Mood and Behaviors of Adolescents With Depression in a Longitudinal Study Before and During the COVID-19 Pandemic.

OBJECTIVE: To investigate whether, compared to pre-pandemic levels, depressive and anxiety symptoms in adolescents with depression increased during the pandemic. METHOD: We used data from National Institute of Mental Health Characterization and Treatment of Depression (NIMH CAT-D) cohort, a longitudinal case-control study that started pre-pandemic. Most of the participants are from the states of Maryland and Virginia in the United States. We compared depressive symptoms (1,820 measurements; 519 measurements pre-pandemic and 1,302 during the pandemic) and anxiety symptoms (1,800 measurements; 508 measurements pre-pandemic and 1,292 ratings during the pandemic) of 166 adolescents (109 girls, 96 adolescents with depression) before and during the pandemic. Data were collected during yearly clinical visits, interim 4-month follow-up visits, inpatient stays, and weekly outpatient sessions, with additional data collection during the pandemic. Pre-pandemic, healthy volunteers (HVs) had a median of 1 depressive and anxiety rating (range, 1-3), and adolescents with depression had a median of 2 ratings (anxiety rating range, 1-25; depressive rating range, 1-26). During the pandemic, HVs had a median of 8 anxiety ratings and 9 depressive ratings (range, 1-13), and adolescents with depression had a median of 7 anxiety and depressive ratings (range, 1-29). We also analyzed adolescent- and parent-reported behaviors in the CoRonavIruS Health Impact Survey (CRISIS), totaling 920 self-reported measures for 164 adolescents (112 girls, 92 adolescents with depression). HVs had a median of 7 surveys (range, 1-8), and adolescents with depression had a median of 5 surveys (range, 1-8). RESULTS: Pre-pandemic, adolescents with depression had a mean depressive score of 11.16 (95% CI = 10.10, 12.22) and HVs had a mean depressive score of 1.76 (95% CI = 0.40, 3.13), a difference of 9.40 points (95% CI = 7.78, 11.01). During the pandemic, this difference decreased by 22.6% (2.05 points, 95% CI = 0.71, 3.40, p = .003) due to 0.89 points decrease in severity of scores in adolescents with depression (95% CI = 0.08, 1.70, p = .032) and 1.16 points increase in HVs' depressive symptoms (95% CI = 0.10, 2.23, p = .032). Compared to their pre-pandemic levels, adolescents with depression reported overall lower anxiety symptoms during the pandemic. Parent-on-child reports also were consistent with these results. CONCLUSION: Contrary to our hypothesis, we found that both depressive and anxiety symptoms were lower for adolescents with depression during the pandemic compared to before. In contrast, the depression scores for the HVs were higher during the pandemic relative to their pre-pandemic ratings; these scores remained much lower than those of adolescents with depression. CLINICAL TRIAL REGISTRATION INFORMATION: Characterization and Treatment of Adolescent Depression; https://clinicaltrials.gov/; NCT03388606.

Clinical utility of family history of depression for prognosis of adolescent depression severity and duration assessed with predictive modeling.

BACKGROUND: Family history of depression (FHD) is a known risk factor for the new onset of depression. However, it is unclear if FHD is clinically useful for prognosis in adolescents with current, ongoing, or past depression. This preregistered study uses a longitudinal, multi-informant design to examine whether a child's FHD adds information about future depressive episodes and depression severity applying state-of-the-art predictive out-of-sample methodology. METHODS: We examined data in adolescents with current or past depression (age 11-17 years) from the National Institute of Mental Health Characterization and Treatment of Adolescent Depression (CAT-D) study. We asked whether a history of depression in a first-degree relative was predictive of depressive episode duration (72 participants) and future depressive symptom severity in probands (129 participants, 1,439 total assessments). RESULTS: Family history of depression, while statistically associated with time spent depressed, did not improve predictions of time spent depressed, nor did it improve models of change in depression severity measured by self- or parent-report. CONCLUSIONS: Family history of depression does not improve the prediction of the course of depression in adolescents already diagnosed with depression. The difference between statistical association and predictive models highlights the importance of assessing predictive performance when evaluating questions of clinical utility.

Great Expectations: A Critical Review of and Suggestions for the Study of Reward Processing as a Cause and Predictor of Depression.

Both human and animal studies support the relationship between depression and reward processing abnormalities, giving rise to the expectation that neural signals of these processes may serve as biomarkers or mechanistic treatment targets. Given the great promise of this research line, we scrutinized those findings and the theoretical claims that underlie them. To achieve this, we applied the framework provided by classical work on causality as well as contemporary approaches to prediction. We identified a number of conceptual, practical, and analytical challenges to this line of research and used a preregistered meta-analysis to quantify the longitudinal associations between reward processing abnormalities and depression. We also investigated the impact of measurement error on reported data. We found that reward processing abnormalities do not reach levels that would be useful for clinical prediction, yet the available evidence does not preclude a possible causal role in depression.

Oxytocin-Induced Changes in Intrinsic Network Connectivity in Cocaine Use Disorder: Modulation by Gender, Childhood Trauma, and Years of Use.

Cocaine use disorder (CUD) is a major public health concern with devastating social, economic, and mental health implications. A better understanding of the underlying neurobiology and phenotypic variations in individuals with CUD is necessary for the development of effective and targeted treatments. In this study, 39 women and 54 men with CUD completed a 6-min resting-state functional magnetic resonance imaging scan after intranasal oxytocin (OXY) or placebo administration. Graph-theory network analysis was used to quantify functional connectivity changes caused by OXY in striatum, anterior cingulate cortex (ACC), insula, and amygdala nodes of interest. OXY increased connectivity in the right ACC and left amygdala in males, whereas OXY increased connectivity in the right ACC and right accumbens in females. Machine learning was then used to associate treatment response (placebo minus OXY) in nodes of interest with years of cocaine use and severity of childhood trauma separately for males and females. Childhood trauma and years of cocaine use were associated with OXY-induced changes in ACC connectivity for both men and women, but connectivity changes in the amygdala were associated with years of cocaine use in men and connectivity changes in the right insula were associated with years of cocaine use in women. These findings suggest that salience network nodes (ACC and insula) are potential OXY treatment targets in CUD, with the amygdala as a treatment target for men and the accumbens as a treatment target for women.

Network Analysis of Intrinsic Functional Brain Connectivity in Male and Female Adult Smokers: A Preliminary Study.

Background: The goal of this study was to conduct a preliminary network analysis (using graph-theory measures) of intrinsic functional connectivity in adult smokers, with an exploration of sex differences in smokers. Methods: Twenty-seven adult smokers (13 males; mean age = 35) and 17 sex and age-matched controls (11 males; mean age = 35) completed a blood oxygen level-dependent resting state functional magnetic resonance imaging experiment. Data analysis involved preprocessing, creation of connectivity matrices using partial correlation, and computation of graph-theory measures using the Brain Connectivity Toolbox. Connector hubs and additional graph-theory measures were examined for differences between smokers and controls and correlations with nicotine dependence. Sex differences were examined in a priori regions of interest based on prior literature. Results: Compared to nonsmokers, connector hubs in smokers emerged primarily in limbic (parahippocampus) and salience network (cingulate cortex) regions. In addition, global influence of the right insula and left nucleus accumbens was associated with higher nicotine dependence. These trends were present in male but not female smokers. Conclusions: Network communication was altered in smokers, primarily in limbic and salience network regions. Network topology was associated with nicotine dependence in male but not female smokers in regions associated with reinforcement (nucleus accumbens) and craving (insula), consistent with the idea that male smokers are more sensitive to the reinforcing aspects of nicotine than female smokers. Implications: Identifying alterations in brain network communication in male and female smokers can help tailor future behavioral and pharmacological smoking interventions. Male smokers showed alterations in brain networks associated with the reinforcing effects of nicotine more so than females, suggesting that pharmacotherapies targeting reinforcement and craving may be more efficacious in male smokers.