Longitudinal Impact of Childhood Adversity on Early Adolescent Mental Health During the COVID-19 Pandemic in the ABCD Study Cohort: Does Race or Ethnicity Moderate Findings?

Background During the COVID-19 pandemic in the United States, mental health among youth has been negatively affected. Youth with a history of adverse childhood experiences (ACEs), as well as youth from minoritized racial-ethnic backgrounds, may be especially vulnerable to experiencing COVID-19–related distress. The aims of this study are to examine whether exposure to pre-pandemic ACEs predicts mental health during the COVID-19 pandemic in youth and whether racial-ethnic background moderates these effects. Methods From May to August 2020, 7983 youths (mean age, 12.5 years; range, 10.6–14.6 years) in the Adolescent Brain Cognitive Development (ABCD) Study completed at least one of three online surveys measuring the impact of the pandemic on their mental health. Data were evaluated in relation to youths\u27 pre-pandemic mental health and ACEs. Results Pre-pandemic ACE history significantly predicted poorer mental health across all outcomes and greater COVID-19–related stress and impact of fears on well-being. Youths reported improved mental health during the pandemic (from May to August 2020). While reporting similar levels of mental health, youths from minoritized racial-ethnic backgrounds had elevated COVID-19–related worry, stress, and impact on well-being. Race and ethnicity generally did not moderate ACE effects. Older youths, girls, and those with greater pre-pandemic internalizing symptoms also reported greater mental health symptoms. Conclusions Youths who experienced greater childhood adversity reported greater negative affect and COVID-19–related distress during the pandemic. Although they reported generally better mood, Asian American, Black, and multiracial youths reported greater COVID-19–related distress and experienced COVID-19–related discrimination compared with non-Hispanic White youths, highlighting potential health disparities

Correspondence Between Perceived Pubertal Development and Hormone Levels in 9-10 Year-Olds From the Adolescent Brain Cognitive Development Study.

Aim: To examine individual variability between perceived physical features and hormones of pubertal maturation in 9-10-year-old children as a function of sociodemographic characteristics. Methods: Cross-sectional metrics of puberty were utilized from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study—a multi-site sample of 9–10 year-olds (n = 11,875)—and included perceived physical features via the pubertal development scale (PDS) and child salivary hormone levels (dehydroepiandrosterone and testosterone in all, and estradiol in females). Multi-level models examined the relationships among sociodemographic measures, physical features, and hormone levels. A group factor analysis (GFA) was implemented to extract latent variables of pubertal maturation that integrated both measures of perceived physical features and hormone levels. Results: PDS summary scores indicated more males (70%) than females (31%) were prepubertal. Perceived physical features and hormone levels were significantly associated with child\u27s weight status and income, such that more mature scores were observed among children that were overweight/obese or from households with low-income. Results from the GFA identified two latent factors that described individual differences in pubertal maturation among both females and males, with factor 1 driven by higher hormone levels, and factor 2 driven by perceived physical maturation. The correspondence between latent factor 1 scores (hormones) and latent factor 2 scores (perceived physical maturation) revealed synchronous and asynchronous relationships between hormones and concomitant physical features in this large young adolescent sample. Conclusions: Sociodemographic measures were associated with both objective hormone and self-report physical measures of pubertal maturation in a large, diverse sample of 9-10 year-olds. The latent variables of pubertal maturation described a complex interplay between perceived physical changes and hormone levels that hallmark sexual maturation, which future studies can examine in relation to trajectories of brain maturation, risk/resilience to substance use, and other mental health outcomes

Sex-Based Impact of Creatine Supplementation on Depressive Symptoms, Brain Serotonin and SSRI Efficacy in an Animal Model of Treatment-Resistant Depression

Background: Rates of major depressive disorder (MDD) increase with living at altitude. In our model, rats housed at moderate altitude (in hypobaric hypoxia) exhibit increased depression-like behavior, altered brain serotonin and a lack of antidepressant response to most selective serotonin reuptake inhibitors (SSRIs). A forebrain deficit in the bioenergetic marker creatine is noted in people living at altitude or with MDD. Methods: Rats housed at 4500 ft were given dietary creatine monohydrate (CRMH, 4% w/w, 5 weeks) vs. un-supplemented diet, and impact on depression-like behavior, brain bioenergetics, serotonin and SSRI efficacy assessed. Results: CRMH significantly improved brain creatine in a sex-based manner. At altitude, CRMH increased serotonin levels in the female prefrontal cortex and striatum but reduced male striatal and hippocampal serotonin. Dietary CRMH was antidepressant in the forced swim test and anti-anhedonic in the sucrose preference test in only females at altitude, with motor behavior unchanged. CRMH improved fluoxetine efficacy (20 mg/kg) in only males at altitude: CRMH + SSRI significantly improved male striatal creatine and serotonin vs. CRMH alone. Conclusions: Dietary CRMH exhibits sex-based efficacy in resolving altitude-related deficits in brain biomarkers, depression-like behavior and SSRI efficacy, and may be effective clinically for SSRI-resistant depression at altitude. This is the first study to link CRMH treatment to improving brain serotonin

BECs (mg/dl) in ethanol naïve sham and lesioned rats following 1 g/kg IP ethanol injection.

<p>BECs (mg/dl) in ethanol naïve sham and lesioned rats following 1 g/kg IP ethanol injection.</p

Escalation and stability of voluntary ethanol consumption.

<p>(A) Mean ethanol consumption did not differ between sham and lesioned groups in the first week (3 sessions) of IEA. Each symbol indicates the average ethanol intake for a single rat in the first week of IEA. Mean values of each group are indicated by horizontal bars. (B) Lesioned rats drank significantly more ethanol in the eighth week of IEA. (C) Lesioned rats escalated ethanol intake at higher rates than sham rats over the first 5 weeks of IEA (sessions 1–15), but not during the last 3 weeks of access (sessions 16–24). Bars graphs indicate the average slope of ethanol intake over the intervals shown. (D –E). Significant differences in ethanol consumption between groups were stably maintained after a period of abstinence. Rats were withdrawn from IEA for approximately 7 weeks (46 days), and then restored to IEA for an additional two weeks. Lesioned rats drank more than sham rats both before and after this period of abstinence. Asterisk (D) indicates significant main effect of lesion (p<0.05) on ethanol intake.</p

Extinction and reinstatement of ethanol and sucrose seeking.

<p>(A) The number of lever presses in lesioned and sham rats did not differ during extinction of operant responding for 20% ethanol. (B) Yohimbine administration reinstated ethanol seeking in sham but not lesioned rats. The number of lever presses by sham rats after yohimbine injection was significantly higher than that occurring after vehicle injection, and higher than lever presses performed by lesioned rats after yohimbine administration. Brackets indicate significant posthoc differences. (C) Sham and lesioned rats showed similar rates of extinction of responding for 2% sucrose. (D) Yohimbine administration induced reinstatement of sucrose seeking in sham but not lesioned rats.</p

Summary of experimental groups and timeline of procedures. Numbered experiments indicated the order in which experiments within each group were carried out.

<p>* A single lesioned rat died during intermittent ethanol access; the 9 remaining lesioned rats were trained in operant ethanol self-administration.</p

Inactive lever presses following vehicle or yohimbine administration during reinstatement of ethanol or sucrose seeking.

<p>Inactive lever presses following vehicle or yohimbine administration during reinstatement of ethanol or sucrose seeking.</p

Taste preference.

<p>(A) Aversion to quinine did not differ between sham and lesioned rats. (B) Preference for saccharin did not significantly differ between sham and lesioned rats, despite quantitatively increased preference in lesioned rats at saccharin concentrations of 0.5 mM and above. (C) Saccharin intake was significantly higher in lesioned rats at concentrations of 0.5 mM saccharin and above. (D) Timeline of saccharin (left panel) and ethanol (right) intake over 24 hour sessions. The pattern of saccharin intake over 24 hours did not differ between sham and lesioned animals. Rates of intake were similar in the first hour of saccharin access and highest for both groups in the first hour of the dark cycle. By contrast, rates of 20% ethanol intake were higher in lesioned rats specifically during the first hour of access.</p

Voluntary ethanol consumption during intermittent access.

<p>(A) Lesioned rats consumed significantly more 20% ethanol over the course of 2-bottle choice drinking sessions (3 sessions/week for 8 weeks, 24 sessions total). Symbols indicate mean ethanol intake ± SEM. In this figure and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092701#pone-0092701-g002" target="_blank">Figures 2</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092701#pone-0092701-g005" target="_blank">5</a>, filled symbols indicate lesioned animals, open symbols indicate sham animals, and asterisks indicate significant differences (p<0.05). (B) Alcohol preference in lesioned rats was significantly higher than that in sham rats. (C) Water intake decreased progressively in both groups, and rats in the lesioned group consumed significantly less water starting in the 5^th week (14^th session) of the paradigm. (D) Total fluid intake (water + ethanol) did not differ significantly between the two groups. (E) Blood ethanol concentrations (BECs) were significantly correlated with voluntary ethanol intake for both groups. Broken line indicates linear fit for sham group; solid line indicates linear fit for lesioned group. (F) Mean (± SEM) BEC measured after the first 30 minutes of 20% ethanol access was significantly higher in lesioned vs. sham rats (p<0.05).</p