Total cortisol output during an acute stressor predicts youths' internalizing symptoms during the COVID-19 pandemic.

Individual differences in cortisol output may influence adolescents' adjustment to the COVID-19 pandemic; however, boys and girls may differ in terms of associations between cortisol output and internalizing symptoms in the context of COVID-19-related stress. We examined whether pre-pandemic cortisol output during an acute stressor, assessed approximately three years prior to the pandemic, predicted change in adolescents' internalizing symptoms early during the COVID-19 pandemic. Consistent with previous work on other life stressors, girls' cortisol output was positively associated with anxious and somatic symptoms early in the pandemic. Conversely, cortisol output and depressive symptoms were negatively associated for boys; boys with higher cortisol had depressive symptoms which significantly decreased over time. Findings suggest that hypothalamic-pituitary-adrenal axis stress functioning plays a role in shaping differences between adolescent boys' and girls' adjustment during the experience of a ubiquitous chronic stressor.

Associations between childhood irritability and neural reactivity to maternal feedback in adolescence.

Early irritability, a transdiagnostic vulnerability for psychopathology, is associated with alterations in neural reactivity to emotional stimuli and reward; however, associations between childhood irritability and neural markers of risk may be mitigated by the quality of caregiving youth receive. We examined longitudinal relationships between irritability in childhood and young adolescents' neural activity of regions typically associated with emotion regulation and reward processing during processing of maternal feedback and tested whether these associations were moderated by youth's perceptions of the parent-child relationship quality. Eighty-one adolescents (Mage = 11.1 years) listened to maternal critical and praising feedback while undergoing functional magnetic resonance imaging. Age 3 irritability, assessed observationally, was negatively associated with age 11 neural reactivity to maternal criticism in a cluster in the right dorsolateral prefrontal cortex (dlPFC), particularly for youths who reported more positive maternal parenting. Given the role of the dlPFC activation in the effortful processing of emotional stimuli, decreased activation may reflect disengagement from negatively valenced interpersonal feedback in the context of a positive caregiving environment, thereby mitigating psychopathology risk associated with irritability.

Development and Preliminary Validation of the Pandemic Avoidance and Concern Scales (PACS).

The COVID-19 pandemic has led to radical disruptions to the routines of individuals and families, but there are few psychometrically assessed measures for indexing behavioural responses associated with a modern pandemic. Given the likelihood of future pandemics, valid tools for assessing pandemic-related behavioral responses relevant to mental health are needed. This need may be especially salient for studies involving families, as they may experience higher levels of stress and maladjustment related to school and business closures. We therefore created the Pandemic Avoidance and Concern Scales (PACS) to assess caregivers' and youths' adjustment to COVID-19 and future pandemics. Concern and Avoidance factors derived from exploratory factor analyses were associated with measures of internalizing symptoms, as well as other indices of pandemic-related disruption. Findings suggest that the PACS is a valid tool for assessing pandemic-related beliefs and behaviors in adults and adolescents. Preliminary findings related to differential adjustment between caregivers and youths are discussed.

Children's neural reactivity to maternal praise and criticism: Associations with early depressive symptoms and maternal depression.

Caregiving experiences are implicated in children's depression risk; however, children's neural reactivity to positive and negative feedback from mothers, a potential mediator of depression risk, is poorly understood. In a sample of 81 children (Mage = 11.12 years, SDage = 0.63), some of whom were recruited based on a maternal history of depression (n = 29), we used fMRI to characterize children's neural responses to maternal praise and criticism. Maternal history of depression was unrelated to children's brain activity during both the praise and criticism conditions; however, ROI analyses showed that children's self-reported depressive symptoms were negatively associated with functional activity in the left anterior insula and right putamen while hearing maternal criticism. Whole-brain analyses showed that children's depressive symptoms were positively associated with left inferior frontal gyrus activity while listening to maternal praise. These findings complement past work implicating these brain regions in the processing of emotionally salient stimuli, reward processing, and internal speech. Given associations between early depressive symptoms and later disorder, findings suggest that maladaptive neural processing of maternal feedback may contribute to children's early emerging risk for depression.

Structural Brain Correlates of Childhood Inhibited Temperament: An ENIGMA-Anxiety Mega-analysis.

Temperament involves stable behavioral and emotional tendencies that differ between individuals, which can be first observed in infancy or early childhood and relate to behavior in many contexts and over many years.1 One of the most rigorously characterized temperament classifications relates to the tendency of individuals to avoid the unfamiliar and to withdraw from unfamiliar people, objects, and unexpected events. This temperament is referred to as behavioral inhibition or inhibited temperament (IT).2 IT is a moderately heritable trait1 that can be measured in multiple species.3 In humans, levels of IT can be quantified from the first year of life through direct behavioral observations or reports by caregivers or teachers. Similar approaches as well as self-report questionnaires on current and/or retrospective levels of IT1 can be used later in life.

Resting-state functional connectivity and reading subskills in children.

Individual differences in reading ability have been linked to characteristics of functional connectivity in the brain in both children and adults. However, many previous studies have used single or composite measures of reading, leading to difficulty characterizing the role of functional connectivity in discrete subskills of reading. The present study addresses this issue using resting-state fMRI to examine how resting-state functional connectivity (RSFC) related to individual differences in children's reading subskills, including decoding, sight word reading, reading comprehension, and rapid automatized naming (RAN). Findings showed both positive and negative RSFC-behaviour relationships that diverged across different reading subskills. Positive relationships included increasing RSFC among left dorsal and anterior regions with increasing decoding proficiency, and increasing RSFC between the left thalamus and right fusiform gyrus with increasing sight word reading, RAN, and reading comprehension abilities. In contrast, negative relationships suggested greater functional segregation of attentional and reading networks with improved performance on RAN, decoding, and reading comprehension tasks. Importantly, the results suggest that although reading subskills rely to some extent on shared functional networks, there are also distinct functional connections supporting different components of reading ability in children.

Orbitofrontal cortex grey matter volume is related to children's depressive symptoms.

Adults with a history of depression show distinct patterns of grey matter volume (GMV) in frontal cortical (e.g., prefrontal cortex, orbitofrontal cortex) and limbic (e.g., anterior cingulate, amygdala, hippocampus, dorsal striatum) structures, regions relevant to the processing and regulation of reward, which is impaired in the context of depression. However, it is unclear whether these GMV associations with depression precede depressive disorder onset or whether GMV is related to early emerging symptoms or familial depression. To address these questions, we used voxel-based morphometry (VBM) to examine GMV in 85 community-dwelling children (M = 11.12 years, SD = 0.63 years) screened for current and lifetime depression. Associations between children's depressive symptoms (self- and mother-report of children's symptoms), children's maternal depression history, and GMV were examined. Although maternal depression history was unrelated to children's GMV, child GMV in the orbitofrontal cortex (OFC) was negatively related to children's self-reported depressive symptoms, using both a priori ROI and whole-brain analyses. Moderated regression analyses indicated that girls' GMV was negatively related to girls' depressive symptoms (as indexed by both self- and mother-report of girls' symptoms), whereas boys' symptoms were positively related to GMV. Our findings suggest that brain morphology in the OFC, a region with functional roles in processes relevant to depressive symptoms (i.e., reward-based learning and reward processing), is associated with early depressive symptoms prior to the development of clinically significant depression.

Neural Activity During Self-referential Processing in Children at Risk for Depression.

BACKGROUND: According to cognitive theories of depression, more negative and less positive self-schemas are thought to play a causal role in the disorder. Existing evidence speaks to the neural substrates of self-referential processes in both healthy and depressed individuals, but little is known about how the brain relates to self-referential processing in the context of depression risk in children. We therefore studied the neural substrates of self-referential processing in never-depressed preadolescent children at high and low risk for depression based on maternal depression history. METHODS: A total of 87 never-depressed 10-12-year-old children (29 with maternal depression) completed a self-referential encoding task during a functional magnetic resonance imaging session, in which they were presented a series of positive and negative trait adjectives and endorsed whether each word was self-descriptive. Small volume correction analyses were conducted within 7 regions of interest that are important for self-referential and emotion-related processes. RESULTS: Analyses of small volume correction indicated that high-risk children showed greater activation in the ventrolateral prefrontal cortex and ventromedial prefrontal cortex during the positive-word self-referential encoding task condition than low-risk children. Ventrolateral prefrontal cortex activation mediated the association between maternal depression and child depressive symptoms only when children had lower positive self-schemas, indicating that more positive self-schemas may protect at-risk children from developing depressive symptoms. CONCLUSIONS: Cortical midline and prefrontal regions are important to self-, emotion-, and regulation-related processes. Heightened activation within these regions in never-depressed high-risk children indicates that these neurobiological substrates may mediate early vulnerability to depression in the context of cognitive processes relevant to self-concepts.

Girls' internalizing symptoms and white matter tracts in Cortico-Limbic circuitry.

Dysfunction in cortico-limbic circuitry is implicated in internalizing disorders (i.e., depressive and anxious disorders), but less is known about whether structural variations precede frank disorder and thus potentially mark risk. We therefore examined associations between white matter (WM) tract microstructure in cortico-limbic circuitry at age 7 and concurrent and longitudinal patterns of internalizing symptoms in 42 typically developing girls using Diffusion Tensor Imaging (DTI). Girls' internalizing symptoms were concurrently associated with reduced fractional anisotropy (FA) in segments of the cingulum bundle (CB) and the uncinate fasciculus (UF), bilaterally. Moreover, latent profile analysis showed that girls with increasing internalizing symptoms, based on assessments at ages 3, 6, 7, and 8, had reduced FA in these segments compared to girls with stably low symptoms. These results point to a putative neural mechanism underlying the course of childhood internalizing symptoms.

Youth-focused group mindfulness-based intervention in individuals with early psychosis: A randomized pilot feasibility study.

AIM: To assess the feasibility of a randomized pilot trial that evaluated the acceptability and potential clinical utility of the Mindfulness Ambassador Program (MAP), a unique, standardized 12-session facilitated group mindfulness-based intervention (MBI) for youth experiencing early psychosis. METHODS: Twenty-one patients of an early psychosis intervention program were randomized to receive MAP (n = 11) or treatment as usual (n = 10). Acceptability was measured by group attendance rate and client satisfaction; feasibility of the study design was measured by the recruitment and retention rate. The means, standard deviations, and 95% confidence intervals were described for outcomes of interest. RESULTS: MAP is associated with a high degree of acceptability and has beneficial effects for depression and fatigue. The randomized trial design is feasible. CONCLUSIONS: This study provides important pilot data supporting a larger randomized trial of effectiveness for MAP as a group MBI for early psychosis. Details of MAP and study limitations are discussed.

The BDNF gene val66met polymorphism and behavioral inhibition in early childhood.

Stably elevated behavioural inhibition (BI) is an established risk factor for internalizing disorders. This stability may be related to genetic factors, including a valine-to-methionine substitution on codon 66 (val66met) of the brain-derived neurotrophic factor (BDNF) gene. Past work on the BDNF met variant has inconsistently linked it to vulnerability to internalizing problems; some of this inconsistency may stem from the failure to consider gene-trait interactions in shaping the course of early BI. Toward elucidating early pathways to anxiety vulnerability, we examined gene-by-trait interactions in predicting the course of BI over time in 476 children, assessed for BI using standardized laboratory methods. We found that children with the met allele showed lower stability of BI between ages 3 and 6 than those without this allele. While the mechanisms that underlie this effect are unclear, our findings are consistent with the notion that the met variant, in the context of early BI, influences the stability of this trait in early development.

Determinants of self-esteem in early psychosis: The role of perceived social dominance.

Self-esteem plays a role in the formation and maintenance of symptoms and in the recovery from psychotic illness. This study examines the relative contribution of perceived social dominance and other known predictors in determining self-esteem in 102 individuals in an early intervention program for psychosis. Regression analysis demonstrated that scores on the Perceived Relational Evaluation Scale (PRES), depressed mood, social dominance, gender and positive symptoms significantly contributed to the prediction of scores on the Rosenberg Self-esteem Scale (RSES), whereas self-stigma and negative symptoms did not. Our study suggests that low self-esteem in early psychosis can be understood in part as a reflection of low levels of perceived social value and status.

Negative future self as a mediator in the relationship between insight and depression in psychotic disorders.

Awareness of illness in psychotic disorders is associated with better clinical outcomes, but also poorer psychological well-being. This is known as "The Insight Paradox". Understanding of the paradox has focused on the role of self-stigma. This study examines possible future self as a mediator in the relationship between insight and depression in 102 individuals in an early intervention program for psychosis. Mediation analysis demonstrated that negative possible self was the sole significant independent mediator in a model which included self-stigma. Our study shows that awareness of mental illness and perception that it will negatively impact future self increases likelihood of depression.