The associations among sleep-related difficulties, anxiety, and error-related brain activity in youth.

Given the high prevalence of anxiety disorders and their associated impairment, elucidating neural mechanisms related to these disorders has been increasingly prioritized. The error-related negativity (ERN) has been identified as a neural marker that indexes risk for anxiety across development. The ERN seems to confer risk for developing anxiety, especially in the context of stressful life events. The present study sought to examine sleep-related difficulties as another stressful factor that might impact the ERN. In a sample of 221 girls, aged 8 to 15 years old, we first examined the relationship between longer-term (i.e., over the past month) and shorter-term (i.e., over the past week) sleep difficulties and the ERN. We then investigated whether specific sleep difficulties uniquely predict the ERN. In exploratory analyses, we assessed whether sleep difficulties moderate the relationship between the ERN and anxiety. Results indicated that youth who report longer-term lower sleep duration, longer-term worse sleep, and shorter-term lower sleep duration on school days over the past week have a larger (i.e., more negative) ERN. Additionally, only shorter-term sleep duration on school days over the past week uniquely predicted the ERN. Finally, an elevated ERN predicted greater clinical anxiety in the context of longer-term sleep difficulties. Future studies should clarify the direction of these associations via longitudinal designs.

An Experimental Therapeutics Approach to the Development of a Novel Computerized Treatment Targeting Error-Related Brain Activity in Young Children.

In the current study, we utilize an experimental medicine approach to examine the extent to which a single-session, computerized intervention impacts a transdiagnostic neural marker of risk (i.e., the error-related negativity [ERN]) in 70 children between the ages of 6 and 9 years. The ERN is a deflection in the event-related potential occurring after an individual makes a mistake on a lab-based task and has been shown to be transdiagnostically associated with a variety of anxiety disorders (e.g., social anxiety, generalized anxiety), obsessive-compulsive disorder, and depressive disorders in over 60 studies to date. Building on these findings, work has been done to link an increased ERN to negative reactions to, and avoidance of, making mistakes (i.e., error sensitivity). In the current study, we capitalize on this previous work by examining the extent to which a single-session, computerized intervention may engage the target of "error sensitivity" (measured by the ERN, as well as self-report of error sensitivity). We examine the convergence of multiple measures of the construct of "error sensitivity" (i.e., child self-report, parent report on child, and child electroencephalogram [EEG]). We also examine relationships between these three measures of "error sensitivity" and child anxiety symptoms. Overall, results suggested that treatment condition predicted changes in self-reported error sensitivity but not changes in ERN. Based on the lack of previous work in this area, we view this study as a novel, preliminary, first step toward using an experimental medicine approach to examine our ability to engage the target of the ERN (i.e., error sensitivity) early in development.

Relational victimization prospectively predicts increases in error-related brain activity and social anxiety in children and adolescents across two years.

Recent research has focused on identifying neural markers associated with risk for anxiety, including the error-related negativity (ERN). An elevated ERN amplitude has been observed in anxious individuals from middle childhood onward and has been shown to predict risk for future increases in anxiety development. The ERN is sensitive to environmental influences during development, including interpersonal stressors. Of note, one particular type of interpersonal stressor, relational victimization, has been related to increases in anxiety in adolescents. We tested whether relational victimization predicts increases in the ERN and social anxiety symptoms across two years in a sample of 152 child and adolescent females (ages 8 - 15). Results indicated that children and adolescents' baseline ERN was positively related to the ERN two years later. Furthermore, greater relational victimization at baseline predicted greater increases in the ERN two years later, controlling for baseline ERN. Moreover, relational victimization at baseline predicted increases in social anxiety, and this relationship was mediated by increases in the ERN. These results suggest that relational victimization impacts the developmental trajectory of the neural response to errors and thereby impacts increases in social anxiety among children and adolescents.

The relation between executive functions, error-related brain activity, and ADHD symptoms in clinically evaluated school-aged children.

Two event-related potentials (ERPs) elicited following errors, the error-related negativity (ERN) and error positivity (Pe), have been proposed to reflect cognitive control, though the specific processes remain debated. Few studies have examined the ERN and Pe's relations with individual differences in cognitive control/executive functioning using well-validated tests administered separately from the inhibition tasks used to elicit the ERN/Pe. Additionally, neurocognitive tests of executive functions tend to strongly predict ADHD symptoms, but the extent to which task-based and EEG-based estimates of executive functioning/cognitive control account for the same variance in ADHD symptoms remains unclear. The current study addressed these limitations by examining relations between the ERN/Pe and three core executive functions (working memory, inhibitory control, set shifting) in a clinically-evaluated sample of 53 children ages 8-12 (Mage = 10.36, SD = 1.42; 77.4% White/Non-Hispanic; 16 girls) with and without ADHD. Results demonstrated that neither the ERN nor Pe were related to overall cognitive control/executive functioning, or to working memory or set shifting specifically (all 95%CIs include 0.0). In contrast, a larger Pe was associated with better-developed inhibitory control (ß=-.35, 95%CI excludes 0.0), but did not capture aspects of inhibitory control that are important for predicting ADHD symptoms. Neither the ERN nor Pe predicted ADHD symptoms (95%CIs include 0.0). Results were generally robust to control for age, sex, SES, ADHD symptom cluster, and anxiety, and emphasize the need for caution when interpreting the ERN/Pe as indices of broad-based cognitive control/executive functioning, as well as using the ERN/Pe to examine cognitive processes contributing to ADHD symptomatology.

Ethnoracial status, intersectionality with gender, and psychotherapy utilization, retention, and outcomes.

OBJECTIVE: Psychotherapy access, utilization, retention, and effectiveness require continued improvement, especially for groups for whom availability and outcomes may be currently suboptimal, including ethnoracial minorities. Further, ethnoracial status' intersectionality with other identity variables (e.g., gender) may relate to structural barriers to care and effectiveness of care, an area in need of further research. METHOD: The Florida State University Psychology Clinic, a low-cost population-facing treatment center, has routinely collected clinically relevant information on all consenting clients, including severity of clinical presentation at intake and over time, number of therapy sessions attended and of no-shows, premature termination, demographics, etc. A large sample of clients (N = 2,076; 57% women; 67.9% non-Hispanic White) on whom we collected and entered at least some data, though missing data were common, has accrued. We conducted chi-square tests to examine treatment utilization gaps, analysis of variance to measure differences in intake severity, and analysis of covariance to measure differences in treatment effectiveness. RESULTS: Based on the percentages of ethnoracial minority groups with mental disorders in the broader local community, we are falling short in outreach to Black clients, and when we do engage them, we retain them suboptimally. Once well engaged, however, results across groups suggest few differences in outcomes by ethnoracial status, gender, or their intersection. Ethnoracial match was associated with more sessions attended in Black people. CONCLUSIONS: Psychotherapy effectiveness has the potential to be optimized for everyone, and a promising direction in this regard is the case conceptualization of a cultural formulation interview and cultural humility mindset. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The relationship between stressful life events and the error-related negativity in children and adolescents.

The error-related negativity (ERN) has been cited as a neural marker that indexes risk for anxiety in children and across development. Environmental factors, such as punishment in the lab and parenting styles, have been shown to impact the ERN. However, little is known about how other environmental factors may shape this neural risk marker. The current study examines how the environmental factor of stressful life events may relate to the ERN in children and adolescents. In a sample of 176 females, ages 8-15 years, we examined associations between the frequency of recent stressful life events and the ERN. We also investigated whether interpersonal dependent life events or non-interpersonal life events uniquely relate to the ERN. Finally, we explored whether recent stressors differentially relate to the ERN based on age. Results suggest that youth who have experienced more frequent stressful life events have an increased (i.e., more negative) ERN. Moreover, more frequent interpersonal dependent stressors uniquely predicted the magnitude of the ERN. Lastly, results supported a moderation model wherein the relationship between the frequency of interpersonal dependent stressors and the ERN was moderated by age, such that the relationship between stressors and the ERN was significant only for younger children.

Error-related negativity predicts increases in anxiety in a sample of clinically anxious female children and adolescents over 2 years.

BACKGROUND: An increased neural response to making errors has emerged as a biomarker of anxiety. Error negativity (Ne) or errorrelated negativity (ERN) is an event-related potential generated when people commit errors; the Ne/ERN is greater among people with anxiety and predicts increases in anxiety. However, no previous study has examined whether the Ne/ERN can be used as a prognostic indicator among people with current anxiety. The present study addressed this gap by examining whether the Ne/ERN prospectively predicts increases in anxiety symptoms in clinically anxious children and adolescents. METHODS: The sample included 34 female participants between the ages of 8 and 14 years who met the criteria for a clinical anxiety disorder based on clinical interview. The Ne/ERN was measured using a flanker task. RESULTS: Increased Ne/ERN at baseline predicted increases in total anxiety symptoms 2 years later, even when accounting for baseline symptoms. The Ne/ERN predicted increases in the symptom domains of generalized anxiety, social anxiety and harm avoidance/perfectionism, but not panic, separation anxiety, school avoidance or physical symptoms. LIMITATIONS: The sample size was small, which may have inflated the false discovery rate. To mitigate this possibility, we used multiple self-report measures, and the results for the 2 measures (as well as their symptom domains) converged. CONCLUSION: These data suggest that the Ne/ERN can delineate specific risk trajectories, even among those who already meet the criteria for a clinical anxiety disorder. Considering the need for prognostic markers among people with clinical anxiety, the current findings are an important and novel extension of previous work.

Data-driven parcellation and graph theory analyses to study adolescent mood and anxiety symptoms.

Adolescence is a period of rapid brain development when psychiatric symptoms often first emerge. Studying adolescents may therefore facilitate the identification of neural alterations early in the course of psychiatric conditions. Here, we sought to utilize new, high-quality brain parcellations and data-driven graph theory approaches to characterize associations between resting-state networks and the severity of depression, anxiety, and anhedonia symptoms-salient features across psychiatric conditions. As reward circuitry matures considerably during adolescence, we examined both Whole Brain and three task-derived reward networks. Subjects were 87 psychotropic-medication-free adolescents (age = 12-20) with diverse psychiatric conditions (n = 68) and healthy controls (n = 19). All completed diagnostic interviews, dimensional clinical assessments, and 3T resting-state fMRI (10 min/2.3 mm/TR = 1 s). Following high-quality Human Connectome Project-style preprocessing, multimodal surface matching (MSMAll) alignment, and parcellation via the Cole-Anticevic Brain-wide Network Partition, weighted graph theoretical metrics (Strength Centrality = CStr; Eigenvector Centrality = CEig; Local Efficiency = ELoc) were estimated within each network. Associations with symptom severity and clinical status were assessed non-parametrically (two-tailed pFWE < 0.05). Across subjects, depression scores correlated with ventral striatum CStr within the Reward Attainment network, while anticipatory anhedonia correlated with CStr and ELoc in the subgenual anterior cingulate, dorsal anterior cingulate, orbitofrontal cortex, caudate, and ventral striatum across multiple networks. Group differences and associations with anxiety were not detected. Using detailed functional and clinical measures, we found that adolescent depression and anhedonia involve increased influence and communication efficiency in prefrontal and limbic reward areas. Resting-state network properties thus reflect positive valence system anomalies related to discrete reward sub-systems and processing phases early in the course of illness.

Anhedonia as a clinical correlate of inflammation in adolescents across psychiatric conditions.

Objectives: Peripheral inflammation has been associated with multiple psychiatric disorders, particularly with depression. However, findings remain inconsistent and unreproducible, most likely due to the disorder's heterogeneity in phenotypic presentation. Therefore, in the present study, in an effort to account for inter-individual differences in symptom severity, we utilised a dimensional approach to assess the relationships between a broad panel of inflammatory cytokines and key psychiatric symptoms (i.e. depression, anhedonia, anxiety, fatigue and suicidality) in adolescents across psychiatric disorders. We hypothesised that only anhedonia (reflecting deficits of reward function) will be associated with inflammation.Methods: Participants were 54 psychotropic medication-free adolescents with diverse psychiatric conditions and 22 healthy control (HC) adolescents, aged 12-20. We measured 41 cytokines after in vitro lipopolysaccharide stimulation. Mann-Whitney U and Spearman correlation tests examined group comparison and associations, respectively, while accounting for multiple comparisons and confounds, including depression severity adolescent.Results: There were no group differences in cytokine levels. However, as hypothesised, within the psychiatric group, only anhedonia was associated with 19 cytokines, including haematopoietic growth factors, chemokines, pro-inflammatory cytokines, and anti-inflammatory cytokines.Conclusions: Our findings suggest that general inflammation may induce reward dysfunction, which plays a salient role across psychiatric conditions, rather than be specific to one categorical psychiatric disorder.

Elevated striatal γ-aminobutyric acid in youth with major depressive disorder.

BACKGROUND: Alterations in γ-aminobutyric acid (GABA) have been hypothesized to play a role in the pathogenesis of psychiatric illness. Our previous work has specifically linked anterior cingulate cortex (ACC) GABA deficits with anhedonia in youth with major depressive disorder (MDD). As anhedonia reflects alterations within the reward circuitry, we sought to extend this investigation and examine GABA levels in another key reward-related region, the striatum, in the same adolescent population. METHODS: Thirty-six youth [20 with MDD and 16 healthy controls; (HC)], ages 12 to 21 years old, underwent J-edited proton magnetic resonance spectroscopy (1H MRS) whereby GABA levels were measured in striatal and ACC voxels. GABA levels were compared between groups and between voxel positions and were examined in relation to clinical symptomatology, such as depression severity, anhedonia, anxiety, and suicidality. RESULTS: Depressed youth had unexpectedly higher GABA levels in the striatum compared to HC. In both depressed and healthy youth, GABA levels were higher in the striatum than in the ACC, while the differences in depressed youth were greater. Moreover, in depressed youth, higher striatal GABA above the mean of HCs was correlated with lower ACC GABA below the mean of HCs. Striatal GABA was not correlated with clinical symptomatology in this small sample. CONCLUSIONS: Together, these findings suggest that higher striatal GABA levels may serve some compensatory function as a result of lower ACC GABA in depressed adolescents. It is also possible that, like lower ACC GABA, higher striatal GABA might simply be another pathological feature of adolescent depression.