Use of Tobacco Products and Suicide Attempts Among Elementary School-Aged Children.

Importance: The use of tobacco products, including e-cigarettes and vaping, has rapidly increased among children. However, despite consistent associations found between smoking cigarettes and suicidal behaviors among adolescents and adults, there are limited data on associations between emerging tobacco products and suicidal behaviors, especially among preadolescent children. Objective: To examine whether the use of tobacco products is associated with nonsuicidal self-injury (NSSI), suicidal ideation (SI), and suicide attempts (SAs) among preadolescent children. Design, Setting, and Participants: This cohort study, conducted from September 1, 2022, to September 5, 2023, included participants in the Adolescent Brain Cognitive Development study, a population-based cohort of 11 868 US children enrolled at 9 and 10 years of age. The cross-sectional investigation focused on 3-year periods starting from the baseline to year 2 of follow-up. Statistical analysis was performed from October 1, 2022, to June 30, 2023. Main Outcomes and Measures: Children's use of tobacco products was assessed based on youth reports, including lifetime experiences of various nicotine-related products, supplemented with hair toxicologic tests. Main outcomes were children's lifetime experiences of NSSI, SI, and SAs, assessed using the K-SADS-5 (Kiddie Schedule for Affective Disorders and Schizophrenia for the DSM-5). Multivariate logistic regression was conducted to examine the associations of the use of tobacco products with NSSI, SI, and SAs among the study participants. Sociodemographic, familial, and children's behavioral, temperamental, and clinical outcomes were adjusted in the analyses. Results: Of 8988 unrelated study participants (median age, 9.8 years [range, 8.9-11.0 years]; 4301 girls [47.9%]), 101 children (1.1%) and 151 children (1.7%) acknowledged lifetime use of tobacco products at baseline and at 18-month follow-up, respectively. After accounting for various suicide risk factors and potential confounders, children reporting use of tobacco products were at a 3 to 5 times increased risk of SAs (baseline: n = 153 [adjusted odds ratio (OR), 4.67; 95% CI, 2.35-9.28; false discovery rate (FDR)-corrected P < .001]; year 1: n = 227 [adjusted OR, 4.25; 95% CI, 2.33-7.74; FDR-corrected P < .001]; and year 2: n = 321 [adjusted OR, 2.85; 95% CI, 1.58-5.13; FDR-corrected P = .001]). Of all facets of impulsivity measures that were significant correlates of use of tobacco products, negative urgency was the only independent risk factor for SAs (adjusted OR, 1.52 [95% CI, 1.31-1.78]; FDR-corrected P < .001). In contrast, children's alcohol, cannabis, and prescription drug use were not associated with SAs. Conclusions and Relevance: This study of US children suggests that the increased risk of SAs, consistently reported for adolescents and adults who smoke cigarettes, extends to a range of emerging tobacco products and manifests among elementary school-aged children. Further investigations are imperative to clarify the underlying mechanisms and to implement effective preventive policies for children.

Brain tissue iron neurophysiology and its relationship with the cognitive effects of dopaminergic modulation in children with and without ADHD.

Children with attention-deficit/hyperactivity disorder (ADHD) exhibit impairments in response inhibition. These impairments are ameliorated by modulating dopamine (DA) via the administration of rewards or stimulant medication like methylphenidate (MPH). It is currently unclear whether intrinsic DA availability impacts these effects of dopaminergic modulation on response inhibition. Thus, we estimated intrinsic DA availability using magnetic resonance-based assessments of basal ganglia and thalamic tissue iron in 36 medication-naïve children with ADHD and 29 typically developing (TD) children (8-12 y) who underwent fMRI scans and completed standard and rewarded go/no-go tasks. Children with ADHD additionally participated in a double-blind, randomized, placebo-controlled, crossover MPH challenge. Using linear regressions covarying for age and sex, we determined there were no group differences in brain tissue iron. We additionally found that higher putamen tissue iron was associated with worse response inhibition performance in all participants. Crucially, we observed that higher putamen and caudate tissue iron was associated with greater responsivity to MPH, as measured by improved task performance, in participants with ADHD. These results begin to clarify the role of subcortical brain tissue iron, a measure associated with intrinsic DA availability, in the cognitive effects of reward- and MPH-related dopaminergic modulation in children with ADHD and TD children.

Biobehavioral correlates of an fMRI index of striatal tissue iron in depressed patients.

Dopaminergic function is a critical transdiagnostic neurophysiological dimension with broad relevance in psychiatry. Normalized T2*-weighted (nT2*w) imaging has been previously investigated as a method to quantify biological properties of tissue in the striatum (e.g., tissue iron), providing a widely available, in vivo marker with potential relevance to dopaminergic function; but no prior study to our knowledge has examined this neuroimaging marker in clinical depression. In a treatment-seeking, clinically depressed sample (n = 110), we quantified tissue iron (nT2*w) in striatal regions. We assessed test-retest reliability and correlated values with dimensional features across levels of analysis, including demographic/biological (sex, age, Body Mass Index), neuroanatomical (hippocampal atrophy, which was quantified using a recently validated machine-learning algorithm), and performance-based (Affective Go/NoGo task performance) indices with relevance to depressive neurocognition. Across patients, decreased tissue iron concentration (as indexed by higher nT2*w) in striatal regions correlated with indices of decreased cognitive-affective function on the Affective Go/NoGo task. Greater caudate nT2*w also correlated with greater hippocampal atrophy. Striatal tissue iron concentrations were robustly lower in female patients than males but gender differences did not explain relations with other neurocognitive variables. A widely available fMRI index of striatal tissue properties, which exhibited strong psychometric properties and can be readily quantified from most fMRI datasets irrespective of study-specific features such as task design, showed relevance to multiple biobehavioral markers of pathophysiology in the context of moderate-to-severe, treatment-resistant depression. Striatal tissue iron may play a role in dimensional and subgroup-specific features of depression, with implications for future research on depression heterogeneity.

Assessing Changes in Symptoms of Depression and Anxiety During Four Weeks of Cannabis Abstinence Among Adolescents.

Background: Cannabis use is prevalent among adolescents, and many report using in attempts to alleviate negative mood and anxiety. Abstinence from substances such as alcohol and tobacco has been reported to improve symptoms of anxiety and depression. Few studies have examined the effect of cannabis abstinence on symptoms of anxiety and depression. Objective: To test the effect of 4 weeks of continuous cannabis abstinence on depressive and anxious symptoms. Methods: Healthy, non-treatment seeking adolescents who used cannabis at least weekly (n = 179) were randomized to either 4 weeks of cannabis abstinence achieved through a contingency management paradigm (CB-Abst) or cannabis use monitoring without an abstinence requirement (CB-Mon). Abstinence was assessed by self-report verified with quantitative assay of urine for cannabinoids. Anxiety and depressive symptoms were assessed weekly with the Mood and Anxiety Symptom Questionnaire (MASQ). Results: Symptoms of depression and anxiety decreased throughout the study for all participants (MASQ-AA: stnd beta = -0.08, p = 0.01, MASQ-GDA: stnd beta = -0.11, p = 0.003, MASQ-GDD: stnd beta = -0.08, p = 0.02) and did not differ significantly between randomization groups (p's > 0.46). Exploratory analyses revealed a trend that abstinence may be associated with greater improvement in symptoms of anxiety and depression among those using cannabis to cope with negative affect and those with potentially hazardous levels of cannabis use. Conclusions: Among adolescents who use cannabis at least weekly, 4 weeks of cannabis abstinence was not associated with a significant change in anxiety or depressive symptoms compared to continued use. For recreational cannabis users who may be concerned about reducing their use for fear of increased symptoms of anxiety and depression, findings suggest that significant symptom worsening may not occur within the first 4 weeks of abstinence. Further studies are needed in clinical populations where anxiety and depression symptoms are measured more frequently and for a longer period of abstinence. Future studies are also needed to determine whether there are subgroups of adolescents who are uniquely impacted by sustained cannabis abstinence.