrus within the default network, a pattern related to sustained positive connectivity between these regions across sliding windows. In contrast, the MDD group exhibited increased dynamic (more variable) RSFC between MPFC and regions of insula, and higher severity of depression was related to increased dynamic RSFC between MPFC and dorsolateral prefrontal cortex. These patterns of highly variable RSFC were related to greater frequency of strong positive and negative correlations in activity across sliding windows. Secondary analyses indicated that increased dynamic RSFC between MPFC and insula was related to higher levels of recent rumination. These findings provide initial evidence that depression, and ruminative thinking in depression, are related to abnormal patterns of fluctuating communication among brain systems involved in regulating attention and self-referential thinking.

The National Institute of Mental Health (NIMH) ‘fast-fail’ approach seeks to improve too-often-misleading early-phase drug development methods by incorporating biomarker-based proof-of-mechanism (POM) testing in phase 2a. This first comprehensive application of the fast-fail approach evaluated the potential of κ-opioid receptor (KOR) antagonism for treating anhedonia with a POM study determining whether robust target engagement favorably impacts the brain circuitry hypothesized to mediate clinical effects. Here we report the results from a multicenter, 8-week, double-blind, placebo-controlled, randomized trial in patients with anhedonia and a mood or anxiety disorder (selective KOR antagonist (JNJ-67953964, 10 mg; n  = 45) and placebo ( n  = 44)). JNJ-67953964 significantly increased functional magnetic resonance imaging (fMRI) ventral striatum activation during reward anticipation (primary outcome) as compared to placebo (baseline-adjusted mean: JNJ-67953964, 0.72 (s.d. = 0.67); placebo, 0.33 (s.d. = 0.68); F (1,86) = 5.58, P  < 0.01; effect size = 0.58 (95% confidence interval, 0.13–0.99)). JNJ-67953964, generally well tolerated, was not associated with any serious adverse events. This study supports proceeding with assessment of the clinical impact of target engagement and serves as a model for implementing the ‘fast-fail’ approach. A phase 2 proof-of-mechanism trial shows that a κ-opioid receptor antagonist improves reward-related functioning in the brain and a clinical measure of anhedonia in patients with mood and anxiety disorders, serving as a model for implementing the ‘fast-fail’ approach to psychiatric treatment development.

Despite the heterogeneous symptom presentation and complex etiology of major depressive disorder (MDD), functional neuroimaging studies have shown with remarkable consistency that dysfunction in mesocorticolimbic brain systems are central to the disorder. Relatively less research has focused on the identification of biological markers of response to antidepressant treatment that would serve to improve the personalized delivery of empirically supported antidepressant interventions. In the present study, we investigated whether resting-state functional brain connectivity (rs-fcMRI) predicted response to Behavioral Activation Treatment for Depression, an empirically validated psychotherapy modality designed to increase engagement with rewarding stimuli and reduce avoidance behaviors. Twenty-three unmedicated outpatients with MDD and 20 matched nondepressed controls completed rs-fcMRI scans after which the MDD group received an average of 12 sessions of psychotherapy. The mean change in Beck Depression Inventory-II scores after psychotherapy was 12.04 points, a clinically meaningful response. Resting-state neuroimaging data were analyzed with a seed-based approach to investigate functional connectivity with four canonical resting-state networks: the default mode network, the dorsal attention network, the executive control network, and the salience network. At baseline, the MDD group was characterized by relative hyperconnectivity of multiple regions with precuneus, anterior insula, dorsal anterior cingulate cortex (dACC), and left dorsolateral prefrontal cortex seeds and by relative hypoconnectivity with intraparietal sulcus, anterior insula, and dACC seeds. Additionally, connectivity of the precuneus with the left middle temporal gyrus and connectivity of the dACC with the parahippocampal gyrus predicted the magnitude of pretreatment MDD symptoms. Hierarchical linear modeling revealed that response to psychotherapy in the MDD group was predicted by pretreatment connectivity of the right insula with the right middle temporal gyrus and the left intraparietal sulcus with the orbital frontal cortex. These results add to the nascent body of literature investigating pretreatment rs-fcMRI predictors of antidepressant treatment response and is the first study to examine rs-fcMRI predictors of response to psychotherapy.

Anhedonia remains a major clinical issue for which there is few effective interventions. Untreated or poorly controlled anhedonia has been linked to worse disease course and increased suicidal behavior across disorders. Taking a proof-of-mechanism approach under the auspices of the National Institute of Mental Health FAST-FAIL initiative, we were the first to show that, in a transdiagnostic sample screened for elevated self-reported anhedonia, 8 weeks of treatment with a kappa-opioid receptor (KOR) antagonist resulted in significantly higher reward-related activation in one of the core hubs of the brain reward system (the ventral striatum), better reward learning in the Probabilistic Reward Task (PRT), and lower anhedonic symptoms, relative to 8 weeks of placebo. Here, we performed secondary analyses of the PRT data to investigate the putative effects of KOR antagonism on anhedonic behavior with more precision by using trial-level model-based Bayesian computational modeling and probability analyses. We found that, relative to placebo, KOR antagonism resulted in significantly higher learning rate (i.e., ability to learn from reward feedback) and a more sustained preference toward the more frequently rewarded stimulus, but unaltered reward sensitivity (i.e., the hedonic response to reward feedback). Collectively, these findings provide novel evidence that in a transdiagnostic sample characterized by elevated anhedonia, KOR antagonism improved the ability to modulate behavior as a function of prior rewards. Together with confirmation of target engagement in the primary report (Krystal et al., Nat Med, 2020), the current findings suggest that further transdiagnostic investigation of KOR antagonism for anhedonia is warranted.

Research has demonstrated support for the efficacy of mindfulness-based stress reduction (MBSR) in alleviating psychological distress and symptoms. Less is known, however, about the mechanisms through which MBSR achieves its outcomes. This study examined mindfulness and self-compassion as potential mediators of MBSR's effects on several processes and behaviors related to emotion regulation, using data from a randomized trial of MBSR versus waitlist (WL), in which MBSR participants demonstrated significantly greater improvements in worry, fear of emotion, difficulties in emotion regulation, suppression of anger, and aggressive anger expression. Mediation analysis using bootstrap resampling indicated that increases in self-compassion mediated MBSR's effects on worry, controlling for change in mindfulness. Increases in mindfulness mediated the intervention's effects on difficulties in emotion regulation, controlling for change in self-compassion. Both variables mediated MBSR's effects on fear of emotion. These findings highlight the importance of mindfulness and self-compassion as key processes of change that underlie MBSR's outcomes.

To assess the relationship of multiple domains and facets of the five-factor model of personality with presence, onset, and severity of late-life depression. Cross-sectional analysis of depression status, and age of onset. Retrospective analysis of baseline severity. Longitudinal analysis of severity after 3 and 12 months of psychiatric treatment. Private university-affiliated medical center in the Southeastern United States. One hundred twelve psychiatric patients with a current episode of unipolar major depression, and 104 nondepressed comparison subjects, age 60 and older (mean: 70, SD: 6). Revised NEO Personality Inventory, Diagnostic Interview Schedule, and Montgomery-Åsberg Depression Rating Scale. Binary logistic regression found that depression was related to higher neuroticism (and all its facets) and to lower extraversion (and facets of assertiveness, activity, and positive emotionality) and conscientiousness (and facets of competence, order, dutifulness, and self-discipline). Multinomial logistic regression found some of these relationships held only for depression with onset before age 50 (hostility, self-consciousness, extraversion, assertiveness, positive emotions, order, and dutifulness). Linear regression found that personality was unrelated to depression severity at the beginning of treatment, but improvement after 3 months was related to lower neuroticism (and facets depressiveness and stress-vulnerability) and higher warmth and competence. Improvement after 12 months was related to lower neuroticism, depressiveness, and stress-vulnerability. Specific personality facets are related with depression and treatment outcomes. Screening for certain personality traits at the start of treatment may help identify patients at risk of worse response to treatment after 3 months.

During times of emotional stress, individuals often engage in emotion regulation to reduce the experiential and physiological impact of negative emotions. Interestingly, emotion regulation strategies also influence memory encoding of the event. Cognitive reappraisal is associated with enhanced memory while expressive suppression is associated with impaired explicit memory of the emotional event. However, the mechanism by which these emotion regulation strategies affect memory is unclear. We used event-related fMRI to investigate the neural mechanisms that give rise to memory formation during emotion regulation. Twenty-five participants viewed negative pictures while alternately engaging in cognitive reappraisal, expressive suppression, or passive viewing. As part of the subsequent memory design, participants returned to the laboratory two weeks later for a surprise memory test. Behavioral results showed a reduction in negative affect and a retention advantage for reappraised stimuli relative to the other conditions. Imaging results showed that successful encoding during reappraisal was uniquely associated with greater co-activation of the left inferior frontal gyrus, amygdala, and hippocampus, suggesting a possible role for elaborative encoding of negative memories. This study provides neurobehavioral evidence that engaging in cognitive reappraisal is advantageous to both affective and mnemonic processes.

Mindfulness-based interventions are effective for reducing depressive symptoms. However, the psychological and neural mechanisms are unclear. This study examined which facets of trait mindfulness offer protection against negative bias and rumination, which are key risk factors for depression. Nineteen male volunteers completed a 2-day functional magnetic resonance imaging study. One day utilized a stress-induction task and the other day utilized a mindful breathing task. An emotional inhibition task was used to measure neural and behavioral changes related to state negative bias, defined by poorer performance in inhibiting negative relative to neutral stimuli. Associations among trait mindfulness [measured by the Five Facet Mindfulness Questionnaire (FFMQ)], trait rumination, and negative bias were examined. Non-reactivity scores on the FFMQ correlated negatively with rumination and negative bias following the stress induction. Non-reactivity was inversely correlated with insula activation during inhibition to negative stimuli after the mindful breathing task. Our results suggest non-reactivity to inner experience is the key facet of mindfulness that protects individuals from psychological risk for depression. Based on these results, mindfulness could reduce vulnerability to depression in at least two ways: (i) by buffering against trait rumination and negative bias and (ii) by reducing automatic emotional responding via the insula.