Protocol for teen inflammation glutamate emotion research (TIGER): Toward predictors of treatment response and clinical course in depressed adolescents.

Adolescent-onset depression is a prevalent and debilitating condition commonly associated with treatment refractory depression and non-response to first-line antidepressants. There are, however, no objective tests to determine who may or may not respond to antidepressants. As depressed adolescents are especially vulnerable to the lifelong consequences of ineffectively-treated depression, it is critical to identify neurobiological predictors of treatment non-response in this population. Here, we describe the scientific rationale and protocol for the Teen Inflammation Glutamate Emotion Research (TIGER) study, a prospective 18-month investigation of 160 depressed adolescents who will be assessed before and after treatment with selective serotonin reuptake inhibitors. TIGER will be using ultra-high field imaging to test the effects of acute stress and antidepressant treatment on inflammatory and glutamatergic processes hypothesized to underlie depression maintenance. Results from this work will motivate future studies testing alternative therapeutics for depressed adolescents at risk for treatment resistant depression. ClinicalTrials.gov Identifier: NCT05329441.

Neighborhood Socioeconomic Disadvantage and White Matter Microstructure of the Arcuate Fasciculus and Uncinate Fasciculus in Adolescents.

Background: Neighborhood- or area-level socioeconomic disadvantage is associated with neural alterations across the life span. However, few studies have examined the effects of neighborhood disadvantage on white matter microstructure during adolescence, an important period of development that coincides with increased risk for psychopathology. Methods: In 200 adolescents (ages 13-20 years; 54.5% female, 4% nonbinary) recruited from 2 studies enriched for early adversity and depression, we examined whether neighborhood socioeconomic disadvantage derived from census tract data was related to white matter microstructure in several major white matter tracts. We also examined whether depressive symptoms and sex moderated these associations. Results: Greater neighborhood socioeconomic disadvantage was associated with lower fractional anisotropy (FA) in the left arcuate fasciculus (ß = -0.24, false discovery rate [FDR]-corrected p = .035) and right uncinate fasciculus (ß = -0.32, FDR-corrected p = .002) above and beyond the effects of family-level socioeconomic status. Depressive symptoms significantly moderated the association between left arcuate fasciculus FA and both neighborhood (ß = 0.17, FDR-corrected p = .026) and unemployment (ß = 0.22, FDR-corrected p = .004) disadvantage such that these associations were only significant in adolescents who reported less severe depression. Sex did not moderate the association between socioeconomic disadvantage and FA in these tracts. Conclusions: Greater neighborhood socioeconomic disadvantage, particularly poverty and educational attainment levels, was associated with lower FA in the arcuate fasciculus and uncinate fasciculus above and beyond the effects of family-level measures of socioeconomic status. These patterns were only observed in adolescents with low levels of depression, suggesting that we must be cautious about generalizing these findings to youths who struggle with mental health difficulties.

Effects of the COVID-19 Pandemic on Mental Health and Brain Maturation in Adolescents: Implications for Analyzing Longitudinal Data.

Background: The COVID-19 pandemic has caused significant stress and disruption for young people, likely leading to alterations in their mental health and neurodevelopment. In this context, it is not clear whether youth who lived through the pandemic and its shutdowns are comparable psychobiologically to their age- and sex-matched peers assessed before the pandemic. This question is particularly important for researchers who are analyzing longitudinal data that span the pandemic. Methods: In this study we compared carefully matched youth assessed before the pandemic (n=81) and after the pandemic-related shutdowns ended (n=82). Results: We found that youth assessed after the pandemic shutdowns had more severe internalizing mental health problems, reduced cortical thickness, larger hippocampal and amygdala volume, and more advanced brain age. Conclusions: Thus, not only does the COVID-19 pandemic appear to have led to poorer mental health and accelerated brain aging in adolescents, but it also poses significant challenges to researchers analyzing data from longitudinal studies of normative development that were interrupted by the pandemic.

A Social Gradient of Cortical Thickness in Adolescence: Relationships With Neighborhood Socioeconomic Disadvantage, Family Socioeconomic Status, and Depressive Symptoms.

BACKGROUND: Mental and physical health are affected by family and neighborhood socioeconomic status (SES). Accelerated maturation in the context of lower SES is one mechanism that might contribute to underlying health disparities; few studies, however, have considered neighborhood SES in relation to putative markers of brain maturation in adolescents. METHODS: In 120 adolescents 13 to 18 years of age, we examined family and neighborhood SES in relation to cortical thickness adjusted for age. We also examined whether cortical thickness was related to depressive symptoms and explored regions of interest. RESULTS: Controlling for age, neighborhood socioeconomic disadvantage was associated with a thinner cortex in the left hemisphere (standardized ß = -0.20), which was related to more severe depressive symptoms (standardized ß = -0.33). Family SES was not significantly associated with age-adjusted mean cortical thickness in either hemisphere after controlling for relevant covariates. In exploratory, covariate-adjusted analyses of cortical thickness at the regional level, neighborhood socioeconomic disadvantage was associated with reduced cortical thickness in the left superior frontal gyrus (standardized ß = -0.27), fusiform gyrus (standardized ß = -0.20), and insula (standardized ß = -0.21), whereas family SES was positively associated with cortical thickness in the right lateral and right medial orbitofrontal cortex (standardized ß = 0.21 and standardized ß = 0.19, respectively) and left transverse temporal gyrus (standardized ß = 0.22). CONCLUSIONS: Our findings provide evidence for a social gradient of cortical thickness during adolescence. Adolescents living in less advantaged community or family contexts appear to have a thinner cortex according to global and regional measures. Reduced cortical thickness in the left hemisphere may indicate increased risk for depression in adolescence.