Modeling Shared and Specific Variances of Irritability, Inattention, and Hyperactivity Yields Novel Insights Into White Matter Perturbations.

OBJECTIVE: Irritability, inattention, and hyperactivity, which are common presentations of childhood psychopathology, have been associated with perturbed white matter microstructure. However, similar tracts have been implicated across these phenotypes; such non-specificity could be rooted in their high co-occurrence. To address this problem, we use a bifactor approach parsing unique and shared components of irritability, inattention, and hyperactivity, which we then relate to white matter microstructure. METHOD: We developed a bifactor model based on the Conners Comprehensive Behavioral Rating Scale in a sample of youth with no psychiatric diagnosis or a primary diagnosis of attention-deficit/hyperactivity disorder or disruptive mood dysregulation disorder (n = 521). We applied the model to an independent yet sociodemographically and clinically comparable sample (n = 152), in which we tested associations between latent variables and fractional anisotropy (FA). RESULTS: The bifactor model fit well (comparative fit index = 0.99; root mean square error of approximation = 0.07). The shared factor was positively associated with an independent measure of impulsivity (ρS = 0.88, pFDR < .001) and negatively related to whole-brain FA (r = -0.20), as well as FA of the corticospinal tract (all pFWE < .05). FA increased with age and deviation from this curve, indicating that altered white matter maturation was associated with the hyperactivity-specific factor (r = -0.16, pFWE < .05). Inattention-specific and irritability-specific factors were not linked to FA. CONCLUSION: Perturbed white matter microstructure may represent a shared neurobiological mechanism of irritability, inattention, and hyperactivity related to heightened impulsivity. Furthermore, hyperactivity might be uniquely associated with a delay in white matter maturation.

Momentary impulsivity interferes with emotion regulation strategy prioritization in everyday life in remitted depression.

BACKGROUND: Selectively prioritizing some emotion regulation (ER) strategies over others has been shown to predict well-being; however, it is unclear what mechanisms underlie this process. Impulsivity, which captures both top-down control of and bottom-up reactivity to emotions, is one potential mechanism of interest. METHODS: Using multilevel mediation modeling, we investigated whether lower ER strategy prioritization (i.e., lower between-strategy variability) mediates the relationship between greater momentary impulsivity and lower ER success in 82 individuals with remitted depression or no history of a mental disorder (1558 observations). To determine the specific effect of impulsivity, we covaried for mean regulatory effort and negative affect. RESULTS: The indirect effect of impulsivity on ER success was significant at the within-person, but not between-person, level. Specifically, in moments when individuals endorsed more impulsivity than usual, they showed less ER strategy prioritization than usual, which predicted less successful ER. Individuals who, on average, reported more impulsivity indicated lower ER strategy prioritization, but no difference in ER success. CONCLUSION: ER strategy prioritization mediated the within-person relationship between greater impulsivity and lower ER success. Interventions focused on training individuals to selectively prioritize ER strategies may improve ER success, particularly when individuals are feeling more impulsive than usual.

Autonomic complexity dynamically indexes affect regulation in everyday life.

Affect regulation often is disrupted in depression. Understanding biomarkers of affect regulation in ecologically valid contexts is critical for identifying moments when interventions can be delivered to improve regulation and may have utility for identifying which individuals are vulnerable to psychopathology. Autonomic complexity, which includes linear and nonlinear indices of heart rate variability, has been proposed as a novel marker of neurovisceral integration. However, it is not clear how autonomic complexity tracks with regulation in everyday life, and whether low complexity serves as a marker of related psychopathology. To measure regulation phenotypes with diminished influence of current symptoms, 37 young adults with remitted major depressive disorder (rMDD) and 28 healthy comparisons (HCs) completed ambulatory assessments of autonomic complexity and affect regulation across one week in everyday life. Multilevel models indicated that in HCs, but not rMDD, autonomic complexity fluctuated in response to regulation cues, increasing in response to reappraisal and distraction and decreasing in response to negative affect. Higher complexity across the week predicted greater everyday regulation success, whereas greater variability of complexity predicted lower (and less variable) negative affect, rumination, and mind-wandering. Results suggest that ambulatory assessment of autonomic complexity can passively index dynamic aspects of real-world affect and regulation, and that dynamic physiological reactivity to regulation is restricted in rMDD. These results demonstrate how intensive sampling of dynamic, nonlinear regulatory processes can advance our understanding of potential mechanisms underlying psychopathology. Such measurements might inform how to test interventions to enhance neurovisceral complexity and affect regulation success in real time. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A meta-analysis on the uncinate fasciculus in depression.

Aberrant microstructure of the uncinate fasciculus (UNC), a white matter (WM) tract implicated in emotion regulation, has been hypothesized as a neurobiological mechanism of depression. However, studies testing this hypothesis have yielded inconsistent results. The present meta-analysis consolidates evidence from 44 studies comparing fractional anisotropy (FA) and radial diffusivity (RD), two metrics characterizing WM microstructure, of the UNC in individuals with depression (n = 5016) to healthy individuals (n = 18 425). We conduct meta-regressions to identify demographic and clinical characteristics that contribute to cross-study heterogeneity in UNC findings. UNC FA was reduced in individuals with depression compared to healthy individuals. UNC RD was comparable between individuals with depression and healthy individuals. Comorbid anxiety explained inter-study heterogeneity in UNC findings. Depression is associated with perturbations in UNC microstructure, specifically with respect to UNC FA and not UNC RD. The association between depression and UNC microstructure appears to be moderated by anxiety. Future work should unravel the cellular mechanisms contributing to aberrant UNC microstructure in depression; clarify the relationship between UNC microstructure, depression, and anxiety; and link UNC microstructure to psychological processes, such as emotion regulation.

Persistent Frustration-Induced Reconfigurations of Brain Networks Predict Individual Differences in Irritability.

OBJECTIVE: Aberrant responses to frustration are central mechanisms of pediatric irritability, which is a common reason for psychiatric consultation and a risk factor for affective disorders and suicidality. This pilot study aimed to characterize brain network configuration during and after frustration and test whether characteristics of networks formed during or after frustration relate to irritability. METHOD: During functional magnetic resonance imaging, a transdiagnostic sample enriched for irritability (N = 66, mean age = 14.0 years, 50% female participants) completed a frustration-induction task flanked by pretask and posttask resting-state scans. We first tested whether and how the organization of brain regions (ie, nodes) into networks (ie, modules) changes during and after frustration. Then, using a train/test/held-out procedure, we aimed to predict past-week irritability from global efficiency (Eglob) (ie, capacity for parallel information processing) of these modules. RESULTS: Two modules present in the baseline pretask resting-state scan (one encompassing anterior default mode and temporolimbic regions and one consisting of frontoparietal regions) contributed most to brain circuit reorganization during and after frustration. Only Eglob of modules in the posttask resting-state scans (ie, after frustration) predicted irritability symptoms. Self-reported irritability was predicted by Eglob of a frontotemporal-limbic module. Parent-reported irritability was predicted by Eglob of ventral-prefrontal-subcortical and somatomotor-parietal modules. CONCLUSION: These pilot results suggest the importance of the postfrustration recovery period in the pathophysiology of irritability. Eglob in 3 specific posttask modules, involved in emotion processing, reward processing, or motor function, predicted irritability. These findings, if replicated, could represent specific intervention targets for irritability.